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Title: Psychiatry lecture notes
Description: A detailed and comprehensive set of psychiatry lectures notes. Covers all aspects of mental health. Diagrams included to aid learning. Very useful for medical students.

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PSYCHIATRY  REVISION  NOTES  
 
PSYCHIATRIC  HISTORY  TAKING  
 
Information  from  patient  and  other  informants  (collateral  history):  
 
• Presenting   complaint   and   history   of   presenting   complaint:   SOCRATES:   Affective   (mood)  
disorder   (mania   or   depression)   –   how   is   you   mood?     Is   it   up   or   down?   Psychotic   disorder  
(psychosis)   –   any   strange   thoughts   or   feelings?   Any   strange   voices   or   images?   Personality  
disorder?    Alcohol/drug  dependency?    Self  harm?    Anxiety  –  do  you  every  worry  about  stuff?  
Do  a  psychiatric  systematic  enquiry  to  screen  for  all  the  major  diorders
...
    Previous   alcohol   or   drug  
problems
...
g
...
   Technical  description  of  the  following  factors  should  be  documented:  
 
• Appearance:  age,  facial  expressions,  activity  (e
...
 fidgeting  or  sitting  still),  posture,  clothing,  
effort   with   appearance,   evidence   of   self   neglect,   evidence   of   self   harm,   evidence   of   drug  
abuse   or   alcohol   dependency,   signs   of   physical   ill   health,   signs   of   weight   loss,   signs   of  
malnutrition  
 
• Behaviour:   describe   what   the   patient   is   doing   and   the   appropriateness   for   the   situation,   eye  
contact,  attitude/rapport,  cooperative/uncooperative,  hostile,  guarded,  suspicious,  anxious,  
psychomotor   agitation   (unintentional   and   purposeless   motions   that   stem   from   mental  
tension  and  anxiety  of  an  individual),  psychomotor  retardation  (involves  a  slowing-­‐down  of  
thought   and   a   reduction   of   physical   movements   in   an   individual),   other   abnormal  
movements  (e
...
 choreiform,  tics,  myoclonics,  bradykinesia,  hyperkinesia)  







 
Speech:   volume,   rate,   tone,   articulation,   accent,   vocabulary,   sudden   silences,   poverty   of  
speech  (minimal  verbal  communication),  echolalia  (repetition  of  another  person's  words)  
 
Mood  and  affect  (including  suicidality)  
! Mood:   subjective   description   using   patients   own   words   (can   rate   mood   on   a  
scale)   e
...
  neutral,   euthymic,   dysphoric,   euphoric,   anxious,   angry,   apathetic,  
irritable,   suicidal   ideation   or   self-­‐harm
...
g
...
    Also  
include   doctors   objective   description   of   mood   e
...
  appeared   anxious   due   to  
sweating  and  fidgeting  
! Suicidality:   very   important   to   ask,   “Have   you   ever   thought   about   harming  
yourself?”    If  so  then  further  enquire  into  plan,  reasons  to  die,  reasons  to  live  etc
...
g
...
g
...
g
...
g
...
 
 
Neuropsychiatric   examination:   The   MSE   may   include   a   brief   neuropsychiatric   examination   in  
some   situations   e
...
  to   assess   for   basal   ganglia   pathology   in   suspected   PD   (bradykinesia,  
rigidity,  tremor,  postural  instability)  or  cerebellar  disease  (“DANISH  PT”)  
 

 
DEPRESSED  MOOD  
 
Depressed  mood  is  not  necessarily  a  psychiatric  disorder
...
g
...
g
...
  It   is   often   one   of   the   early   symptoms   of  
hypothyroidism)  –  organic  low  mood  –  MUST  ALWAYS  RULE  OUT  
• A  side  effect  of  some  drugs  or  medical  treatments  
• Must  always  rule  out  organic  causes  before  diagnosing  psychiatry  cause!  
 
Clinical  depression  
• Clinical   depression   (major   depressive   disorder   MDD)   is   a   psychiatric   disorder   characterized  
by   a   pervasive   and   persistent   low   mood   which   is   accompanied   by   a   variety   of   symptoms  
such   as   low   energy   (anergia),   loss   of   interest   or   pleasure   in   normally   enjoyable   activities  
(anhedonia),  low  self  esteem,  disturbed  sleep,  weight  loss  and  if  severe  –  psychosis,  ideas  of  
self  harm  and  suicide
...
g
...
   The  model  specifies  that  depression  
results   when   a   pre-­‐existing   vulnerability   (e
...
  genetics,   early   adverse   life   experiences,  
personality  traits)  is  activated  by  stressful  life  events  
• Always  consider  BIOPSYCHOSOCIAL  FACTORS  
• Pathophysiology:   Due   to   the   clinical   and   etiological   heterogeneity   of   major   depressive  
disorder,   it   has   been   difficult   to   elucidate   its   pathophysiology
...
  These   substances   are   serotonin  
(5HT),   norepinephrine   (noradrenaline   NA),   and   dopamine   (DA)
...
   Most  antidepressant  medications  increase  the  levels  
of   one   or   more   of   the   monoamines:   the   neurotransmitters   serotonin,   norepinephrine   and  






dopamine,  in  the  synaptic  cleft  between  neurons  in  the  brain
...
 
Very  complicated  pathophysiology  –  not  fully  understood
...
g
...
   If  suicidal  =>  severe
...
   Have  you  had  any  strange  thoughts  or  feelings?    Have  
you  seen  or  heard  anything  that  no  one  else  has?  
Physical  symptoms    
Pseudodementia  (decrease  in  cognitive  ability)  
Self  harm  and  suicide  (always  enquire  about)  –  specifically  ask  about  thought  of  harm  or  
suicide
...
    Plans   etc
...
    Reasons   to   live
...
     

 
 
 
MSE  
 
The  MSE  is  important  for  fully  assessing  the  patient  and  most  importantly  assessing  for  evidence  of  
self  harm,  suicidal  thought  and  drug/alcohol  abuse
...
g
...
   The  triad  
involves  negative  thoughts  about:  
 
• The  self  (e
...
 the  self  is  worthless,  helpless  and/or  unlovable)  
• The  world/environment  (e
...
 the  world  is  unfair)  
• The  future  (e
...
 the  future  is  hopeless)
...
     
 
 
Subtypes  of  clinical  depression  
The   DSM-­‐IV-­‐TR   recognizes   five   further   subtypes   of   major   depressive   disorder   (clinical   depression),  
called  specifiers:  
• Melancholic   depression   is   characterized   by   a   loss   of   pleasure   in   most   or   all   activities,   a  
failure  of  reactivity  to  pleasurable  stimuli,  a  quality  of  depressed  mood  more  pronounced  
than   that   of   grief   or   loss,   a   worsening   of   symptoms   in   the   morning   hours,   early-­‐morning  
waking,   psychomotor   retardation,   excessive   weight   loss   (not   to   be   confused   with   anorexia  
nervosa),   or   excessive   guilt
...
     
• Atypical   depression   is   characterized   by   mood   reactivity   (paradoxical   anhedonia)   and  
positivity,   significant   weight   gain   or   increased   appetite   (hyperphagia,   comfort   eating),  
excessive   sleep   or   sleepiness   (hypersomnia),   a   sensation   of   heaviness   in   limbs   known   as  
leaden  paralysis,  and  significant  social  impairment  as  a  consequence  of  hypersensitivity  to  
perceived   interpersonal   rejection
...
   May  respond  better  to  MAO-­‐A  
inhibitors  e
...
 meclobemide
...
  Here   the   person   is   mute   and   almost   stuporous  
(decreased   consciousness),   and   either   remains   immobile   or   exhibits   purposeless   or   even  





bizarre  movements
...
   Indication  for  ECT
...
   Postpartum  depression  has  an  incidence  rate  of  
10–15%  among  new  mothers
...
 It  has  been  said  
that  postpartum  depression  can  last  as  long  as  three  months
...
     
Seasonal  affective  disorder  (SAD)  is  a  form  of  depression  in  which  depressive  episodes  come  
on   in   the   autumn   or   winter,   and   resolve   in   spring
...
 
 

 
Atypical  Depression  
 
Diagnostic  criteria  requires  two  (or  more)  of  the  following  
• Paradoxical  anhedonia  (mood  reactivity)  e
...
 improved  mood  in  response  to  positive  events  
(reactive  affect,  rather  than  blunted)  
• Significant  weight  gain  or  increase  in  appetite  -­‐  hyperphagia  (comfort  eating)  
• Hypersomnia  (excessive  sleepiness)  
• Leaden  paralysis  (that  is,  heavy,  leaden  feelings  in  arms  or  legs)  
• Long-­‐standing   pattern   of   interpersonal   rejection   sensitivity   (not   limited   to   episodes   of   mood  
disturbance)  that  results  in  significant  social  or  occupational  impairment  
 
 
Depression  differential  diagnosis  
 
There   are   many   psychiatric   and   medical   (organic)   conditions   that   may   mimic   some   or   all   of   the  
symptoms  of  clinical  depression,  or  may  occur  co-­‐morbid  to  it
...
g
...
g
...
g
...
g
...
g
...
  They   include  
depressions   due   to   physical   organic   illness   (directly   or   indirectly),   chronic   pain,   medications,   and  
substance  abuse
...
  This   condition   is   determined   based   on   history,   laboratory   findings,   or   physical  
examination
...
   In  
such  cases,  a  substance  is  judged  to  be  aetiologically  related  to  the  mood  disturbance
...
  Low  
mood  or  loss  of  interest  (anhedonia)  must  be  present  and  delusions  and  hallucinations  are  absent
...
 
 
While   this   disorder   may   interfere   with   social   or   occupational   functioning,   the   disturbance   is   not  
severe   enough   to   qualify   for   a   diagnosis   of   major   depressive   disorder   (clinical   depression)
...
  Also,   people   with   only   partial   recovery   from   a   major   depression   are   not   classified   as  
dysthymic
...
 The  symptoms  are  not  as  severe  as  those  for  major  depression,  
although   people   with   dysthymia   are   vulnerable   to   secondary   episodes   of   major   depression  
(sometimes  referred  to  as  double  depression)
...
   Older  people  were  sometimes  misdiagnosed  as  having  dementia  
when  further  investigation  showed  they  were  suffering  from  a  major  depressive  episode
...
       






It   has   long   been   observed   that   in   the   differential   diagnosis   between   dementia   and  
pseudodementia,   depressive   pseudodementia   appears   to   be   the   single   most   difficult  
disorder   to   distinguish   from   "organic"   categories   of   dementia,   especially   degenerative  
dementia  of  the  Alzheimer  type
...
   
Investigations  such  as  SPECT  imaging  of  the  brain  show  reduced  blood  flow  in  areas  of  the  
brain   in   people   with   Alzheimer's   disease,   compared   with   a   more   normal   blood   flow   in   those  
with  pseudodementia  
Complex  pathophysiology  


 
 
Management  of  depression  
 
The  three  most  common  treatments  for  depression  are:  
• Psychotherapy   e
...
  CBT   (first   line   management;   CBT   has   the   greatest   evidence   base   for  
effectiveness)  
• Medication:   SSRIs   usually   first   line   medication   due   to   relatively   mild   side   effects;   often   used  
in  conjunction  with  psychotherapy  
• Electroconvulsive  therapy  (last  resort  or  for  emergencies  e
...
 Tx  resistant  severe  depression  
or  catatonia)  
 
 
ECT  
• Electroconvulsive  therapy  (ECT)  is  a  procedure  whereby  pulses  of  electricity  are  sent  through  
the   brain   via   two   electrodes,   usually   one   on   each   temple,   to   induce   a   seizure   while   the  
person  is  under  a  brief  period  of  general  anaesthesia
...
   
• Can  also  be  used  for  catatonic  states  
• ECT  can  have  a  quicker  effect  than  antidepressant  therapy  and  thus  may  be  the  treatment  of  
choice   in   emergencies   such   as   catatonic   depression   where   the   person   has   stopped   eating  
and  drinking,  or  where  a  person  is  severely  suicidal
...
  However,   when   ECT   is   used   on   its   own,   the   relapse   rate   within   the   first   six  
months  is  very  high  (a  recent  controlled  trial  found  rates  of  84%  even  with  placebos)
...
     
• Although   memory   disturbance   after   ECT   usually   resolves   within  one  month,  ECT  remains  a  
controversial  treatment,  and  debate  on  its  efficacy  and  safety  continues
...
  Care   is   usually   given   on   an   outpatient   basis,   whereas  
treatment  in  an  inpatient  unit  is  considered  if  there  is  a  significant  risk  to  self  or  others  

 
 
Bipolar  affective  disorder  
• Bipolar   disorder,   also   known   as   bipolar   affective   disorder,   manic-­‐depressive   disorder,   or  
manic  depression,  is  a  mental  illness  classified  by  psychiatry  as  a  mood  (affective)  disorder
...
   
• Bipolar  disorder  is  characterized  by  two  or  more  episodes    
• Mania/hypomania   is   the   defining   feature   of   bipolar   disorder   (and   must   occur   at   least   once  
out  of  the  two  defining  episodes)  
• Repeated   episodes   of   hypomania   or   mania   only   are   still   classified   as   bipolar   disorder   –   a  
depressive  episode  is  NOT  required  to  meet  the  diagnostic  criteria  
• Mean  age  of  onset  21  years  
• Types:  
! Bipolar  type  1  (mania):  prevalence  1%  
! Bipolar  type  2  (hypomania):  prevalence  1
...
g
...
g
...
g
...
  Substance   abuse   may   predate   the   appearance   of  
bipolar  symptoms,  further  complicating  the  diagnosis
...
     
• Mania  can  occur  with  different  levels  of  severity
...
     
• As   mania   becomes   more   severe,   individuals   begin   to   behave   erratically   and   impulsively,  
often  making  poor  decisions  due  to  unrealistic  ideas  about  the  future,  and  may  have  great  
difficulty  with  sleep
...
    People   with   bipolar   disorder   exhibiting   psychotic   symptoms   can  
sometimes  be  misdiagnosed  as  having  schizophrenia
...
     

Manic  and  depressive  episodes  last  from  a  few  days  to  several  months
...
  Generally,   hypomania   does   not   inhibit  
functioning  (in  contrast  to  mania)
...
 


 
Hypomania  has  same  symptoms  as  mania  but  often  milder  e
...
 
• Mild  elevation  of  mood  
• Pressure  of  speech  and  activity  
• Feelings  of  wellbeing  and  efficiency  
• Increased  energy  and  activity  
• Sometimes  irritability  
• Some  disturbance  of  function  
• NO  PSYCHOSIS  
 
 
Depressive  phase  
Signs  and  symptoms  of  the  depressive  phase  of  bipolar  disorder  include:  
• Depressed  (low  mood)  
• Anhedonia  
• Anergia  
• Loss  of  appetite  
• Sleep  disturbance    
• Loss  of  interest  in  sexual  activity  
• Morbid  suicidal  thoughts
...
  These   symptoms   include   delusions   or,   less   commonly,  
hallucinations,  usually  unpleasant
...
 
 
Lamotrigine   is   a   useful   second   line   agent   for   pts   who   have   depression   predominant   bipolar
...
 
 
 
Mixed  Affective  State  
• In   the   context   of   bipolar   disorder,   a   mixed   affective   state   is   a   condition   during   which  
symptoms  of  mania/hypomania  and  depression  occur  simultaneously
...
 
• Individuals   may   also   feel   very   frustrated   in   this   state,   for   example   thinking   grandiose  
thoughts  while  at  the  same  time  feeling  like  a  failure
...
 
 
 
 

Diagnosis  
• History  
• We  can  use  MSE  to  clinically  evaluate  suspected  bipolar  patients
...
     
• There  is  no  simple  physiological  test  to  confirm  the  disorder
...
    In   particular,   it   can   be   difficult   to   distinguish   depression   caused   by   bipolar  
disorder  from  pure  unipolar  depression
...
  The   criteria   takes   into  
account  the  presence  and  duration  of  certain  signs  and  symptoms
...
g
...
   
Very  important  to  fully  asses  sot  including  blood  and  potentially  imaging
...
  Although   there   are   no  
biological   tests,   which   confirm   bipolar   disorder,   tests   may   be   carried   out   to   exclude   medical  
(organic)   illnesses   such   as   hypo-­‐   or   hyperthyroidism,   metabolic   disturbance,   a   systemic   infection  
or   chronic   disease,   and   syphilis   or   HIV   infection   (which   may   be   the   cause   or   exacerbator   of   the  
psychiatric   presentation)
...
 Investigations  are  not  generally  repeated  for  relapse  unless  there  is  a  specific  
medical  indication
...
   
• These  disorders  range  from  bipolar  type  1  disorder  (featuring  full-­‐blown  manic  episodes)  
to   cyclothymia   (featuring   less   prominent   hypomanic   episodes)   to   bipolar   type   2   disorder  
(featuring  hypomanic  episodes)
...
 
 
 

Criteria  and  subtypes:    DSM  classification  
• Bipolar  type  I  disorder:  One  or  more  manic  episodes
...
    This   is   the   most   severe   bipolar   with   the  
worse  prognosis
...
 
• Cyclothymia:  A  history  of  hypomanic  episodes  with  periods  of  depression  that  do  not  meet  
criteria   for   major   depressive   episodes
...
     Cyclothymia  is  a  mild  
form  of  bipolar  disorder,  however,  the  symptoms  do  not  meet  the  diagnostic  requirements  
for   any   other   type   of   bipolar   disorder
...
  These   include   schizophrenia,   schizoaffective   disorder,   attention   deficit  
hyperactivity   disorder   (ADHD),   delirium,   non-­‐bipolar   psychosis,   and   some   personality  
disorders,  including  borderline  personality
...
g
...
   
 
 
 
Schizoaffective  disorder  
• Episodic  disorders  
• Schizophrenic   symptoms   (e
...
  First   rank   symptoms)   and   mood   symptoms   present   to   the  
same  degree  in  the  same  episode  -­‐  at  same  time  or  within  days  of  each  other  
• In   contrast,   acute   episodes   of   schizophrenia   are   NOT   normally   associated   with   affective  
(mood  symptoms)  at  the  same  time  
• More  discussion  in  schizophrenia  lecture    
 
 
Management  of  bipolar  
• Psychosocial  e
...
 CBT  



Medication  e
...
 lithium  (often  first  line),  sodium  valproate  (good  for  mania  predominance),  
and  lamotrigine  (good  for  depressive  predominance)  

 
A   number   of   medications   are   used   to   treat   bipolar   disorder
...
   Lithium  reduces  the  risk  of  suicide,  self-­‐harm,  and  
death  in  people  with  bipolar  disorder
...
 
 
 
THE  NEUROBIOLOGY  OF  MOOD  DISORDERS  
 
Appetitive/Approach  Systems:  Reward  system  
This  system  functions  to  mediate  seeking  and  approach  behaviours  (including  pleasure)  e
...
 reward  
pathways
...
     DA  projections  are  selectively  confined  to  specific  parts  of  brain
...
g
...
   
The   major   part   of   this   system   is   the   noradrenaline   and   ascending   serotonin   systems
...
     
 
Components  include:  
• Cortex    
• Limbic  system:  
! Central   nucleus   of   amygdale   (activates   hypothalamus   to   generate   flight   or   fright  
response)  
! Hippocampus    
! Hypothalamus  (actives  ANS  for  flight  or  fright  response)  
• Periaqueductal  gray  matter  
 
 

 
 
 
 
Neurobiology  of  Depression  
 
Clinical  features  of  Major  Depressive  disorder  
 
Core  symptoms:  
• Low  (depressed)  mood  
• Anhedonia  (lack  of  pleasure)  
• Anergia  (lack  of  energy)  
 
Other  symptoms  (ICD  10):  
• Disturbed  sleep  
• Diminished  appetite  
• Reduced  concentration  and  attention  

 






Reduced  self  esteem  and  self  confidence  
Ideas  of  guilt  and  unworthiness  
Bleak  and  pessimistic  views  of  the  future  
Ideas  or  acts  of  self  harm  or  suicide  (never  forget  to  enquire  about  suicide  and  self  harm:  
both  in  the  past,  present,  or  thoughts  about  future)  

 
 
Linking  neurobiology  to  depressive  symptoms  
• Dysfunction  of  the  aversive/defensive  systems  is  the  main  thing  associated  with  depression,  
and  
these  
systems  
are  
primarily  
mediated  
by  
serotonin  
(and  
noradrenaline/norepinephrine)
...
   
• Increasing  serotonin  in  the  synapse  itself  doesn’t  appear  to  be  the  direct  way  that  SSRIs  treat  
depression  (takes  about  16  hours  for  an  SSRI  to  increase  the  serotonin  level,  but  2-­‐6  weeks  
for   it   to   work)   but   changes   in   serotonin   receptors   as   a   result   of   the   increase   in   serotonin,  
which   may   then   affect   secondary   messengers   and   in   turn   gene   expression,   seem   to   be  
involved
...
g
...
     
• Such   atrophy   is   centred   in   a   brain   region   called   the   hippocampus
...
g
...
     
• The   hippocampus   belongs   to   the   limbic   system   and   plays   important   roles   in   the  
consolidation   of   information   from   short-­‐term   memory   to   long-­‐term   memory   and   spatial  
navigation
...
 
 
 
 
Bipolar  Disorder  neurobiology  
 
Linking  neurobiology  to  mania  symptoms  
• Mania/Hypomania   symptoms   can   be   explained   by   disordered   appetitive/approach   (reward  
system:   dopamine   pathways)   functioning   AND   disordered   aversive/defensive   (serotonin  
and  noradrenaline  pathways)
...
 
• PSYCHOLOGICAL  AND  PHYSICAL  COMPONENT  
• Anxiety  can  be  a  normal  response  to  a  threat  (therefore  not  an  anxiety  disorder)  
• Psychological  component:    fear,  dread,  unease,  avoidance,  worry,  panic  
• Physical  component:    dry  mouth,  globus  pharyngeus,  chest  tightness,  SOB,  tingling,  urinary  
and  bladder  dysfunction,  muscle  tightness,  tremor,  palpitations  


 
Anxiety  is  a  bio-­‐psycho-­‐social  state  with  the  following  elements:  
• Bodily  responses:  autonomic  (increased  sympathetic  activity  due  to  flight  or  fright  response)  
and  hormonal  (e
...
 increased  cortisol  due  to  stress)  
• Psychological:   thoughts   and   emotions   such   as   unease,   fear   or   dread,   panic   (which   are  
disproportionate  to  the  situation)  
• Social:  Impact  upon  interaction  in  the  environment  e
...
 facial  expressions,  speech,  coughing,  
swallowing,  avoidance  of  situations    
 
 
Normal  response  to  threat  
 
The  amygdala  plays  a  central  role  in  responding  to  threat
...
g
...
e
...
    Aberrant   overactivity   in   the   amygdala   may   well   play   an   important   role   in   anxiety   disorders
...
 Cognitive-­‐Behaviour  theory:  Behavioural  theory  =>  anxiety  is  a  conditioned  response  to  specific  
environmental  stimuli
...
      Patients   with   anxiety   disorders   overestimate   the   degree   of   danger   and  
probability   of   harm   in   a   given   situation   underestimate   their   own   ability   to   cope   with   perceived  
threats
...
 
 
 
Types  of  anxiety  disorder  (DSM  IV)  
• Generalised   Anxiety   Disorder:   Remember   that   anxiety   is   a   mood
...
    There   are   no   specific   identifiable   triggers   in   GAD
...
     
• Anxiety   Disorder   due   to   a   general   medical   condition   (anxiety   can   be   a   symptom   of   many  
medical  conditions  -­‐  don’t  forget  about  hyperthyroidism,  Cushings,  hypercalcaemia)  
• Substance-­‐induced  anxiety  disorder  e
...
 cannabis  
• Panic  disorder:  The  individual  experiences  recurrent  panic  attacks  (severe  brief  episodes  of  
anxiety   –   psychological   and   physical   manifestations)   that   are   not   consistently   associated  
with  a  specific  situation  or  object,  and  which  often  occur  spontaneously
...
   May  occur  with  agrophobia  (agoraphobia  with  panic  disorder)  
• Social  phobia:  Marked  fear  or  avoidance  of  being  the  focus  of  attention  or  of  behaving  in  a  
way,   which   will   be   embarrassing   or   humiliating
...
   However  note  that  
the  individual  wants  to  be  social,  but  it  causes  fear
...
g
...
   Associated  with  anxiety  symptoms  and  emotional  distress  and  recognition  
that  symptoms  are  excessive/unreasonable
...
     
Specific   phobia:   Marked   fear   or   avoidance   of   a   specific   object   or   situation   not   included   in  
agoraphobia  or  social  phobia
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
    There   is   future  
potential  for  the  other  mediators  and  receptors,  especially  for  possible  repair  in  CNS
...
 
 
 
Cholinergic  system  
• NT=  Acetylcholine  (ACh)  -­‐  monoamine  NT  
• Receptors:   nicotinic   (ligand   gated   ion   channels:   ionotropic)   and   muscarinic   (metabotropic  
GPCR)    
• In  the  CNS:  Important  for  motor  control,  learning  and  memory,  and  attentional  processes    
• In   the   ANS:   important   for   both   sympathetic   (presynaptic   release   of   ACh)   and  
parasympathetic  (both  pre-­‐  and  post-­‐synaptic  release)  components  
• In  the  PNS  important  for  NMJ  transmission  (nicotinic  ion  channel)  
• Main  projecting  nuclei  =  Nucleus  basalis  of  Meynert  
 
Unlike   the   amino   acid   neurotransmitters   (GABA   and   glutamate)   and   NA/5HT,   it   has   a   much   more  
localised  distribution  in  the  CNS
...
g:  
• Striatum   (caudate   nucleus   and   putamen)   in   basal   ganglia:   role   in   motor   control   which   is  
relevant   to   some   treatments   for   Parkinson’s   disease,   where   anti-­‐cholinergics   can   be   used   to  
decrease  ACh  activity  =>  increase  relative  concentration  of  DA  in  basal  ganglia  system  
• Hippocampus:  role  in  learning  &  memory  (relevant  to  Alzheimer’s  disease)  
• Longer   projection   systems   from   the   nucleus   Basalis   of   Meynert   (degeneration   of   this   ACh  
rich  structure  is  also  implicated  in  Alzheimer’s  disease  =>  acetylcholinesterase  inhibitors  can  

be   used   in   AD   e
...
  Rivastigmine,   donepezil   and   galantamine)   to   cortex,   thalamus   and  
amygdale:  roles  in  attention  and  cognitive  function  
 
 

 
 
 
Noradrenergic  system  
• NT=  Noradrenaline  (NA)  /    Norepinephrine  (NE)  -­‐  monoamines  
• Receptors:  α  and  β-­‐adrenoceptors  (metabotropic  GPCRs)  
• Important  for  arousal  and  emotion  
• Aversive/defensive  system  
• Two  main  projecting  nuclei  in:  (i)  locus  coeruleus  (LC)  and  (ii)  brain  stem  (pons/medulla)  
• Each   noradrenaline   (NA)   containing   neurone   has   many   terminals   and   innervates   many   other  
cells  (diffuse  projections)  
• LC  neurones  may  be  involved  in  arousal  (silent  during  sleep)  and  mood  regulation  
• Control  of  blood  pressure  through  NA  synapses  in  the  medulla  (CV  centre)  
• NA   neurotransmitter   is   also   found   in   the   sympathetic   nervous   system   (postsynaptic  
neurones   release   NA;   except   with   sympathetic   nerves   innervating   the   adrenal   gland   which  
are  presynaptic  cells  and  release  ACh)  

 

 
 
 
 
Dopaminergic  system  
• NT=  Dopamine  (DA)  -­‐  monoamine  
• Receptors:  D1  and  D2  family  
• Appetitive/approach  (reward)  system  
• Important  for  motor  control,  motivation,  and  reward  
• Also   important   for   inhibition   of   prolactin   release   -­‐   thus   antipsychotics   (dopamine  
antagonists)  are  potent  stimulants  of  prolactin  release  and  can  cause  hyperprolactinaemia  
• Nigrostriatal   pathway   (in   the   basal   ganglia)   contains   70%   of   all   brain   dopamine   and   is  
involved  in  motor  control
...
 
• Mesocortical/mesolimbic  involved  in  motivation/reward,  emotion,  and  cognitive  functions  
• Minor   projection   to   pituitary   to   control   hormone   release:   (i)   Major   inhibitor   of   prolactin  
(under  constant  inhibition)  release  (ii)  Minor  inhibition  of  GH  

 

 
 
Serotonergic  (5HT)  system  









NT=  Serotonin  (5-­‐hydroxytryptamine  5HT)  -­‐  monoamine  
Aversive/defensive  system  –  major  NT  involved  
Receptors:  many  subtypes  5HT1,  5HT2,  5HT3  (most  of  them  G-­‐protein  linked  apart  from  the  
5-­‐HT3  receptor)  
Best   known   as   a   transmitter   in   several   brain   areas:   (i)   sleep   regions,   (ii)   limbic   system   and    
mood  control  regions  and  (iii)  pain  suppression  system  
Diffuse  projections  
Important   NT   for:   mood,   memory,   sleep,   cognition,   feeding   behavior,   sensory   perception  
and  analgesia  
May  play  an  important  role  in  hallucinations  
Happy  NT?  Ecstasy?  




Nuclei   confined   almost   exclusively   to   the   Raphe   nucleus   of   the   brain   stem   (RS   =   Raphe  
nucleus  and  serotonin)  
Virtually  every  neuron  in  the  brain  may  be  contacted  by  a  serotonergic  fibre  
 

 

 
Neuropeptides  






Small  proteins  that  can  act  as  neurotransmitters  
Synthesized  in  the  nucleus  and  then  transported  down  axonal  transport  system  to  synaptic  
terminal
...
 
Packaged  in  large  dense  core  vesicles  
Substance   P   and   opioid   peptides   (enkephalins)   found   in   spinal   cord   and   higher   brain  
centres    
Play  a  role  in  perception  of  pain  

 
 
Synaptic  transmission  (chemical)    
Common  mechanisms:  








Formation:    
! Non-­‐peptides  (e
...
 ACh,  DA,  NA,  5HT)  are  formed  in  the  nerve  terminal
...
g
...
 
Storage:  inside  vesicles  (with  the  help  of  VMAT),  small  synaptic  or  dense  core  
Release:   an   action   potential   invades   the   terminal   and   causes   Ca2+   influx   and   a   rise   in  
intracellular   calcium   =>   the   vesicles   fuse   with   the   terminal   membrane   to   allow   the  
neurotransmitter  into  the  synaptic  space
...
   
Occasionally  there  is  metabolism  in  the  synaptic  cleft  e
...
 by  MAO  enzymes  

 
Targets  for  drug  action  





Ion  channels  
Receptors  
Enzymes  
Transport  proteins  

Drugs   normally   interact   with   protein   molecules   in   or   on   neurones   in   order   to   alter   synaptic  
transmission   e
...
  presynaptic   receptor,   postsynaptic   receptor,   transporter,   OR   by   acting   on  
metabolic  chemicals  e
...
 acetlycholinesterase
...
g
...
g
...
     
 
Entry  of  drugs  into  brain  and  the  BBB    






BBB  (astrocytes)  is  protective  e
...
 protects  unwanted  disruption  of  brain  activity  
In   general,   lipid   soluble   (liophillic   or   hydrophobic)   drugs   get   in,   and   water   soluble  
(hydrophilic  or  liphophobic)  drugs  kept  out
...
 
Brain   penetration   predicted   by   oil/water   partition   coefficient
...
 
Specific  transporters  or  carrier  molecules  present  

 
Classification  of  drugs    




By  structure  e
...
 benzodiazepine  (BDZs)  
By  pharmacological  action  e
...
 monoamine  oxidase  inhibitor  (MOI)  
By  clinical  action  e
...
 antipsychotic  

 
 
PHARMACOLOGY  OF  ANTI-­‐DEPRESSANTS  AND  MOOD  STABALISERS  

Types  of  Antidepressant  drugs  
There  are  various  types  of  Anti-­‐depressants  (ADs):  





Monoamine   reuptake   inhibitors:   (i)   Tricyclics   (TCA)   &   related,   (ii)   Selective   serotonin  
reuptake   inhibitors   (SSRI),   (iii)   Other   non-­‐selective   and   selective   reuptake   inhibitors   e
...
 
SNRIs  (venlafaxine)  and  NaSSA  (e
...
 mirtazapine)    
Monoamine  oxidase  inhibitors  (MAO  inhibitors)  e
...
 meclobemdie  
Atypical  drugs  (post-­‐synaptic  receptor  effects)  

Most  of  the  drugs  used  have  a  similar  efficacy  but  different  profile  of  side  effects
...
g
...
g
...
  This   is   accomplished   by  
vesicular  monoamine  transporter  (VMAT)  in  the  lipid  bilayer  of  the  vesicle
...
 







Extracellular   uptake   of   NA   into   the   cytosol   is   done   either   presynaptically   (uptake   1)   or   by  
non-­‐neuronal  cells  in  the  vicinity  (uptake  2)
...
 
Reserpine   irreversibly   blocks   the   vesicular   monoamine   transporter   (VMAT)
...
  Unprotected   neurotransmitters   are   metabolized   by   MAO   (as   well   as   by  
COMT)   in   the   cytoplasm   and   consequently   never   excite   the   post-­‐synaptic   cell
...
   
As   the   result   of   decreased   dopamine   activity,   reserpine   can   be   used   to   treat   psychosis  
(reserpine  is  an  anti-­‐psychotic),  however  it  can  cause  drug-­‐induced  Parkinson's  disease
...
     
 
 

Serotonergic  (5HT)  system  















NT=  Serotonin  (5-­‐hydroxytryptamine/5HTP)  –  monoamines  
Aversive/defensive  system  –  DOMINANT  NT  
Receptors:   many   subtypes   5HT1,   5HT2,   5HT3   (Many   subtypes   of   receptor,   most   of   them   G-­‐
protein  linked  apart  from  the  5-­‐HT3  receptor)  
Best   known   as   a   transmitter   in   several   brain   areas:   (i)   sleep   regions,   (ii)   limbic   system   and    
mood  control  regions  and  (iii)  pain  suppression  system  
Important   NT   for:   mood,   memory,   sleep,   cognition,   feeding   behavior,   sensory   perception  
and  analgesia  
Nuclei  confined  almost  exclusively  to  the  Raphe  nucleus  of  the  brain  stem
...
 
Serotonin  transporters  (SERT)  transport  serotonin  back  into  presynaptic  terminal  
Monamine   oxidases   (MAO)   degrade   serotonin   in   the   cytoplasm   and   synaptic   cleft   =>   MAO  
inhibitors  can  increase  5HT  in  synaptic  cleft  

 
Reserpine    










Anti  psychotic  (as  decreases  DA  levels  =>  puts  brake  on  disordered  appetitive/approach  DA  
system)  
Resperine   is   a   drug   which   irreversibly   blocks   the   vesicular   monoamine   transporter   (VMAT)  
e
...
 reserpine  is  a  VMAT  inhibitor  
VMATs  primary  function  is  to  transport  free  norepinephrine,  serotonin,  and  dopamine  from  
the  cytoplasm  of  the  presynaptic  nerve  terminal  into  storage  vesicles  for  subsequent  release  
into  the  synaptic  cleft  ("exocytosis")
...
    Unprotected  
neurotransmitters   are   metabolized   by   MAO   (monoamine   oxidase)   in   the   cytoplasm   and  
consequently  never  reach  the  synapse
...
 
As   the   result   of   above,   reserpine   can   cause   drug-­‐induced   Parkinsonism   (due   to   decreased  
DA  activity)  and  drug  induced  low  mood  (due  to  decreased  5HT)  

 
Monoamine  oxidase  inhibitors  (MAOI)  
There  are  two  different  subtypes  of  MAO  with  a  slightly  different  substrate  preference:  









They   are   found   bound   to   the   outer   membrane   of   mitochondria   in   most   cell   types   in   the  
body  
MAOs  have  a  vital  role  in  the  inactivation  of  neurotransmitters,  therefore  MAO  dysfunction  
(too  much  or  too  little  MAO  activity)  is  thought  to  be  responsible  for  a  number  of  psychiatric  
and  neurological  disorders  
MAOA  (expressed  in  NA  neurons)  –  selective  for  NA,  5-­‐HT,  DA,  tyramine,  tryptamine  
MAOB  (expressed  in  5-­‐HT  neurons)  –  selective  for  DA,  tyramine,  tryptamine    
Appreciate  that  both  subtypes  are  selective  for:  DA,  tyramine,  tryptamine    
Appreciate  that  MAO  expressed  in  5-­‐HT  neurons  (MAOB)  doesn’t  actually  break  down  5-­‐HT
...
   
Compounds   that   enter   neurons   can   be   toxic/halllucinogenic   –   one   of   the   reasons   MAO   is  
there  to  protect  neuron  from  other  substances  it  may  get  in
...
 


MAO   inhibitors   can   result   in   (i)   excessive   levels   of   catecholamines   (epinephrine,   norepinephrine,  
and  dopamine;  particularly  in  MAO-­‐A  inhibitors  e
...
 meclobemide)  which  may  lead  to  a  hypertensive  
crisis   or   (ii)   excessive   levels   of   serotonin   which   may   lead   to  serotonin   syndrome
...
     



MAO-­‐A   inhibitors   (e
...
  meclobemide)   act   as   antidepressant   and   antianxiety   (anxiolytic)  
agents  (as  can  boost  5HT,  NA  and  DA  levels)  
MAO-­‐B   inhibitors   are   used   alone   or   in   combination   to   treat   Alzheimer’s   and   Parkinson’s  
diseases  e
...
 Selegiline  used  for  Parkinson’s  (can  boost  dopamine  levels)  

MAJOR  COMPLICATIONS  =  HT  CRISIS  (catecholamine  driven)  and  SEROTONIN  SYNDROME  
 
MAO  inhibitors:  mechanism  of  action  
Site  of  action:  MAO  inhibitors  inhibit  the  action  of  MAO  primarily  found  on  the  mitochondrial  outer  
membrane
...
 Therefore,  this  results  in  inhibition  of  
NT  breakdown  =>  increase  levels  of  NT  long  term  =>  increasing  function  at  synapse
...
g
...
g
...
g
...
g
...
 
Food   interactions   may   cause   hypertensive   crisis:   Interactions   with   foodstuffs   containing  
tyramine  (e
...
 cheese,  pickled  herrings,  marmite)
...
   
Excessive   tyramine   can   produce   a   hypertensive   crisis   (as   stimulates   sympathetic   system)
...
   
Therefore  patients  should  have  a  low  tyramine  diet
...
g
...
g
...
g
...
g
...
   Excessive  levels  of  serotonin  produce  a  spectrum  of  
specific   symptoms   including   cognitive,   autonomic,   and   somatic   effects
...
 
Because   of   potentially   lethal   dietary   and   drug   interactions,   monoamine   oxidase   inhibitors  
have  historically  been  reserved  as  a  last  line  of  treatment,  used  only  when  other  classes  of  
antidepressant   drugs   (for   example   selective   serotonin   reuptake   inhibitors   and   tricyclic  
antidepressants)  have  failed
...
   
They  are  named  by  structure  not  target  (unlike  monoamines)
...
g
...
     
They   are   also   used   to   treat   a   wide   variety   of   other   medical   conditions   (e
...
  neuropathic   pain  
and  migraine  prophylaxis)  and  psychiatric  disorders
...
    This   results   in   an   elevation   of   the   synaptic   concentrations   of   these  
neurotransmitters,  and  therefore  an  enhancement  of  neurotransmission  (particularly  useful  
in   treating   MDD;   as   these   monamines   are   closely   linked   to   the   disorder   e
...
  disordered  
appetitive/aversive   system)
...
     



Due   to   the   non-­‐specificity   of   reuptake   =>   they   therefore   have   many   more   side   effects   in  
comparison  to  SNRIs  such  as  venlafaxine  (which  is  SELECTIVE)  



Notably,  the  TCAs  have  negligible  affinity  for  the  dopamine  transporter  (DAT),  and  therefore  
have   no   efficacy   as   dopamine   reuptake   inhibitors   (DRIs)   =>   not   used   in   PD   or   related  
conditions
...
 



Anti-­‐cholinergic   (anti-­‐muscarinic)   and   anti   histamine   properties:   The   TCAs   also   have  
varying  but  typically  high  affinity  for  antagonising  the  H1  and  H2  histamine  receptors,  as  well  
as   the   muscarinic   (acetylcholine)   receptors
...
  These   properties   are   generally  
undesirable   in   antidepressants,   however,   and   likely   contribute   to   their   large   side   effect  
profiles
...
     
! Anti   muscarinic   effects   include   dry   eyes,   dry   eyes,   urinary   retention,   constipation,  
blurred  vision  



Most,   if   not   all,   of   the   TCAs   also   potently   inhibit   sodium   channels   and   L-­‐type   calcium  
channels,   and   therefore   act   as   sodium   channel   blockers   and   calcium   channel   blockers,  
respectively
...
    OD   is   Tx   with  
bicarbonate
...
       



In   OD:     supportive   therapy   is   given   if   necessary,   including   respiratory   assistance,  
maintenance  of  body  temperature,  and  administration  of   intravenous  sodium  bicarbonate  
as   an   antidote,   which   has   been   shown   to   be   an   effective   treatment   for   resolving   the  
metabolic  acidosis  and  cardiovascular  complications  of  TCA  poisoning
...
g
...
e
...
   For  
this  reason  they  are  not  commonly  used  to  treat  depression  (suicide  risk)  due  to  newer  drugs  (e
...
 
SSRIs)  with  less  toxicity
...
   



SSRIs   are   also   frequently   prescribed   for   anxiety   disorders,   such   as   social   anxiety   disorder,  
panic   disorders,   obsessive   compulsive   disorder   (OCD),   eating   disorders,   chronic   pain   and  
occasionally,  and  for  post-­‐traumatic  stress  disorder  (PTSD)
...
   For  clinical  depression,  SSRIs  are  
recommended   by   NICE   over   tricyclic’s   (TCAs)   due   to   their   superior   tolerability   and   less  
toxicity
...
 



SSRIs   are   believed   to   increase   the   extracellular   level   of   the   neurotransmitter   serotonin   by  
inhibiting   its   reuptake   into   the   presynaptic   cell,   increasing   the   level   of   serotonin   in   the  
synaptic  cleft  available  to  bind  to  the  postsynaptic  receptor
...
 



SSRIs  inhibit  the  reuptake  of  the  neurotransmitter  serotonin  (5-­‐hydroxytryptamine  or  5-­‐HT)  
into  the  presynaptic  cell,  increasing  levels  of  5-­‐HT  within  the  synaptic  cleft
...
 Activation  of  the  autoreceptors  (by  agonists  like  serotonin)  triggers  a  throttling  back  
of  serotonin  production  =>  initial  serotonin  deficiency  (can  initially  increase  anxiety  levels)
...
  The   body   adapts   gradually   to   this   situation   by  
lowering  (downregulating)  the  sensitivity  of  the  autoreceptors
...
 

 
SSRIs  include:  





Citalopram    
Fluoxetine  (prozac)  –  used  in  children  (children  get  FLU  all  the  time)  and  in  pregnancy    
Paroxetine    -­‐  used  in  breast  feeding  (parrot  on  the  breasts)  
Sertraline  (dont  confuse  with  the  MAO-­‐B  inhibitor  selegiline  used  in  PD  to  increase  DA  
levels)  

 
Improvements  over  MAOIs  &  tricyclics  (TCAs)    
Non  sedative  (less  anti-­‐histamine  effects)  
Less  anti-­‐muscarinic  effects  (e
...
 less  dry  mouth,  less  bradycardia,  less  visual  problems,  less  
constipation  and  less  urinary  retention)  
• Less  cardiac  effects    
 
 
Adverse  effects  
• GI:    Nausea/diarrhoea/indigestion  (high  presence  of  serotonin  and  serotonic  receptors  in  GI  
tract)  
• Headache    
• Insomnia  
• Sexual  dysfunction  (increased  levels  of  serotonin  in  brain  results  in  decreased  levels  of  
dopamine  and  NA  which  can  result  in  sexual  dysfunction)  
• Hyponatremia  
• Suicidal  behavior?    
• Initial  anxiety    



General  side  effects  are  mostly  present  during  the  first  one  to  four  weeks  while  the  body  adapts  to  
the  drug  (with  the  exception  of  sexual  side  effects,  which  tend  to  occur  later  in  treatment)
...
   
 
Serotonin-­‐norepinephrine  reuptake  inhibitor  (SNRI)    




Dual  reuptake  inhibitors  e
...
 venlafaxine    
Mode  of  action:  Block  the  reuptake  of  monoamines  (noradrenaline  and  5-­‐HT)  into  
presynaptic  terminals
...
g
...
g
...
   
ONLY  EVER  GIVE  AD  TOGETHER  WITH  A  MOOD  STABALISER
...
     
 

 
 
Stabilize  mood  and  prevent  recurrence  (prophylaxis)  



Lithium  salts  –  good  for  preventing  mania  in  particular    
Anticonvulsants  (e
...
 sodium  valproate  and  lamotrigine  and  carbamazepine)  

! Sodium  valproate  very  good  for  mania  predominance  
! Lamotrigine  very  good  for  depressive  predominance  
 
Lithium  therapy  
Lithium  carbonate  is  used  to  treat  mania,  the  elevated  phase  of  bipolar  disorder
...
g
...
g
...
g
...
g
...
g
...
g
...
   All  adults  are  presumed  to  have  sufficient  
capacity   to   decide   on   their   own   medical   treatment   unless   there   is   significant   evidence   to   suggest  
otherwise
...
 
The  impairment  or  disturbance  means  the  person  is  unable  to  make  a  decision  at  the  current  
time
...
g
...
     



Emergency  Detention  (section  36)  
Short  Term  Detention  (section  44)  
 

Criteria  for  Emergency  Detention  (section  36)  
1)  Likely  to  have  a  mental  disorder  
2)  Significantly  impaired  decision-­‐making  ability  regarding  treatment,  due  to  mental  disorder    
3)  Detention  in  hospital  is  necessary  as  a  matter  of  urgency  to  determine  what  treatment  is  needed  
4)  Risk  to  health,  safety  or  welfare  of  the  person,  or  safety  of  others  

5)  Making  arrangements  for  section  44  would  involve  undesirable  delay    
 
Criteria  for  Short  Term  Detention  (section  44)  
1)  Has  a  mental  disorder  
2)  Significantly  impaired  decision-­‐making  ability  regarding  treatment,  due  to  mental  disorder    
3)  Detention  in  hospital  is  necessary  for  assessment  or  treatment  (but  non-­‐urgent)  
4)  Risk  to  health,  safety  or  welfare  of  the  person,  or  safety  of  others  
5)  Cannot  be  treated  voluntarily  
 
Note:       MHA   is   used   for   detention!     If   pt   needs   treated   for   a   medical   disorder,   and   they   lack  
capacity,  but  they  don’t  need  detention  then  can  use  AWI
...
     
Under  16’s  can  consent  to  medical  treatment  on  their  own  behalf  if  they  have  capacity  to  
do   so   in   the   opinion   of   a   qualified   medical   practitioner   attending   them   e
...
  a   12   year   old  
may  have  the  capacity  to  consent  to  an  injection  but  not  surgery  

 
EASTING  DISORDERS  




Anorexia  Nervosa  
Bulimia  Nervosa  
Binge  Eating  Disorder  

 
Aetiology  of  eating  disorders  


Genetics:  
! Influence   of   genes   on   control   of   appetite   and   feeding   via   hypothalamus   (leptin,  
ghrelin)  
! Personality  type  
! 10  x  risk  in  families  with  affected  individual  



 
Environmental  
! In  utero  nutrition  
! Childhood  adverse  experiences  

! Developmental  
! Puberty  


 
Brain  chemistry  
 

Anorexia  Nervosa  


Anorexia  nervosa  is  an  eating  disorder  characterized  by:  
! Low  body  weight  (low  BMI  <  17
...
 This  restriction  of  food  intake  causes  metabolic  and  hormonal  disorders
...
   



It  is  a  serious  mental  illness  with  a  high  incidence  of  comorbidity  and  similarly  high  mortality  
rates  to  serious  psychiatric  disorders
...
 The  high  levels  of  ghrelin  suggests  
that  their  bodies  are  desperately  trying  to  make  them  hungry;  however,  that  hunger  call  is  
being  suppressed,  ignored,  or  overridden
...
 



Note:  leptin  is  the  hunger  suppressant  hormone    

 
Clinical  features  
History  




Weight  loss  (BMI  <  17
...
g
...
g
...
 

 
Physical  Signs  










Low  BMI  (<17
...
5  or  less  
Self-­‐induced  weight  loss  (strict  dieting,  vomiting,  excessive  exercise,  medication)  
Body  image  disturbance  (dysmorphobia)  
Fear  of  fatness  
Hypothalamic  dysfunction  (hormone  dysfunction):  Amenorrhoea  (females)  or  loss  of  libido  
(males)  
NB:  loss  of  appetite  is  NOT  generally  a  feature  of  anorexia  nervosa  

 
Starvation  Effects  on  Brain  





 

Loss  of  grey  and  white  matter  resulting  in  Brain  atrophy  
Hypothalamic  dysfunction  resulting  in  hormonal  imbalances  e
...
 amenorrhoea  
Increased  compulsive  behaviour  
Reduced  attention  and  memory  (pseudodementia)  
Poor  concentration  and  decision  making  

These  effects  will  improve  with  re-­‐feeding
...
g
...
g
...
5  
• Moderate  risk:  BMI=15-­‐16  
• High  risk:  13-­‐14
...
0  
• Weigh  loss>  1kg/week  
• Prolonged  QT  
• HR<40  
• SBP  <  80  
• Core  temp  <  34C  
• Unable  to  rise  from  squat  without  using  arms  for  leverage      
• Cognitive  impairment    
 
Treatment  






Family  therapy  beneficial  in  adolescents  
Psychological  therapies  e
...
 CBT  
Dietician    
Medical  monitoring  
Inpatient   treatment   for   high   risk   (mental   health   act   if   refuse   Tx):   Re-­‐feeding   (beware   of  
refeeding  syndrome  –  hypophosphatemia  and  hypokalemia)  
 
 
 

Mental  Health  Act  (Care  and  Treatment)  (Scotland)  2003  
This  act  allows  for  treatment  of  mental  disorder  or  physical  consequences  of  mental  disorders  in  
someone   without   capacity   to   consent   to   treatment   e
...
  for   treatment   of   anorexia   (mental   health  
disorder)  or  any  of  its  physical  complications  (in  a  patient  who  refuses  treatment)  



Emergency   Detention   (section   36)   e
...
  for   life   threatening   long   QT   syndrome   or   life  
threatening  electrolyte  imbalance  (in  a  pt  who  needs  detained  as  they  refuse  to  stay)  
Short  Term  Detention  (section  44)  e
...
 for  non  life  threatening  complications  and  high  risk  
patients  (in  a  pt  who  needs  detained  as  they  refuse  to  stay)  
 

MARSIPAN  




Management  of  really  sick  patients  with  anorexia  nervosa  
RCPsych  and  RCPhysicians    
Aim  to  reduce  mortality  of  starved  patients  admitted  to  medical  wards  

 
Refeeding  Syndrome  


Caused   by   depletion   of   already   inadequate   stores   of   nutrients   e
...
  magnesium,   potassium,  
phosphate  which  are  quickly  used  up  as  body  starts  to  repair  itself
...
    Phosphate   levels   are  
normally  the  worse  affected
...
   



 It  is  generally  a  result  of  an  extensive  concern  for  body  weight  e
...
 a  fear  of  becoming  fat
...
     



Many  individuals  with  bulimia  nervosa  also  have  an  additional  psychiatric  disorder
...
 
Patients  may  also  cycle  between  bulimia  and  anorexia  



Antidepressants,   especially   SSRIs   (fluoxetine),   are   widely   used   in   the   treatment   of   bulimia  
nervosa
...
g
...
 





Parotid  hypertrophy  
Dental  caries  (due  to  acid  regurgitation)  
Normal  weight  (usually)  
 
 
 

 
 
 
 
Medical  Complications  
• Oesophageal  reflux  =>  caries  (decay)  
• Oesophageal  tears/rupture  e
...
 Mallory–Weiss  tear  
• Hypokalaemia   due   to   excessive   vomiting   (may   cause   cardiac   arrhythmias)
...
     
• Metabolic  alkalosis  due  to  excessive  vomiting  of  HCl  
• Subconjunctival  haemorrhage  (due  to  strain  of  retching)  
• Nutritional  deficiencies    
• Dehydration    
• Seizures  due  to  metabolic  abnormalities  
 
 
Treatment  
• Guided  self-­‐help  
• CBT  
• SSRI   e
...
  citralopram,   fluoxetine,   paroxitine,   sertraline   (don’t   get   this   confused   with  
selegiline  which  is  a  MAO-­‐B  inhibitor  used  in  PD  to  increase  DA  activity)  
 
 
MEDICALLY  UNEXPLAINED  SYMPTOMS  
Terminology  



The   terminology   is   confusing   in   this   area,   as   many   terms   are   used   interchangeably
...
     



It  is  possible  for  one  patient  to  fulfil  diagnostic  criteria  for  several  somatoform  disorders  at  
one   time   (e
...
,   somatoform   pain   disorder   and   dissociative   disorder)   which   has   led   to  
criticism   of   current   diagnostic   systems,   and   it   is   likely   that   future   versions   of   ICD/DSM   will  
change  how  such  disorders  are  defined
...
 Take,  for  example,  a  woman  who  suffers  from  
a  wide  number  and  range  of  symptoms  for  which  no  adequate  pathological  cause  has  been  
found
...
  The   woman’s   medically   unexplained   symptoms   include   fatigue,  
dizziness,   headache,   subjective   limb   weakness   and   painful   joints
...
    In   the   field   of   the  
somatoform   disorders,   the   labels   often   say   more   about   the   specialty   of   the   person  
applying   them   than   any   underlying   pathology
...
 



Failure  to  identify  a  pathology  can  lead  to  frustration  and   uncertainty,  from  both  the  doctor  
and  the  patient
...
e
...
     
“Functional  disorders”  with  no  known  organic  pathology  
They   cannot   be   explained   fully   by   a   general   medical   condition   or   by   the   direct   effect   of   a  
substance,  and  are  not  attributable  to  another  mental  disorder
...
 
The  main  feature  of  somatoform  disorders  is  repeated  presentation  of  physical  symptoms,  
together   with   persistent   requests   for   medical   investigations,   in   spite   of   repeated   negative  
findings  and  reassurances  by  doctors  that  the  symptoms  have  no  physical  basis
...
     
Somatoform   disorders   are   not   the   result   of   conscious   malingering   (fabricating   or  
exaggerating  symptoms  for  secondary  motives  e
...
 external  gain  such  as  monetary  gain)  or  
conscious   factitious   disorders   (deliberately   producing,   feigning,   or   exaggerating   symptoms   -­‐  
to  play  the  “sick  patient”  and  receive  attention  –  for  internal  gain)
...
 

 
Key  features  
There  are  3  central  features  of  somatoform  disorders:    
 
• Physical  complaints  without  identifiable  organic  basis  (“functional”  disorders)
...
   



The   main   features   are   multiple,   recurrent,   and   frequently   changing   physical   symptoms
...
 



Marked  depression  and  anxiety  are  frequently  present  and  may  justify  specific  treatment
...
   

 
Somatization  disorder  ICD10  diagnostic  criteria  




Physical  symptoms  suggesting  a  physical  disorder  but  with  no  evidence  of  organic  disease    
At  least  2  years  of  multiple  and  variable  physical  symptoms  for  which  no  adequate  physical  
explanation  has  been  found;  
Symptoms   linked   to   psychological   factors/conflicts   –   may   manifest   subconsciously   as  
physical  symptoms    

 
Conversion  disorder  


A   conversion   disorder   causes   patients   to   suffer   from   neurological   symptoms,   such   as  
numbness,  blindness,  paralysis,  or  fits  without  a  definable  organic  cause
...
    Conversion   disorder   is   considered   a   psychiatric   disorder   in   the   Diagnostic  
and  Statistical  Manual  of  Mental  Disorders  fifth  edition  (DSM-­‐5)
...
 



Can  use  Hoovers  test  of  lower  limbs  to  assess  for  functional  or  organic  leg  weakness  
 

How  common  are  somatoform  disorders?  




33%  of  new  Neurology  outpatients  =>  VERY  COMMON  
50%   of   patients   admitted   to   hospital   with   apparent   Status   Epilepticus   (who   are   actually  
having  a  psychogenic  seizure)  
5%  of  new  referrals  to  Movement  disorder  clinics  

 
Aetiology  of  Somatoform  Disorders  



Predisposing  e
...
 genetics,  adverse  childhood  experiences,  temperaments  
Precipitating  e
...
 stressful  life  events,  physical  health  disorder,  psychiatric  illness  

Perpetuating   e
...
  over-­‐investigation   of   patient   can   perpetuate   the   disorder   by   causing  
anxiety  and  helplessness  
 
 
Management  


Management  will  depend  on  the  patient
...
g
...
     
The  sign  relies  on  the  principle  of  synergistic  contraction
...
   
It  has  been  neglected,  although  it  is  a  useful  clinical  test
...
 If  you  feel  pressure  from  the  weak  leg,  the  weakness  is  
likely   non   organic   (e
...
  functional)
...
 If  no  pressure  is  felt,  this  is  more  likely  organic  limb  weakness
...
 

 
 
 
Summary  











 Somatoform   disorders   are   characterized   by   bodily   symptoms   without   any   identifiable  
organic  (physical)  cause  
May  be  heightened  sense  of  awareness  of  normal  “symptoms”  
May  be  normal  functional  processes  functioning  abnormallye
...
 altered  physiology    
Very  complex  pathophysiology    
Five  major  types  of  somatoform  disorders:  
! Conversion  disorder  (unexplained  neurological  symptoms)  
! Pain  disorder  (unexplained  pain  symptoms)  
! Somatization   disorder   (many   unexplained   symptoms   from   different   bodily  
systems  over  at  least  2  years)    
! Body   dysmorphic   disorder   (excessive   concern   about   and   preoccupation   with   a  
perceived  defect  of  their  physical  appearance)  
! Hypochondriasis  (excessive  preoccupancy  or  worry  about  having  a  serious  illness)  
Remember:   symptoms   might   be   exaggerated   and   irrational   for   us,   but   they   are   REAL   for   the  
patients  
Treat  the  concomitant  psychiatric  problem  
Focus  on  anxiety  reduction,  not  physical  symptoms  
Treat  the  dominant  symptom(s)  e
...
 amitriptylline  for  pain  and  a  SSRI  for  anxiety  

 
PSYCHIATRIC  GENETICS  

Huntington’s  disease  (HD)  








Huntingtons  disease  is  a  genetic  disorder  –  neuropsychiatric    
Autosomal  dominant  
Huntingtin  gene  codes  for  huntingtin  protein  
HD  occurs  due  to  expansion  of  the  CAG  triplet  repeat  
CAG   is   code   for   the   amino   acid   glutamine,   so   more   CAG   repeats   causes   a   longer   chain   of  
glutamines  in  the  protein,  which  causes  the  huntingtin  protein  to  be  misshapen
...
 
Anticipation  =  earlier  onset  in  each  generation    
 

Motor  symptoms  







Choreiform  movements:  Brief,  semi-­‐directed,  irregular  movements  that  are  not  repetitive  or  
rhythmic,  but  appear  to  flow  from  one  muscle  to  the  next  (“dance  like”)  which  occurs  due  to  
basal  ganglia  dysfunction  
Rigidity  (non-­‐spastic  hypertonia)  due  to  basal  ganglia  dysfunction  
Problems  chewing,  swallowing,  and  speaking    
Gait  disturbance    
All  actions  requiring  muscle  control  can  become  impaired    

 
Psychiatric  symptoms  







Depression  (depression  and/or  anxiety  can  be  first  signs)  
Anxiety  
Psychosis  (patient  may  present  as  if  they  have  schizophrenia)  
Aggression  and  other  behavioural  disturbances  
Suicidality  
Compulsions  

 
Cognitive  symptoms  




Decline  in  executive  function  (planning,  abstract  thinking,  cognitive  flexibility)  
Short  and  long  term  memory  deficits    
Dementia  (progressive  decline  in  global  cognition)    
 

Genetics  of  Huntington’s  




Autosomal  dominant  
Usually  asymptomatic  until  adulthood  (>35s)  
Slow  onset  neurological  and  psychological  symptoms  






Currently  irreversible  and  unstoppable  
Only  symptomatic  treatment  is  possible  
Very  easy  genetic  test    
Does   the   patient   want   a   genetic   test?   Genetic   counseling   is   required   to   help   them   reach  
this  decision
...
   
• Life  expectancy  average  7  years  after  diagnosis
...
    Tau   protein   involved   in   the   microtubules   (important   for  
structure   of   neuron   and   intracellular   transport)   is   hyperphosphorylated   and   causes   the  
tangles
...
   
We   do   know   that   one   of   the   first   areas   affected   by   Alzheimers   disease   is   the   nucleus   basalis  
of  Meynert,  in  the  basal  forebrain,  which  is  where  most  of  the  cholinergic  pathways  in  the  
brain   start
...
      Increasing   cholinergic   transmission   with   cholinesterase   inhibitors   (e
...
 
rivastigmine,   galantamine   and   donepezil   RGD)   seems   to   slow   the   decline   in   Alzheimer’s  
disease,   but   does   not   affect   the   actual   neuropathology,   and   so   cannot   stop   or   reverse   the  
disease
...
     
• Early   onset   familial   AD   (EOFAD)   mutations   (believed   to   be   autosomal   dominant)   may   be  
found   in   PSEN1   (presenilin   1),   PSEN2   (presenilin   2)   or   APP   (amyloid   precursor   protein)  
genes
...
g  idiopathic  AD,  MDD  and  bipolar  
Monogenic   disease   e
...
     



OCD   is   an   anxiety   disorder   characterized   by   intrusive   thoughts   (obsessions)   that   produce  
anxiety,   uneasiness,   apprehension,   fear,   or   worry;   and/or   repetitive   behaviours  
(compulsions)   aimed   at   reducing   the   associated   anxiety;   or   by   a   combination   of   such  
obsessions  and  compulsions
...
 These  symptoms  
can   be   alienating   and   time-­‐consuming,   and   often   cause   severe   emotional   and   financial  
distress
...
   
To  be  diagnosed  by  OCD  the  obsession  and/or  compulsions  must  be  a  cause  of  anxiety  and  
there  must  be  other  features  
 
 
Aetiology  of  OCD  
 
• Genetics:  MZ‘v’DZ  twins:  63-­‐87%  ‘v’  15-­‐45%  (suggesting  genetics  plays  a  role)  
• Autoimmunity:   beta   haemolytic   (complete   haemolysis)   Streptococcal   infection   (GAS   e
...
 
Strep   pyogenes)   &   generation   of   autoantibodies   to   basal   ganglia   (some   researchers   also  
believe   this   play   a   role   in   Tourettes   syndrome);   which   may   be   associated   with   Rheumatic  
fever  
• PANDAS:     There   is   gradually   accumulating   evidence   that   there   are   some   children   who  
experience   sudden   onset   of   a   neuropsychiatric   disorder   (usually   obsessive-­‐compulsive  
disorder  (OCD)  or  tics)  following  a  Group  A  beta-­‐haemolytic  streptococcal  infection  (GABHS)
...
 
! Syndenhams  chorea  –  major  diagnostic  criteria  for  Rheumatic  fever  
! OCD  
! Tic  disorders  
 


Obsessions  






Recurrent,  intrusive  and  distressing  thoughts,  ideas,  images,  memories,  impulses  
Unwanted  
Usually  resisted  
Recognised  as  originating  from  own  mind    
Associated  with  the  emergence  or  increase  of  anxiety  
 
 

Common  obsessions  in  OCD  









Contamination  from  dirt,  germs,  viruses,  bodily  fluids  or  faeces,  chemicals,  sticky  substances,  
dangerous  material  etc  
Fear  of  harm  e
...
 door  locks  are  not  safe  
Excessive  concern  with  order  or  symmetry  
Obsessions  with  body  or  physical  symptoms  
Religious,  sacrileligious,  or  blasmphemous  thoughts  
Sexual  thoughts  
Urge  to  hoard  useless  or  worn  out  items  
Thoughts  of  violence  or  aggression  
 

Compulsions  






Repetitive,  seemingly  purposeful  behaviours  that  individual  feels  driven  to  perform  
Can  include  physical  and  mental  rituals  
Carrying   out   compulsions   tends   to   reduce   anxiety   (which   occurs   as   a   result   of   obsessions)  
e
...
 handwashing  
Resistance  to  performing  a  compulsion  increases  anxiety  
Usually  recognised  as  ‘irrational’  
 

Common  compulsions  in  OCD  








Checking  e
...
 doors  and  gas  taps  
Cleaning  and  washing  
Repeating  acts  
Mental  compulsions  e
...
 special  words  or  prayers  repeated  in  a  set  manner  
Ordering,  symmetry  or  exactness  
Hoarding  and  collecting  
Counting  
 

OCD  diagnostic  criteria  (ICD  10)  

For   a   definite   diagnosis,   obsessional   symptoms   or   compulsive   acts,   or   both,   must   be   present   on  
most   days   for   at   least   2   successive   weeks   and   be   a   source   of   distress   (anxiety)   or   interference   with  
activities
...
   Persons  with  OCPD  are  
usually   inflexible   and   controlling
...
 In  contrast  to  people  with  obsessive-­‐compulsive  disorder  (OCD),  behaviours  are  
rational  and  desirable  to  people  with  OCPD  (egosyntronic)
...
 
Perfectionism  interfering  with  task  completion  
Excessive  devotion  to  work  
Overconscientious,  scrupulous  and  inflexible  
Unable  to  discard  worthless  objects  
Reluctance  to  delegate,  need  to  be  in  control  
Rigidity  and  stubbornness  
 

OCD   is   often   confused   with   the   separate   condition   obsessive   compulsive   personality   disorder  
(OCPD)
...
 Because  ego  dystonic  disorders  go  against  a  person's  self-­‐concept,  they  tend  to  cause  much  
distress
...
 
As  a  result,  people  with  OCD  are  often  aware  that  their  behaviour  is  not  rational,  are  unhappy  about  
their  obsessions  but  nevertheless  feel  compelled  by  them,  and  may  be  ridden  with  anxiety
...
 

OCD   sufferers   are   more   likely   to   meet   criteria   for   a   personality   disorder   (PD)   than   controls   however,  
this  would  more  likely  be  dependent,  avoidant,  histrionic  or  mixed  PD
...
g
...
g
...
   If  patient  doesn’t  respond  to  first  SSRI  
then   try   a   different   SSRI
...
     
OCD   is   strikingly   responsive   to   SSRIs   but   not   much   else
...
     
 
CBT  for  OCD:  exposure  and  response  prevention  (desensitisation)  




Deliberate  exposure  to  obsessional  stimuli  
Prevention  of  compulsions  typically  used  to  lessen  the  distress  associated  with  feared  stimuli  
Repeated   exposure   to   the   obsessional   cues   whilst   employing   strict   response   prevention  
leads  to  habituation    

 
Five  screening  questions  to  help  identify  OCD:  
1
...
 Do  you  check  things  a  lot?  
3
...
 Do  your  daily  activities  take  along  time  to  finish?  
5
...
g
...
 The  locus  coeruleus  is  the  principal  site  for  brain  
synthesis  of  norepinephrine  (noradrenaline)
...
   But  serotonin  is  believed  to  be  a  key  regulatory  
mechanism   of   this   system   (e
...
  regulates   fear,   pain   and   anxiety   etc)
...
    Indeed   SSRIs   can   cause   increased   anxiety   in   the   initial   few   days   before   becoming  
effective  anti  anxiety  (anxiolytic)  agents
...
  Serotonin   is   thought   to   have   a   role   in  
regulating   anxiety
...
 It  is  hypothesized  that  the  
serotonin   receptors   of   OCD   sufferers   may   be   relatively   understimulated
...
     



It   seems   unlikely   that   a   solitary   disturbance   in   serotonin   function   can   fully   account   for   the  
pathophysiology   of   obsessive   compulsive   disorder
...
  Additional   studies   are   needed   to   more   directly   evaluate   dopamine  
function  in  patients  with  obsessive  compulsive  disorder
...
g
...
g
...
g
...
g
...
g
...
g
...
      For   people   who   have   experienced   this   response:   they   may   be   riddled  
with   guilt   for   not   having   fought   courageously   or   not   saved   someone
...
 
 
 
 
The  limbic  brain:    Feeling  brain  (Lizard  brain)  
 
• Hippocampus:   important   for   forming   new   memories   (anterograde   memories)   and   locating  
memories  in  the  right  time,  place  and  context  
• Amygdala:   stores   emotionally   charged   memories
...
    The   amygdala   is   also  
important  for  controlling  autonomic,  emotional  and  sexual  behaviours      
• There  are  many  other  connections  from  limbic  brain  to  prefrontal  cortex    
• Important  for  survival  instincts    
• Sense  of  danger  overrides  logic  
 
 
Amygdala  
 
• The  amygdala  stores  emotionally  charged  memories
...
    The   amygdale   is   also  
important  for  controlling  autonomic,  emotional  and  sexual  behaviours
...
 It  stores  emotionally  charged  
memories:  good  and  bad
...
 
 
 

Post-­‐traumatic  reactions  
• Acute  stress  disorder  (2  hours  –  28  days  after  trauma)  
• Simple  (type  1:  single  incident)  PTSD  (from  28  days  to  3  months  after  trauma)  
• Complex  (type  2:  multiple  incidents)  PTSD  (from  28  days  to  3  months  after  trauma)  
• Chronic  PTSD  (greater  than  3  months  after  trauma)  
• Dissociative  disorders  
 
Acute  Stress  Disorder  


Occurring  within  1  month  of  the  trauma  and  lasting  at  least  2  days
...
 
 
 
Post-­‐traumatic  stress  disorder  (PTSD)  
 
• Posttraumatic  stress  disorder  (PTSD)  is  a  severe  condition  that  may  develop  after  a  person  is  
exposed   to   one   (simple:   type   1)   or   more   (complex:   type   2)   traumatic   events,   such   as   sexual  
assault,  serious  injury  or  the  threat  of  death  (e
...
 assault  or  health  condition)
...
 



Posttraumatic   stress   disorder   is   classified   as   an   anxiety   disorder
...
  Typically   the  
individual  with  PTSD  persistently  avoids  all  thoughts,  emotions  and  discussion  of  the  stressor  
event  and  may  experience  amnesia  for  it
...
 



Most   people   who   experience   a   traumatizing   event   will   not   develop   PTSD
...
    Children   are   less   likely   to   experience   PTSD   after   trauma   than   adults,  
especially  if  they  are  under  10  years  of  age
...
 


PTSD   symptoms   may   result   when   a   traumatic   event   causes   an   over-­‐reactive   adrenaline  
response,  which  creates  deep  neurological  patterns  in  the  brain
...
   



During  traumatic  experiences  the  high  levels  of  stress  hormones   (cortisol)  secreted  suppress  
hypothalamic  activity,  which  may  be  a  major  factor  towards  the  development  of  PTSD
...
  Most   people   with   PTSD   show   a   low   secretion   of  
cortisol   (adrenal   burnout)   and   high   secretion   of   catecholamines   in   urine   (hypervigilent  
flight  or  fright  state)
...
   We  have  
raised   catecholamines   (e
...
  adrenaline)   as   the   body   is   still   in   a   high   alert   mode   (fight   or  
flight  sympathetic  activation)    



Why  low  cortisol?    It  is  proposed  that  it  is  due  to  Adrenal  exhaustion  due  to  prolonged  and  
persistent  overactivity  of  the  stress  response
...
 
Hippocampus:  during  high  stress  times  the  hippocampus  is  suppressed
...
   In  PTSD  the  
event   fails   to   get   stored   away   in   long   term   memory   because   the   limbic   brain/emotional  
brain  keeps  on  getting  triggered
...
 
These  are  not  conscious  worries  or  ruminations    
They  seem  to  intrude  and  engulf  the  person  
They  are  unwelcome  ,  painful  and  unpleasant  
They   often   lead   to   fear,   panic,   anger,   rage,   sadness,   guilt   shame   and   increased   sense   of  
vulnerability  
 

Nightmares  



These  occur  commonly  
Patients  often  describe  wakening  up  shouting,  screaming  and  drenched  in  sweat  or  hot  and  
trembling  

 
Increased  arousal  






Hypervigilance:   constantly   on   guard,   scanning   their   environment   for   potential   threat
...
     
The  person  may  feel  like  they  are  observing  themselves  from  above
...
 
Dissociative  flashbacks  
Dissociative  identity  disorder  
Amnesia  
 

 
Physical  clinical  features  of  stress  disorders  
Clinical  features  are  anxiety  symptoms  due  to  increased  sympathetic  nervous  system  activity:  






Muscle  tension  
Headaches  
Nausea  
Shakes  and  tremors  
Choking  sensation  




Palpitations  
Dizziness  

 
Outcome  of  mental  trauma  
Mental  trauma  can  result  in:  













Acute  stress  disorder:  2  hours  to  28  days  (at  least  two  days)  
Simple  (type  1)  PTSD:  28  days  to  3  months  
Complex  (type  2)  PTSD:  28  days  to  3  months  
Chronic  PTSD:  >3months  
Dissociative  disorders  
Adjustment   disorder:   occurs   when   an   individual   is   unable   to   adjust   to   or   cope   with   a  
particular  stressor,  like  a  major  life  event  (not  as  potent  a  stressor  as  is  seen  in  PTSD)  
Depression  
Anxiety  disorder  including  panic  disorder  
BPD  
Somatisation    
Enduring  personality  change  
Or  a  combination  of  any  of  the  above  
 
 

DSM  Diagnostic  criterion  for  PTSD  
A
...
 The  traumatic  event  is  persistently  re-­‐experienced  (e
...
   re-­‐collections,  dreams/nightmares,  and  
feelings)  
C
...
  These   are   all   physiological  
response  issues,  such  as  difficulty  falling  or  staying  asleep,  or  problems  with  anger,  concentration,  or  
hypervigilance
...
 
E:  Duration  of  symptoms  which  continue  for  more  than  4  weeks  after  the  last  traumatic  incident
...
 
 
Specify  if:  



Acute:  if  duration  of  symptoms  is  less  than  three  months  after  the  stressor  
Chronic:  if  duration  of  symptoms  is  more  than  three  months  after  the  stressor  



Delayed  onset:  if  onset  of  symptoms  is  at  least  six  months  after  the  stressor  
 

Management  





Psychological  
Medication  
If  trauma  symptoms  are  mild  and  present  for  less  than  4  weeks:  watchful  waiting  should  be  
implemented  with  review  within  one  month  
Remove  or  manage  continuing  threat  

 
Psychological  interventions  







Trauma   focused   CBT   is   generally   the   first   line   management:   There   may   be   avoidance   of  
trauma  memories  as  they  are  distressing
...
 
EMDR  (eye  movement  desensitization  and  reprocessing)  
Exposure  therapy  (technique  in  behaviour  therapy)  -­‐  desensitisation  
If  depression  is  also  present  treat  PTSD  first  
Non  trauma  focused  interventions  such  as  relaxation  or  non  directive  therapy  which  do  not  
address  trauma  symptoms  should  not  routinely  be  offered  to  those  suffering  from  PTSD  

 
Medications  
When  symptoms  persist  pharmacological  treatment  in  addition  to  psychotherapy  is  required:  
SSRIs   are   considered   to   be   a   first-­‐line   drug   treatment
...
     
• Alternative  class  of  antidepressant  should  be  considered  if  SSRIs  not  helping  
• Olanzapine  (atypical  antipsychotic)  can  be  used  as  an  adjunct  to  antidepressant  medication  
 
 
 
PHARMACOLOGY  OF  ANXIOLYTIC  DRUGS  


Drugs  used  to  treat  anxiety  





Benzodiazepines  (BDZs)  –  short  term  use  only    
Antidepressant  drugs  
Pregabalin  (AED)  
β-­‐blockers  (propanolol)  –  for  somatic  sympathetic  NS  symptoms    

 
Benzodiazepines  









Benzodiazepines   can   be   used   as   minor   tranquilizers,   anxiolytics,   hypnotics,   and   sedatives  
(NOT  ADs)  
Should  not  be  used  long  term  due  to  addictive  properties  
Many  types  (“pam”)  e
...
 midazolam,  lorazepam,  temazepam,  nitrazepam,  diazepam  (valium)  
etc  
Choice  usually  depends  on  half  life  
Majority  can  be  used  for  sedation  at  low  dose  
Higher  dose  for  sleep  
Don’t  want  to  use  one  with  a  long  half  life  to  induce  sleep  as  sleep  will  have  a  long  duration  

 
Pharmacological  effects  of  benzodiazepines  
Reduce  anxiety  and  aggression  
Hypnosis/sedation  
Muscle  relaxation  
Anticonvulsant  effect  
Anterograde  amnesia  
 
Some  may  produce  one  or  other  to  a  different  degree,  but  all  produce  these  effects    






The  choice  of  drug  is  determined  by  duration  of  action
...
     
 
Gamma  amino  butyric  acid  (GABA)  






GABA  is  the  main  inhibitory  NT  in  the  brain  
GABA  is  a  CNS  depressant  
Widespread  distribution  (found  in  all  neurons  unlike  monoamines)  
GABA   causes   hyperpolarisation   (Cl-­‐   influx   to   make   Em   more   -­‐ve)   of   target   cells   e
...
 
stabilizes  cells  and  inhibits  AP’s  from  firing  
NB:  Glycine  is  another  major  inhibitory  NT  restricted  to  spinal  cord  and  brain  stem  

 
GABA  Receptors  



GABA  (A)  =  ionotropic  ligand  gated  ion  channel  (main  target  for  benzodiazepines)    
GABA  (B)  receptor  =  GPCR  

 
GABA  (A)  receptor  



Main  target  for  benzodiazepines  (BDZs)  
Ionotropic  ligand  gated  ion  channel  





Multi  unit  receptor  linked  to  chloride  channel  
When   GABA   binds   =>   conformational   change   =>   chloride   ions   flow   in   =>   inside   cell   more  
negative  =>  hyperpolarised  =>  neurone  less  likely  to  fire  an  AP    
Therefore  we  can  appreciate  that  GABA  is  inhibitory  (stabalises  neurones)  

 
Action  of  BDZs  





BDZs  act  at  a  different  site  separate  from  GABA  binding  site  
They  have  no  activity  until  the  natural  ligand  (GABA)  also  binds  to  its  binding  site  
When   GABA   binds   =>   increase   in   openings   =>   increase   in   Cl-­‐   influx   =>   increased  
hyperpolarisation  
We   get   more   activity   than   you   would   without   the  BDZ   being   bound   to   GABA   (A)   receptor   =>  
enhance  GABA  effects  
 

Clinical  uses  of  benzodiazepines  
Acute  treatment  of  extreme  anxiety  
Rapid  tranquillisation  e
...
 in  aggressive  or  highly  agitated  patient  
Mania  
Delirium  
Status  epilepticus  (as  benzos  are  muscle  relaxant  and  AED)  
Premedication  before  surgery  or  during  minor  procedures  
Alcohol  withdrawal  -­‐  chlordiazepoxide  
Hypnosis  
 
Benzos  should  only  be  used  acutely,  never  chronically  or  long  term  (due  to  addictive  properties)
...
     
 









 
Other  modulators  





The  GABA  receptor  (A)  has  a  lot  of  different  modulating  sites  
Barbiturates  act  on  the  barbiturate  site
...
  Similar   end   point   in   terms   of   action   but   they   increase  
time  duration  the  channel  stays  open  for
...
g
...
    Withdrawal   results   in   anxiety/convulsions   possibly   due   to   decreased  
density   of   BDZ   receptors,   which   results   in   decreased   inhibition   of   electrical   activity   =>   increased  
glutamate  stimulation
...
     
Rapid  withdrawal  of  a  benzodiazepine  may  cause:  









Confusion    
Toxic  psychosis  
Convulsions  
Insomnia  
Anxiety  
Loss  of  appetite    
Tremor  
Perceptual  disturbances  

 
How  to  withdraw  benzodiazepines:    Titrate  down  slowly    
1
...
Reduce   dose   every   2–3   weeks   in   steps   of   2   or   2
...
Reduce   dose   further,   if   necessary   in   smaller   steps;   it   is   better   to   reduce   too   slowly   rather  
than  too  quickly  
4
...
   The  increased  NTs  in  the  limbic  
system  is  associated  with  negative  mood  states/stress
...
   BDZs  can  act  on  GABA  
(A)   receptors   to   stop   neurons   from   firing   off   in   stressful   event   resulting   in   decreased   release   of  
5HT  and  NA
...
     
 
How  do  antidepressants  help?  



Acutely   SSRIs   increase   extracellular   5-­‐HT   and   have   anxiogenic   properties   however   after  
several  weeks  the  anxiolytic  properties  appear  
Mechanisms   not   understood
...
g
...
g
...
g
...
    For   example   many   individuals   who   suffer   from  
agoraphobia   (fear   of   public   places)   also   suffer   from   panic   disorder
...
     
 
In   addition,   anxiety   disorders   are   commonly   comorbid   to   other   conditions   such   as   depression   and  
bipolar
...
g
...
g
...
g
...
     
Psychotherapy   primarily   targets   deep   rooted   issues   and   fears   etc   and   focuses   on   changing  
behaviour  and  thought  process/content  in  the  attempt  to  offer  a  long  term  solution  to  the  
problem
...
     
In   severe   cases,   pharmacological   measures   will   almost   certainly   be   required
...
     

 
GAD  management  
Step  1:    Provide  Education  and  options  for  treatment
...
g
...
g
...
   Desensitisation  is  also  called  exposure  therapy
...
   Characterised  by:  





The   person   fears   that   he/she   will   appear   anxious,   embarrassed   or   be   humiliated   in   social  
situations  
The  person  recognises  that  the  fear  is  unreasonable  or  excessive  
There  is  avoidance  of  people  and  situations  
Social  phobia  can  possibly  progress  to  panic  attacks  
 

Common  symptoms:  




Reluctance  to  speak  in  public  
Inability  to  write,  eat  or  use  public  conveniences  
Blushing  



Anxiety   symptoms   e
...
  headache,   dizziness,   light   headedness,   dry   mouth,   palpitations,  
racing  heart,  chest  pain  or  discomfort,  SOB,  tremor,  nausea,  sweating,  trembling  
 

Management:  





CBT    
Desensitisation  (a  form  of  behaviour  therapy  which  involves  being  gradually  exposed  over  a  
period   of   time   to   the   object   or   situation   of   your   fear   so   that   you   start   to   feel   less   anxious  
about  it)
...
   
Medication  e
...
 SSRI,  beta  blockers  

 
Agoraphobia  
Agoraphobia   is   an   anxiety   disorder   characterized   by   anxiety   in   situations   where   the   sufferer  
perceives  certain  environments  as  dangerous  or  uncomfortable,  often  due  to  the  environment's  vast  
openness  or  crowdedness
...
   Agrophobia  may  or  may  not  result  in  panic  attacks
...
  This   is   also  
sometimes  called  'social  agoraphobia'  which  may  be  a  type  of  "social  phobia"
...
   Some  agoraphobics  have  only  a  fear  of  open  spaces
...
   Desensitisation  is  also  called  exposure  therapy
...
g
...
     



Physical   symptoms   (sympathetic   NS)   of   panic   attacks   include:   headache,   dizziness,   light  
headiness,  dry  mouth,  syncope,  palpitations,  increased  heart  rate,  pounding  heart,  sweating,  
shaking,   trembling,   spasm,   SOB,   nausea,   tingling,   chills,   hot   flushes,   chest   pain   or   chest  
discomfort  



Mental  symptoms  of  panic   attacks  include:  restlessness  or  feeling  on  edge,  irritability,  mind  
going   blank,   sleep   disturbance,   poor   concentration,   feeling   out   of   control   or   detached,   fears  
of  ‘going  mad’,  feeling  of  impending  doom,  avoidance  of  situations  



Appreciate   that   the   physical   symptoms   of   panic   attacks   are   anxiety   symptoms   (as   a   result   of  
overactive  sympathetic  nervous  system)
...
g
...
g
...
 

 
Treatment  for  panic  disorder  
NICE  recommends  CBT  should  be  used  as  first  line  management
...
g
...
g
...
g
...
     
Obsessions:  






Recurrent   and   persistent   thoughts,   impulses   or   images;   which   are   intrusive   and  
inappropriate  &  cause  anxiety  or  distress  
These  are  not  simply  related  to  real  life  problems  
The  person  attempts  to  ward  them  off,  attempting  to  ignore  or  suppressing  them    
 He/she  may  also  try  and  neutralize  them  with  another  thought  or  action  e
...
 compulsions  
 The  obsessions  and  compulsions  are  recognised  as  coming  from  the  persons  own  mind    

 
Compulsions:  




Repetitive   behaviours   (e
...
  cleaning   and   washing   hands)   or   mental   acts   (e
...
  counting,  
praying,   repeating   words)   that   the   person   feels   driven   to   perform   in   response   to   an  
obsessional  thought  
These   behaviours   serve   to   reduce   the   distress   associated   with   the   obsessional  
thought/image  
 
 

NICE  Guidance  for  OCD  
1
...
 
These   include   brief   individual   CBT   (with   exposure   and   response   prevention   ERP)   and   group   CBT  
(ERP)    
 
2
...
g
...
   Adults  with  OCD  with  moderate  functional  impairment  should  be  offered  either:  
• SSRI  
• More  intensive  CBT  (more  than  10  therapist  hours)  
 
Both  of  the  above  are  similarly  efficacious
...
g
...
g
...
   
CBT  should  also  aim  to  identify  any  possible  core  underlying  beliefs  which  may  be  playing  a  
role  in  the  pathophysiology  e
...
 which  may  be  linked  to  an  overvalued  sense  of  responsibility  
or  guilt    
Self  monitoring  using  a  thought  record  diary  
Re-­‐labelling  the  thought  for  what  it  really  is  
Incorporating  anxiety  management    

 
MANAGEMENT  OF  MOOD  (AFFECTIVE)  DISORDERS  
1
...
g
...
   Assess  severity
...
   General  measures  
• Psychoeducation    
• Mood  charting  
• Sleep  hygiene  
4
...
 





Psychoeducation    
CBT  
Medications  
Electroconvulsive  therapy  (ECT)  

 
Pharmacological  management  for  MDD  





For  moderate  to  severe  depression:  Start  on  SSRI  (first  line)  +/-­‐  CBT  and  monitor  response    
If  no  response  after  4  weeks  at  “adequate  dose”  then  consider  switch  to  alternative  SSRI  
If   still   no   response   consider   alternative   SSRI,   venlafaxine   (SNRI)   or   mirtazapine   (NaSSA   –  
NASA  to  mars!)  
If  still  no  suitable  response  then  consider  TCA  (amitriptyline,  imipramine,  clomipramine)  or  
MAO  inhibitor  (e
...
 meclobemide):  these  drugs  are  last  line  due  to  toxicity  
 

Pharmacological  management  for  mania/hypomania  




Review  medication:  stop  antidepressant  (if  relevant)  
Prescribe   anti-­‐manic   drug   or   up   the   dose   e
...
  lithium   carbonate,   sodium   valproate,   or  
antipsychotic  
Review  frequently  and  titrate  dose  to  response  
 
 

Antidepressants  (ADs)  













ADs  do  not  make  non  depressed  people  happier  
AD  drugs  take  2-­‐3  weeks  to  work,  but  they  increase  post-­‐synaptic  serotonin  from  the  first  
dose  
ADs   probably   share   mechanisms   of   action   which   may   involve:   modulation   of   emotional  
processing  and  altering  activity  in  limbic  and  prefrontal  circuitry  
AD  do  not  insert  emotions  which  aren’t  there,  but  change  the  balance  of  emotional  tone  to  
facilitate  emotional-­‐cognitive  processing  and  learning  from  behavioural  feedback  
Antidepressant   drugs   can   be   dangerous   in   overdose   (TCAs   are   particularly   dangerous   =>  
cardiac  arrhythmias  can  occur)  
AD  drugs  are  NOT  addictive  
Stopping   antidepressant   drugs   can   result   in   withdrawal   effects
...
      The   presence   of  
withdrawal  symptoms  does  NOT  imply  addiction
...
g
...
     
Management  of  mild  MDD:  
CBT  or  other  non  pharmacological  intervention  –  first  line  
Consider  AD  (antidepressant)  if  depression  persists  after  other  interventions  
 
For  moderate  to  severe  MDD:  
• Combination   of   AD   medication   (SSRI   usually   first   line)   and   a   high   intensity   psychological  
intervention  (CBT  or  Interpersonal  therapy  IPT)  
 



 
Choice  of  antidepressant  

When   an   antidepressant   is   to   be   prescribed,   it  should  normally  be  an  SSRI  in  a  generic  form  because  
SSRIs  are  equally  effective  as  other  antidepressants  and  have  a  favourable  risk–benefit  ratio
...
g
...
g
...
   The  medication  with  the  best  evidence  
is   lithium,   which   is   effective   in   treating   acute   manic   episodes,   and   preventing   relapses  
(prophylaxis),  more  so  for  manic  than  for  depressive  episodes
...
  Sodium   valproate   has   become   a   commonly  
prescribed  treatment,  and  is  effective  in  treating  manic  episodes
...
g
...
g
...
g
...
g
...
  The  
terms  'antimanic  agent'  or  'antimanic  medication'  are  used  for  treatment  of  an  acute  episode,  and  
'prophylactic  agent'  or  'prophylactic  medication'  for  long-­‐term  maintenance  treatment
...
   The  choice  should  depend  on:    
 
• Response  to  previous  treatments  
• The  relative  risk,  and  known  precipitants,  of  manic  versus  depressive  relapse  
• Physical  risk  factors  (particularly  renal  disease,  obesity  and  diabetes)  
• The  patient’s  preference  and  history  of  adherence  
• Gender  (valproate  should  not  be  prescribed  for  women  of  child-­‐bearing  potential,  as  is  
tetrogenic  and  can  cause  neural  tube  defects)  
 
Lithium  has  the  best  evidence  and  is  the  most  effective  drug  in  the  prophylactic  treatment  of  
Bipolar  disorder
...
   In  addition,  lithium  can  
cause  renal  damage  (e
...
 nephrogenic  DI)  =>  also  important  to  monitor  kidney  function  –    
There  are  high  rates  of  adverse  effects  and  risk  of  inadvertent  toxicity  
Lithium  treatment  requires  regular  blood  monitoring:  renal  function  (U&Es),  CrCl,  thyroid  
function  (TFTs),  lithium  level,  and  calcium  level  

 
Side  effects  of  lithium  therapy  









Nausea,  vomiting,  anorexia,  diarrhea  (GI  effects)  
Tremor  
Visual  changes    
Renal  effects:  polydipsia,  polyuria  –  can  cause  nephrogenic  DI  =>  monitor  U&Es  
Hypothyroidism  and  hyperparathyroidism  (can  cause  hypercalcaemia)  =>  monitor  TFTs  and  
calcium    
Lithium  toxicity  (GI  symptoms,  drowsiness,  ataxia  and  confusion)  =>  monitor  lithium  levels  
Neurotoxic  in  overdose  
Blood  levels  must  be  monitored  (particularly  U&Es,  CrCl  and  TFTs  and  lithium  levels)  

 
Lithium  levels  








Normally  aim  for  level  of  1
...
6-­‐1
...
 
Toxicity  can  occur  >1
...
 Concurrent  use  of  diuretics  that  inhibit  
the  uptake  of  sodium  by  the  distal  tubule  (e
...
 thiazides)  is  hazardous  and  should  be  avoided  
because  this  can  cause  increased  resorption  of  lithium  in  the  proximal  convoluted  tubule,  
leading  to  elevated,  potentially  toxic  levels
...
   
Plasma  concentrations  in  excess  of  2
...
g
...
 
Anticonvulsants   are   also   increasingly   being   used   in   the   treatment   of   bipolar   disorder,   since   many  
seem   to   act   as   mood   stabilizers
...
    The   key   characteristic   of   an   anticonvulsant   is   to   suppress   the   rapid   and  
excessive  firing  of  neurons  that  start  a  seizure
...
g
...
g
...
 

 
 
 
Non-­‐pharmacological  management  of  mood  disorders  
Psychoanalysis  








One  of  the  first  forms  of  therapy  constructed  by  Freud  
His   model   states   that   people   are   driven   by   their   basic   instincts   e
...
  sex   and   aggression
...
     
In  other  words  we  are  driven  by  unconscious  motivations  to  satisfy/regress  sexual  urges  or  
aggression
...
    We   are  
driven  by  our  unconscious
...
g
...
    Our   response   system   brings  
about  particular  consequences  (behaviours)
...
   
Depending  on  our  learnt  behaviours  we  interpret  information  in  different  ways
...
   






Therefore  behaviorists  do  not  look  at  behaviour  disorders  as  something  a  person  has;  they  
see  them  as  a  reflection  of  how  learning  has  influenced  certain  people  to  behave  in  a  certain  
way  in  certain  situations
...
  Those   who   practice  
behaviour   therapy   tend   to   look   more   at   specific,   learned   behaviours   and   how   the  
environment  has  an  impact  on  those  behaviours
...
   
A   schema   is   the   fundamental   underlying   ways   in   which   people   process   information,   about  
the   self,   the   world   or   the   future
...
 It  can  also  be  described  as  a  mental  structure  of  preconceived  ideas,  a  framework  
representing   some   aspect   of   the   world,   or   a   system   of   organizing   and   perceiving   new  
information  
Depressed   people   acquire   such   schemas   through   a   loss   of   a   parent,   rejection   by   peers,  
bullying,   criticism   from   teachers   or   parents,   the   depressive   attitude   of   a   parent   and   other  
negative  events
...
    Therefore   this   theory   says   that   depression   is   brought   on   by  
environmental  triggers
...
  Once   those   thoughts   have   been   challenged,   one's   feelings   about   the   subject  
matter  of  those  thoughts  are  more  easily  subject  to  change
...
  The   therapist   initially   tries   to   highlight   these   distortions,   and   then   encourages  
the  patient  to  change  his  or  her  attitudes
...
   
Beliefs   and   schemas   (the   way   we   think   and   interpret   information)   drives   behaviour   and  
controls  our  feelings  and  emotions  (cognitive  theory)  
Our   (learnt)   behaviour   brings   about   consequences   which   changes   the   way   we   think   and  
changes  moods  and  physical  feelings  (behavioural  theory)  
Educational  therapy  which  teaches  the  patient  to  think  and  interpret  information  differently  
Also  teaches  self  control  
Strong  evidence  base  
AD’s   make   the   patient   more   open   and   more   susceptible   to   CBT   therapy
...
    They   can   result   in   dysfunctional  
assumptions  which  can  drive  negative  thoughts
...
   ECT  clearly  works
...
   
ECT   is   very   useful   for   depression   (without   psychosis)   which   has   not   responded   to   AD  
(treatment  resistant  MDD)  
ECT   is   also   very   useful   for   depression   with   psychotic   symptoms   (e
...
  hallucinations   and  
delusions)    
Useful  for  catatonic  states  
Common  side  effects  include:  confusion,  headache  and  memory  impairment  (short  term)  
Long  term  memory  problems  can  also  occur  
Can  be  performed  as  out  patient  (under  GA)  
Further  Tx  (e
...
 CBT,  medication  and/or  ECT)  is  required  after  to  prevent  relapses  

 
SUICIDE  


Suicide  is  the  act  of  intentionally  causing  one's  own  death
...
    Stress   factors   such   as   financial  
difficulties  or  troubles  with  interpersonal  relationships  often  play  a  role
...
  The   leading   methods   in   different  
regions  include  hanging,  pesticide  poisoning,  and  firearms
...
     



Efforts  to  prevent  suicide  include  limiting  access  to  firearms,  treating  mental  illness  and  drug  
misuse,  and  improving  economic  development
...
     
Parasuicde   =   apparent   attempted   suicide   without   the   actual   intention   of   killing   oneself  
(e
...
 DSH)  
Other  researchers  also  include  those  who  attempt  suicide  with  the  intent  to  kill  themselves  
in  the  definition  of  parasuicide
...
 
Studies   have   found   that   about   half   of   those   who   complete   suicide   have   a   history   of  
parasuicide  =>  DSH  and  parasuicide  are  major  risk  factors  for  future  suicide  

 

Suicide  risk  factors  
Factors  that  affect  the  risk  of  suicide  include:  










Previously  attempted  suicide  
Previous  DSH  
Psychiatric   disorders   e
...
  major   depression   (MDD),   bipolar   (BPD),   psychosis,   schizophrenia  
and  personality  disorders  
Medical  problems  
Drugs  and  alcohol  misuse  
Psychological  states  e
...
 hopelessness,  depression,  anhedonia  and  anxiousness  
Cultural,  family  and  social  situations  e
...
 single  with  reduced  support  network  
Genetics  
Male  
 
 

Pathophysiology  


There  is  no  known  unifying  underlying  pathophysiology  for  suicide
...
 



Low   levels   of   brain-­‐derived   neurotrophic   factor   (BDNF)   are   both   directly   associated   with  
suicide  and  indirectly  associated  through  its  role  in  major  depression,  post-­‐traumatic  stress  
disorder,   schizophrenia   and   obsessive–compulsive   disorder
...
 



Serotonin  is  believed  to  be  low  in  those  who  commit  suicide
...
    Other  evidence  includes  reduced  
levels   of   a   breakdown   product   of   serotonin,   5-­‐Hydroxyindoleacetic   acid   (5-­‐HIAA),   in   the  
cerebral  spinal  fluid
...
 

 
Suicide  prevention  







Identifying  at  risk  patients  and  offering  help  
Treatment  of  psychiatric  conditions  
Treatment  of  drug  and  alcohol  addiction  
CBT  therapy  for  individuals  at  risk  
Efforts  to  increase  social  connection  and  support  network  
Reducing  access  to  certain  methods,  such  as  firearms  or  toxins  reduces  the  risk  

 
Determining  a  patient's  risk  of  suicide  








History  of  DSH  or  “attempted”  suicide  
Suicidal  intent  has  been  found  to  be  a  good  predictor  of  subsequent  attempts
...
 The  most  widely  used  
scales  are  the  Pierce  Suicide  Intent  Scale  and  Beck's  Suicidal  Intention  Scale
...
g
...
  You   may   need   to   consider   referral   to   local   mental  
health  services  for  further  follow-­‐up
...
    If   you   are  
unsure  then  seek  advice  from  mental  health  specialists
...
   
 
 
 

SELF  HARM  AND  RISK  ASSESSMENT  
Deliberate  Self  Harm  (DSH)  


Self-­‐harm   (SH)   or   deliberate   self-­‐harm   (DSH)   includes   self-­‐injury   and   self-­‐poisoning   and   is  
defined  as  direct  injuring  of  body  tissue  most  often  done  without  suicidal  intentions
...
    Behaviours   associated   with   substance   abuse   and   eating  
disorders   are   usually   not   considered   self-­‐harm   because   the   resulting   tissue   damage   is  
ordinarily  an  unintentional  side  effect
...
 
However  patients  with  other  diagnoses  may  also  self-­‐harm,  including  those  with  depression,  
anxiety   disorders,   substance   abuse,   eating   disorders,   post-­‐traumatic   stress   disorder,  
schizophrenia,  and  several  personality  disorders
...
  Self   harm   is   also   often  
associated  with  drug  or  alcohol  abuse
...
     



The   motivations   for   self-­‐harm   vary   and   it   may   be   used   to   fulfill   a   number   of   different  
functions
...
 Selfharm  may  also  be  a  cry  for  help
...
 Many  self-­‐harmers  are  very  self-­‐conscious  of  their  wounds  
and   scars   and   feel   guilty   about   their   behaviour   leading   them   to   go   to   great   lengths   to  
conceal   their   behaviour   from   others
...
   However,  some  individuals  may  be  self  harming  
as  a  cry  for  help  (which  is  not  “attention  seeking”  used  in  the  context  which  it  is  usually  used  
in)
...
  People   who   self-­‐harm   are   not   usually  
seeking  to  end  their  own  life;  it  has  been  suggested  instead  that  they  are  using  self-­‐harm  as  
a   coping   mechanism   to   relieve   emotional   pain   or   discomfort   or   as   an   attempt   to  
communicate  distress
...
 

 
Neurobiology  





Patients   with   Hx   of   deliberate   self   harm   (DSH)   have   lower   5-­‐HIAA   (main   metabolite   of  
serotonin)  in  CSF  (in  comparison  to  controls)  
Low  levels  of  brain-­‐derived  neurotrophic  factor  (BDNF)  
Low   serotonin   (low   5HIAA)   correlated   with   DSH,   attempted   suicide,   assaultiveness,  
instability,  aggression  &  impulsiveness  
Reduced  binding  to  5-­‐HT  transporter  sites  in  Ventral  PreFrontal  Cortex  

 
Suicide  &  Genetics  




MZ  twins  (identical):  concordance  rate  13
...
7%  
This  is  suggestive  of  a  genetic  link  

 
Signs  and  symptoms  of  DSH  






Eighty  percent  of  self-­‐harm  involves  stabbing  or  cutting  the  skin  with  a  sharp  object
...
 
The  locations  of  self-­‐harm  are  often  areas  of  the  body  that  are  easily  hidden  and  concealed  
from  the  detection  of  others
...
 
 

Aetiology  


Mental  illness  






Drugs  and  alcohol:  Substance  misuse,  dependence  and  withdrawal  are  associated  with  self-­‐
harm
...
 Factors  such  as  war,  poverty,  and  unemployment  may  also  contribute
...
   This  is  so  we  can  
identify  patients  at  moderate  to  high  risk  of  suicide  and  treat  them  accordingly
...
g
...
 
Risk  of  suicide  in  12  months  after  DSH  =  1%  
Enquire   about   suicidal   ideations,   thoughts,   plans,   and   motivations   (including   previous  
attempts  and  DSH)    
Psychiatric  conditions  and  alcohol/drug  abuse  are  also  major  risk  factors  
Enquire  and  take  into  account  all  major  risk  factors  
Hopelessness  is  a  robust  predictor  of  eventual  fatal  self-­‐harm  (include  hopelessness  in  your  
MSE)  

 
Management  of  DSH  
Immediate  management  




Calm  the  patient  
Crisis  cannot  usually  be  resolved  without  some  release  of  emotion  
Direct  the  interview  e
...
 privacy  and  deep  breathing  






Ask  about:  background,  the  episode  of  self-­‐harm  and  mental  state  then  &  now  
Perform  a  risk  assessment  and  assess  if  the  patient  has  low,  moderate  or  high  risk  of  suicide  
or  fatal  DSH  
Who  else  needs  to  be  involved?  (depends  on  risk)  
Arrange  &  explain  follow-­‐up  if  this  is  indicated  e
...
 psychiatry/psychology,  counselling  (e
...
 
Rape  Crisis,  Womens’  Refuge),  Social  work  and  Samaritans  

 
SELF  HARM  TUTORIAL  CASES  
Case  1  
A   44   year   old   man   is   brought   to   Carseview   by   the   police   for   emergency   assessment   after   attempting  
to  jump  off  the  Tay  Bridge
...
 He  has  a  diagnosis  of  paranoid  schizophrenia  and  is  
under  the  care  of  the  community  mental  health  team  and  the  clozapine  clinic
...
 He  also  has  significant  negative  symptoms
...
 He  has  not  been  employed  since  being  diagnosed  
with  schizophrenia  nearly  20  years  ago  and  has  little  contact  with  his  family
...
   What  are  negative  symptoms?  
Things   that   would   normally   be   present   in   a   patient   but   are   absent   in   schizophrenia:   withdrawal   and  
social  isolation,  flat/blunt  affect,  anhedonia,  apathy  (lack  of  interest)  etc  
2
...
   What  might  you  find  on  mental  state  examination?  
Positive  or  negative  symptoms    
Formal  thought  disorder,  hallucinations,  delusions,  flat  affect,  low  mood,  odd  behaviours,  cognitive  
impairment  
4
...
  She   is   unemployed   and   has   little   contact   with   other   people
...
  She   has   difficulty  
relating  to  people  and  trusting  them
...
”   She   finds   herself   becoming   very   anxious   and  
describes   physical   symptoms   including   heart   racing,   sweatiness   and   headache
...
 She  also  takes  alcohol  with  the  
paracetamol   at   times
...
  Sometimes   her   overdoses   don’t   come   to   anyone’s   attention   but   at   other  
times   she   realises   she   has   taken   more   than   the   prescribed   amount,   tells   her   sister   and   she   takes   her  
to   A+E
...
 
1
...
 What  is  going  on  physiologically  in  her  body  when  she  is  watching  this?    
Panic  attack:  excessive  activation  of  sympathetic  nervous  system  
3
...
   Why  do  you  think  she  takes  the  paracetamol?    
Form  of  deliberate  self-­‐harm  
5
...
g
...
   
• However,  the  event  is  commonly  relived  by  the  individual  through  intrusive,  
recurrent  recollections,  flashbacks  and  nightmares  
 
6
...
 Stigma  may  then  be  affixed  to  such  a  person,  by  the  greater  society,  who  differs  from  their  
cultural  norms
...
  Attributes  
associated   with   social   stigma   often   vary   depending   on   the   geopolitical   and   corresponding  
sociopolitical  contexts  employed  by  society,  in  different  parts  of  the  world
...
     



Psychosis   is   a   description   of   symptoms   (a   syndrome)   rather   than   a   diagnosis
...
 



Psychosis  is  generally  given  to  noticeable  deficits  in  normal  behaviour  (negative  signs)  and  
more   commonly   to   positive   signs   such   as   diverse   types   of   hallucinations   or   delusional  
beliefs  (e
...
 grandiosity,  delusions  of  persecution)
...
g
...
g
...
g
...
g
...
g
...
g
...
 Put  simply,  
delusions   are   false   beliefs,   outwith   the   social   and   cultural   norms   of   the   pt,   which   a   person  
holds   on   to   with   absolute   conviction,   without   adequate   evidence
...
     



It  may  be  difficult  to  change  the  belief  even  with  evidence  to  the  contrary
...
  However,   they   are   of   particular   diagnostic  
importance   in   psychotic   disorders   including   schizophrenia,   manic   episodes   of   bipolar  
disorder,  and  depression  with  psychosis
...
 
Non-­‐bizarre   delusion:   A   delusion   that,   though   false,   is   at   least   possible,   e
...
  the   affected  
person  mistakenly  believes  that  he  is  under  constant  police  surveillance
...
g
...
   Common  themes  of  delusions  are:  






Persecutory  (person  believes  that  others  are  out  to  harm  him/her)  
Grandiose  (person  believing  that  he  or  she  has  special  powers  or  skills,  or,  is  god),    
Poverty  –  person  believes  that  they  are  poor  when  they  are  not  
Sin  
Guilt  




Nihilism  (persistent  beliefs  that  a  person  does  not  exist  or  is  dead  or  is  dying)  
Self  reference  –  person  believes  things  are  related  to  them    
 
Depressed  persons  may  have  delusions  consistent  with  their  low  mood  e
...
 delusions  that  they  have  
sinned,  or  have  contracted  serious  illness  etc
...
g
...
g
...
   These  sorts  of  delusions  are  called  secondary  delusions
...
  They   feel   like   they   are   coming   from   outside   of  
me"
...
     
However  these  inner  experiences  may  lead  onto  delusions  and  a  patient  may  start  to  think  
"they   are   being   transmitted   by   the   Mafia"
...
     

 
Self-­‐referential  experiences  





The  belief  that  external  events  are  related  to  oneself
...
   
In   particular,   the   dopamine   hypothesis   of   psychosis   has   been   influential   and   states   that  
psychosis   results   from   an  overactivity  of  dopamine  function  in  the  brain,   particularly   in   the  
mesolimbic  pathway
...
e
...
   
However,   increasing   evidence   in   recent   times   has   pointed   to   a   possible   dysfunction   of   the  
excitory  neurotransmitter  glutamate,  in  particular,  with  the  activity  of  the  NMDA  receptor
...
g
...
g
...
g
...
   If  present  in  psychotic  phase  =>  suggestive  
of  schizoaffective  disorder  
Third  person  delusions  are  characteristic  (e
...
 voices  talking  about  the  individual)  
Visual  hallucinations  are  NOT  normally  a  feature  (these  are  suggestive  of  delirium  or  DLB)  

 
 
Drug  induced  Psychosis  





May   be   florid   symptoms   or   chronic   symptoms   but   tend   to   be   short   lasting   if   access   to   the  
psychoactive  substance  is  removed
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
g
...
 He  has  also  tried  to  buy  a  Porsche  on  credit
...
 
He  feels  full  of  energy  and  new  ideas  and  can’t  see  that  he  has  done  anything  wrong
...
    So   a   new-­‐onset  
episode  of  psychosis  cannot  be  considered  to  be  a  sign  of  a  psychiatric  disorder  until  other  
relevant  and  known  (medical/drug)  causes  of  psychosis  are  properly  excluded,  or  ruled  out
...
g
...
   Illicit  substance-­‐induced  psychosis  should  also  be  ruled  out
...
 
! B12/Folate  assay  
 
Other  investigations  which  may  be  performed  include:  
 
• EEG  to  exclude  epilepsy  and  encephalitis  
• MRI  or  CT  scan  of  the  head  to  exclude  brain  lesions  
 

 
SCHIZOPHRENIA  
What  is  schizophrenia?  







A  group  of  brain  disorders    
Chronic   disorder   resulting   in   positive   and   negative   symptoms   resulting   in   problems   with  
dealing  with  reality  and  functioning    
Characteristic  features  are  distortions  of:  
! Thought  process  (thought  disorder)  
! Thought  content  (delusions)  
! Perception  (hallucinations)  
! Behaviour  
! Emotion  
No   pathognomonic   symptoms   (e
...
  no   symptoms   specific   to   schizophrenia,   although   third  
person  hallucinations  are  suggestive)  
Aetiology=  Neurodevelopmental  +  Genetic  +  Environment  (Biopsychosocial)  

 
Key  clinical  features  
Delusions  
Hallucinations  
Thought  disorder  
Negative  symptoms:    apathy,  anhedonia,  blunted  affect,  social  isolation  and  withdrawal  
Emotional  disorder  
Motor  and  behavioural  disorder  
Cognitive  dysfunction    
 
 
Positive  and  negative  symptoms  

















In   describing   mental   disorders,   especially   schizophrenia,   symptoms   can   be   divided   into  
positive  and  negative  symptoms
...
   
Examples   of   positive   symptoms   include   hallucinations,   delusions,   and   bizarre   behaviour  
(Tx  with  anti  dopaminergics  which  block  DA  in  the  mesolimbic  pathway)  
Negative   symptoms   are   functions   that   are   normally   found   in   healthy   persons,   but   that   are  
diminished   or   not   present   in   affected   persons
...
     
Examples   of   negative   symptoms   are   social   withdrawal,   apathy   (lack   of   interest),  
flat/blunted   affect   (no   emotion   in   response   to   something   that   would   normally   illicit   an  
emotion),  inability  to  experience  pleasure  (anhedonia)  and  defects  in  attention  control
...
   









The   mesolimbic   pathway   is   a   dopaminergic   pathway   in   the   brain
...
 The  mesolimbic  dopamine  system  is  widely  believed  to  be  a  "reward"  pathway
...
    The   mesocortical   pathway   is   a   neural   pathway   that  
connects   the   ventral   tegmentum   (VTA)   to   the   cerebral   cortex,   in   particular   the   frontal   lobes  
(PFC)
...
  It   is   essential   to   the  
normal  cognitive  function  of  the  dorsolateral  prefrontal  cortex  (part  of  the  frontal  lobe),  and  
is   thought   to   be   involved   in   cognitive   control,   motivation,   and   emotional   response
...
       
Anti-­‐psychotics   are   good   at   Tx   positive   symptoms   but   not   so   good   at   Tx   negative  
symptoms
...
     

 
Positive  symptoms  




Delusions:     standard   delusions,   delusions   of   control   (pasitivity   phenomenon),   thought  
interference,  delusional  perception    
Hallucinations:    third  person,  thought  echo,  running  commentary    
Formal   thought   disorder   (which   manifests   as   disorganised   speech)   e
...
  knights   move  
thinking   (loosening   of   associations),   neologism,   and   thought   interference  
(blocking/insertions/broadcasting)  

 
Negative  symptoms  






Apathy  and  flat  affect  
Anhedonia  
Lack  of  volition  
Social  withdrawal  
Cognitive  impairment    

 
 
Schneider’s  First  Rank  Symptoms  
Schneider's  first-­‐rank  symptoms  of  schizophrenia  are  symptoms,  which,  if  present,  are  strongly  
suggestive  of  schizophrenia
...
g
...
    The   individual   feels   that   some  
external   agent   is   controlling   them   to   feel   emotions,   to   desire   to   do   things,   to  
perform  actions  or  to  experience  bodily  sensations
...
  This   six-­‐month   period   must  
include  at  least  one  month  of  symptoms  as  stated  above  (or  less,  if  symptoms  remitted  with  
treatment)
...
     
Psychotic   symptoms   may   be   present   in   several   other   mental   disorders,   including   bipolar  
disorder,  borderline  personality  disorder,  and  MDD
...
   









A   small   number   of   people   withdrawing   from   benzodiazepines   experience   a   severe  
protracted  withdrawal  syndrome  which  can  resemble  schizophrenia  and  be  misdiagnosed  as  
such
...
   
It   may   be   necessary   to   rule   out   a   delirium,   which   can   be   distinguished   by   visual  
hallucinations,   acute   onset   and   fluctuating   level   of   consciousness,   and   indicates   an  
underlying   medical   illness
...
 
 

 
Schizophreniform  disorder  (DSM)  










Schizophreniform  disorder  is  a  mental  disorder  diagnosed  when   symptoms  of  schizophrenia  
are   present   for   a   significant   portion   of   the   time   within   a   one-­‐month   period,   but   signs   of  
disruption   are   not   present   for   the   full   six   months   required   for   the   diagnosis   of  
schizophrenia  (DSM  IV  criteria)  
The  symptoms  of  both  disorders  can  include  delusions,  hallucinations,  disorganized  speech,  
disorganized  or  catatonic  behavior,  and  social  withdrawal
...
   
While   the   onset   of   schizophrenia   is   often   gradual   over   a   number   of   months   or   years,   the  
onset  of  schizophreniform  disorder  can  be  relatively  rapid
...
g
...
)  designed  to  reduce  the  social  and  emotional  impact  of  the  illness
...
 

 
Schizoaffective  disorder  





Schizoaffective   disorder   is   a   mental   disorder   characterized   by   psychosis   and   abnormal  
emotional/affective  responses  (mood  disorder)  –  in  the  same  time  period  (separated  by  at  
least  2  weeks)  
Common   symptoms   of   psychosis   include   auditory   hallucinations,   paranoid   delusions,   and  
disorganized  speech  and  thinking
...
    The  
bipolar   type   is   distinguished   by   symptoms   of   mania,   hypomania,   or   mixed   episodes;   the  
depressive  type  by  symptoms  of  depression  exclusively
...
  When   there   is   risk   to   self   or  
others,   usually   early   in   treatment,   brief   hospitalization   may   be   necessary
...
g
...
 
In   DSM-­‐5   and   ICD-­‐10   (which   is   being   revised   to   ICD-­‐11,   to   be   published   in   2015),  
schizoaffective   disorder   is   in   the   same   diagnostic   class   as   schizophrenia,   but   not   in   the   same  
class  as  mood  disorders
...
 Only  when  a  psychotic  condition  lasts  
two-­‐weeks   continuously   or   longer   without   mood   symptoms,   is   the   diagnosis   either  
schizophrenia  or  schizoaffective  disorder
...
   
Positive   symptoms   include   hallucinations,   delusions,   passivity   phenomenon,   and   thought  
interference,  and  are  often  the  most  responsive  to  anti-­‐psychotic  treatment
...
   
In   addition   to   positive,   negative,   aggressive   and   cognitive   symptoms,   patients   with  
schizophrenia  often  exhibit  affective  disorders,  including  depression  and  anxiety
...
 
There   is   substantial   overlap   among   these   different   symptom   domains   and   it   can   be  
particularly   difficult   to   distinguish   negative   symptoms   from   affective   symptoms   (including  
depression  and  anxiety)  
The  comorbidity  of  affective  symptoms,  especially  depression,  can  have  dire  consequences  
for   the   quality   of   life   and   life   span   of   those   with   schizophrenia;   thus   it   is   important   that  
affective  symptoms  are  properly  diagnosed  and  treated  optimally
...
  If  
affective  symptoms  are  present  they  are  not  generally  severe
...
 
However   in   the   lifelong   course   of   schizophrenia,   depressive   symptoms   are   common   -­‐   not  
necessarily  as  part  of  a  psychotic  relapse  as  they  can  occur  at  any  time  and  do  not  have  to  be  
related   to   psychotic   symptoms
...
 
The   issue   of   schizoaffective   disorder   is   complex   and   a   little   controversial   -­‐   the   best   way   to  
think   of   it,   without   getting   into   the   complex   arguments   is   to   say   that   although   "pure"  
schizophrenia   is   recognisable   in   many   patients,   and   "pure"   BPD/MDD   is   recognisable   in  
many   others,   there   are   also   many   patients   who   have   features   of   both   schizophrenia   and  
BPD/MDD   and   for   whom   it   is   impossible   to   say   they   have   one   or   the   other   -­‐   they   have  

features   of   both
...
  Schizoaffective   disorder   can  
be   classified   as   depressive   or   bipolar   type
...
 
• Schizophrenia  and  schizoaffective  disorder  are  lifelong  chronic  illnesses  which  relapse  and  
remit  
• Schizophreniform   disorder   is   a   mental   disorder   diagnosed   when   symptoms   of  
schizophrenia  are  present  for  a  significant  portion  of  the  time  within  a  one-­‐month  period,  
but   signs   of   disruption   are   not   present   for   the   full   six   months   required   for   the   diagnosis   of  
schizophrenia  (DSM  IV  criteria)
...
g
...
g
...
g
...
  dendrites   and   glial   cells)   and   not  
neuron  loss    
 
Consistent  reductions  





Temporal  cortex  (especially  superior  temporal  gyrus)  
Medial  temporal  lobe  (especially  hippocampus)  

 
Variable  reductions  




Orbitofrontal  cortex  
Parietal  cortex  
Basal  ganglia  
 

In  patients  with  poor  prognosis  



Reduced  frontal  lobe  volume  
Reduced  frontal  lobe  grey  matter  




Enlarged  lateral  ventricle  volume  
White  matter  abnormalities  

 
 
What  causes  the  brain  pathology?  



Identified  gene  alterations:  neuregulin,  dysbindin,  DISC-­‐1    
Glutamatergic  hypothesis:  altered  NMDA  receptor  subunit  expression  (ketamine  is  an  NMDA  
receptor  antagonist  and  can  also  induce  psychotic  symptoms)  results  in  decreased  glutamate  
activity  

 
DA  hypothesis  of  schizophrenia  
It   is   assumed   there   is   overactivity   of   certain   DA   pathways   (in   particular   the   mesolimbic)   in   the  
brain
...
g
...
 
• Amphetamine  can  make  schizophrenics  worse  
• Dopamine   receptor   antagonists   (anti-­‐psychotics)   are   used   to   treat   the   positive   symptoms  
of  schizophrenia  and  psychosis
...
   
Dopamine   receptors   are   implicated   in   many   neurological   processes,   including   motivation,  
pleasure,   cognition,   memory,   learning,   and   fine   motor   control,   as   well   as   modulation   of  
neuroendocrine  signaling
...
 Thus,  dopamine  receptors  are  common  neurologic  drug  
targets
...
 

 
 
Is  the  dopamine  system  dysfunctional  in  SZ?  
Reformulation  of  dopamine  hypothesis:  


 



Subcortical   (mesolimbic   pathway)   DA   hyperactivity   leads   to   psychosis   and   hallucinations  
(positive  symptoms)  
Mesocortical  DA  hypoactivity  leads  to  negative  and  cognitive  symptoms  

This  is  based  on  evidence  that  negative  and  cognitive  symptoms  persist  despite  D2  blockade  with  
antipsychotics
...
     



Anti-­‐psychotics  =  dopamine  antagonists  (dopamine  receptor  blockers)  –  but  have  a  range  of  
NT  channel  profiles    

 
Typical  antipsychotics  
Vague   definition,   which   describes   the   drugs   originally   developed   or   even   drugs   that   do   not   have  
atypical  properties:  

 





Haloperidol  
Chlorpromazine  
Significant  extra-­‐pyramidal  symptoms  (due  to  DA  blockade  in  the  basal  ganglia)  

Atypical  (2nd  generation)  antipsychotics  







Less  likely  to  induce  EPS  (extra-­‐pyramidal  basal  ganglia  symptoms)  
High  5-­‐HT2A  to  D2  receptor  ratio  
Better  efficacy  against  negative  symptoms  
However  greater  risk  of  metabolic  syndrome:    weight  gain,  DM,  hyperlipidaemia    
Effective  in  patients  unresponsive  to  typical  drugs  
Atypicals  include  clozapine,  olanzapine,  and  risperidone  (“ROC”)  

Remember:    Risperidone  can  be  given  as  depot  
 
Anti-­‐psychotics:  mechanism  of  action  
• All  antipsychotic  drugs  tend  to  block  D2  receptors  in  the  dopamine  pathways  of  the  brain
...
 
• In   addition   of   the   antagonistic   effects   of   dopamine,   antipsychotics   (particular   atypical  
antipsychotics)  also  block  serotonin  receptors
...
  Blocking   D2   receptors   in   these  





other   pathways   is   thought   to   produce   some   of   the   unwanted   side   effects   that   the   typical  
antipsychotics   can   produce   (e
...
  extra-­‐pyramidal   motor   symptoms   and   prolactin  
hypersecretion  -­‐  hyperprolactinaemia)
...
  5-­‐HT2A  
antagonism  also  increases  dopaminergic  activity  in  the  nigrostriatal  pathway,  leading  to  a  
lowered  extrapyramidal  side  effect  liability  among  the  atypical  antipsychotics
...
  They   also   have   a   lower  
propensity   for   causing   extrapyramidal   side   effects
...
  In   addition,  
many   atypical   antipsychotics   are   compared   to   haloperidol   (a   traditional   antipsychotic   that  
yields   numerous   extrapyramidal   side   effects)   and   therefore   it   is   not   surprising   that   the  
atypical   antipsychotics   have   an   improved   extrapyramidal   side   effect   profile   in   comparison
...
     

 
 
Key  points  
• Anti-­‐psychotics  =  dopamine  (D2)  blockers  
• Typicals   (haloperidol,   chlorpromazine)   are   not   particularly   selective   and   also   block   DA   in   the  
nigrostratial  pathway  leading  to  EPS  e
...
 Parksinonian  symptoms)
...
     
• In   addition   of   the   antagonistic   effects   of   dopamine,   antipsychotics   (particular   atypical  
antipsychotics)  also  block  serotonin  receptors
...
   Atypical  antispyschotics  are  
better   at   treating   negative   symptoms   in   addition   to   positive   symptoms
...
  5-­‐HT2A   antagonism   also  
increases   dopaminergic   activity   in   the   nigrostriatal   pathway,   leading   to   a   lowered  
extrapyramidal  side  effect  liability  among  the  atypical  antipsychotics
...
g
...
 
! In  pt  with  Parkinsonism  =>  atypical  
! In  pt  with  CVD  and  multiple  CV  risk  factors  =>  typical    
 
 
Relative  receptor  binding  profiles  
Anti  psychotics  not  only  bind  to  dopamine  receptors  but  they  can  also  bind  to:  





Serotonin  receptors  
Adrenergic  receptors  
Histamine  receptors  
Cholinergic  (muscarinic)  receptors  
 

Different  anti-­‐psychotics  have  different  receptor  binding  profiles  
 
Adverse  effects  of  Anti-­‐Psychotics  
Dopamine  D2  receptor  blockade:    more  prominent  in  typicals  



Hyperprolactinaemia   (as   dopamine   acts   to   suppress   prolactin   release)   which   may   cause        
galactorrhoea,  gynaecomastia,  sexual  dysfunction  (in  both  sexes)  and  osteoporosis  
Extra-­‐pyramidal   side   effects   (EPSE)   due   to   disruption   of   dopamine   signalling   (nigrostriatal  
pathway)   in   the   basal   ganglia   system   which   may   result   in   dystonia   (inc   oculogyric   crisis),  
bradykinesia,   tremor,   muscle   rigidity   (non   spastic   hypertonia),   parkinsonism,   Akathisia,  
tardive  dyskinesia,  etc
...
g
...
    The   more   common   include   extreme   constipation,   bed-­‐
wetting,   night-­‐time   drooling,   muscle   stiffness,   sedation,   tremors,   orthostatic   hypotension,  
hyperglycemia,   and   weight   gain   (e
...
  the   more   common   side   effects   are   due   to   anti-­‐
dopamine,  anti-­‐histamine  and  anti-­‐cholinergic  effects)  
Clozapine   also   has   a   risk   of   causing   serious   side   effects   such   as   agranulocytosis,   CNS  
depression,   seizure   disorder,   bone   marrow   suppression,   dementia,   hypotension,   and  
myocarditis
...
 It  is,  however,  one  of  
the  very  effective  anti-­‐psychotic  treatment  choices
...
   
Typically  C-­‐reactive  protein  (CRP)  increases  with  the  onset  of  fever  and  rises  in  the  cardiac  
enzyme,  troponin,  occur  up  to  5  days  later
...
 
If  spreads  to  pericardium  resulting  in  pericarditis  then  O/E  we  may  observe  a  pericardial  rub  
Perform  ECG  if  suspected  myocarditis/pericarditis  

 
 
MANAGEMENT  OF  SCHIZOPHRENIA  


The  primary  treatment  of  schizophrenia  is  antipsychotic  medications,  often  in  combination  
with  psychological  and  social  supports
...
 Long-­‐term  hospitalization  is  
uncommon  since  deinstitutionalization  beginning  in  the  1950s,  although  it  still  occurs
...
   



Some   evidence   indicates   that   regular   exercise   has   a   positive   effect   on   the   physical   and  
mental  health  of  those  with  schizophrenia
...
  Antipsychotics,   however,   fail  
to  significantly  ameliorate  the  negative  symptoms  and  cognitive  dysfunction
...
 



The   choice   of   which   antipsychotic   to   use   is   based   on   benefits,   risks,   and   costs
...
    Both   have  
equal   drop-­‐out   and   symptom   relapse   rates   when   typicals   are   used   at   low   to   moderate  
dosages
...
     



KEY   POINT:     With   respect   to   side   effects   typical   antipsychotics   are   associated   with   a   higher  
rate   of   extrapyramidal   side   effects   (and   hyperprolactinaemia)   while   atypicals   are  
associated  with  considerable  weight  gain,  diabetes  and  risk  of  metabolic  syndrome
...
    It   remains  
unclear   whether   the   newer   antipsychotics   reduce   the   chances   of   developing   neuroleptic  
malignant  syndrome,  a  rare  but  serious  neurological  disorder
...
 
Aggression  can  take  a  variety  of  forms  and  can  be  physical  or  be  communicated  verbally  or  
non-­‐verbally  
Remember  that  their  may  be  an  organic  cause  of  aggression  so  check  patients  vital  signs,  
assess  for  infections  etc  

 
Management  of  Aggressive  Behaviour  










Prediction  e
...
 body  language  and  verbal  cues  
Prevention:  de-­‐escalation,  reasoning,  compromise,  observations,  room  lay  out  etc  
Intervention:  restraint,  seclusion,  rapid  tranquillisation  
Level  of  observations:    physical  and  psychiatric  
May  wish  to  observe  medication  free  initially  
Immediate   treatment   include   management   of   withdrawals,   management   of   disturbed   or  
aggressive  behaviour  
Physical  fluid  balance,  food  charts,  sleep  charts  etc  
Check  SEWS  –  may  be  caused  by  acute  illness,  hypoxia  etc  
Don’t  forget  that  hypoxia  can  cause  change  in  behaviour!  
 

Mental  Health  Act  Legislation  



Applies  to  a  "patient"  who  has  or  appears  to  have  a  mental  disorder  
Mental  disorder:    
! Any  mental  illness  
! Any  personality  disorder  
! Any  learning  disability  (NOT  learning  disorder)  

 
Emergency  Detention  









Mental  Health  (Care  and  Treatment)  (Scotland)  Act  2003:    Allows  for  treatment  of  mental  
disorder   or   physical   consequences   of   mental   disorder   in   someone   without   capacity   to  
consent  to  treatment
...
 
Short  term  detention  is  section  44  
Applied  by  AMP  (approved  medical  practitioner)  
Requires  MHO  (mental  health  officer)  for  consent  
More  rights  for  patient  and  named  person  
Authorises  treatment    
Lasts  for  maximum  of  28  days  (one  month)  –  after  this  CTO  required    
Right  of  appeal  to  Tribunal  and  Mental  Welfare  Commission  

 
Criteria  for  short  term  detention:  






The  patient  has  mental  disorder  
Significantly  impaired  decision-­‐making  ability  regarding  treatment,  due  to  mental  disorder    
Detention  in  hospital  is  necessary  for  assessment  or  treatment  
Risk  to  health,  safety  or  welfare  of  the  person,  or  safety  of  others  
Cannot  be  treated  voluntarily  
 

 
Compulsory  Treatment  Order  (CTO)  











Application  made  by  MHO  supported  by  two  medical  reports  
One  MUST  be  from  an  AMP  
Other  report  usually  from  patient’s  GP  
Right  of  appeal,  may  have  legal  representation  
Authorises  treatment  
Requires  to  have  tribunal  hearing  
Care  Plan  prepared  by  MHO  (in  consultation  with  team)  can  impose  conditions  ie  residency,  
attendance  at  services  
Last  for  up  to  6  months  
Patient  can  be  in  hospital  or  community  
Replaced  section  18  MH(S)A  1984  

 
 
 
 
Tayside  Rapid  Tranquillisation  Policy  
 

1
...
    If   history   unknown,   cardiac   disease   (haloperidol   is   contraindicated),   no   history   of   typical  
antipsychotics,  or  current  illicit  drug  use  then:  
• Consider  oral  Lorazepam  (BDZ)  1-­‐2mg  (BDZ  are  sedatives)  
• If   oral   unsuccessful   or   an   effect   required   within   30   minutes   then   consider   injection  
(Lorazepam  1-­‐2mg  intramuscular)    
• Wait  30  minutes:  Repeat  lorazepam  injection  once  IM  if  necessary  
• If  no  response  to  second  injection  seek  advice  from  senior  experienced  doctor  
 
3
...
e
...
    Do   not   mix   in   same   syringe
...
g
...
g
...
g
...
  Delirium   represents   an   organically   caused   acute   decline   from   a  
previously  attained  baseline  level  of  cognitive  function
...
   
 
It  typically  involves  other  cognitive  deficits,  changes  in  arousal  (hyperactive,  hypoactive,  or  
mixed),   perceptual   deficits,   altered   sleep-­‐wake   cycle,   and   psychotic   features   such   as  
hallucinations  (inparticular  visual  or  auditory)  and  delusions
...
  Delirium   is   most   often   caused   by   a   disease  
process  outside  the  brain  that  nonetheless  affects  the  brain  

 


It  is  a  corollary  of  the  criteria  that  a  diagnosis  of  delirium  cannot  be  made  without  a  previous  
assessment,   or   knowledge,   of   the   affected   person's   baseline   level   of   cognitive   function
...
   Therefore  collateral  history  is  essential  



Treatment   of   delirium   requires   treatment   of   the   underlying   organic   cause(s)
...
   Tranquilization  with  BDZs  may  also  be  justified
...
  It   affects   10-­‐20%   of   all   hospitalized   adults,   and   30-­‐40%   of   elderly   hospitalized  
patients  and  up  to  80%  of  ICU  patients
...
g
...
g
...
g
...
  Clinical   environments   can   also   precipitate   delirium,   and   optimal  
nursing   and   medical   care   is   a   key   component   of   delirium   prevention
...
 alcohol,  benzodiazepines  
Substance  intoxication  
Traumatic  head  injury  

VINDICATE:  Mnemonic  for  differential  diagnosis  and  aetiology  
Differential   diagnosis   is   the   systematic   method   by   which   diseases   of   similar   presentation   are  
distinguished   by   considering   their   various   features
...
  VINDICATE  
stands  for  










V  –  Vascular  
I  –  Inflammatory  
N  –  Neoplastic  
D  –  Degenerative  /  Deficiency  
I  –  Idiopathic,  Intoxication  
C  –  Congenital  
A  –  Autoimmune  /  Allergic  
T  –  Traumatic  or  toxic  
E  –    Endocrine  or  metabolic  

 
 
PERONALITY  DISORDERS  AND  BEHAVIOURAL  PROBLEMS  IN  ADULTS  
Personality  disorders  


Personality   disorders   are   a   class   of   social   disorders   characterised   by   enduring   maladaptive  
patterns   of   behavior,   cognition   and   inner   experience,   exhibited   across   many   contexts   and  
deviating  markedly  from  those  accepted  by  the  individual's  culture
...
     



There  are  many  issues  with  classifying  a  personality  disorder  -­‐  is  it  really  a  disorder,  or  just  
difficulties  getting  on  socially?  

 
Clinical  Personality  Assessment  



MSE  


 

Detailed  history  of  problem  behaviour  and  psychological  history
...
 
Stable  and  long  duration  (late  childhood  /  adolescence)
...
 
Organic  causes  need  to  be  excluded
...
g
...
g
...
   Is  PD  present?  





Long  term  pattern  of  poor  interpersonal  functioning  and  relationships  with  others  
Can  occur  at  any  age  
Is  not  part  of  another  mental  disorder  or  organic  cause  
Leads  to  impairment  or  distress  to  self  or  others  

 
 
2
...
   How  can  it  be  described?  






Schizoid   PD   (negative   symptoms):   detached   e
...
  lack   of   interest   in   social   relationships,   a  
tendency  towards  a  solitary  lifestyle,  loner,  secretiveness,  emotional  coldness,  and  apathy    
Schizotypal   (negative   symptoms   +   strange   thoughts):   A   need   for   social   isolation   (or   being  
alone),   and   often   unconventional   or   out   of   the   ordinary   thoughts   (schizotypal   is   typical   of  
schizophrenia,  with  abnormal  thoughts)  
Anti-­‐social  PD  (dissocial  PD):  dissocial,  lack  of  empathy,  crime,  violence  
Anankastic  (Obsessive  compulsive  PD):  rules,  orderly,  strict,  inflexible,  ego-­‐syntronic  
 

Schizotypal  and  schizoid  PD:  Cluster  A  


Schizoid:   Lack   of   interest   towards   a   social   lifestyle,   bottled   emotions,   detached,   emotional  
coldness,  apathy  (lack  of  interest)  



Schizotypal:  A  need  for  social  isolation  (or  being  alone),  and  often  unconventional  or  out  of  
the  ordinary  thoughts  (typical  of  schizophrenia)  



They   are   similar   in   the   way   that   they   both   reflect   social   isolation,   but   schizotypal   is   to  
'strange'  thoughts  as  schizoid  is  to  unshared  thoughts
...
  There  
may  be  an  impoverished  moral  sense  or  conscience  (lack  of  empathy)  and  a  history  of  crime,  legal  
problems,  impulsiveness  and  aggressive  behaviour
...
 
What  is  the  difference  between  a  sociopath  and  a  psychopath?  It  depends  who  you  ask
...
 



Mental   health   professionals   disagree   about   which   term   to   use,   which   unfortunately   only  
confuses   the   public
...
   Some  people  say  psychopath  describes  personality  traits  and  sociopath  describes  
behaviour
...
    At   least   three   symptoms  
of  impulsive  type  (e
...
 impulsiveness,  explosive,  emotionally  unstable)  and  at  least  2  of  the  following  
must  be  present:  




Self-­‐harm    
Poor  self  image    
Relationship  crisis  




Fear  of  abandonment  
Feelings  of  emptiness  

 
 
Narcissistic  PD:  Cluster  B  
At  least  five  of  the  following  must  be  present:  
Grandiose  (feelings  of  being  superior)  
Arrogant  
Self-­‐opinionated    
High  ideals    
Needs  admiration  
Expects  privilege    
Exploits  others    
Lacks  empathy    
Envy  
 
 
Avoidant  (anxious)  PD:  Cluster  C  
 
• Avoidant   personality   disorder   (also   known   as   anxious   personality   disorder),   is   afflicting  
persons   when   they   display   a   pervasive   pattern   of   social   inhibition,   feelings   of   inadequacy,  
extreme  sensitivity  to  negative  evaluation,  and   avoidance  of  social  interaction
...
   
 

 OCD   on   the   other   hand,   is   characterised   by   ego-­‐dystronic   thoughts   and   behaviour   e
...
  obsessions  
and   compulsions   are   in   conflict   with   the   needs   and   goals   of   the   ego,   or,   further,   in   conflict   with   a  
person's  ideal  self-­‐image
...
g
...
g
...
e
...
g
...
g
...
 It  does  not  infer  a  
particular   aetiology
...
  It   is   important   to  
understand   that   it   is   different   from   mental   illness   –   a   person   with   a   learning   disability   can   also  
develop  mental  illness
...
g
...
 
Prevalence  of  people  with  learning  disability  is  1-­‐2%,  
 

What  it  is  not  




 

Dyslexia  and  any  other  educational  difficulties    
Adult  acquired  head  injury  
Cognitive  decline  due  to  chronic  psychosis,  substance  abuse,  neurological  condition,  or  other  
organic  cause  etc    
Learning  difficulty  ≠  learning  disability  
 

Severity  of  LD  







Severity  
Borderline  LD  
Mild  LD    
Moderate  LD  
Severe  LD  
Profound  LD  

 
 
   
 
 
   

IQ  
70-­‐80  
50-­‐70  
35-­‐50  
20-­‐35  
<20  

 
Diagnosis  




Diagnosis  based  on  clinical  findings  including  IQ  result  
Adaptive  behaviour  dysfunction  e
...
 social  problems  
Psychometric   Assessment:   Most   commonly   used   is   the   Wechsler   Adult   Intelligence   Scale  
(WAIS)  

 
Descriptions  
Borderline  LD  

 




IQ  70-­‐80  
Not  a  category  in  DC-­‐LD,  ICD-­‐10  or  DSM-­‐IV  

Mild  LD  









IQ  50-­‐70  
Most  common  
Delayed  speech  (able  to  use  everyday  speech)  
Full  independence  -­‐  self  care,  practical  &  domestic  skills  
Difficulties  in  reading  and  writing  
Capable  of  unskilled  or  semi-­‐skilled  work  
Problems  if  social  or  emotional  immaturity  
Rarely   organic   aetiology   (moderate   to   profound   LD   are   normally   associated   with   organic  
pathology)  

 
Moderate  LD  


IQ  35-­‐50  

 










Slow  with  comprehension  and  language  
Limited  achievements  
Delayed  self  care  and  motor  skills  
Simple  practical  tasks  -­‐  often  with  supervision  
Usually  fully  mobile  
Discrepant  profiles  
Majority  organic  aetiology  
Epilepsy  and  physical  disability  common  

Severe  LD  





IQ  20-­‐35  
Generally  more  marked  impairment  than  in  moderate  LD  and  achievements  more  restricted  
Epilepsy  common  
Organic  aetiology  

 
Profound  LD  








IQ  less  than  20  (difficult  to  measure)  
Severe  limitation  in  ability  to  understand  or  comply  with  requests  or  instructions  
Little  or  no  self-­‐care  
Often  severe  mobility  restriction  
Physical  disorders  common  
Organic  aetiology  
Basic  or  simple  tasks  may  be  acquired  
 
 

Associated  Problems  
People  with  learning  disability  as  a  group  have  higher  rates  of  physical  and  mental  health  problems  
and   consequently   higher   morbidity   and   mortality   rates
...
g
...
   












Mental  Illness  e
...
 SZ,  MDD,  BPD,  anxiety  disorders  
Epilepsy:  Up  to  1/3  have  epilepsy,  depending  on  severity  LD
...
  Treatment   resistance   and   multiple   seizure   types   more  
common
...
 
Substance  misuse  
Physical  disability  and  mobility  problems  e
...
 Cerebral  palsy  
GI  disorders  
Sensory  impairments  
Autistic  Spectrum  Disorder  
Sexual  abuse  
Family  dysfunction  
Poor  employment  prospects  



Stigma    
 

 
Aetiology  
IQ   levels   follow   a   normal   distribution   curve   for   IQ's   above   70
...
   




Mild   LD   (IQ   50-­‐70):   Cause   often   unidentified,   in   which   case   more   likely   to   be   in   socio-­‐
economic   groups   4   and   5
...
    This  
illustrates  the  interaction  between  genetics  and  environment  i
...
 to  what  extent  you  actually  
fulfil  your  potential  
Moderate/severe   LD:   Organic   cause   often   identified
...
g
...
g
...
g
...
g
...
g
...
  Bilirubin   is   a   highly  
neurotoxic   substance   that   may   become   elevated   in   the   serum,   a   condition   known   as  
hyperbilirubinemia
...
   Only  caused  by  UC  bilirubin  which  is  lipid  soluble  (lipohillic)
...
g
...
   



Addiction   is   the   continued   repetition   of   a   behavior   (psychological   dependency)   despite  
adverse  consequences  



Classic   hallmarks   of   addiction   include   impaired   control   over   substances   or   behavior,  
preoccupation  with  substance  or  behavior,  continued  use  despite  consequences,  and  denial  
=>  psychological  dependency  



Physiological   dependence   occurs   when   the   body   has   to   adjust   to   the   substance   by  
incorporating  the  substance  into  its  'normal'  functioning
...
   



Tolerance  is  the  process  by  which  the  body  continually  adapts  to  the  substance  and  requires  
increasingly   larger   amounts   to   achieve   the   original   effects
...
 



Withdrawal  refers  to  physical  and  psychological  symptoms  experienced  when  reducing  or  
discontinuing   a   substance   that   the   body   has   become   dependent   on
...
 



Addiction  =  dependency  (psychologically  and  physically)  +  tolerance  +  withdrawal  

 
ICD-­‐10  criteria  of  substance  dependence  





Psychological  and  physical  dependency:  
! A  strong  desire  to  take  the  substance  
! Difficulties  in  controlling  substance  use  
! Neglect  of  alternative  pleasures  
! Persistence  despite  evidence  of  harm  
Tolerance  
A  physiological  withdrawal  state  

 
CAGE  
The   CAGE   questionnaire,   the   name   of   which   is   an   acronym   of   its   four   questions,   is   a   widely   used  
method  of  screening  for  alcoholism
...
 
The  questionnaire  asks  the  following  questions:  





Have  you  ever  felt  you  needed  to  Cut  down  on  your  drinking?  
Have  people  Annoyed  you  by  criticizing  your  drinking?  
Have  you  ever  felt  Guilty  about  drinking?  
Have  you  ever  felt  you  needed  a  drink  first  thing  in  the  morning   (Eye-­‐opener)  to  steady  your  
nerves  or  to  get  rid  of  a  hangover?  

 
Neurobiology  of  addiction  
Several  complicated  mechanisms  involved:  





The  reward  pathway  –  appetitive  approach    
The  action  of  drugs  of  abuse  on  the  reward  pathway  
The  role  of  the  Prefrontal  cortex  (executive  functioning  e
...
 will  power  and  self  control  and  
decision  making)  
Role  of  the  hippocampus/  HPA  axis  
 

The  reward  system  (appetitive/approach  system)  
 
• The   major   neurochemical   pathway   of   the   reward   system   in   the   brain   involves   the  
mesolimbic  and  mesocortical  pathways
...
   
 
• The  VTA  is  the  primary  release  site  for  the  neurotransmitter  dopamine
...
   



The   VTA   is   the   origin   of   the   dopaminergic   cell   bodies   of   the   mesocorticolimbic   dopamine  
system   and   is   widely   implicated   in   the   drug   and   natural   reward   circuitry   of   the   brain
...
   



The  VTA  contains  neurons  that  project  to  numerous  areas  of  the  brain,  from  the  prefrontal  
cortex  (PFC)  to  the  NA  to  the  caudal  brainstem  and  several  regions  in  between
...
   Research  
has  indicated  the  nucleus  accumbens  has  an  important  role  in  pleasure  including  laughter,  
reward,   and   reinforcement   learning,   as   well   as   fear,   aggression,   impulsivity,   addiction,   and  
the  placebo  effect
...
g
...
   



Drugs   have   many   different   effects   on   the   brain;   however,   they   all   follow   the   same   path
...
   



After  prolonged  use,  physiological  drug  tolerance  and  sensitization  arises
...
 Dopamine  receptors  are  stimulated  while  someone  is  consuming  a  drug  or  when  
the  thought  of  doing  a  drug  occurs
...
 
 
It   is   important   to   remember   that   many   other   neuronal   circuits   and   NTs   play   a   role   in  
addiction  (dependent  on  the  addictive  substance)  e
...
 serotonin,  GABA,  glutamate,  opioids  
and  canaboids
...
     
 
Neurotransmitters   such   as   these   play   a   major   role   in   the   reward   systems   of   the   brain
...
 The  continued  use  of  drugs  can  cause  degeneration  of  such  neurotransmitters  causing  
personality  disorders  and  prolonged  personality  changes  in  an  individual
...
g
...
  Moreover,   the   prefrontal   cortex,   which   has   bearing   on   judgement,   risk   taking,   and  
impulse   control,   may   be   complicit   in   explaining   why   adolescents   are   more   prone   to   drug-­‐taking  
behavior
...
 
In  an  addicted  brain  we  have:  



Increased  stimulation  of  the  OFC  (from  nucleus  accumbens)  resulting  in  compulsion  to  take  
drug  
Decreased   inhibition   of   the   OFC   (from   prefrontal-­‐cortex)   resulting   in   failure   to   inhibit   the  
compulsion  to  take  drug  

 
Stress  







Acute  stress  triggers  release  of  dopamine  in  the  neural  reward  pathway
...
 
Chronic   stress   leads   to   dampening   of   dopaminergic   activity   through   down   regulation   of   D  
receptors
...
g
...
  Such   drugs  
may  have  very  different  actions
...
 
Drugs   which   overstimulate   dopamine   receptors   leads   to   a   decrease   in   the   number   of  
receptors,  and  the  remaining  receptors  become  less  sensitive  to  dopamine  (desensitization)  
Desensitization   is   better   known   as   tolerance,   where   exposure   to   a   drug   causes   less  
response  than  previously  caused  
Pre  frontal  cortex  puts  the  brakes  on  the  reward  pathway  including  brakes  on  OFC  (which  is  
important  for  motivation  to  act)  
Pre  frontal  cortex  matures  late  (teenage  brain  hardwired  for  addiction?)  
Pre   frontal   cortex   is   dysfunctional   in   addicted   people   (due   to   dysfunction   of   dopamine  
reward  pathways)  
Hippocampus/amygdala/HPA  axis  also  implicated  in  the  development  of  addiction  (memory  
of  drug  taking  experiences/feelings  example)  

 
 
MEDICAL  TREATMENTS  FOR  HEROIN  ADDICTION  
Principles  of  Treatment  
Prevention  
Harm   reduction   e
...
  education,   needle   exchange   programmes,   Hep   B   immunisation,  
overdose  prevention  (distribution  of  naloxone  to  heroin  users),  heroin  replacement  therapy  
(prescription  of  “safe”  heroin),  HIV  testing,  Hep  B/C  testing  
• Recovery:  cessation  of  substance  use  
 
 
 
Drug  recovery  (rehabilitation)  
 
Detoxification    
 
• For   some   addicts,   the   beginning   of   treatment   (recovery/rehabillitation)   is   detoxification
...
   By  itself,  
this   is   not   a   solution,   because   most   addicts   will   eventually   resume   taking   the   drug   unless  
they  get  further  help    
• Drug   detoxification   is   used   to   reduce   or   relieve   withdrawal   symptoms   while   helping   the  
addicted   individual   adjust   to   living   without   drug   use;   drug   detoxification   is   not   meant   to  
treat  addiction  but  rather  an  early  step  in  long-­‐term  treatment  
• The  withdrawal  symptoms  of  heroin  includes  agitation,  anxiety,  tremors,  muscle  aches,  hot  
and  cold  flashes,  sometimes  nausea,  vomiting,  and  diarrhoea
...
   The  intensity  of  the  reaction  depends  on  the  dose  and  
speed  of  withdrawal
...
 
• No  single  approach  to  detoxification  is  guaranteed  to  be  best  for  all  addicts
...
 
! Benzodiazepines:  can  have  a  role  in  detoxification  
! Opiate  blockade  with  naloxone  (still  limited  option,  only  impulsive  relapsers)  

 
Opioid  replacement  therapies  (ORT)  



 





Methadone   or   buprenorphine:   Synthetic   opioids   which   can   be   used   to   treat   opioid  
addiction  
Form  of  harm  reduction  (but  can  also  be  used  in  detox  by  gradually  decreasing  the  dose)  +
...
   How  could  these  be  made  
specific   and   verifiable?     For   example,   abstinence   from   heroin   use   in   methadone  
maintenance  patients  could  be  verified  by  urine  drug  screening
...
   Abstinence  from  heroin  use  in  methadone  maintenance  patients  could  be  
verified  by  urine  drug  screening  
Patients  receive  escalating  funds  for  consecutive  clean  drug  tests  which  they  can  spend  on  
recovery  activities  
Patients  are  entered  into  a  prize  draw  for  each  Hepatitis  B  vaccination  they  receive      

The  evidence  base  for  CM  





The  most  efficacious  psychosocial  intervention  for  substance  misuse  
Effective  in  typical  “treatment  failure”  populations  (e
...
 dual  diagnosis,  cocaine  dependence,  
opiate  dependence)  
Approximately  50%  patients,  across  populations  and  target  behaviours  respond  to  CM  
Research   base   majority   in   US   but   pilot   studies   in   UK   suggest   it   can   be   incorporated   into  
routine  NHS  treatment  

 
 
ALCOHOL  
Adverse  effects  of  alcohol  









One  of  three  biggest  lifestyle  factors  for  death  &  disability  
¼  of  deaths  in  16-­‐24  year  olds  
One  million  alcohol  related  violent  crimes    
Annual  cost  £3
...
2  million  alcohol  Related  Admissions  (7%  of  all  admissions)  
Liver  disease  
Many  cancers  
Drink  driving  

 
Screening  


Screen  with  FAST  (fast  alcohol  screening  test)
...
  It   was   developed   for   busy   clinical   settings   as   a   two-­‐stage   initial  
screening  test  that  is  quick  to  administer  since  >50%  of  patients  are  identified  by  using  just  the  first  
question
...
 


AUDIT  score  0-­‐7:  Low  risk  Drinking  





AUDIT   score   8-­‐15:   Hazardous   Drinking:   A   pattern   of   alcohol   consumption   that   increases  
someone’s  risk  of  harm  
AUDIT   score   16-­‐19:   Harmful   Drinking:   A   pattern   of   alcohol   consumption   that   is   causing  
mental  or  physical  damage  
AUDIT  score  20+  Dependent  Drinking  
 

 
Recommended  limit  
 
• Men  3-­‐4  units  per  day  (21  units  per  week  max)  –  with  two  alcohol  free  days  


Women  2-­‐3  units  per  day  (14  units  per  week  max)  –  with  two  alcohol  free  days  



Binge  >  8  units  men;  >  6  units  women  

 
Hazardous  drinking  


AUDIT  score  8-­‐15  



Management  =  brief  intervention  e
...
 simple  advice  



There   is   consistent   evidence   from   a   large   number   of   studies   that   brief   intervention   in  
primary   care   can   reduce   total   alcohol   consumption   and   episodes   of   binge   drinking   in  
hazardous  drinkers,  for  periods  lasting  up  to  a  year
...
 

 
Harmful  drinking  


AUDIT  score  16-­‐19  



Management   =   extended   brief   intervention   e
...
  simple   advice,   brief   counselling   and  
continued  monitoring  

 
Dependent  drinking  


AUDIT  score  20+  



Management=  referral  to  specialist  for  diagnostic  evaluation  and  treatment    

 
Alcohol  dependence  syndrome  
Categorised  by:    


Compulsion:  strong  desire  to  take  alcohol  (psychological  dependency)    

Impaired  capacity  to  control  substance  taking  behaviour  in  terms  of  onset,  termination  or  
levels  of  use  (psychological  dependency)  
• Preoccupation   with   substance   use   -­‐   neglecting   activities   &   interests   (psychological  
dependency)  
• Persistent   substance   use   despite   clear   evidence   of   harmful   consequences   (psychological  
dependency)  
• Dependency  (all  of  above  suggest  dependency)  
• Tolerance:  need  significantly  increased  amounts  of  the  substance  to  achieve  desired  effects,  
downregulation  of  GABA  receptors    
• Withdrawal  state  when  substance  is  reduced  or  ceased,  downregulation  of  GABA  =>  when  
alcohol  is  removed  we  get  surge  of  glutamate  activity  =>  CNS  hyper-­‐excitability    
 
 
Pathophysiology  


The   development   of   alcohol   dependence   involves   numerous   changes   in   brain   chemistry   (i
...
 
neurotransmission)  that  lead  to  psychological  dependency  as  well  as  the  physiological  signs  
of  tolerance  and  withdrawal  upon  abstinence  from  alcohol    
• Signalling   systems   involved   include   the   neurotransmitters   glutamate,   γ-­‐aminobutyric   acid  
(GABA),   dopamine,   and   serotonin,   as   well   as   on   other   signalling   molecules,   including  
endogenous  opioids  and  corticotrophin-­‐releasing  factor  (CRF)  
• Alcohol's  primary  effect  is  the  increase  in  stimulation  of  the  GABA  (A)  receptor,  promoting  
central  nervous  system  depression
...
    This   contributes   to   the  
withdrawal   effects
...
     
• Researchers   also   are   exploring   the   interaction   of   alcohol   with   endogenous   cannabinoids  
(substances   naturally   produced   in   the   body   that   have   similar   effects   to   cannabis   and   related  
drugs)  and  the  cannabinoid  CB1  receptor
...
  Chronic   alcohol   exposure   alters   both   the   synthesis   of  
endogenous  cannabinoids  and  the  characteristics  of  CB1  receptors
...
     
 
 
Withdrawal  syndrome    









Alcohol  =  depressant  as  stimulates  GABA  (major  CNS  depressant)    
Chronic   use   of   alcohol   leads   to   changes   in   brain   chemistry   especially   in   the   GABAergic  
system
...
   
During  acute  alcohol  withdrawal  (due  to  tolerance  and  down  regulation)  we  get  decreased  
GABA   activity   (due   to   the   down   regulation   which   has   occurred)   =>   increased   brain   activity  
=>  seizures  can  occur  (amongst  other  –ve  effects)  
Neurochemical   changes   occurring   during   alcohol   withdrawal   can   be   minimized   with   drugs  
which  are  used  for  acute  detoxification  e
...
 chlordiazepoxide  (BDZ)
...
    With   abstinence   from   alcohol   and  
cross  tolerant  drugs  these  changes  in  neurochemistry  gradually  return  towards  normal
...
   
 

Clinical  features  of  withdrawal  syndrome  


Clinical  features  of  withdrawal  are  time  dependent:  

 
6  -­‐  8  hours    






Tremor,  sweating,  nausea,  retching  
Increased  heart  rate  and  blood  pressure  (hyper-­‐excitabilty)  
Mild  temperature  
Anxiety  &  agitation  (hyper-­‐excitabilty)  
Subsides  after  2  days  

 
 
0  -­‐  48  hours    
Withdrawal   seizures   (primarily   due   to   decreased   GABA   activity   =>   increased   CNS  
stimulation  by  glutamate)  
• Peak  time  scale  for  seizures  =  48  hours  
 
 
>12  hours    




Auditory,   visual   &   tactile   hallucinations   (duration   5-­‐6   days)   –   due   to   increased   CNS  
stimulation  e
...
 Lilluputian  hallucinations    

 
48  -­‐  72  hours    






Delirium  tremens  (very  serious  form  of  delirium  =>  Tx  immediately  with  chlordiazepoxide)  
Course  tremor  
Confusion  
Delusions  and  hallucinations  
Agitation,  fever,  increased  heart  rate  

 
Management  of  alcohol  withdrawal  




Chlordiazepoxide   (BDZ)   is   the   drug   of   choice   for   acute   alcohol   withdrawal   syndrome   =>  
increases  GABA  activity  
Starting  dose  depends  on  SADQ  (Severity  of  Alcohol  Dependence  Questionnaire)    
Monitor  using  clinical  institute  withdrawal  symptom  for  alcohol  (CIWA-­‐Ar)  

 
Co  morbidities    
Physical  






Neurological:     peripheral   neuropathy,   Wernickes   (b1   thiamine   deficiency),   Korsakoffs   (b1  
thiamine  deficiency)  
Liver:  Alcoholic  hepatitis,  fibrosis,  cirrhosis,  hepatocellular  Ca  
GI:    Pancreatitis,  Peptic  ulcer  
Cancer  (many  types)  
Vitamin  deficiency  related  conditions  e
...
 Vit  B12  (cobalamin)  deficiency  and  thiamine  (B1)  
deficiency   (Wernicke’s   encephalopathy   and   Korsakoff’s   syndrome)
...
     

 
Mental  

 





85%  in  alcohol  treatment  services  had  comorbid  psychiatric  condition  
Depression  &  anxiety  81%  
DSH  

Social  

 








50%  of  violent  crimes  
17%  of  road  fatalities  
17  million  working  days  lost  annually  
Domestic  violence  
60%  child  protection  cases  involve  alcohol  
Homelessness  :  50%  alcohol  dependent  

Thiamine  (vitamin  B1)  deficiency  




Wernicke’s   encephalopathy:   staggering   gait   (ataxia),   visual   problems   e
...
  diplopia   (due   to  
ophthalmoplegia)  and  nystagmus,  confusional  state  (20%  mortality)  
Korsakoff’s  syndrome:  short  term  memory  loss  (amnesia),  resulting  in  confabulations,  clear  
consciousness  (20%  improve  with  thiamine)  
Peripheral   neuropathy   (up   to   70%)   numbness,   pain,   hyperaesthesia,   glove   and   stocking  
distributions,  weakness  (due  to  toxic  effects  of  alcohol  and  Vit  deficiencies)    

 
Wernicke’s  encephalopathy  


Wernicke's   encephalopathy   refers   to   the   presence   of   neurological   symptoms   caused   by  
biochemical  lesions  of  the  central  nervous  system  after  exhaustion  of  B-­‐vitamin  reserves,  in  
particular   thiamine   (B1)
...
   



Causes   of   Wernicke’s   encephalopathy   include:   alcoholism,   malabsorption   disorders   (e
...
 
Crohns  and  coeliac),  excessive  vomiting  (e
...
 hyperemesis  gravidarum),  and  cancer
...
 
However,  only  10%  of  patients  exhibit  all  three  features,  and  other  symptoms  may  also  be  
present
...
     
Ataxia  can  result  in  abnormal  gait  and  coordination  dysfunction
...
    Clinical  
features  include:  






Reduced  consciousness  (if  brain  stem  affected)  
Confusion  (if  diffuse  cerebral  dysfunction)  
Ataxia  (if  vestibular  region  of  medulla  or  cerebellum  affected)  
Ophthalmoplegia  (diplopia  and  squint)  and  nystagmus  (if  brain  stem  affected)  
Hypothermia  and  hypotension  (if  hypothalamus  affected)  
 

 
Management:  



Thiamine  oral  (if  low  risk  of  Wenickes)  
Pabrinex  (contains  multiple  B  vitamins  including  thiamine)  IV/IM  (if  higher  risk  of  Wernicke’s  
or  overt  Wernickes  symptoms)  

 
Inpatient  Criteria  







Drinking  30+  units  daily  (e
...
g
...
 


 
 
FAST  screening  
 
 

 

 

 
CLINICAL  EXAMPLE  TUTORIALS  
Alcohol  Disorders  -­‐  Case  Example    
 
• 19  y/o  med  student  
• Ankle  injury  (tripped  on  club  floor)  after  heavy  night  drinking  alcohol  
• X-­‐Ray  showed  NBI  (no  bone  injury)  
• Initial  management:  RICE  (rest,  ice,  compression  and  elevation)  and  paracetamol  +/-­‐  NSAIDs  
• Should  prompt  an  opportunity  to  pry  if  there  is  greater  problems  with  alcohol  
• FH  of  alcohol  problem  indicates  a  genetic/environmental  predisposition  
• Personal   history:   Perfectionist   traits   +   social     anxiety   =>   may   be   more   predisposed   (as   use   to  
relax  in  uncomfortable  environments)  
• PMH:  head  injury  (happened  in  context  of  alcohol  intoxication)  
• Alcohol  history:  2x/week,  12-­‐14  pint/night  (approx
...
 60  units  per  week  






















We   definitely   need   to   discuss   alcohol   use   with   this   patient   (extended  brief   intervention)
...
  Symptoms   of   withdrawal   may   be  
fatal  =>  in-­‐patient  management  (chlordiazepoxide)
...
   
Alcohol  has  significant  association  with  completed  suicide  and  therefore  this  should  also  be  
discussed    
Alcohol  works  on  GABA  and  in  alcohol  abuse  the  body  adjusts  by  reducing  GABA  receptors  
and   oversensitising   glutamate   =>   GABA   system   doesn't   work   well   as   down-­‐regulated  
(sensitised)  
On  withdrawal  of  alcohol  we  get  an  excess  of  glutamate  activity  (due  to  decreased  GABA  
activity)   results   in   =>   anxiety,   tremor,   N&V,   increased   HR/BP,   pyrexia,   seizures,  
hallucinations,  delirium  tremens  etc  
BDZs   (chlordiazepoxide)   for   detox:   act   on   GABA   like   alcohol   does   (could   technically   do   detox  
with   alcohol   with   gradual   reducing)
...
 
Gradually   reduce   benzos   over   7-­‐10   days
...
  Short   half   life   BDZs   would   result   in  
fluctuating  withdrawal  symptoms
...
   
Also  need  to  hydrate,  treat  infections,  keep  orientated
...
 Very  serious  illness,  can  be  fatal
...
 Key  clinical  features  are  opthalmoplegia  (diplopia,  squint,  nystagmus),  ataxic  gait,  
and  confusion
...
 
Fitness  to  practice  issues
...
 
Indications  for  inpatient  detox:  suicide  risk/self  harm,  history  of  seizures  or  delirium  tremens  
(DTs),  lack  of  social  support,  other  physical  co-­‐morbidities  

 
 
Drug  Disorders:  Case  Example  
 
• Patient  in  hospital  for  heroin  overdose  
• Heroin   use   complications:   infections,   hepatitis   viruses,   endocarditis,   HIV,   TB,   anthrax  
(contamination),  Staph  pneumonia,  and  abscesses    
• Medication  to  prevent  withdrawals:  methadone  or  buprenorphine  –  don’t  withhold!  
• Monitor   withdrawal   by   withdrawal   assessments   scoring   (score   heart   rate,   resp   rate,   clammy  
skin,  vomiting,  tremors,  agitation/aggression  etc)  
• If   very   poorly   functioning   and   families/friends   drug   users   =>   lots   of   effort   to   keep   off  
substances  =>  likely  to  be  on  methadone  life-­‐long  (ORT)  
• If   previously   well   functioning,   highly   motivated,   not   using   long   =>   can   probably   wean   off  
methadone  (detoxification)  
• Possible   to   overdose   on   methadone
...
g
...
    Naloxone   has   short   half   life   so   frequent   administration  
required
...
 
• Involved  in  muscle  action  through  presence  at  neuromuscular  junctions  (specialized  type  of  
nicotinic   synapse   where   neurons   connect   to   muscle   cells)
...
   






ACh   is   the   transmitter   of   the   parasympathetic   half   of   the   autonomic   nervous   system   (pre  
ganglionic  and  post  ganglionic)  
Also   released   by   pre-­‐ganglionic   neurones   in   sympathetic   NS   (pre   ganglions   and   ACh  
stimulate  adrenal  glands)  
ACH  is  NT  in  skeletal  muscle    
People   with   Alzheimer's   disease   are   usually   found   to   have   a   substantially   low   level   of  
acetylcholine
...
g
...
    This   is   why   acetlycholinesterase   inhibtors   are  
indicated  in  mild  AD  (e
...
 rivastigmine,  donepezil  and  galantamine)  

 
 
Dopamine  
 
• Appetitive/approach  system  
• Active  in  selected  areas  of  brain    
• Dopamine  (DA)  is  involved  in  a  wide  variety  of  behaviours  and  emotions,  including  pleasure
...
g
...
  In   other   words,   dopamine  
regulates  the  pleasurable  emotions
...
   
• A  significantly  low  level  of  dopamine  in  basal  ganglia  system  is  associated  with  Parkinson's  
disease  
• Patients  of  schizophrenia  are  usually  found  to  have  excess  dopamine  in  mesolimbic  system  
(resulting  in  positive  symptoms)  and  low  levels  in  mesocortical  (negative  symptoms)  
• DA  is  the  precursor  (chemical  forerunner)  that  is  turned  into  NA,  so  is  closely  related  to  NA  
and   often   affected   by   the   same   drugs
...
   
 
 
DA  is  an  important  transmitter  in  several  brain  systems:  
• Extrapyramidal   basal   ganglia   motor   system   e
...
  nigrostriatal   pathways   (posture   and  
movement  control)  
• Mesolimbic/mesocortical   system   (midbrain   connections   to   limbic   system   and   cortex  
respectively)  which  is  important  for  emotional  and  cognitive  functions  respectively  
• Hypothalamus-­‐pituitary   system   (menstrual   and   other   hormone   regulation)   e
...
  dopamine   is  
a  potent  inhibitor  of  prolactin  release  =>  anti-­‐psychotics  (dopamine  antagonists)  can  result  
in  prolactin  hypersecretion  (particularly  typicals  such  as  haloperidol  and  chlorpromazine)  
 
 
Serotonin  
 
• Widely  distributed  
• Aversive  /  defensive  system  –  major  NT  
• Serotonin  is  an  important  inhibitory  neurotransmitter,  which  can  have  a  profound  effect  on  
emotion,   mood,   and   anxiety
...
 

A   significantly   low   level   of   serotonin   is   believed   to   be   associated   with   conditions   like  
depression,   suicidal   thoughts,   and   obsessive   compulsive   disorder
...
 
• Serotonin  is  a  chemical  cousin  of  the  "catecholamines"  discussed  above
...
 
• The   action   of   5HT   at   a   synapse   is   brought   to   an   end   primarily   via   reuptake
...
 
• Raphe  nucleus    
 
5HT  is  best  known  as  a  transmitter  in  several  brain  areas:  
• Sleep  regions  
• Limbic  system  mood  control  regions  
• Pain  suppression  system  (stimulates  endogenous  opioid  release)  
 
 
Gamma-­‐aminobutyric  acid  (GABA)  
• GABA  is  an  inhibitory  neurotransmitter  that  is  very  widely  distributed  in  the  neurons  of  the  
cortex
...
   
• GABA   is   an   inhibitory   neurotransmitter   that   slows   down   the   activities   of   the   neurons,   in  
order  to  prevent  them  from  getting  over  excited
...
 GABA  can  thus  help  prevent  anxiety
...
 Drugs  like  Valium  and  
other  BDZs  work  by  increasing  the  activity  of  GABA  (mostly  GABA-­‐A  receptors)  
• Alcohol   and   barbiturates   can   also   influence   GABA   receptors
...
     
• Some   drugs   that   increase   the   level   of   GABA   in   the   brain   are   used   to   treat   epilepsy   and   to  
calm  the  trembling  of  people  suffering  from  Huntington’s  disease
...
   
• Glutamate  is  mainly  associated  with  functions  like  learning  and  memory
...
 
• An  excess  of  glutamate  is  however,  toxic  for  the  neurons
...
    Hence   why   Memantine   (NMDA  
blocker   which   blocks   effects   of   glutamate   on   NMDA   receptors)   is   used
...
     
 
 
Epinephrine  




Epinephrine   (also   known   as   adrenaline)   is   an   excitatory   neurotransmitter,   that   controls  
attention,  arousal,  cognition,  and  mental  focus
...
 An  increased  secretion  of  norepinephrine  raises  the  heart  rate  
and  blood  pressure
...
 
• Norepinephrine   is   a   neurotransmitter   that   is   important   for   attentiveness,   emotions,  
sleeping,   dreaming,   and   learning
...
 
 
• Norepinephrine  plays  a  role  in  mood  disorders  such  as  manic  depression
...
 
• NE  is  the  primary  transmitter  carrying  messages  from  the  sympathetic  half  (postganglionic)  
of   the   autonomic   nervous   system   to   body   organs   and   glands   (with   the   exception   of   the  
adrenal  gland)  
• The  action  of  NE  at  a  synapse  is  brought  to  an  end  primarily  via  reuptake
...
 
• Locus  coerulus    
 
 
Endorphins  
• Endorphins   are   the   neurotransmitters   that   resemble   opioid   compounds,   like   opium,  
morphine,  and  heroin  in  structure
...
 In  fact,  the  name  'endorphin'  is  actually  the  short  form  for  'endogenous  
morphine'
...
   
• The  opioid  drugs  produce  similar  effects  by  attaching  themselves  to  the  endorphin  receptor  
sites
...
  It   basically   controls   the   sleep-­‐wake   cycle
...
  The   production   of   melatonin   is   dependent   on   light
...
 
 
 
Summary  
NT  

Major  functions  

Excess  is  associated  with  

Deficiency   is   associated  
with  

Acetyl   choline   Muscle  
movement,   Relative   excess   of   ACh   to  
(Ach)  
attention,  
arousal,   DA   in   PD   =>   hence   why  
memory,  
emotion
...
    Nucleus   use  
basalis  of  Meynert
...
    Localised
...
   
in  the  mesolimbic  system  
Mesolimbic
...
     

Alzheimer’s  disease  

Endorphins  

 

Parkinsonism   (in   the  
nigrostriatal   patheay   of  
basal  ganglia)  
 
Schizophrenia   (negative  
symptoms)  
in  
the  
Mesocortical  system    
Serotonin  
Sleep,  
wakefulness,   Serotonin  syndrome  (e
...
 in   MDD  
(5HT)  
appetite,  
mood,   MAO   inhibotors   such   as  
 
aggression,   impulsivity,   meclobemide)  
sensory  
perception,  
temperature   regulation,  
pain  
suppression
...
 
NA  
Learning,  
memory,   Anxiety,  HT  crisis    
MDD  
(noradrenaline)   dreaming,  
awakening,  
emotion,   stress-­‐related  
increase   in   heart   rate,  
stress-­‐related   slowing   of  
digestive  
processes
...
     
GABA  
Main  
inhibitory   Alcohol  use  
Alcohol  withdrawal  
neurotransmitter   in   the   BDZ  
brain
...
     
Glutamate  
Main  
excitatory   MS  
 
neurotransmitter   in   the   Alcohol  withdrawal  
brain  
Pain  relief,  pleasure  

 

 
 
SUMMARY  OF  ADDICTION  





Addiction   is   a   compulsive   seeking,   and   then   obtaining,   of   a   substance   while   behavior  
increasingly  becomes  out  of  control    
Addiction  is  caused  by  a  combination  of  genetics,  environment  and  stress  
Many  types  of  neurotransmitters  play  an  important  role  including    dopamine,  serotonin,  and  
noradrenaline  
Some  sources  focused  solely  on  dopamine  or  a  dopamine  variants,  while  others  credited  the  
neurotransmitters  gamma-­‐aminobutyric  acid  (GABA),  glutamate,  and  opioids  as  playing  roles  
in  addiction  as  well
...
   
















Stress   is   a   key   trigger   for   most   addictions
...
 When  you  experience  
something  pleasurable,  dopamine  is  released  to  the  reward  center  (the  nucleus  accumbus)  
of  your  brain
...
     
Neurotransmitters   are   then   sent   to   the   memory   center   (the   temporal   lobe)
...
  Reward   highways   are   built   from   highly   pleasurable   one-­‐time   experiences   or   less  
pleasurable   experiences   that   are   repeated
...
 The  stronger  
the   reward   highway,   the   more   the   brain   wants   to   repeat   the   experience   that   created   the  
reward  highways
...
   
Some   of   the   most   addictive   drugs   cause   increased   dopamine   activity   (e
...
  cocaine)   either   by  
mimicking   dopamine   or   causing   increased   natural   dopamine   to   accumulate   in   the   synaptic  
cleft
...
   
Down   regulation   of   receptors   and   desensitisation   occurs   and   triggers   the   need   for   more,  
resulting   in   the   person   using   more   cocaine   e
...
  tolerance   develops
...
    These   changes   also   ultimately   result   in   the   withdrawal   effects   if   the  
stimulus  is  removed
...
   Less  harmful  stimulants  such  as  caffeine  and  sugar  are  also  accepted  as  dopamine  
mimics
...
 These  drugs  
will  also  help  prevent  problematic  behaviors  that  could  have  caused  the  harmful  addiction  in  
the   first   place
...
 

 
 
FORMATIVE  QUESTIONS  1  
 
1
...
If  the  patient  is  intelligent  and  articulate  with  good  insight,  there  is  no  reason  to  take  a  
collateral  history  
B
...
A  psychiatric  history  should  be  documented  using  technical  terms  
D
...
Older  patients  should  not  be  asked  about  illicit  drug  use  in  case  they  are  offended    
 
2
...
“the  patient  is  dishevelled,  wearing  dirty  clothes”  –  appearance    
B
...
“the  patient’s  mother  thinks  he  has  been  responding  to  auditory  hallucinations”  
D
...
“she  is  orientated  in  time,  place  and  person”  –  cognition    
 
3
...
People  generally  take  overdoses  either  as  a  suicide  attempt  or  as  a  cry  for  help  
B
...
Asking  patients  about  suicidal  thoughts  can  be  dangerous  as  it  may  suggest  the  idea  to  them  
D
...
Doctors  are  at  a  low  risk  of  suicide  compared  to  the  general  population,  as  they  are  social  
class  1    
 
4
...
Morbid  dread  of  fatness  
B
...
Sexual  dysfunction  in  men  
D
...
Loss  of  interest  in  food  
 
5
...
Electrocardiogram  
B
...
CT  brain  
D
...
Full  blood  count    
 
6
...
Internal  locus  of  control  
B
...
Misdiagnosis  of  conversion  symptoms  
D
...
Childhood  sexual  abuse    
 
7
...
Inhibits  reuptake  of  serotonin  and  dopamine  
B
...
Increases  release  of  serotonin  and  norepinephrine    
D
...
Acts  as  an  agonist  at  serotonin  and  norepinephrine  receptors    
 
8
...
Decreased  thyroid  releasing  hormone  in  CSF  –  TRH  raised  in  MDD  
B
...
Decreased  excretion  of  cortisol  in  the  urine  –  cortisol  raised  in  MDD  
D
...
Increased  hippocampal  volume    
 
9
...
Specific  genes  have  been  found  to  predispose  to  early-­‐onset  OCD  
B
...
You  can  have  obsessions  and  compulsions  but  not  have  OCD  

D
...
Most  patient  with  OCD  have  no  other  mental  illness  as  very  specific  parts  of  the  brain  are  
affected  
 
10
...
People  with  no  mental  illness  tend  not  to  have  any  schemas  
B
...
Changing  a  patient’s  schemas  is  quite  straightforward  with  the  right  therapy  
D
...
The  content  of  someone’s  assumptions  and  automatic  thoughts  tells  us  about  their  schemas  

 
 

Answers  
1
...
C  
3
...
E  
5
...
E  
7
...
B  
9
...
E  
 
 
FORMATIVE  QUESTIONS  2  
 
5
...
 I’ve  been  waking  up  very  early  in  the  
morning  and  can’t  get  back  to  sleep,  I  just  lie  awake  worrying  about  my  situation
...
 I’m  very  
tired  and  I  can’t  be  bothered  doing  anything,  not  even  meeting  up  with  my  friends  or  playing  
football
...
 I  don’t  really  
see  the  point  in  anything  anymore,  maybe  it  would  be  better  if  I  wasn’t  here
...
Lithium  carbonate  
B
...
Selective  serotonin  reuptake  inhibitor  
D
...
Tricyclic  antidepressant    
 
2
...
“Since  I  had  my  baby  I  keep  getting  thoughts  in  my  head  about  dropping  her  or  letting  go  of  
her  pram  on  a  hill
...
 
B
...
“I  can’t  stand  the  house  not  being  perfectly  tidy,  I  spend  hours  on  the  housework”  
D
...
My  neighbours  are  putting  thoughts  into  my  head  about  horrible  things  happening  to  my  
children
...
 Which  piece  of  information  would  you  give  a  patient  who  is  considering  ECT?  
A
...
ECT  can  only  be  given  to  hospital  inpatients  
C
...
You  will  need  further  treatment  after  the  course  of  ECT  
E
...
What  is  the  best  description  of  this  woman’s  current  mood  state?  
 “I  felt  great  a  few  weeks  ago,  couldn’t  have  been  better,  I’m  still  very  restless  but  now  
feeling  ill-­‐at-­‐ease
...
 I  can’t  get  the  thoughts  of  dying  a  painful  death  out  of  my  mind
...
 I  can’t  sit  still-­‐  the  nurses  keep  telling  to  stop  
fidgeting  and  pacing  about  the  ward,  but  I  can’t
...
 
A
...
Mania  without  psychotic  symptoms  
C
...
Mixed  affective  state  
E
...
Someone  who  was  attacked  at  knifepoint  three  months  ago  makes  the  following  
statements-­‐which  would  not  be  explained  by  post  traumatic  stress  disorder?  
A
...
“Sometimes  when  I  can’t  sleep  at  night,  I  feel  like  I  can  hear  his  voice  and  smell  his  
aftershave  and  I  panic”  
C
...
“I  have  bad  dreams  about  the  attack”  
E
...
Under  which  legislation  would  you  treat  the  following  patient?  
Mrs  Y  is  an  81  year  old  lady  who  was  brought  to  the  emergency  department  with  a  few  
hours  history  of  agitation,  aggressive  behaviour  and  confusion
...
 Her  bloods  show  that  she  is  very  dehydrated
...
 She  does  not  understand  why  she  is  in  hospital  and  repeatedly  
attempts  to  leave  the  ward  in  order  to  go  home
...
 No  psychiatrist  is  available
...
Mental  Health  (Care  and  Treatment)  (Scotland)  Act  2003-­‐  Emergency  Detention  Certificate  –  
as  she  wants  to  leave  and  thus  needs  detention    
B
...
Adults  with  Incapacity  (Scotland)  Act  2000-­‐  Section  47  
D
...
Common  Law  
 
Answers  

1
...

3
...

5
...


C  
A  
D  
D  
A  
A  –  as  she  requires  detention    

 
 
ANATOMY  OF  THE  LIMBIC  SYSTEM  AND  MEMORY  


The  limbic  system  is  believed  to  have  a  special  role  in   emotional  experience  and  visceral  
(ANS   and   endocrine)   regulation
...
  It   is   now   obvious   that   some   components   act  
primarily  in  other  capacities  (e
...
 the  hippocampus  functions  mainly  in  memory)
...
g
...
 



The   name   comes   from   its   location   on   the   medial   rim   (limb)   of   the   inferior   cerebral  
hemispheres   (although   with   time,   regions   distant   from   this   area,   but   connected   to   these  
original  structures,  have  been  added)
...
 
The   cingulate   cortex   is   a   part   of   the   brain   situated   in   the   medial   aspect   of   the   cerebral  
cortex
...
  It   is   an   integral   part   of   the   limbic   system,   which   is   involved   with   emotion   formation  
and  processing,  learning,  and  memory
...
g
...
 
This  role  makes  the  cingulate  cortex  highly  important  in  disorders  such  as  depression  and  
schizophrenia
...
g
...
    They   also   project   information   onto   the   hypothalamus   which   also  
has  multiple  functions  in  particular  regulating  autonomic  and  endocrine  functions
...
  It   may   be   thought   of   as   a   kind   of   switchboard   of  
information
...
  In   particular,   every   sensory   system   (with   the   exception   of   the  
olfactory   system)   includes   a   thalamic   nucleus   (e
...
  lateral   geniculate   nucleus   for   visual  
information)   that   receives   sensory   signals   and   sends   them   to   the   associated   primary   cortical  
area
...
     







In   order   for   new   memories   to   be   acquired,   the   circuit   of   Papez   must   be   intact   in   at   least   one  
hemisphere
...
g
...
g
...
  For   example,   damage   to   Broca’s   (frontal   lobe)   or   Wernicke’s   areas  
(temporal  lobe)  of  the  brain,  which  are  specifically  linked  to  speech  production  and  language  
information,  would  probably  cause  language-­‐related  memory  loss
...
    This   suggests   that   the   hippocampus   is   critical   not   only   for   the   efficient   encoding  
and   hence   normal   recall   of   new   information   but   also   for   the   recall   of   episodic   information  
acquired  before  the  onset  of  amnesia
...
 



Important   for   storing   emotionally   charged   memories   (with   the   help   of   the   hippocampus)  
essential  for  survival  


 

Found  near  the  temporal  pole,  deep  to  parahippocampul  gyrus  

Important  for  activating  ANS  (via  the  hypothalamus)  in  flight  or  fright  situations  

 
 
 
Olfactory  System  








The  Olfactory  tract  terminates  in  the  primary  olfactory  cortex  (several  regions)  
Olfactory   (mitral)   cells   send   their   axons   to   a   number   of   brain   areas,   including   the   anterior  
olfactory  nucleus,  piriform  cortex,  the  medial  amygdala,  and  the  entorhinal  cortex
...
   
The   medial   amygdala   is   involved   in   social   functions   such   as   mating   and   the   recognition   of  
animals   of   the   same   species   (therefore   it   should   be   obvious   why   the   olfactory   system  
connects  to  the  amygdala)  
The  entorhinal  cortex  is  associated  with  memory  e
...
 to  pair  odours  with  memories
...
 
 

 
Hippocampus  






The  hippocampus  is  an  ancient  area  of  cerebral  cortex  that  has  three  layers
...
  The   hippocampus   has   several   parts
...
  There   is   a   curved   area   of   cortex   called   the  Cornu   Ammonis   (CA)   that   is   divided  
into   four   regions   called   the   CA   fields
...
  These   contain  
prominent  pyramidal  cells
...
 These  are  primarily  from  the  neocortex  
and  cingulate  cortex  and  from  the  septum  and  hypothalamus  (via  the  fornix)    
There  are  many  outputs  (efferents)  
The  loop  starting  with  the  hippocampus  projecting  to  the  mamillary  bodies,  which  relay  to  
the   anterior   thalamic   nucleus,   which   then   relay   onto   the   cingulate   gyrus   and   entorhinal  
cortex,  which  finally  relay  back  to  the  hippocampus  was  thought  to  be  an  important  circuit
...
 It  helps  control  corticosteroid  production
...
 
Additionally   the   hippocampus   is   critically   involved   in   many   declarative   (explicit)   memory  
functions  (in  particular  in  the  formation  of  new  memories)  
Hippocampal  neurons  have  been  studied  extensively  in  terms  of  long-­‐term  potentiation
...
   Long  term  
potentiation  is  a  major  cellular  mechanisms  that  underlies  learning  and  memory  
 

 
Types  of  memory  
 
• Explicit  (declarative  memory)  refers  to  the  memory  of  facts  and  events
...
 Storage  of  explicit  memories  depends  
on  the  medial  temporal  lobe  and  the  relationship  between  the  hippocampus  and  entorhinal  
region   of   the   parahippocampal   gyrus   (Papez   circuit)
...
 The  hippocampus  plays  a  critical  role  in  conversion  of  short-­‐term  memory  
to  long-­‐term  memory
...
 These  lesions  are  more  likely  to  affect  new  declarative  (explicit)  learning  resulting  
in  anterograde  amnesia  
• Implicit  (non-­‐declarative  memory)  is  the  learning  of  skills  (including  motor  skills  processed  
via   the   basal   ganglia   and   cerebellum)   as   well   as   associative   learning
...
   
• It   has   recently   been   shown   that   the   hippocampus   is   not   only   active   in   encoding   memories  
but   also   in   retrieval   of   them
...
 
 
 
The  hypothalamus  






The   hypothalamus   is   the   primary   output   node   for   the   limbic   system,   and   has   many  
important  connections
...
g
...
     
In   order   to   perform   its   essential   functions,   the   hypothalamus   requires   several   types   of  
inputs
...
 













It   also   receives   afferent   inputs   from   the   hippocampus   (via   the   fornix),   the   septum   and   the  
amygdala
...
   
It  also  has  internal  sensors  for  temperature,  osmolarity,  glucose  and  sodium  concentration
...
  These  
include  steroid  hormones,  and  other  hormones  as  well  as  internal  signals  (such  as  hormones  
involved  in  appetite  control  such  as  leptin)
...
 There  
are   localized   areas   in   the   hypothalamus   that   will   activate   the   sympathetic   nervous   system  
and  some  that  will  increase  parasympathetic  activity
...
   
There  are  also  projections  to  the  reticular  formation  that  are  involved  in  certain  behaviors,  
particularly  emotional  reactions  and  arousal
...
 This  nucleus  is  responsible  for  entraining  circadian  rhythms  to  the  day-­‐night  
cycle
...
 
They   regulate   autonomic   and   endocrine   function,   particularly   in   response   to   emotional  
stimuli
...
   
Additionally,  many  of  these  areas  are  critical  to  particular  types  of  memory  (e
...
 emotionally  
charged  memories)  and  storage  of  long  term  memories  
Functions  of  the  limbic  system  include  regulation  of:  energy  and  water  balance,  autonomic  
functions,   temperature,   endocrine   functions,   sexual   behaviour,   emotional   behaviour,  
reward/reinforcement,  learning  and  memory  
Some   of   these   regions   are   closely   connected   to   the   olfactory   system,   since   this   system   is  
critical  to  the  survival  of  many  species
...
 
Cingulate   gyrus:     Autonomic   functions   regulating   heart   rate,   blood   pressure   and   cognitive  
and  attentional  processing
...
 
Orbitofrontal  cortex:  Required  for  decision  making  

Piriform  cortex:  The  function  of  which  relates  to  the  olfactory  system
...
  The   hippocampus   consists   of   two   “horns”  
that   curve   back   from   the   amygdalae
...
 If  the  hippocampus  is  damaged,  a  person  
cannot   build   new   memories   and   lives   instead   in   a   strange   world   where   everything   he   or   she  
experiences  just  fades  away,  even  while  older  memories  from  the  time  before  the  damage  
are  untouched  (anterograde  amnesia)  
Amygdala:   Involved   in   signalling   the   cortex   of   motivationally   significant   stimuli   such   as   those  
related   to   reward   and   fear   in   addition   to   social   functions   such   as   mating
...
  The   amygdalae   also   stimulate   the   hippocampus   to   remember   many  
details   surrounding   the   situation   (in   particular   situations   involving   extreme   emotion   e
...
 
fear)  
Fornix:   C-­‐shape   bundle   of   axons   that   carries   signals   from   the   hippocampus   to   the  
mammillary  bodies  (part  of  hypothalamus)  and  septal  nuclei
...
 They  are  involved  with  the  process  of  recognition  memory
...
 The  septal  nuclei  play  a  role  in  
reward  and  reinforcement  along  with  the  nucleus  accumbens
...
 
Hypothalamus:  has  many  nuclei  with  many  functions  e
...
 ANS  and  endocrine  regulation  

 
 
NEUROCHEMISTRY  OF  MEMORY  









Memory  is  the  process  in  which  information  is  encoded,  stored,  and  retrieved
...
 In  this  first  stage  we  must  change  the  information  so  that  
we  may  put  the  memory  into  the  encoding  process
...
  This   entails   that   we   maintain   information  
over  periods  of  time
...
 We  must  locate  
it  and  return  it  to  our  consciousness
...
 
Remember   that   other   higher   brain   functions   (e
...
  concentration)   can   affect   how   well   tasks  
are  learned/memories  stored  
The  loss  of  memory  is  described  as  forgetfulness,  or  as  a  medical  disorder,  amnesia
...
  It   is   sometimes   called   explicit   memory,   since   it  
consists   of   information   that   is   explicitly   stored   and   retrieved
...
 
These  can  be  memories  that  happened  to  the  person  directly  or  just  memories  of  
events   that   happened   around   them
...
    Autobiographical   memory   is   a   subset   of  
episodic  memory    
! Semantic   memory   consists   of   all   explicit   memory   that   is   not   autobiographical
...
 
• In  contrast,  procedural  memory  (or  implicit  memory)  is  not  based  on  the  conscious  recall  of  
information,  but  on  implicit  learning
...
  It   is   categorised   by   an   individual   doing   better   in   a   given   task   due   only   to  
repetition   (with   no   new   explicit   memories   being   formed)
...
  Procedural   memory   involved   in   motor  
learning  depends  on  the  cerebellum  and  basal  ganglia
...
  The   duration   of   short-­‐term   memory  
(when   rehearsal   or   active   maintenance   is   prevented)   is   believed   to   be   in   the   order   of  
seconds
...
 This  has  been  shown  to  depend  on  circuitry  involving  the  frontal  and  
parietal  lobes
...
   
Encoding   involves   working   with   the   hippocampus   (e
...
  circuit   of   Papez)   to   organize   and  
select  which  information  should  be  stored  more  permanently  (therefore  the  hippocampus  is  
essential  for  storage  of  new  memories)  





In  addition  to  encoding,  the  cortex  can  be  involved  with  pulling  memories  out  of  storage  in  a  
process  called  retrieval
...
   
Key  points:  
! The  frontal  lobes  (e
...
 PFC)  are  important  for  short  term  and  working  memory
...
 Circuit  of  Papez)  is  important  
for  encoding  of  long-­‐term  memory  
 

 
Basal  ganglia  and  cerebellum  
 
• The  basal  ganglia  and  cerebellum  contribute  to  procedural  (implicit)  memory  
 
 
The  limbic  system  
 
• Encoding   of   long-­‐term   memory   occurs   in   the   diencephalon   (thalamus,   mammillary   bodies)  
and  medial  temporal  lobe  (hippocampus,  amygdala)  =>  Circuit  of  Papez  
• Therefore  lesions  of  these  regions  can  produce  anterograde  amnesia  
• It  also  believed  that  lesions  of  these  regions  can  produce  variable  retrograde  amnesia
...
    Damage   to   the   hippocampus   and   surrounding   area   can   cause   anterograde  
amnesia,  the  inability  to  form  new  memories
...
  The   amygdalae   are   associated   with   both   emotional   learning   and   memory,   as   it  
responds  strongly  to  emotional  stimuli,  especially  fear
...
 Furthermore,  the  rest  of  the  brain  is  involved  
with   strategies   for   learning   and   recall,   as   well   as   attention,   all   of   which   are   critical   for  
effective  learning  and  memorization
...
     
Frontal  traumatic  brain  injury  may  lead  to  difficulty  with  working  memory,  meaning  that  it  is  
difficult  to  keep  information  in  mind  long  enough  for  it  to  be  encoded
...
     
 

 
AD  










Alzheimer   disease   (AD)   is   the   most   common   neurodegenerative   disease   in   adulthood   and  
the  most  common  disease  that  affects  the  episodic  memory  system
...
g
...
 
Therefore,  patients  with  AD  often  initially  develop  an  anterograde  amnesic  disorder,  leaving  
them   impaired   or   unable   to   learn   new   information   (generally   impairment   of   anterograde  
episodic  memory  initially)
...
  Thus,   it   might   be   expected   that   some   patients   with   AD   will   exhibit  
similar   types   of   memory   distortions   that   patients   with   frontotemporal   or   multi-­‐infarct  
dementia  show
...
   
Finally,   as   the   pathology   of   AD   begins   to   affect   more   widespread   areas   of   the   brain,   these  
patients  develop   problems   with   other   cognitive   abilities   and   are  unable   to   perform   activities  
of  daily  living  such  as  eating,  dressing  and  bathing
...
  These   patients   have   a   ‘two-­‐way’   naming   deficit:   they   are  
unable  to  name  an  item  when  it  is  described  and  they  are  also  unable  to  describe  the  item  
when  given  its  name
...
 
Those   who   have   this   disease   have   problems   with   both   their   working   memory,   spatial  
memory   and   implicit   motor   memory
...
 He  or  she  would  also  have  trouble  encoding  this  visual  and  spatial  
information  into  long-­‐term  memory
...
   
People  with  Parkinson's  disease  display  working  memory  impairment  during  sequence  tasks  
and   tasks   involving   events   in   time
...
 
As  PD  progresses  it  can  also  result  in  dementia  with  loss  of  explicit  memory  
 

 
Summary  of  memory  disorders  
 

 
 
 

 
Types  of  amnesia  


Anterograde  amnesia  refers  to  the  inability  to  create  new  memories  due  to  brain  damage,  
while   long-­‐term   memories   from   before   the   event   remain   intact
...
 
The   two   brain   regions   related   with   this   condition   are   medial   temporal   lobe   and   medial  
diencephalon  (e
...
 hippocampus  and  circuit  of  Papez)
...
 One  may  
be   able   to   encode   new   memories   after   the   incident
...
 Episodic  memory  
is  more  likely  to  be  affected  than  semantic  memory
...
   



Dissociative   amnesia   (non-­‐organic   amnesia)   results   from   a   psychological   cause   (e
...
  PTSD)  
as   opposed   to   direct   damage   to   the   brain   caused   by   head   injury,   physical   trauma   or   disease,  
which  is  known  as  organic  amnesia
...
  This   form   of  
amnesia   is   distinct   in   that   abnormalities   in   the   hippocampus   can   sometimes   be   visualized  
using   a   special   form   of   magnetic   resonance   imaging   of   the   brain   known   as   diffusion-­‐
weighted   imaging   (DWI)
...
 The  cause  of  this  syndrome  is  not  
clear
...
 Patients  are  typically  amnestic  of  events  more  than  a  
few  minutes  in  the  past,  though  immediate  recall  is  usually  preserved
...
 It  is  caused  by  
brain   damage   due   to   a   vitamin   B1   deficiency   (thiamine)   and   will   be   progressive   if   alcohol  
intake  and  nutrition  pattern  are  not  modified
...
 It  should  be  noted  that  the  person's  short-­‐
term   memory   may   appear   to   be   normal,   however   the   person   may   have   a   difficult   time  
attempting  to  recall  a  past  story,  or  with  unrelated  words,  as  well  as  complicated  patterns
...
    Patients   may   confabulate,   with  
loved  ones  may  interpret  as  lies
...
    It   is   one   of   several  
phenomena   underlying   synaptic   plasticity,   the   ability   of   chemical   synapses   to   change   their  
strength  in  response  to  particular  stimuli
...
 
Even   though   the   neurons   of   the   hippocampus   may   seem   like   just   a   transit   point   in   the  
establishment   of   long-­‐term   memory,   they   actually   display   a   great   deal   of   plasticity
...
     
The  most  interesting  characteristic  of  LTP  is  that  it  can  cause  the  long-­‐term  strengthening  
of  the  synapses  between  two  neurons  that  are  activated  simultaneously
...
 
Glutamate,   the   neurotransmitter   released   into   these   synapses,   binds   to   several   different  
sub-­‐types  of  receptors  on  the  post-­‐synaptic  neuron
...
 
The   AMPA   (non-­‐NDMA)   receptor   is   paired   with   an   ion   channel   (ionotropic)   so   that   when  
glutamate   binds   to   this   receptor,   this   channel   lets   sodium   ions   enter   the   post-­‐synaptic  
neuron
...
 
The  NMDA  receptor  is  also  paired  with  an  ion  channel  (ionotropic),  but  this  channel  admits  
calcium   ions   into   the   post-­‐synaptic   cell
...
  For   these   magnesium   ions   to   withdraw   from   the  
channel,  the  dendrite’s  membrane  potential  must  be  depolarized
...
 
This   increased   concentration   of   calcium   in   the   dendrite   sets   off   several   biochemical  
reactions  that  make  this  synapse  more  efficient  (and  stronger)  for  an  extended  period
...
  The   necessity   for   these   two   simultaneous  





conditions   gives   this   receptor   associative   properties
...
 
But   if   this   receptor   is   blocked   with   a   drug,   or   if   the   gene   involved   in   its   construction   is  
disabled,  or  if  the  neurones  involved  are  damaged,  then  LTP  cannot  occur
...
 

 
Why  is  this  so  important?  




Properties  of  the  NMDA  receptor  allow  it  to  act  as  a  coincidence  detector  
This   is   a   mechanism   for   associating   two   pieces   of   information   being   conveyed   by   different  
sets  of  afferents  to  same  postsynaptic  cell  
Important  for  learning  and  memory  

 
Modulation  by  neurotransmitters  







Glutamate  
GABA  
Noradrenaline  
Corticosteroids  
Dopamine  
Acetylcholine  

 
Glutamate  receptor  modulators  




NMDA   receptor   antagonists
...
  They   are   used   as  
anesthesia  for  animals  and  for  humans;  the  state  of  anesthesia  they  induce  is  referred  to  as  
dissociative  anesthesia
...
   Drugs  include:  
! Ketamine    
! Memantine  (counter-­‐intuitively  used  in  AD)  
 
AMPAkines  
 

GABA  receptor  modulators  


 

Benzodiazepines  (enhance  affects  of  GABA)  
Anaesthetics  (enhance  affects  of  GABA)  

Stress  and  memory  function  









 

The   effects   of   stress   on   memory   include   interference   with   one’s   capacity   to   encode   and  
ability   retrieve   information
...
   
Stress  can  cause  acute  and  chronic  changes  in  certain  brain  areas  which  can  cause  long-­‐term  
damages
...
       
One   type   of   stress   hormone   responsible   for   affecting   memory   negatively   is   the  
glucocorticoids   (GCs),   also   known   as   cortisol
...
 
Pseudomentia  can  occur  in  Cushings  and  depression  induced  psudo-­‐Cushings    
Remember   depression   is   associated   with   raised   cortisol,   failure   of   dexa   to   supress,   and  
raised  TRH  
PTSD  is  associated  with  raised  catecholamines,  and  decreased  cortisol  (adrenal  burn  out)  

 
Noradrenaline,  memory  &  LTP  







Extreme  emotion  and  release  of  NA  can  enhance  a  memory  representation  
This   enhancement   is   called   a   flashbulb   memory:   a   highly   detailed,   exceptionally   vivid  
'snapshot'   of   the   moment   and   circumstances   in   which   a   piece   of   surprising   and  
consequential  (or  emotionally  arousing)  news  was  heard  
Also  an  effect  in  PTSD    
Activation  of  beta-­‐adrenergic  receptors  can  promote  LTP  in  the  hippocampus  
Can  be  inhibited  by  beta-­‐adrenergic  antagonists  (beta  blockers)  

 
Corticosteroid  receptors  



Glucocorticoid  receptor  (GR)  
Mineralocorticoid  receptor  (MR)  

 
Excess  GCs  are  associated  with  memory  impairment:    




Cushing’s  syndrome  (can  cause  pseudodementia)  
Major  depression  (can  cause  pseudodementia)  
Alzheimer’s  disease  

 
Dopamine,  memory  &  LTP  








Working  memory  is  the  system  that  actively  holds  multiple  pieces  of  transitory  information  
in  the  mind,  where  they  can  be  manipulated
...
g
...
g  mephylphenidate  is  
a  dopamine  reuptake  inhibitor  =>  increases  dopamine  levels  in  synaptic  cleft)  

 
 
Acetylcholine  and  memory  


Cholinergic   neurotransmission   at   the   CNS   level   is   thought   to   regulate   sleep,   wakefulness,  
and  memory
...
g
...
g
...
 Targeting  the  glutamatergic  system,  specifically  NMDA  receptors,  offers  a  novel  approach  to  
treatment  in  view  of  the  limited  efficacy  of  existing  drugs  targeting  the  cholinergic  system  





Memantine   =   low-­‐affinity   voltage-­‐dependent   non-­‐competitive   antagonist   of   NMDA  
receptors  
Licensed  to  treat  moderate  to  severe  Alzheimer’s  disease  
May   preferentially   inhibit   excessive   NMDA   receptor   activation   associated   with   excitotoxicity  
and  spare  normal  function  
 

 
ASSESSMENT  AND  LOCALISATION  OF  COGNITIVE  FUNCTION  
Memory  Problems  
Some  general  rules:  







Take  collateral  history  from  next  of  kin  =>  always!  
Get  some  idea  of  how  reported  problems  interfere  with  ADL  (activities  of  daily  living)  
Be  aware  that  mood  and  anxiety  can  greatly  affect  memory    
Consider  potential  medical  causes  (e
...
 non  psychiatric  cause)  
Be  aware  of  patients  attending  alone!  
Perform   a   dementia   screen   (examination   +   routine   bloods   +   specific   blood   tests   e
...
 
syphilis/HIV  screen,  endocrine  screen,  and  vitamin  assay)  

 
Medical  conditions  to  consider:  











Dementia  (primary  and  secondary)  
Depression  (common  cause  of  “pseudodementia”)  
B12  deficiency  
Other   vitamin   deficiency   e
...
  thiamine   B1   (Korsakoffs   syndrome   results   in   amnesia   and   is  
frequently  a  result  from  chronic  alcoholism)  
Hypothyroidism  
Metabolic/toxic/endocrine  abnormalities  (e
...
 Cushings  can  result  in  pseudodementia)  
Infections  
Anoxia  e
...
 due  to  sleep  apnoea,  respiratory  problem  or  cardiac  problem  
SOL  (space  occupying  lesion)  e
...
 brain  tumour  
Consider  drug  history  

 
Dementia  





Progressive  global  cognitive  decline  –  not  just  memory    
Represent  a  decline  from  previous  levels  of  functioning  and  performing  
Interferes  with  the  ability  to  function  at  work  or  at  usual  activities  
Not  explained  by  delirium  or  other  psychiatric  disorder  









The   cognitive   or   behavioural   impairment   involves   a   minimum   of   two   of   the   following  
domains:   memory   (amnesia),   reasoning,   visual-­‐spatial   abilities   (agnosia),   language  
(aphasia),  motor  planning  (apraxia)  and  personality/behaviour  
Severe,  acquired  and  must  involve  more  than  one  brain  function  (one  of  which  is  memory)  
Dementia  is  not  only  a  single  disease  entity  e
...
 there  are  many  different  syndromes  
Dementia  is  not  only  a  disease  of  the  elderly    
Dementia  is  sometimes  reversible  
Be   aware   that   common   medical   and   psychiatric   conditions   may   present   with   “cognitive  
problems”  

 
Dementia  or  not?  





Simple  bedside  cognitive  assessment  may  allow  evaluation  of  cognitive  function  
Large  number  of  assessments  
Folstein  MMSE  (score  out  of  30)  
Addenbrookes  Cognitive  assessment  (score  out  of  100)  

 
 
Aetiology  
Primary  causes  






AD  (commonest  cause):  affects  frontal,  temporal  and  parietal  lobes  
Frontotemporal  dementia  (FTD)  including  Picks  
Dementia  with  Lewy  bodies  (DLB)-­‐  second  commonest  cause  
Huntington’s  disease  (HD)  
PD  with  dementia  

 
 
Secondary  causes  







 

Vascular  dementia  –  common  cause  
Drugs  
Metabolic/toxic/endocrine  disorders  
Infection  e
...
 HIV,  syphilis  and  CJD  
SOL  
Post  stroke  
Traumatic  brain  injury  

 
 
 
Purpose  of  assessment  
1
...
What  is  the  underlying  pathological  process?  
Appreciate   that   bedside   cognitive   assessment   may   be   a   valuable   diagnostic   tool   and   that   pattern  
recognition  may  allows  a  confident  clinical  diagnosis  or  differential  to  be  established  
 
Assessment  process  





History  including  functional  status  –  including  collateral    
Physical  Examination  (often  less  relevant)  
Cognitive  Assessment  (MMSE  and  ACE-­‐R)  
Relevant  Investigations  e
...
 MRI,  CT,  SPECT,  CSF,  bloods  etc  

 
History  





Take  history  from  patient  and  always  from  next  of  kin  (collateral)  
Presenting   complaint:   consider   the   functional   domain   (e
...
  amnestic,   visuospatial/agnosia,  
language/aphasia,   behaviour,   reasoning,   motor   planning/apraxia)   and   associated   lesion  
location    
PMH:   Vascular   disease   including   stroke   (and   vascular   risk   factors),   trauma,   cancer,   major  
mental  health  issues  




DH:   prescribed   drugs   (care   with   anti-­‐cholinergic   in   the   elderly   as   these   can   cause   memory  
problems),  OTC  drugs,  illicit  drugs,  alcohol  (life-­‐long  history)  
FH  

 
Cognitive  domains  
Discrete  brain  regions  have  selective  functions  
Dementia   may   selectively   involve   certain   “cognitive   functions”   in   such   a   way   that   one   can  
provide  a  clinical  diagnosis  by  recognising  pattern  
 
 
Cognitive  functions  











Attention/  concentration  (frontal  lobe)  
Executive  function  (frontal  lobe)  including  behavioural  changes  
Language  (expressive-­‐  Brocas  area  in  the  dominant  frontal  lobe;  receptive-­‐  Wernickes  area  in  
the  dominant  temporal  lobe)  
Memory:  Frontal  (short  term  and  working)  and  temporal/limbic  (long  term)  
Visuospatial  function  (agnosia):  parietal  
Orientation  (time,  place,  person)  
Praxias  (motor  skills)  –  including  basal  ganglia,  cerebellum  and  parietal    
 

 
 

 
 
Executive  Function    




Impairment  often  seen  in  association  with  behavioural  changes  
Impaired  reasoning  and  handling  of  complex  tasks,  poor  judgment
...
   

 
Visuospatial  


Symptoms   include:   inability   to   recognize   faces   or   common   objects   or   to   find   objects   in  
direct   view   despite   good   visual   acuity,   inability   to   operate   simple   implements,   or   orient  
clothing  to  the  body
...
   
Defects  result  in  dysphasia/aphasia  –  expressive  or  receptive    

Assessment  of  cognitive  function  






Bedside   assessment   allows   a   reasonably   quick,   easy   and   reproducible   assessment   to   be  
undertaken  as  a  screening  tool  
During  the  test  consider  “where  is  the  lesion”?  
There  is  no  substitute  for  formal  input  and  testing  from  a  trained  neuropsychologist  
Simple  bedside  cognitive  assessment  may  allow  evaluation  of  cognitive  function  
Large  number  of  assessments  available  

 
Common  cognitive  assessment  methods  



Folstein  MMSE  (score  out  of  30)  
Addenbrookes  Cognitive  assessment  (score  out  of  100)  

 
Testing  evaluates  both  the  extent  of  the  problem  and  also  the  pattern  of  impairment  
 
Folstein  MMSE  (mini  mental  state  examination)  assessment  
Tests  (MLOV):    





Memory  (frontal,  temporal,  limbic)  
Language  (frontal,  temporal)  
Orientation  
Visuospatial  (parietal)  

 
The  MMSE  is  scored  out  of  30:  


MMSE>27  “excludes”  dementia  (Sensitivity:  0
...
7)  



MMSE  <24  “supports”  dementia  (Sensitivity:  0
...
86)  

This  is  a  crude  test  and  can  be  normal  particularly  in  the  young  and  at  an  early  stage  of  dementia  
Interpretation   must   take   into   account   the   background   history   including   associated   medical   and  
psychiatric  co-­‐morbidity  
Advantages:  
Quick  
Reproducible  
Available  in  different  languages  
Useful  screening  tool  
 
Disadvantages:  









Not  adjusted  for  age  
Poor  examining  of  executive  function  and  praxias  
Poor  in  severe  impairment  (“floor  effect”)  

 
Addenbrookes  cognitive  assessment  (ACE-­‐r)  
Examines  (MLAVE):  






Memory  (frontal,  temporal  and  limbic)  
Attention/  Concentration  (frontal)  
Language  (frontal  and  temporal)  
Visuospatial  (parietal)  
Executive  function  (frontal)  

 
Purpose:  



Extent  impairment  
Pattern  of  impairment  

 
 
1
...
g
...
   After  subject  repeats,  say:  “Try  to  remember  them  as    I  am  going  to  ask  you  them  
later”  
 

Localisation  
Areas  of  the  brain  important  for  attention,  concentration  and  arousal  include:  




Prefrontal  cortex  (frontal  lobe)  
Reticular  activating  system  (brainstem)  
Thalamus    

 
 
2
...
g
...
g
...
 
Episodic  memory  refers  to  life  events  that  people  remember
...
 Episodic  Memory  



Pathological   process   affecting   episodic   memory:   early   Alzheimer's   disease,   limbic  
encephalitis
...
g
...
g
...
 Semantic  memory  





Semantic  memory  loss  is  loss  of  general  knowledge  about  the  world  including  words    
Semantic  memory  loss  is  often  accompanied  with  a  marked  reduction  in  verbal  fluency  and  
impairment  of  irregular  words  (dyslexia)  e
...
 pint  
Example  of  disease:  Semantic  dementia  (variant  of  Frontotemporal  dementia)    
Localisation?  Anterior  temporal  lobe  atrophy  

 
 
ACE-­‐r  assessment    of  memory  
 
Memory:  anterograde  memory  


Give  patient  an  address  (repeat  up  to  3  times)  and  ask  them  to  repeat  later  

Memory:  retrograde  memory  
Name  of  current  prime  minster  
Name  of  the  woman  who  was  prime  minister  
Name  of  the  USA  president  
 
Memory:  recall  






Ask:  “which  3  words  did  I  ask  you  to  repeat  and  remember?”  

Language:  reading  


Ask  the  subject  to  read  the  words  on  the  assessment  form  e
...
 sew,  pint,  soot,  dough,  height  

Language:  naming  


Ask  the  subject  to  name  objects  e
...
 “which  one  is  a  marsupial?”  

 
3
...
 
In  the  over  65  age  group,  FTLD  is  probably  the  fourth  most  common  cause  of  dementia  after  
Alzheimer's  disease,  dementia  with  Lewy  bodies  and  vascular  dementia
...
 In  some  patients  the  
symptoms  of  FTLD  and  Alzheimer's  may  overlap
...
 Language  
Variants  of  frontotemporal  dementia  may  selectively  involve  language
...
   Visuospatial  


Localisation:   non   dominant   hemisphere   (non   dominant   parietal   lobe   e
...
  usually   left  
hemisphere)  

Example  of  disease:  





Stroke  (non-­‐  dominant  occipitoparietal)  
PD  
Parkinson  plus  syndromes  eg
...
 Pentagons,  cubes,  3-­‐D  letters,  dots  counting  

 

 
 
Does  this  patient  have  dementia?  





Overall  score=100  
>88  “excludes”  dementia  (88/100  sensitivity:  83%  Specificity:  71%)  
<83  “supports”  dementia  (83/100  sensitivity:  82%  Specificity:  96%)  
But  always  consider  not  only  score  and  pattern  but  any  potential  confounders    

 
 
Likely  pathological  process  

 
 

 

 

 

 

 

 

 
 
Summary  






Bedside   cognitive   testing   may   have   localising   value   and   pattern   recognition   may   allow   a  
confident  clinical  diagnosis  to  be  reached  
Always  obtain  collateral  history  (and  beware  of  the  patient  attending  alone)  
ACE-­‐r  provides  a  reliable,  reproducible  bedside  cognitive  test  
Always  consider  associated  psychiatric  and  medical  co-­‐morbidity  
Series  of  ACE-­‐r  are  more  valuable  than  a  single  result    

 
 
CLINICAL  ASPECTS  OF  DEMENTIA  
What  is    dementia?  
ICD   10   Dementia   definition:   ‘Syndrome   due   to   disease   of   the   brain,   usually   chronic   or   progressive   in  
nature   in   which   there   is   disturbance   of   multiple   higher   cortical   function   including   memory  
(amnesia),   thinking,   orientation,   comprehension   (receptive   aphasia),   verbal   expression   (expressive  
aphasia),  calculation  (acalculia),  learning  capacity,  language  and  judgment  
Dementia  can  also  result  in:  
BPSD  (behavioural  and  psychological  symptoms  of  dementia)  
Personality  changes  (particularly  in  FTD  e
...
 Picks  disease)  
 
Prevalence  of  dementia  rises  with  age  but  dementia  is  not  caused  by  ageing  
 
• 5%  of  those  over  65  






20%  of  those  over  80  
33%  of  those  over  85  

 
Diagnostic  Challenge  of  Dementia:  




Differentiate  dementia  from  patients  without  illness  
Diagnosis  of  sub-­‐types  of  dementia  
Vitally  important  that  we  diagnose  and  treat  dementia  

 
Differential  diagnosis  of  dementia  







Primary  or  secondary  dementia  
Depression  (pseudodementia)  
Other  psychiatric  condition  
Delirium  
Amnesia  syndromes  
Other  medical  conditions  causing  pseudodementia  e
...
 Cushings  

 
Types  of  dementia  
Primary  dementias:  




Alzheimer’s  disease    
Mixed  dementias  
Lewy  body  dementia  

(60%)  
(10-­‐15%)  
(5-­‐10%)  

 
Secondary  dementias:  
• Vascular  dementia  
• Many  medical  causes  (many  of  which  are  reversible)  =>  perform  dementia  screen  e
...
 FBC,  
TFTs,  HIV/syphilis  screen,  LFTs,  U&Es,  CRP/PV,  biochem,  full  endocrine  screen  
• VINDICATE  
• Dementia  secondary  to  other  neurological  condition  e
...
 PD  and  HD  
 
Alzheimer’s  disease  






Characteristic  neuropathological  findings  of  intracellular  neurofibrillary  tangles  (tau  protein)  
and  extracellular  beta  amyloid  plaques  
Multiple   neurotransmitter   abnormalities   with   profound   cholinergic   loss   (nuclus   basalis   of  
Meynert)  =>  acetylcholinesterases  inhibitors  are  useful  
Insidious   development   over   10   years   or   more,   with   prominent   impairment   of   episodic  
memory  (initially)  
Average  survival  time  from  diagnosis  is  8  years  
Pathological  increase  in  glutamate  activity  =>  NMDA  blocker  Memantine  is  useful    

 
Idiopathic  AD  risk  factors  





Age  
ApoE  e4  allele  (most  prominent  genetic  risk  factor  in  idiopathic  AD)  
Vascular  disease  
Family  history  

 
Presentation  of  Alzheimer’s  disease  












Progressive   (slow   and   insidious)   deterioration   of   memory   function   with   earlier   memories  
becoming  more  impaired  
Disturbance  of  recent  memory  (in  particular  episodic)  resulting  in  anterograde  amnesia  
Repeating  conversations  
Loss  of  ability  to  carry  out  key  daily  tasks  
Changes  in  language  function  
Impairment  of  insight,  judgement  and  planning  
Orientation  problems  
Neuropsychiatric   symptoms   such   as   hallucinations,   irritability,   depression,   personality  
change  and  psychosis  are  common  but  mostly  self  limiting  
BPSD  prominent  throughout  and  associated  with  carer  stress  and  institutionalization  
Gradual  progression  over  time  
End   stage   AD   presents   with   incontinence,   motor   disturbance,   extra-­‐pyramidal   signs,  
stereotyped  behaviour  and  primitive  reflexes  (reflexes  seen  in  babies/infants)  

 
Alzheimer's  disease  diagnostic  criteria  






Progressive  deterioration  in  memory  
Deficits  in  2  or  more  areas  of  cognition  (in  particular  episodic  memory)  
Onset  most  often  after  age  65  
Absence  of  systemic  disorders  that  could  account  for  impairments  
No  disturbance  of  consciousness  

 
Vascular  Dementia  (VaD)  







Vascular  dementia  or  "multi-­‐infarct  dementia"  is  dementia  caused  by  problems  in  supply  of  
blood  to  the  brain,  typically  by  a  series  of  minor  strokes
...
   
Psychomotor  slowing  and  gait  disturbance  common  
Emotional  lability  (especially  if  frontal  lobes  affected)  
Dysexecutive  syndrome  includes  items  such  as:  
! Impairment   of   goal   formulation,   initiation,   planning,   organizing,   sequencing   and  
execution
...
  Patients   with   dementia  
and   vascular   disease   frequently   have   mixed   pathology   (ie,   both   Alzheimer   disease   and   vascular  
dementia;  “mixed  dementia”)
...
g
...
   
It  is  characterized  anatomically  by  the  presence  of  Lewy  bodies  (clumps  of  alpha-­‐synuclein  
and  ubiquitin  protein  in  neurons)  detectable  in  post  mortem  brain  histology
...
 same  time  in  DLB  
Visual  hallucinations  
Falls  
Sensitivity   to   neuroleptic   (anti-­‐psychotic)   drugs   due   to   Parkinsonism:   sensitivity   to  
neuroleptic   (anti-­‐psychotic)   and   antiemetic   (dopamine   blocker   and   cholinergic   blocker  
varieties)  medications  that  affect  dopaminergic  and  cholinergic  systems-­‐  in  the  worst  cases,  
a   patient   treated   with   these   drugs   could   become   catatonic,   lose   cognitive   function   and/or  
develop  life-­‐threatening  muscle  rigidity  (due  to  decreased  dopamine  activity)  

 
Other  causes  of  dementia  




FTD  (frontotemporal  dementia)  
Neurological:    Huntingdons,  PD,  CJD  and  MS  
Secondary  dementias  (which  may  be  reversible)  

 
PSYCHIATRIC  COMPLICATIONS  OF  PHYSICAL  DISORDERS  
Delirium  
Delirium,   or   acute   confusional   state,   is   a   syndrome   that   presents   as   severe   confusion   and  
disorientation,   developing   with   relatively   rapid   onset   and   fluctuating   in   intensity
...
 

Delirium   represents   an   organically   caused   decline   from   a   previously   attained   baseline   level   of  
cognitive  function
...
  It   typically   involves   other   cognitive   deficits,   changes   in   arousal  
(hyperactive,   hypoactive,   or   mixed),   perceptual   deficits,   altered   sleep-­‐wake   cycle,   and   psychotic  
features  such  as  hallucinations  and  delusions  (psychosis)  
Delirium  itself  is  not  a  disease,  but  rather  a  clinical  syndrome  (a  set  of  symptoms),  which  result  from  
an  underlying  disease,  from  medications  administered  during  treatment  of  that  disease  in  a  critical  
phase,  from  a  new  problem  with  mentation  or  from  varying  combinations  of  two  or  more  of  these  
factors
...
g
...
g
...
g
...
 liver  failure,  pancreatitis)  
GU  disorders  (e
...
 UTI,  renal  failure)  

 
There   may   be   no   identifiable   cause   however…this   DOES   NOT   exclude   the   diagnosis
...
g
...
g
...
g
...
 
Collateral  history  may  be  necessary:  recent  activities,  prescriptions,  past  hx
...
g
...
5mg   in   elderly)   –   unless   contraindicated   e
...
  cardiac   disease,   DLB,   Parkinsonian  
disorders  
Sedating  drugs  can  worsen  delirium  by  increasing  confusion  and  unsteadiness  
Alcohol   withdrawal   requires   reducing   scale   of   benzodiazepines:   commonly  
Chlordiazepoxide  or  Diazepam  

 
Review:  





Review  patients  with  delirium  frequently  
Patients  can  improve  quickly  (and  no  longer  need  prescribed  meds)  
Patients  can  worsen  quickly  and  suffer  seizures,  injuries  and  sudden  death  
Follow  Up:    Repeat  the  MMSE  to  avoid  misdiagnosis  of  dementia  

 
Pharmacological  management    







Haloperidol   0
...
g
...
 
For   Parkinson’s,   Lewy   Body   Dementia,   and   Neuroleptic   (antipsychotic)   Sensitivity:  
Lorazepam  (not  diazepam)  0
...
 

 
 
THYROID  DYSFUNCTION  




 
 

Remember  that  thyroid  dysfunction  can  result  in  neurological/psychiatric  symptoms  
Hyperthyroidism  can  result  in  anxiety,  tremor  and  mood  liability  
Hypothyroidism   can   result   in   decreased   cognition   and   reversible   dementia   (if  
prolonged/severe),  as  well  as  depression  and  pseudodementia  
TFTs  in  all  pts  with  anxiety  or  depression  

MEMORY  
 
• Types  of  memory  include:  short  term  memory,  working  memory  and  long  term  memory  
• Long  term  memory  can  be  divided  into  semantic  memory,  episodic  memory  and  procedural  
memory  
• Consciously  accessible  (explicit)  long  term  memory  can  be  divided  into:  Semantic  (memory  
of  facts  and  concepts  and  language  etc)  and  episodic  (specific  events)  
• Autobiographical  memory  is  a  subset  of  episodic  memory  
• Semantic   memory   can   be   defined   as   knowledge   that   is   retained   irrespective   of   the  
circumstances  under  which  it  was  acquired    
• To  test  semantic  memory:  ask  questions  about  general  knowledge  e
...
 what  is  the  capital  of  
France  and  who  is  the  current  UK  prime-­‐minister?  
• Episodic   memory   can   be   defined   as   memory   for   the   events   of   your   life   that   you   have  
experienced  e
...
 recollection  of  time,  place  and  associated  emotions  at  the  time  of  the  event  
• To  test  episodic  memory:  ask  about  specific  events  which  have  happened  in  the  individuals  
life  e
...
 what  did  you  have  for  breakfast  or  where  were  you  when  you  heard  about  the  twin  
towers?  
• Whether   semantic   and   episodic   long   term   memory   represents   truly   separate   memory  
systems   is   still   unclear
...
    This   is   important   for   complex  
motor  functions  e
...
 riding  a  bike
...
g
...
g
...
 Consciousness  
is   not   clouded
...
”  

BPSD   (behavioural   and   psychological   symptoms   of   dementia)   often   characterise   the   different   sub-­‐
types  of  dementia:    







AD:  emotional  lability,  aggression,  illusions  and  delusions  
Vascular   dementia   (VaD):   depression,   abrupt   onset,   stepwise,   CV   disease,   previous  
strokes/TIA  
Dementia   with   Lewy   bodies   (DLB):   visual   hallucinations,   fluctuating   course   and   paranoid  
ideas,  Parkinsonism  <  1  year  after  onset  of  dementia    
Frontotemporal  dementia  (FTD):    
! Behavioural  variant  and  Picks:  personality  change  
! Semantic  dementia:  semantic  memory  loss  (preservation  of  episodic)  
! Progress  non  fluent  aphasia:  problem  with  naming  objects  and  verbal  fluency  
Subcortical   dementia   (e
...
  PD   and   HD):   lack   of   initiation   and   other   movement   dysfunction  
and  visulospatial  dysfunction  

 
Impaired   memory   is   a   central   feature   of   dementia
...
  The   term   cognition   refers   to   the   human  
processing   of   information,   and   includes   domains   such   as   language,   praxis,   gnosis,   visuospatial   ability  
and  executive  function
...
 The  development  of  multiple  cognitive  deficits  manifested  by  both  
1)   Memory   impairment   (impaired   ability   to   learn   new   information   or   to   recall   previously   learned  
information),  and  
2)  One  (or  more)  of  the  following  cognitive  disturbances:  
Aphasia  (language  disturbance)  
Apraxia  (impaired  ability  to  carry  out  motor  activities  despite  intact  motor  function)  
Agnosia  (failure  to  recognize  or  identify  objects  despite  intact  sensory  function)  
Disturbance  in  executive  function  (e
...
 planning,  organizing,  sequencing,  abstracting)  
 
B
...
 





 
Important  points  




Dementia   is   a   syndrome   characterised   by   global   cognitive   decline   (not   just   memory  
problems)
...
 These  include:  









Hypothyroidism  
Vitamin  B1  deficiency  (thiamine)  
Vitamin  B12  deficiency  (cobalamin)    
Normal  pressure  hydrocephalus  (“wet,  whacky  and  wobbly”)  
Space  occupying  lesion  (SOL)  
Pseudodementia  (many  causes  including  depression)  
Infective  causes  e
...
 HIV  and  syphilis    
Metabolic  causes  

 
 
Investigations  (dementia  screen)  









Urea  and  electrolytes  (U+Es)  
Thyroid  function  tests  (TFTs)  
B12  and  folate  
FBE  (full  blood  exam)  
Syphilis  and  HIV  serology  
EEG  (usually  abnormal  in  early  AD,  in  contrast  to  frontotemporal  dementia)  
CT  (not  considered  essential)  
SPECT  (where  regional  dementias  are  suspected)
...
   Many  other  symptoms  can  occur  such  
as  behaviour  and  personality  changes,  depression,  problems  with  language  etc    
The   brain   is   lighter   (due   to   atrophy   of   brain   tissue)   with   more   prominent   sulci   (widened  
sulci)  and  narrowed  gyri  and  enlarged  ventricles
...
 
The   regions   of   gray   matter   with   the   most   marked   cell   loss   are   the   basal   forebrain,  
hippocampus,  entorhinal,  and  temporal  cortices
...
    It   is   this   region   of   the   brain   which   is   very   important   for   storage  
of  long  term  episodic  memories
...
 It  was  observed,  in  the  1970s,  
that   acetylcholine   containing   neurons   of   the   basal   forebrain   (nucleus   basalis   of   Meynert)  
are   particularly   susceptible
...
g
...
 While   still   important,   the   cholinergic   hypothesis   is  
now  regarded  as  an  oversimplification
...
  It   is   proposed   they   be   the  
products  rather  than  the  cause  of  a  degenerative  process
...
 

 

 
 
Genetics  






Genetic   variation   is   an   important   contributor   to   the   risk   for   idiopathic   AD,   underlying   an  
estimated  heritability  of  about  70%
...
   
Certain  mutations  in  each  of  these  genes  are  autosomal  dominant  and  cause  AD  in  anyone  
who   carries   them
...
  These   mutations   have   been   found   in   only   a   few  
families  around  the  world,  and  account  for  only  a  small  minority  of  AD
...
   Confirmation  is  awaited  with  interest
...
   







The   nucleus   basalis   of   Meynert   is   the   main   source   of   acetylcholine   for   the   cortex
...
 
Cholinesterase  inhibitors  block  the  action  of  acetylcholinesterase,  an  enzyme  that  removes  
acetylcholine   from   the   synapse;   they   therefore   increase   ACh   in   the   synapse   and   improve  
cholinergic  transmission
...
   
 
 

Pharmacological  management  of  Alzheimers  disease  



Cholinesterase  inhibitors  
Memantine    

 
Acetylcholinesterase  inhibitors  (AChE  Inhibitors)  
The  cholinesterase  inhibitors  in  current  clinical  use  are:  
Donepezil  
Rivastigmine  
Galantamine  
 
They   do   not   affect   the   underlying   pathological   processes   in   Alzheimers   disease,   but   do   slow  
cognitive  decline  by  increasing  cholinergic  transmission
...
   Rivastigmine  is  also  licensed  for  
use   in   DLB
...
    AChE   inhibitors   are   also   used   to   increase   ACh   levels   in   myasthenia  
gravis,   however   if   the   dose   is   too   high   then   a   cholinergic   crisis   can   occur   resulting   in   paralysis   of  
skeletal  muscles  including  the  diaphragm  =>  respiratory  failure  can  occur
...
  It   works   by  
blocking  NMDA-­‐type  glutamate  receptors  (antagonist  of  glutamate  NMDA  receptors)  
Glutamate   is   the   main   excitatory   neurotransmitter   in   the   brain   and   it   is   thought   that  
neurons  are  damaged  by  glutamate  over-­‐activation  (excitotoxicity)  in  Alzheimers  as  well  as  
in  many  other  neurodegenerative  disorders
...
 
 
Vascular  dementia  







The   diagnosis   of   vascular   dementia   (VaD)   depends   on   the   cognitive   disturbances   and   the  
presence   of   significant   cerebrovascular   disease
...
     
25-­‐35  %  of  patients  with  dementia  have  cerebral  ischaemic  lesions  that  are  a  major  factor  in  
the  dementing  process
...
6%  in  people  above  60  years  
Dementia   is   diagnosed   in   >30%   of   people   three   months   after   acute   stroke
...
   
Left  hemisphere  (dominant  hemisphere)  strokes  are  more  likely  to  produce  dementia
...
  The  
vascular   pathology   may   include   atherosclerosis,   arteriosclerosis,   lipohyalinosis,   amyloid  
angiopathy,  and  senile  arteriolar  sclerosis
...
 
 
 
The  clinical  diagnosis  of  VaD  vs  AD  is  based  on:  



Sudden  onset  
Stepwise  progression  
Focal  neurological  abnormalities  
Fluctuating  course  with  day-­‐to-­‐day  improvement  
Occurrence  of  one  or  more  strokes  
Evidence  of  coronary  or  other  major  arterial  disease  
Labile  emotional  state  
Tendency  for  retained  insight  
Vascular  risk  factors  e
...
 smoker,  hypertension,  hyperlipidaemia  and  DM  
 
The   Hachinski   Ischameic   score   (HIS)   is   a   quick   and   easy   test   that   can   help   in   the   clinical  
differentiation  of  Alzheimers  disease  and  vascular  dementia
...
 
 
The  prognosis  of  VaD  is  less  favourable  than  AD,  with  a  5  year  mortality  of  >63%  (compared  to  AD  
<32  %)
...
  Reduction   in   the   prevalence   of   vascular   dementia   will  
require  reduction  in  the  rate  of  cerebrovascular  disease
...
g
...
  On   histological   examination,   all  
patients  with  Parkinson’s  disease  (PD)  and  DLB,  and  40%  of  patients  with  AD  have  Lewy  bodies  (LBs)
...
     
Frederick   Lewy   first   described   Lewy   bodies   (eosinophilic,   round,   cytoplasmic   inclusions)   in  
the  cells  of  the  substantia  nigra  in  patients  with  PD  in  1914
...
   A  classical  
Lewy  body  is  an  eosinophilic  cytoplasmic  inclusion  consisting  of  a  dense  core  surrounded  by  
a  halo  of  10-­‐nm-­‐wide  radiating  fibrils,  the  primary  structural  component  of  which  is  alpha-­‐
synuclein
...
 
! Parkinsonian   features,   such   as   loss   of   spontaneous   movement   (bradykinesia),  
rigidity   (muscle   stiffness),   tremor,   and   shuffling   gait,   to   AD-­‐type   symptoms   including  
memory  loss,  acute  confusion,  and  fluctuating  cognition
...
  If   PD   (movement   dysfunction   only)   has   been   present   for   1   year   or   longer   before  
cognitive   impairment,   the   disorder   is   termed   PD   with   dementia,   otherwise   it   is   designated  
DLB
...
  LBs   are   also   found   in   the   cortex   of   many   people   with   PD   and   all   people  
with  DLB
...
 DLB  is  a  slowly  progressive  disorder  for  which  there  is  no  cure
...
 
Anti-­‐parkinsonian   medication   (increase   dopamine   activity)   which   may   help   reduce   tremor,  
reduce   hypertonia   (rigidty),   and   improve   movement,   however   may   worsen   hallucinations  
and  delusions  (as  increased  dopamine  plays  a  role  in  psychosis  pathophysiology)    
Antipsychotic   drugs   (decrease   dopamine   activity)   which   may   reduce   psychiatric   symptoms,  
however  may  markedly  worsen  movement  symptoms
...
   
Depression   may   respond   to   SSRIs,   which   do   not   appear   to   introduce   particular  
complications
...
 The  two  conditions  are  distinguished  clinically  
by  the  timing  of  the  symptoms
...
   
• The   first   was   described   by   Pick   (Pick’s   disease)   and   has   characteristic   histopathology   of  
ballooned   neurones   (Pick’s   cells)   and   argentophilic   globes   (Pick’s   bodies)
...
   
• The   frontal   and   temporal   lobes   control   personality   and   speech
...
 
 
 
Subtypes  of  FTD  
 
Progressive  Language  Decline  (aphasia)  
 






Semantic  dementia  (SD):  SD  is  characterised  by  loss  of  semantic  memory  in  both  the  verbal  
and  non-­‐verbal  domains
...
   
Progressive  nonfluent  aphasia  (PNFA)
...
 People  lose  their  ability  to  generate  words  easily,  and  their  speech  becomes  
halting,  "tongue-­‐tied"  and  ungrammatical
...
 

 
 
Progressive  Behaviour/Personality  Decline  
 
• Behavioural  variant  FTD  (BVFTD):  takes  its  greatest  toll  on  personality  and  behavior
...
 As  BVFTD  progresses  people  
often   develop   disinhibition,   a   striking   loss   of   restraint   in   personal   relations   and   social   life
...
   Memory  generally  intact  
• Picks  disease  
 
 
Progressive  Motor  Decline  
 
• FTD  with  amyotrophic  lateral  sclerosis  (FTD-­‐ALS  -­‐  MND)  
• FTD  with  parkinsonism  
• Progressive  supranuclear  palsy  (PSP):  Parkinson  plus  syndrome  (parkinsonism,  bulbar  palsy,  
supranuclear  ophthalmoplegia,  dementia)  
• Multi-­‐system   atrophy:   Parkinson   plus   syndrome   (parkinsonism,   cerebellar   involvement,  
significant  ANS  involvement)  
 
 
Summary  of  differential  features  
Alzheimer’s  disease  (AD)    
 

Dementia  with  cerebrovascular  disease  (VaD)    
 
Dementia  with  Lewy  bodies  (DLB)    
 

Cognitive  impairment:    
Anterograde   amnesia   (inability   to   learn   and  
retain   new   information   in   particular   episodic  
memory),    
 
Plus  impairment  in  one  of  the  following:    
Reasoning    
Visuospatial  ability  (agnosia)  
Orientation    
Language    
Cognitive  impairment  as  for  AD    
Plus  evidence  of  cerebrovascular  disease    
Cognitive  impairment  as  for  AD,    
Plus  two  of  the  following:    
Parkinsonism  

Frontotemporal  dementia  (FTD)    
 

Visual  hallucinations    
Fluctuations  in  arousal    
REM  sleep  behaviour  disorder
...
  Decline   in   regulation   of   personal   or  
interpersonal   conduct   (loss   of   empathy   for  
others;   socially   inappropriate   behavior   that   are  
rude   or   sexually   explicit;   mental   rigidity;   decline  
in  personal  hygiene;  obsessional  behaviors),  or    
2
...
   
3
...
   
Atrophy   of   the   whole   brain   (and   hippocampus   in   particular)   accelerates   as   the   patient  
moves  from  normality  to  cognitive  impairment,  and  as  dementia  progresses
...
 



Cognitive   decline   may   develop   as   a   direct   result   of   the   vascular   injury   (eg,   multi-­‐infarcts   or   a  
single  stroke  affecting  a  strategic  location)  and/or  lowering  the  threshold  for  the  expression  
of  concomitant  pathology,  such  as  AD
...
 



Lacunar   infarctions,   therefore,   occur   in   the   basal   ganglia,   putamen,   internal   capsule,  
thalamus,  corona  radiata  and  centrum  and  lateral  brainstem
...
 They  are  cavitating,  round,  oval  or  
slit-­‐like,  and  on  CT  are  hypodense  



Small-­‐vessel   disease,   or   leukoaraiosis,   is   another   player   in   subcortical   vascular   dementia
...
 

 
Dementia  With  Lewy  Bodies  






This  accounts  for  10%  of  dementias
...
     
An   absence   of   MTA   (medial   temoral   lobe   atrophy)   strongly   suggests   dementia   with   Lewy  
bodies  rather  than  AD  or  vascular  dementia
...
   
Therefore,   decreased   DAT   (dopamine   uptake   transporter)   uptake   in   the   basal   ganglia   is   a  
potential  biomarker    

 
 
 
MANAGEMENT  OF  DEMENTIA  
Medical  Management  







MDT  
Diagnosis  and  postdiagnostic  involvement:  need  for  explanation  of  the  illness,  its  symptoms  
and  progression
...
 
The   use   of   behavioural   and   pharmacological   approaches   to   symptoms   associated   with  
dementia
...
 



They   have   also   been   used   clinically   in   Dementia   with   Lewy   Bodies   where   patients   are   particularly  
sensitive  to  neuroleptic  medication
...
 
Degeneration   of   cholinergic   neurones   and   reduction   in   levels   of   ACh   in   synapse   is   a   key  
feature  of  AD  
ACh  is  metabolised  by  acetylcholinesterase  (AChE)
...
 
Neurological:  epilepsy,  Parkinson’s  Disease
...
 
Genitourinary:  urinary  outflow  obstruction,  recovering  from  bladder  surgery
...
 
Safe  and  well  tolerated  but  vertigo,  excitation  and  insomnia  reported
...
 

Behavioural  and  Psychological  Symptoms  of  Dementia  (BPSD)  
Can  present  at  any  stage  of  the  illness  (90%)  and  include:  
Depression  
Delusions  
Hallucinations  
Aggression  
Apathy    
Agitation  
 
Effects  of  BPSD:  major  source  of  stress  for  carers  and  predicts  more  rapid  decline  and  admission  to  
Care  Home  







 
Pharmacotherapy  for  BPSD  
Psychotropic  medication  has  limited  efficacy  (although  it  increases  if  specific  psychiatric   symptoms  
are  targeted)  and  potential  side  effects
...
 
Prior  to  their  use:    


Physical   causes   for   change   in   behaviour   should   be   excluded:   delirium,   dehydration,   pain,  
medication  side  effects,  sensory  impairment  etc  

 
Antipsychotic  drugs  







Also  known  as  neuroleptics
...
 
Should   only   be   used   if   absolutely   necessary   to   treat   psychotic   symptoms   (delusion,  
hallucinations)  and  extreme  aggression  and  the  golden  rule  applies
...
 
Clinical  trials  have  shown  that  for  most  people  with  dementia  neuroleptic  withdrawal  can  be  
achieved   with   no   detrimental   effect   and   only   a   small   group   of   patients   with   more   severe  
symptoms  might  benefit  from  continuous  treatment
...
g
...
g
...
 
 
Atypical  neuroleptics    






Group  of  newer  drugs  with  less  or  no  EPSE
...
 
Increased  serotonin  effects  can  result  in  metabolic  syndrome  meaning  that  these  drugs  are  
contraindicated  in  some  patients,  and  typical  anti-­‐psychotics  may  be  preferred  
Risperidone  is  now  licensed  also  for  short-­‐term  treatment  (6/52)  of  persistent  aggression  in  
moderate  to  severe  Alzheimer’s  dementia
...
g
...
   
Others  (lorazepam,  diazepam)  can  be  used  short-­‐term  for  extreme  anxiety/agitation
...
 
Other   antidepressants   such   as   Venlafaxine   (SNRI)   and   Mirtazapine   (NaSSA)   are   used   but  
there  is  less  research  evidence
...
g
...
g
...
g
...
g
...
g
...
   All  adults  are  presumed  to  have  sufficient  
capacity   to   decide   on   their   own   medical   treatment   unless   there   is   significant   evidence   to   suggest  
otherwise
...
 
•  The   impairment   or   disturbance   means   the   person   is   unable   to   make   a   decision   at   the  
current  time
...
    Most   other   Tx,   verbal   consent  
suffices
...
g
...
     
• It   is   not   always   necessary   to   detain   an   adult   formally   under   the   2003   MHA   because   they   are  
unable   to   consent   to   treatment   for   a   mental   disorder
...
     
• But  remember  mental  illness  does  NOT  imply  that  they  lack  capacity!    
• The  wording  in  the  2000  Act  is  that  the  medical  practitioner  shall  have  "authority  to  do  what  
is   reasonable   in   the   circumstances,   in   relation   to   the   medical   treatment   to   safeguard   or  
promote  the  physical  or  mental  health  of  the  adult"  (sec  47(2))
...
 However  other  areas  such  as  the  inability  
to  manage  money  or  to  agree  to  discharge  arrangements  may  be  important  
 
 

 
 
 
Principles  of  the  Adults  With  Incapacity  (Scotland)  Act  2000  
• Intervention  must  benefit  the  adult  
• Intervention  is  for  a  treatment  of  a  medical  condition  (including  psychiatric)  
• Such  benefit  cannot  reasonably  be  achieved  without  the  intervention  
• Take  account  of  past  and  present  wishes  




Consult  with  other  relevant  persons  
Encourage  the  adult  to  use  residual  capacity  

 
Mental  Health  (Care  and  Treatment)  (Scotland)  Act  2003  
• This   act   allows   for   treatment   of   mental   disorder   or   physical   consequences   of   mental  
disorders  in  someone  with  impaired  decision  making  ability  AND  who  requires  detention    
! Emergency  Detention  (section  36)  
! Short  Term  Detention  (section  44)  
! CTO’s  
 
Criteria  for  Emergency  Detention  (section  36)  
1)  Likely  to  have  a  mental  disorder  
2)  Significantly  impaired  decision-­‐making  ability  regarding  treatment,  due  to  mental  disorder  (note  
that  this  criteria  does  NOT  mean  lack  of  capacity,  as  they  may  indeed  have  a  degree  of  capacity)  
3)  Detention  in  hospital  is  necessary  as  a  matter  of  urgency  to  determine  what  treatment  is  needed  
4)  Risk  to  health,  safety  or  welfare  of  the  person,  or  safety  of  others  
5)  Making  arrangements  for  section  44  would  involve  undesirable  delay    
 
 
Criteria  for  Short  Term  Detention  (section  44)  
1)  Has  a  mental  disorder  
2)  Significantly  impaired  decision-­‐making  ability  regarding  treatment,  due  to  mental  disorder  (note  
that  this  criteria  does  NOT  mean  lack  of  capacity,  as  they  may  indeed  have  some  capacity)  
3)  Detention  in  hospital  is  necessary  for  assessment  or  treatment  (but  non-­‐urgent)  
4)  Risk  to  health,  safety  or  welfare  of  the  person,  or  safety  of  others  
5)  Cannot  be  treated  voluntarily  
 
 
NOTE:    IF  PT  DOES  NOT  NEED  DETAINED,  THEN  CAN  USE  AWI  (IF  THEY  LACK  CAPACITY)  
 
 
Age  of  Legal  Capacity  (Scotland)  Act  1991  
• Assume  capacity  if  aged  over  16  (unless  proven  otherwise)
...
g
...
g
...
     
• Depends  on  situation  and  child
...
 
       
 
Emergency  Detention  Certificates  (section  36)  
The   part   of   the   MHA   that   you   need   to   know   most   about   is   the   Emergency   Detention   Certificate  
(EDC),  as  you  may  need  to  use  this  in  clinical  practice  from  FY2  onwards
...
  Fill   in   an   Emergency   Detention   Certificate   form   (DET1)
...
      The   MHO   (Mental   health   officer)   is   a   social   worker   who   is  
highly  trained  in  the  use  of  the  MHA  
• Call   psychiatrist   to   discuss   case   and   request   that   an   AMP   [1]   come   to   do   a   Short   Term  
Detention  Certificate
...
   
 
 
Short  Term  Detention  Certificates  (section  44)  
 
Criteria:  
• Has  a  mental  disorder  
• Significantly   impaired   decision-­‐making   ability   regarding   treatment,   due   to   mental   disorder  
(may  or  may  not  have  lack  of  capacity,  but  will  most  likely  have  lack  of  insight)  
• Detention  in  hospital  is  necessary  for  assessment  or  treatment  (not  emergency)  
• Risk  to  health,  safety  or  welfare  of  the  person,  or  safety  of  others  
• Cannot  be  treated  voluntarily  
 
STDCs  require  an  AMP  and  an  MHO
...
  Sometimes   this   can   be  
difficult  if,  for  instance,  you  are  too  unwell  to  make  your  own  decisions
...
 
• If   you   have   made   a   valid   advance   statement   then   it   must   be   taken   into   account   when  
decisions   are   taken   about   your   care   and   treatment   by   those   who   are   responsible   for   your  
care
...
 
• In  an  advance  statement  you  can  say  which  treatments  work  well  for  you,  and  which  ones  
you   would   not   want
...
 It  might  be  helpful  if  you  can  include  any  reasons  for  your  views
...
 
• Doctors  would  then  see  whether  there  were  other  treatments  which  would  help  you
...
 Your  advance  
statement  will  be  taken  into  account  with  all  the  other  aspects  of  your  care
...
 
• If   a   decision   is   made   which   goes   against   your   advance   statement   you   will   be   given   the  
reasons   in   writing
...
 
 
 
Compulsory  Treatment  Orders  
 
The  main  points  that  you  need  to  know  about  CTOs  are:    
 
• A  CTO  lasts  6  months  and  has  to  be  renewed  if  the  patient  requires  ongoing  detention
...
 
• The   MHO   applies   for   the   CTO   and   submits   2   medical   reports,   one   by   RMO   (psychiatrist  
responsible  for  the  patient’s  care)  and  one  by  the  patient’s  own  GP  a  or  second  psychiatrist  
not  working  in  the  same  service
...
   
• A  CTO  can  be  hospital  or  community  based
...
g
...
    The   Power   of   Attorney   (PoA)   document   contains   the  
name   of   the   person(s)   whom   you   want   to   help   you,   i
...
  the   attorney   and   a   list   of   the  
individual  powers  that  you  want  your  attorney  to  have
...
 The  
PoA  will  also  include  when  your  attorney  is  to  begin  acting  for  you
...
 The  PoA  provides  legal  authority  
for  the  attorney  to  make  decisions  for  you  e
...
 medical  decisions  and  financial  decisions
...
    This   person   is  
known   as   a   welfare   guardian
...
   
The  court  can  also  overturn  a  PoA  and  appoint  a  guardian  if  the  PoA  is  abusing  their  trust
...
    There   is   no   question   of   a   third  
party   “applying”   for   power   of   attorney,   in   respect   to   someone   who   lacks,   or   has   already   lost  
capacity
...
   
For   example,   if   someone   was   believed   to   be   abusing   their   role   as   POA,   the   court   could  
overrule   them   and   appoint   a   guardianship   order
...
     
• Intervention  orders  are  also  applied  for  to  the  court
...
g
...
g
...
   
The  MHA  says  the  least  possible  force  must  be  used  as  possible  
AWI  can  used  to  treat  physical  or  mental  conditions  (and  is  indeed  the  preferred  method  if  
detention  is  not  required)
...
 It  will  be  important,  therefore,  for  practitioners  and  others  to  retain  clarity  about  why  
the  legislation  might  be  required'  (Gordon  2004)
...
12  Two  areas  of  particular  relevance  to  this  review  are  the  interface  between  the  Acts  in  relation  
to   definitions   of   capacity   regarding   treatment   decisions   for   mental   disorder   and   treatment   in   the  
community
...
13   Gordon   describes   the   distinction   in   relation   to   a   treatment   decision   as   '   one   of   the   more  
complex  interfaces'  between  the  two  Acts
...
 
 
5
...
1)
...
 
 

 

 

 
 
 
 
 

 

MHA,  capacity  and  consent  in  relation  to  ECT  
• Just  because  a  patient  is  detained  does  NOT  mean  that  they  lack  capacity
...
g
...
     Note  that  these  patients  will  likely  lack  capacity  anyhow
...
g
...
 
Grooming  –  evidence  of  self-­‐neglect?    
Effort  with  appearance  
Scars  –  self  harm,  fights  
Physique,  build  –  e
...
 underweight  
Tattoos,  piercings    



 

Signs  of  physical  ill  health  –  e
...
 stick,  insulin  pump  
Evidence  of  drug/alcohol  misuse  –  track  marks,  flushing,  jaundice,  spider  naevi,  parotid  swelling  

Behaviour  






 

Gaze  /  eye  contact  
Level  of  activity  –  hypoactive,  hyperactive,  neutral  
Psychomotor  agitation  /  retardation  
Attitude  /  Rapport:  cooperative/  uncooperative,  hostile,  guarded,  suspicious  
Unusual  /  abnormal  movements  –  e
...
 tics,  myoclonus,  catatonic  movements  
Socially  appropriate  behaviour  

Speech  












 

Quantity  
Quality  
Rate,  rhythm,  volume,  and  tone  (character)  
Form  of  speech  
Pressure  or  poverty  of  speech  
Spontaneous  speech  
Latency  
Articulation  
Accent  
Vocabulary  
Abnormalities  of  articulation  –  stammer,  dysarthria  
Dysphasia  /  aphasia  

Mood  &  Affect  
Mood  




Mood  =  ‘Climate’  
Predominant  emotional  state  of  patient  (depressed,  anxious,  angry)  
Objective  and  subjective  description  of  mood  
! Neutral,   euthymic   (display   normal   range   of   emotion),   dysphoric,   euphoric,   anxious,  
angry,  apathetic,  irritable  
! Rating  of  mood  on  a  scale  (current  mood,  and  what  “normal”  mood  would  be)  

 
Affect  






 

Affect  =  ‘Weather’  
Intensity:  normal,  blunted,  exaggerated,  flat,  heightened  
Extent  to  which  affect  changes:  restricted,  labile,  reactive,  stable  
Consider  how  the  patient  makes  you  feel  to  judge  affect  
Mood  congruent  =>  when  mood  &  affect  are  the  same    
Mood  incongruent  =>  when  mood  &  affect  are  opposite  each  other  

Risk  assessment  





Suicidality:   part   of   mood   &   affect   assessment
...
  Questions   will   not   make  
anyone  feel  suicidal
...
e
...
 
! Also  ask  about  thoughts  of  life  not  worth  living  &  thoughts  of  wanting  to  harm  self
...
 
Also  important  to  establish  if  there  is  any  risk  of  harm  to  other  individuals    
Assess   for   suicide   risk   demographic   factors   in   the   history:     previous   DSH,   psychiatric  
problem,   physical   problem,   alcohol   or   drug   dependency,   loneliness,   lack   of   social   support,  
no  job,  poor  finances  

 
Thought  process  (thought  form)  




How  the  thoughts  are  formed  /  verbalised  
Ask  patient  if  they  have  had  any  strange  thoughts?    Thoughts  racing?    Thoughts  slowed  down?    
What  sort  of  stuff  do  you  tend  to  think  about?  
Formal   thought   disorder   -­‐   disorder   of   the   form   (e
...
  disorder   of   the   way   in   which   thought   are  
formed),  as  opposed  to  the  content,  of  the  thought
...
   Specific  thought  disorders  include  poverty  
of  speech,  tangentiality,  illogicality,  neologism,  and  thought  blocking  
! Poverty   of   thought   -­‐   global   reduction   in   the   quantity   of   thought
...
  Seen   in   depression,   dementia
...
   
Manifests  as  poverty  of  speech
...
 In  schizophrenia,  this  may  link  into  a  delusion  e
...
 thought  interference
...
  Usually   seen   in   mania,   may   also   be   seen   in  
schizophrenia  &  extreme  anxiety
...
 
! Flight   of   ideas   -­‐   words   are   associated   together   inappropriately   because   of   their  
meaning/rhyme   =>   speech   loses   its   aim,   patient   wanders   from   original   theme
...
 Usually  seen  in  mania    
! Loosening  of  Associations  -­‐  muddled,  illogical,  difficult  to  follow  and  cannot  be  clarified
...
     Mania  
! Knight’s  Move  Thinking  -­‐  jumps  from  topic  to  topic  with  no  connection  between  them
...
     
! Tangential   Thinking   -­‐   wandering   from   the   topic   on   tangents   (loosely   associated)   and  
never  returning  to  it  or  providing  the  information  requested
...
     
! Circumstantial   -­‐   inability   to   answer   a   question   without   giving   excessive,   unnecessary  
detail
...
 
! Word  salad  -­‐  confused  or  unintelligible  mixture  of  seemingly  random  words  and  phrases
...
 Often  seen  in  schizophrenia  
 
 
Thought  content  
• Assess  for  unusual  beliefs,  overvalued  ideas,  delusions,  obsessions    
! Do  you  have  any  strange  thoughts?    Anything  you  worry  about?    What  do  you  tend  to  
think  about?    Do  you  hear  or  see  things  that  other  people  cant?  
• Delusion  =  a  false  belief,  inappropriate  to  the  patient’s  socio-­‐cultural  background,  firmly  held  in  the  
face   of   logical   argument   (not   amenable   to   logic)   or   evidence   to   the   contrary
...
  Themes  
usually   persecutory,   jealous,   grandiose,   religious,   hypochondriacal,   health,   nihilistic
...
  May   be   an   origin,   such   as   an   attempt   to   explain   an  
anomalous  experience,  e
...
 hallucinations
...
     
• Phobias  
• Obsession  =  An  undesired,  unpleasant  intrusive  thought  that  cannot  be  suppressed  
• Preoccupation  =  Not  fixed,  false  or  intrusive  (not  a  delusion)  but  have  an  undue  prominence  in  the  
persons  mind  
• Overvalued  Idea  =  An  unreasonable,  sustained  belief  that  is  held  with  less  than  delusional  intensity  
e
...
 hypochondriasis  
• Rumination  =  Rumination  is  the  compulsively  focused  attention  on  the  symptoms  of  one's  distress,  
and   on   its   possible   causes   and   consequences,   as   opposed   to   its   solutions
...
   Ruminating  is  like  a  record  that’s  stuck  and  keeps  
repeating  the  same  lyrics
...
 It’s  retracing  past  
mistakes
...
 
! Thought   broadcasting:   The   experience   that   one's   thoughts   are   being   transmitted   from  
one's  mind  and  broadcast  to  everyone
...
 
! Thought  withdrawal:  The  experience  of  thoughts  being  removed  or  extracted  from  one's  
mind
...
 These  may  therefore  include  
'made   acts   and   impulses'   where   the   individual   feels   they   are   being   made   to   do   something   by  
another,   'made   movements'   where   their   arms   or   legs   feel   as   if   they   are   moving   under   another's  
control,   'made   emotions'   where   they   are   experiencing   someone   else's   emotions,   and   'made  
thoughts'  which  are  categorised  elsewhere  as  thought  insertion  and  withdrawal  
 
Perceptions  
Perception:   abnormalities   in   any   of   the   5   sensory   modalities   (visual,   auditory,   gustatory,   tactile,  
olfactory)
...
 




Derealisation  (world  around  patient  is  unreal)  
Depersonalisation  (patient  is  unreal)  
Déjà  vu  




Illusions  –  external  stimulus  present  but  perceived  wrongly  (pseudo-­‐hallucination  /  misperception)  
Hallucinations   -­‐   Perception   in   the   absence   of   an   external   stimulus
...
g
...
  Hallucinations   may   be   organic   (e
...
  delirium   or   DLB)   if  
predominantly  visual
...
 
! Auditory   hallucinations   –   internal   /   external   space?   Open   to   conscious   manipulation?   2nd  
(someone  else  talking  to  patient)  or  3rd  (voices  talking  about  patient)  person?    Second  person  
are   suggestive   of   depression   with   psychosis   or   mania   with   psychosis
...
  Number   of   voices?   Gender?   Content?   Running   commentary?   Thoughts  
spoken  aloud?  Do  the  voices  command  the  patient?  Do  they  feel  compelled  to  act  on  them?  
! Auditory  hallucinations  can  also  take  the  form  of  a  running  commentary:    first  rank  symptom  
for  SZ  
! Auditory  hallucinations  can  also  take  the  form  of  thought  echo:    thoughts  spoken  aloud    
 
 

Cognition  










Orientation:  time,  place,  person  (e
...
 address,  DOB)  –  useful  for  assessing  delirium    
Attention,  concentration  and  memory  (remote  &  recent)  
! Serial  7s  (subtract  7s  from  100)  –  useful  for  assessing  delirium  
! Digit   span   (ask   patients   to   remember   and   repeat   a   series   of   numbers)   –   useful   for  
assessing  delirium  
When  appropriate  (e
...
 dementia,  alcohol)  
! MSQ  
! MMSE  (30  Qs)  
! Addenbrookes  Cognitive  Examination  (ACE-­‐R:  100  points  in  total  covering  all  aspects  of  
cognition)  
Calculation  
Language  –  naming  /  repeating  objects  
Visuo-­‐spatial  
Executive   Functioning:   similarities   between   objects,   verbal   fluency
...
 
Does   they   believe   their   symptoms   are   a   result   of   illness?   Do   they   think   the   illness   is  
psychiatric?  
! Appraisal  or  analysis  of  consequences  of  such  symptoms  
! Acceptance   of   treatment   Do   they   think   treatment   will   help?   Will   they   accept   medical  
advice?  
Not  a  present  or  absent  state  
Ask  what  family  think  about  them    

 
 
MSE  examples  
Schizophrenia  


Appearance  



Behaviour  
! Withdrawal  
! Suspicious  
! Paranoia  
! Lack  of  eye  contact  



Speech  



Mood  and  affect  
! Flat  affect  
! Incongruous    
! “Odd”  



Thought  process  (thought  form)  
! Formal  thought  disorder  (disorganized  thinking  as  evidenced  by  disorganized  
speech)  
! Poverty  of  thought  (negative  symptom):  global  reduction  in  quantity  of  thought  
! Thought  blocking  (mind  empties  of  thoughts):  may  be  linked  to  delusion  
! Word  salad:  confused  or  unintelligible  mixture  of  seemingly  random  words  and  
phrases  
! Neologisms:  made  up  words  or  phrases  
! Knights  move  thinking:  jumps  from  topic  to  topic  with  no  connection  between  
them
...
g
...
g
...
 
! The  classic  signs  of  psychosis  are  hallucinations  and  delusions  (positive  signs)
...
   Knightsmove  thinking  has  no  apparent  connection  



Thought  content  
! Delusions  (if  psychosis)  of  grandeur,  special  ability,  persecution,  religiosity  



Perceptions  
! Hallucinations  (if  psychosis):  auditory  (typically  second  person  e
...
 God’s  voice)  



Cognition  



Insight  
 

 
Analysis  examples  


If  a  pt  appears  to  be  delusional  state  that  “I  think  there  is  evidence  of  possible  delusions  but  
as  their  beliefs  have  not  been  specifically  challenged  it  is  impossible  to  say  whether  or  not  
they  are  amenable  to  logic”
...
  It   normally   recovers  
within  72  hours,  is  characterised  by  tearfulness  but  no  loss  in  sense  of  reality
...
 It  is  a  self  limiting  condition
...
   Peaks  at  around  3-­‐4  weeks  post-­‐birth
...
 This  behaviour  may  include  threats  to  
harm  herself,  partner  or  the  baby
...
 
The  Edinburgh  Postnatal  Depression  Scale  may  be  used  to  screen  for  depression:  
10-­‐item  questionnaire,  with  a  maximum  score  of  30  
Indicates  how  the  mother  has  felt  over  the  previous  week  
Score  >13  indicates  a  'depressive  illness  of  varying  severity'  
Sensitivity  and  specificity  >  90%  
Includes  a  question  about  self-­‐harm  
 
 
'Baby-­‐blues'  
Postnatal  depression  
Puerperal  psychosis  






Seen  in  around  60-­‐
70%  of  women  –  
normal!!!  

Affects  around  10%  of  women  

Affects  approximately  0
...
g
...
g
...
 This  behaviour  
may  include  threats  to  harm  herself,  
partner  or  the  baby
...
   
Review  in  day  or  so  
and  there  should  be  
marked  
improvement
...
 Certain  SSRIs  such  as  
sertraline  and  paroxetine*  may  be  
used  if  symptoms  are  severe**  -­‐  
whilst  they  are  secreted  in  breast  
milk  it  is  not  thought  to  be  harmful  
to  the  infant  

Admission  to  hospital  is  usually  required  
 
 
There  is  around  a  20%  risk  of  
recurrence  following  future  pregnancies  

 
*paroxetine  is  recommended  by  SIGN  because  of  the  low  milk/plasma  ratio  
**fluoxetine  is  best  avoided  due  to  a  long  half-­‐life  

 
 
Psychiatry  exam  advice  


Know  structural  brain  changes  in  MDD  and  BPD  



Neurobiology:  
! Dopamine  is  closely  linked  to  appetitive/approach  (reward)  system  
! Serotonin  and  NA  is  closely  linked  to  aversive/defensive  system:  MDD  is  
associated  with  dysfunctional  aversive  system  primarily  
! Know  hormonal  changes  e
...
 increased  cortisol  in  MDD  (pseudo-­‐Cushings;  failure  
of  dexa  to  supress),  increased  TRH  in  MDD,  low  cortisol  and  high  catecholamines  
in  PTSD  

 
OSCE  exam  
Potential  OSCE  stations:  


Watch  video  and  perform  MSE  



Take  a  history  including  psychiatric  history  +  brief  MSE  



If  have  a  potential  suicide  patient  (e
...
 many  psychiatric  patients)  then  must  ask  directly:  
“Do  you  have  any  thoughts  of  suicide  or  harming  yourself?”    Must  explicitly  ask  about  
thoughts  of  taking  ones  life  –  not  just  about  self  harm
Title: Psychiatry lecture notes
Description: A detailed and comprehensive set of psychiatry lectures notes. Covers all aspects of mental health. Diagrams included to aid learning. Very useful for medical students.