2. “Detecting an illness early is of
value only if effective treatment
is readily available”
- Falloon 1998
3. In next 30 minutes..
• History
• Concepts
• Prodrome, DUP,ARMS.
• Neurobiology of onset of FEP
• Assessment
• Management
• Guidelines
4. DUNEDIN PROSPECTIVE STUDY
• Minor quasi-psychotic symptoms are more likely to
be manifested by children who are destined to
develop schizophrenia later as early as 11 yrs of age
• Follow up of 15 yrs
• Strength/frequency progresses prodrome
• 25% of children who endorsed 2 or more of 5
questions qualified for a diagnosis of Schizophrenia
@26yrs (vs 2% Odds 16.1)
Poulton 2000 Archives of Gen. Psy.
5. HISTORY
• Entangled with Schizophrenia
• Diagnostic dilemmas in FEP
• Focus on established psychosis
• Focus on chronic patients
• Shifting focus on drug naïve patients
• Arrival of S G A
6. FEP – EVOLUTION
• Johnston and Crow – Northwick Park
Study – B J P 1986
• EPPIC – Melbourne
• TIPS – Denmark
• EIS- Birmingham UK
• EPP and PEPP –Canada
• Hong Kong and Singapore
7. CURRENT SCENARIO
• IEPA – Newcastle Declaration – 2002
(Edwards and Mc Gorry)
• Public health importance
• Advocacy
• NHS has recognized it as one of the three
priority areas – 50 Early Intervention
Services have started in UK
• Scenario in INDIA ?
8. FEP?
• Include all non- organic psychosis
• Polymorphic presentation
• Embrace or at least tolerate diagnostic uncertainties
• F23 20,21,22,25,29,31
• Pre-psychotic stages – PMP,UHR, ARMS, Prodrome
• Watchful expectancy but NOT masterly inactivity!
9. Diagnostic Stability
• 142 FEP cases (which excluded Bipolar
Disorders) in an Estonian study (Lass J et. al
2008 J Cl Ph and Ther)
• F20= 26
• F21=3
• F22=17
• F23=80
• F25=11
• F28=3
• F29=2
10. Critical Period
• First Episode is the “critical period” for
intervention
• Untreated psychosis may be biologically
toxic to brain ( Wyatt1993 BJP).
Deterioration occurs aggressively in the
first 2-3 years and plateaus by 5 years.
• Timely intervention at this stage might alter
the subsequent course of the illness
(Birchwood 1998)
15. NAPLS( North America Prodrome
Longitudinal Study)
• Mc Glashan et al (Schiz Res 2008 v 98)
• 291 clinically at risk patients 30 month follow up
(SIPS) 35% conversion into psychosis
• Predictive power increased to 68% when,
positive FH, substance abuse and impairment in
social functioning were also included
• Argues for inclusion of Prodrome in DSM V
• Hypopsychosis ( Larsen T K 2004)
• BLIPS – Brief Limited Intermittent Psychotic
Symptoms
17. DUP and outcome of FEP
• Worse outcome when DUP> 3/12
• In schizophrenic spectrum subgroup, DUP
> 1 year
• Beyond this watershed deficits endure
• DUP has emerged as an independent
predictor for short, medium and long term
outcome
• An 8 year prospective study (MG Harris –
Melbourne – Schiz Res 2005)
19. UHR/ARMS FEP
• AFFECTIVE SYMPTOMS-
DEPRESSION, SOCIAL ANXIETY
• ANXIETY FACILITATES DEVELOPMENT
OF ABERRANT COGNITIVE SCHEMES
AND BELIEFS
• INFLUENCE ANOMALOUS
EXPERIENCE & MAINTENANCE OF
DELUSIONS
(Freeman & Garety 2003)
20. Social Factors FEP
• URBAN BIRTH & UPBRINGING
• MIGRATION
• SOCIAL ADVERSITIES
– SOCIAL ISOLATION SENSITIZATION OF
DA SYSTEM (Boydell 2004)
– GOING DOWN IN SOCIAL HEIRARCHY
HYPERDOPAMINERGIC
STATE(Morgan2002)
21. DOPAMINERGIC SENSITIZATION BY
PSYCHOACTIVE DRUGS
• REPEATED EXPOSURE SENSITIZATION
• GENETICALLY AND DEVELOPMENTALLY VULNERABLE individuals
are prone.
• POLYMORPHISM IN COMT GENE INCREASES THE RISK OF
PSYCHOSIS INDUCED BY CANNABIS ( Caspi 2005)
• MESO-LIMBIC – CORTICAL – STRIATAL CIRCUITS ARE PRONE TO
SENSITIZATION
(Liebermann 2001 Biol. Psychiatry)
22. DA – THE WIND OF THE PSYCHOTIC
FIRE
Affectively
Neutral
Stimuli
Attractive
or
Aversive
M L D A
Hedonic vector
Providing salience / Significance
(Shitij Kapur – AJP 2003 Psychosis as Aberrant Salience)
23. PSYCHOSIS AS ABERRANT SALIENCE
MLDA PFC
HC AMG
(MS Kesavan 2002, Grace 2004)
• Normal
– HC sets current
environmental stimuli in
the background of
previous experiences
– Allows only appropriate
response patterns to
MLDA
• Psychosis
– Amygdaloid over ride
– Loss of PFC ‘ break’
– ↑MLDA
– ABERRANT SALIENCE
24. Psycho(neurobio)logy of Delusional
Reasoning
• MEANINGFULCONNECTIONS ARE
ESTABLISHED BETWEEN COINCIDENT
EXTERNAL EVENTS/PERCEPTIONS
AND THOUGHTS /EVENTS/
RECOLLECTIONS IN CONSCIOUSNESS
(Hemsley 1993)
• HC MLDA system, heightened DA
transmission formation of “meaningful
connections”
25. WORKING MEMORY TRANSFER
HC (WM in children)
(Off load) (Transfer)
PFC (WM in Adolescence)
Dampens/Accentuates
emotional
AMG responsivity to
benign stimuli
Primary PFC dysfunction
↑sub cortical stress response
Structural damage to HC
Enhance DA in MLDA
Drugs & Social Adversity
26. BRAIN STRUCTURE IN FEP
• Sequential MRI studies – evidence of
subtle structural changes in genetically HR
cases and reduction in temporal lobe
structures in UHR status patients who
developed into FEP (Pantelis2005)
• Evidence for PROGRESSIVE
NEURODEGENRATIVE changes in first 2
years (Steen RG BJP 2006,v188)
27. Structural brain changes in FEP
• Progressive structural brain changes occur
at / immediately before FEP (Phillips2002)
• Stress high cortisol levels (HPA
acivation) HC volume reduction &
Pitutary volume increrase
• ? Consequence
• Also demonstrated in UHR patients
(Pariante2004)
28. WHAT CAUSES FEP?
FAULTY GENES
↓
INSULTS DURING NEURODEVELOPMENT
↓
EXPOSURE TO ADVERSITIES/STRESS/DRUGS DURING
ADOLESCENCE
↓
ABERRANT PRUNING
DOPAMINE DYSREGULATION
29. WHAT CAUSES FEP?
↓
DA INDUCED MISINTERPRETATION OF
ENVIRONMENT
↓
ABNORMAL PERCEPTUAL EXPERIENCE
↓
BIASED COGNITIVE APPRAISAL
PROCESSES
31. PRINCIPLES FOR BEST PRACTICE
MANAGEMENT OF FIRST EPISODE
PSYCHOSIS
• A strategy for early detection and
assessment of frank psychosis
• A specific focus on therapeutic engagement
• A comprehensive assessment
• An embracing of diagnostic uncertainty
• Treatment in the least restrictive setting
using low-dose medication
32. AIMS IN THE MANAGEMENT OF FIRST
EPISODE PSYCHOSIS
• To reduce the time between onset of psychotic
symptoms and effective treatment
• To accelerate remission through effective
biological and psychosocial interventions
• To reduce the individual’s adverse reactions to the
experience of psychosis and to maximize social
and work functioning
• To prevent relapse and treatment resistance
33.
34.
35.
36.
37. RECOMMENDATIONS FOR PHARMACO-
THERAPY OF FIRST EPISODE PSYCHOSIS
1. An antipsychotic-free observation period
2. A low threshold for the use of atypical
antipsychotic medications
3. The use of low-dose Antipsychotics plus
benzodiazepines
4. The aim of remission
5. Early assessment of treatment resistance
6. Maintenance of medication for at least 1– 2 years
in non-affective psychosis (except in some cases
with short duration of untreated psychosis)
38. NICE Guidelines (UK)
• Low dose Atypical AP
• Do Not use loading dose
• Conventional AP 300- 1000mg/day of CPZ
equivalent
• Avoid polypharmacy except when
switching
• For rapid tranquillization, i/m Lorazepam,
HPL and OLZ
52. Psychosocial treatments in FEP
• Multimodal interventions – COP
• Single Element Interventions –CBT
• 2 RCTs – CRATES – (cognitive reality
alignment therapy in early schizophrenia)-
Lewis and Tarrier- short term and medium
term outcome -2002 & 2004 – BJP
• No difference in persisting symptoms,
nonadherence, relapse or rehospitalization
• Adaptation to illness and subjective QoL
53. CBT in Prodrome / ARMS
• CBT alone in prodrome RCT
(Morrison2004)
• CBT + RSPD ( Mc Gorry2002)
• Significant effect on transition rates to
psychosis- 22% vs 6% and 36% vs 10%
• Disorder specific and phase specific
models of CBT
• MANUAL OF CBT for IHR – French &
Morrison 2004
54. Take Home
• It is crucial to identify psychosis even in the
prodrome
• The neurobiological mechanisms of onset of
psychosis integrates biology and cognitive
psychology
• Bringing down the DUP can have beneficial
outcome in the short and long course
• Guidelines for pharmacological and
psychosocial treatments need to be developed
and followed for optimal care of FEP
• Need to develop dedicated services for FEP
55. Suggested reading
1.What causes the onset of Psychosis?
(M R Broome et al Schiz Res 79(2005)
2.Management of FEP
(E Spencer, M Birchwood Adv Psych Treatment (2001)vol7)
3.Understanding and Treating FES
(Peter J Weiden, Peter f Buckley PCNA 30(2007)
4. Neurodevelopmental theory of Schizophrenia (MS Kesavan et al in
APA Text Book of Schizophrenia 2006 Ed J A Lieberman)
5. Psychosocial treatment of FEP: A research update
( David P Lenn et al AJP 2005 (162)
6. Pharmacological treatment of FES
(Robinson DG Schiz Bulletin 2005)
