This document provides an overview of first episode psychosis (FEP), including its history, concepts, neurobiology, assessment, management, and guidelines. It discusses the prodromal phase and periods like the duration of untreated psychosis. Studies show minor quasi-psychotic symptoms can occur up to 11 years before schizophrenia onset. Prodromal states like the ultra-high risk and attenuated risk mental states are described, which have high transition rates to psychosis. Dopamine dysregulation and social and substance use factors are implicated in the onset of FEP. Assessment and management should follow a low-dose approach with psychosocial support to reduce time to treatment and maximize functioning.

1. FIRST EPISODE PSYCHOSIS

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)

11. Transitions involved in the trajectory
of FEP

13. UHR AND ARMS
• UHR Cognitive Dysfunction + Attenuated
Negative Sx+ Sub threshold Positive Sx
(Cornblatt 2001)
• ARMS = UHR+ Family History +
Schizotypal PMP + Decline in functioning
– 40% transition in 12 months (Young 2003)
– 33% transition in 6 months(Cornblatt2002)
– 22% transition in 6 months (Morrison2002)

14. Prodrome

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

16. DUP

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)

18. First Episode Psychosis

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

30. An integrative model of onset
(3 HIT MODEL)

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

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

39. Medications in FEP

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)