Prodrome of psychosis

Dr Naren Rao
 Prodrome
 heterogeneous group of behaviors temporally related to the onset of psychosis
(Keith and Matthews 1991)
 time interval from the onset of unusual behavioral symptoms to onset of psychotic
symptoms (Loebel et al. 1992)
 duration of time, starting with the onset of decline in the baseline level of
functioning and ending at the time when the criteria for a schizophrenia spectrum
diagnosis are met
 Evolution of symptoms
 Non specific changes  specific prepsychotic symptoms  psychosis
 specific prepsychotic symptoms  neurotic reaction to these changes  psychosis
 Terminology
 Ultrahigh risk
 At-risk mental state
 Clinical high risk
 Psychosis risk syndrome
 Attenuated positive symptoms
 genetic risks and deterioration
 brief-limited psychotic symptoms
 Schizotypal personality
 Assessment measures
 Instrument for the retrospective assessment of onset of schizophrenia -Hafner et al.
1992
 Bonn Scale for the assessment of basic symptoms-Huber et al. 1980
 3. Structured Interview for Prodromal Symptoms (SIPS)- McGlashan 1996
 4. Scale for prodromal symptoms (SOPS) -McGlashan 1996
 5. Multidimensional assessment of psychotic prodrome - Yung and McGory 1996
 6. Comprehensive assessment of ARMS (CAARMS) by McGory et al. 2003.
 Clinical features
 Non-specific
 Differentiating features
 Bipolar - Poor peer relationships, social withdrawal and amotivation
 Depression – flat affect, global decline, cognitive deficits, duration,
pervasiveness
 Personality disorder – BPD/ASPD can be identical
 Attenuated psychosis syndrome – DSM5
 At least one of the following symptoms are present in attenuated form with sufficient severity and/or frequency to warrant
clinical attention:
 delusions/delusional ideas
 hallucinations/perceptional abnormalities
 disorganized speech/communication
 Symptoms in Criterion A must be present at least once per week for the past month.
 Symptoms in Criterion A must have begun or worsened in the past year.
 Symptoms in Criterion A are sufficiently distressing and disabling to the individual and/or legal guardian to lead them to
seek help.
 Symptoms in Criterion A are not better explained by any other DSM-5 diagnosis, including Substance-Related Disorders.
 Clinical criteria for a Psychotic Disorder have never been met
 Conversion to schizophrenia
 20-35%
 Later decreased to 12%
Predictors of transition to psychosis
 Environmental risk factors
 Migration
 Increased striatal dopamine release in migrants
 Increased suspicion
 History of trauma
 Higher rates, but not consistently associated with transition to psychosis. Possible risk
 Cannabis use
 five times more likely to have a current cannabis use disorder compared with healthy
 Cannabis abuse and dependence, but not use, associated with transition to psychosis
 Urban upbringing - doubtful
 Cognitive deficits
 intermediate between healthy controls and first-episode psychosis
 Domains involved with risk of transition
 verbal memory and processing speed,
 verbal learning,
 verbal fluency,
 working memory
 Attention
 Social cognition - inconsistent
 Lower predictive power as it is non-specific
 Poor functioning
 Poor global functioning – predictor of transition
 poor premorbid functioning at late adolescence (16–18 years) has been found to be
associated with a later transition
 Structural Neuroimaging
 increased rate of gray matter loss, particularly in the frontal lobes is a risk factor for
transition
 Higher brain age than chronological age is a risk factor
 Abnormalities in cerebellum, lateral and medial temporal lobes, medial frontal
lobes, and striatum can predict the transition
 Abnormalities in gyrification
 fMRI
 hyperconnectivity in cerebello-thalamo-cortical circuit
 Increased connectivity between thalamus and sensorimotor regions
 Decreased connectivity between thalamus to frontal lobe and cerebellum

 At present, none of the neuroimaging findings can be used to identify CHR

individuals who will transition
 EEG
 most promising EEG parameter for predicting transition is mismatch negativity
 gamma band abnormalities – mixed evidence
 Current source density in resting EEG
 Predictors of conversion
 Higher levels of unusual thought content and suspiciousness
 decline in social functioning
 poorer verbal learning, memory and speed of processing
 younger age

 Clinical features still better than biomarkers

 What happens to those who don’t convert
 40% of ‘non-converters’ continue to experience one or more APS
 50% had anxiety or mood disorder
 Significant dysfunction
 Treatment

 PRIME trial
 2-year study – 1-year olanzapine vs placebo; 2nd year – no treatment
 16.1% of patients receiving olanzapine and 37.9% of patients receiving placebo
experienced a conversion to psychosis during the treatment year.
 conversion rate did not differ significantly between the two groups in the second
year
 Treatment
 German Research Network on Schizophrenia
 Amisulpride + need focused intervention vs need focused intervention
 Amisulpride + need focused intervention- better
 Treatment
 Recognition and Prevention program
 Antidepressant vs SGA
 Antidepressant group – none developed psychosis
 25% in SGA group developed psychosis
 Adherence was an issue with SGA group
 Treatment
 omega-3 polyunsaturated fatty acids (PUFAs) vs placebo
 2800 mg of eicosapentaenoic acid and 1920 mg of docosahexaenoic acid per day
 1-year study (12 weeks trial followed by 40 weeks monitoring)
 At the end of 1 year, conversion to psychosis
 4.9% - Omega 3 PUFA
 27.5% - Placebo group
 Treatment
 EDIE trial - Early Detection and Intervention Evaluation
 cognitive therapy vs monitoring
 1 – year study with 6 month treatment – cognitive therapy better
 3-year follow up – still better
 Conclusions
 Prodrome - non specific concept
 DDs to be considered
 Specific instruments will help in diagnosis
 Lowe level of functioning, negative symptoms and baseline positive symptoms – better
predictors
 Even those who don’t convert – have non-specific symptoms
 Omega-3 fatty acids, SGA, antidepressants, cognitive therapy are likely to be helpful
 Individualized treatment decision in the absence of definite evidence