Jennifer O'Connor

Proportion of patients in south London with first-episode psychosis attributable to use of high potency cannabis: a case-control study

BACKGROUND The risk of individuals having adverse effects from drug use (eg, alcohol) generally depends on the frequency of use and potency of the drug used. We aimed to investigate how frequent use of skunk-like (high-potency) cannabis in south London affected the association between cannabis and psychotic disorders. METHODS We applied adjusted logistic regression models to data from patients aged 18-65 years presenting to South London and Maudsley NHS Foundation Trust with first-episode psychosis and population controls recruited from the same area of south London (UK) to estimate the effect of the frequency of use, and type of cannabis used on the risk of psychotic disorders. We then calculated the proportion of new cases of psychosis attributable to different types of cannabis use in south London. FINDINGS Between May 1, 2005, and May 31, 2011, we obtained data from 410 patients with first-episode psychosis and 370 population controls. The risk of individuals having a psychotic disorder showed a roughly three-times increase in users of skunk-like cannabis compared with those who never used cannabis (adjusted odds ratio [OR] 2·92, 95% CI 1·52-3·45, p=0·001). Use of skunk-like cannabis every day conferred the highest risk of psychotic disorders compared with no use of cannabis (adjusted OR 5·4, 95% CI 2·81-11·31, p=0·002). The population attributable fraction of first-episode psychosis for skunk use for our geographical area was 24% (95% CI 17-31), possibly because of the high prevalence of use of high-potency cannabis (218 [53%] of 410 patients) in our study. INTERPRETATION The ready availability of high potency cannabis in south London might have resulted in a greater proportion of first onset psychosis cases being attributed to cannabis use than in previous studies. FUNDING UK National Institute of Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health, SLaM and the Institute of Psychiatry at Kings College London, Psychiatry Research Trust, Maudsley Charity Research Fund, and th European Communitys Seventh Framework Program grant (agreement No. HEALTH-F2-2009-241909 [Project EU-GEI]).

Neuropsychological, clinical and cognitive insight predictors of outcome in a first episode psychosis study

The outcome of first episode psychosis (FEP) is highly variable and difficult to predict. We studied prospectively the impact of poor insight and neuropsychological deficits on outcomes in a longitudinal cohort of 127 FEP patients. Participants were assessed on 5 domains of cognitive function and 2 domains of insight (clinical and cognitive). At 12 months, patients were assessed again for symptom severity and psychosocial function. Regression analyses revealed that cognitive insight (a measure of self-reflectiveness and self-certainty) was the best baseline predictor of overall psychopathology at 12 months whereas executive function performance at admission to the study indicated later severity of negative symptoms. Other neuropsychological and insight measures were poor predictors of psychosocial function at 1 year. The results suggest that specific neuropsychological and insight factors have separate predictive capacities indicating that they are distinct psychological processes in psychosis. Cognitive insight proved to be a useful prognostic indicator, and should be considered for future studies and as a potential focus for treatment.

Pre-morbid Conduct Disorder symptoms are associated with cannabis use among individuals with a first episode of psychosis

BACKGROUND Early cannabis use has consistently been associated with an increased risk for the later development of psychosis. Studies suggest that Conduct Disorder (CD) is more common amongst young people who later go on to develop psychosis. CD has been associated with greater and earlier cannabis use in general population samples. Based on this evidence, we hypothesised that among patients experiencing their first episode of psychosis, the presence of CD symptoms prior to age 15 would be associated with cannabis use. METHOD 102 patients experiencing a first episode of psychosis were interviewed to assess CD symptoms prior to age 15 and use of cannabis and other substances. RESULTS The number of CD symptoms was significantly associated with lifetime cannabis use (odds ratio=5.41 (1.76-16.57), p=0.03) and with first use of cannabis before age 14 (odds ratio=1.46 (1.12-1.92), p=0.006), after controlling for stimulant/hallucinogen use and level of education. CONCLUSIONS Among patients experiencing a first episode of psychosis, CD symptoms were significantly associated with use of cannabis and with use by age 14. Among individuals vulnerable for psychosis, CD symptoms may independently increase the likelihood of cannabis use which in turn increases the risk of psychosis.

Brain derived neurotropic factor (BDNF) is associated with childhood abuse but not cognitive domains in first episode psychosis

BACKGROUND The Brain-derived Neurotrophic Factor (BDNF) modulates cognitive processes and is associated with increased risk of schizophrenia. Childhood trauma (CT) is frequent in patients with psychosis and severely affects course and outcome. AIMS We investigated the hypothesis that BDNF is associated with both CT and cognitive deficits in a sample of first-episode psychosis (FEP) cases and unaffected controls. METHOD Participants with FEP and healthy controls were recruited between August 2008 and July 2011 from South London, UK. Childhood traumatic events were detected using the Childhood Experience of Care and Abuse Questionnaire (CECA-Q). Neuropsychological data were also collected. BDNF plasma levels were measured from fasting blood samples. RESULTS Data were available on 87 FEP patients and 152 controls. Our results showed a significant effect of separation (F=5.5; df=1,115; p=.02), physical (F=4.7; df=1, 118; p=.03) and sexual abuse (F=5.4; df=1,117; p=.02) on BDNF levels with lower levels among those who experienced the traumatic event compared to those who did not. Physical abuse predicted lower plasma levels of BDNF (β=-.30; p=.03) whereas sexual and/or physical abuse showed a trend (β=-.26; p=.06) in FEP patients but not in unaffected controls. No association between BDNF plasma levels and cognitive functions was found among patients with FEP and controls. CONCLUSION Our findings suggest the possible involvement of BDNF in the onset of first-episode psychosis in individuals exposed to early trauma and propose BDNF as a potential clinical biomarker to detect the detrimental effects of CT on human brain plasticity.

Are there specific neuropsychological deficits underlying poor insight in first episode psychosis

Insight in psychosis is a multi-dimensional phenomenon, and has been hypothesised to have some sort of neuropsychological basis. It is unclear to what extent specific neuropsychological abilities are able to predict insight beyond the effect of generalised cognitive ability. We aimed to test this association, alongside the relationship of insight with illness duration and diagnosis, in a sample of first episode psychosis patients. 110 first episode psychosis patients were recruited and a comprehensive assessment was administered, including insight, symptoms, diagnosis and neuropsychological function. Low insight was related to worse performance in a variety of neuropsychological tasks. Regression analysis tested whether any specific tasks were related to insight (or dimensions of insight) beyond the effect of IQ. Verbal memory had an effect on total insight and all dimensions of insight (except compliance) beyond the effect of IQ. Insight appeared to vary with diagnosis, with those diagnosed with depressive affective psychoses having better insight than those with manic affective psychoses. There was no relationship between insight and DUP, but there was a relationship between time spent in treatment before assessment and insight, even after controlling for severity of symptoms. These results suggest a model of insight in early psychosis with a significant neuropsychological component, particularly with verbal memory but also with generalised cognitive ability. There is likely to be a social component to insight affected by initial time spent in contact with treatment, helping patients to understand and come to terms with their illness.

Insight and suicidality in first-episode psychosis: understanding the influence of suicidal history on insight dimensions at first presentation

Lack of insight is a cardinal feature of psychosis with crucial implications for outcome. Concerns have been raised regarding a link between insight and suicidality. This study aimed to test the relationship between suicidal behaviour preceding first‐episode psychosis (FEP) and insight dimensions at treatment onset.

Interaction between cannabis consumption and childhood abuse in psychotic disorders: preliminary findings on the role of different patterns of cannabis use

Several studies have suggested that lifetime cannabis consumption and childhood abuse synergistically contribute to the risk for psychotic disorders. This study aimed to extend existing findings regarding an additive interaction between childhood abuse and lifetime cannabis use by investigating the moderating role of type and frequency of cannabis use.

Interaction between cannabis consumption and childhood abuse in psychotic disorders

Several studies have suggested that lifetime cannabis consumption and childhood abuse synergistically contribute to the risk for psychotic disorders. This study aimed to extend existing findings regarding an additive interaction between childhood abuse and lifetime cannabis use by investigating the moderating role of type and frequency of cannabis use.

Jumping to conclusions and the persistence of delusional beliefs in first episode psychosis.

BACKGROUND Cognitive biases may contribute to delusion persistence. We tested this in a longitudinal study of first episode psychosis (FEP). METHODS 34 FEP patients completed assessments of delusions and Jumping to Conclusions (JTC) at baseline and 12-month follow-up. RESULTS JTC was associated with baseline delusion severity (t(32)=2.7, p=0.01). Baseline delusions persisted at follow-up for 8/20 participants (40%), who all jumped to conclusions (8/8, 100%), compared to half of those with no or changeable delusions (14/26, 54%; χ(2) (df=1)=5.7, p=0.03; Phi=0.4). CONCLUSION Findings implicate cognitive biases in delusion persistence, and support the potential to reduce delusions through reasoning-focused interventions.

Cognitive impairment and subjective time in schizophrenics

Background: The large variation in individual clinical responses to antipsychotic treatment hampers the management of psychotic disorders. Genetic factors are considered a main cause of this variation. Pharmacogenetics studies have demonstrated significant associations between several candidate genes (a.o. D2, D3, 5HTR2A and 5HTR2C, GRM3, COMT and MTHFR) and the response to antipsychotic drugs. The present study investigates the effect of 12 polymorphisms for an association with antipsychotic treatment response in patients with a psychotic disorder. Methods: 335 Caucasian patients with a non-affective psychotic disorder using antipsychotics were included. All patients participated in the longitudinal GROUP-study in The Netherlands. We genotyped 12 SNPs in 7 candidate genes (DRD2: TaqI-A, TaqI-D, -141-C, C957T; DRD3: Ser9Gly; HTR2A: 102-T/C, His452Tyr; HTR2C: Cys23Ser, -759-T/C; COMT: Val108/158Met; MTHFR: 677-C/T, GRM3: rs274622) using standard protocols. Polymorphisms were based on previous studies showing associations with treatment response. The Clinical Global Impression- Schizophrenia scale was cross-sectionally used to assess improvement in positive psychotic symptoms since the start of current antipsychotic treatment. Ordinal regression was used to test for an association between polymorphisms and improvement in positive symptoms. All polymorphisms were tested in an additive model, with minor allele dose as the dependent variable. Results: Ninety percent of the patients used atypical antipsychotics, with olanzapine (31%) and risperidone (29%) being the most prescribed drugs. Ser9Gly of the dopamine D3 receptor gene (P value .029) and 677-C/T of MTHFR (P value .029) were tested significant. Gly carriers and T-carriers, respectively, showed better clinical improvement on the positive scale. All other polymorphisms did not show any association with treatment response (all P values >.10). Conclusion: We were able to replicate only two of the previously reported associations between polymorphisms and treatment response. Heterogeneity in patient samples and outcome variables as well as publication bias and false positive findings may all play a role in lack of replication, found in our study, as in others. The direction of the associations presented here in D3 (Ser9Gly) and MTHFR (677-C/T) are in line with previous association studies in Caucasian patients. These polymorphisms may be of value for predicting clinical response.