Patients who recover from an acute episode of psychosis are frequently prescribed prophylactic antipsychotics for many years, especially if they are diagnosed as having schizophrenia. However, there ...is a dearth of evidence concerning the long-term effectiveness of this practice, and growing concern over the cumulative effects of antipsychotics on physical health and brain structure. Although controversy remains concerning some of the data, the wise psychiatrist should regularly review the benefit to each patient of continuing prophylactic antipsychotics against the risk of side-effects and loss of effectiveness through the development of supersensitivity of the dopamine D2 receptor. Psychiatrists should work with their patients to slowly reduce the antipsychotic to the lowest dose that prevents the return of distressing symptoms. Up to 40% of those whose psychosis remits after a first episode should be able to achieve a good outcome in the long term either with no antipsychotic medication or with a very low dose.
Epidemiological evidence demonstrates that cannabis use is associated with an increased risk of psychotic outcomes, and confirms a dose‐response relationship between the level of use and the risk of ...later psychosis. High‐potency cannabis and synthetic cannabinoids carry the greatest risk. Experimental administration of tetrahydrocannabinol, the active ingredient of cannabis, induces transient psychosis in normal subjects, but this effect can be ameliorated by co‐administration of cannabidiol. This latter is a constituent of traditional hashish, but is largely absent from modern high‐potency forms of cannabis. Argument continues over the extent to which genetic predisposition is correlated to, or interacts with, cannabis use, and what proportion of psychosis could be prevented by minimizing heavy use. As yet, there is not convincing evidence that cannabis use increases risk of other psychiatric disorders, but there are no such doubts concerning its detrimental effect on cognitive function. All of the negative aspects are magnified if use starts in early adolescence. Irrespective of whether use of cannabis is decriminalized or legalized, the evidence that it is a component cause of psychosis is now sufficient for public health messages outlining the risk, especially of regular use of high‐potency cannabis and synthetic cannabinoids.
We performed a systematic analysis of blood DNA methylation profiles from 4483 participants from seven independent cohorts identifying differentially methylated positions (DMPs) associated with ...psychosis, schizophrenia, and treatment-resistant schizophrenia. Psychosis cases were characterized by significant differences in measures of blood cell proportions and elevated smoking exposure derived from the DNA methylation data, with the largest differences seen in treatment-resistant schizophrenia patients. We implemented a stringent pipeline to meta-analyze epigenome-wide association study (EWAS) results across datasets, identifying 95 DMPs associated with psychosis and 1048 DMPs associated with schizophrenia, with evidence of colocalization to regions nominated by genetic association studies of disease. Many schizophrenia-associated DNA methylation differences were only present in patients with treatment-resistant schizophrenia, potentially reflecting exposure to the atypical antipsychotic clozapine. Our results highlight how DNA methylation data can be leveraged to identify physiological (e.g., differential cell counts) and environmental (e.g., smoking) factors associated with psychosis and molecular biomarkers of treatment-resistant schizophrenia.
Aims Previous population-based studies have identified suicidal ideation (SI) as a potential risk marker for psychosis. We aimed to investigate the prevalence of previous SI in a large sample of ...patients with first episode of psychosis accepted to early intervention services (EIS) in South London and Maudsley (SLaM) NHS Foundation Trust using clinical records. We further aimed to investigate differences in patients with and without recorded SI according to age at diagnosis, gender, ethnicity and neighbourhood deprivation. Methods We designed a retrospective cohort using the Clinical Record Interactive System. Included were patients who were accepted by SLaM EIS from 2015–2018 and received a psychotic disorder diagnosis (n = 1658). We used a natural language processing algorithm that searches deidentified textual clinical records, returning a binary variable indicating presence or absence of SI recorded at any time prior to acceptance to EIS. The algorithm has high precision (97%) and inter-rater reliability (Cohen's k 92%). The t-test was used to compare mean age at first diagnosis in patients with and without recorded SI, while chi-squared tests evaluated differences according to gender, ethnicity and tertiles of index of multiple deprivation (based on 2015 postcode). The significance threshold was p = 0.05. Results The cohort included 1658 patients, of whom 656 (39.6%) were female. The natural language processing algorithm identified 600 patients (36.2%) who had SI recorded in their clinical records at any time prior to acceptance by EIS. On average, patients with recorded SI were younger at first diagnosis of psychotic disorder (mean 27.7 years, standard deviation 10.5) compared with patients without recorded SI (mean 30.1 years, standard deviation 11.2; p < 0.001). There was little evidence for differences on gender (p = 0.950), ethnicity (p = 0.059) or deprivation index (p = 0.597). Conclusion Approximately 1 in 3 patients attending SLaM EIS had evidence of SI recorded prior to acceptance by EIS. Consistent with previous studies, the current findings emphasise the high prevalence of SI in this clinical population. Compared with those without SI, patients with recorded SI were on average 2–3 years younger at diagnosis. This may reflect general population age differences in prevalence of suicidal ideation; increased severity of illness with earlier age of onset; or patterns of contact with services which facilitated earlier diagnosis. There was little evidence that patients with and without recorded SI differed significantly on gender, ethnicity or neighbourhood deprivation. Prospective studies would be helpful to assess whether SI is a risk marker for first episode of psychosis.
Purpose
The EUropean Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI) study contains an unparalleled wealth of comprehensive data that allows for testing ...hypotheses about (1) variations in incidence within and between countries, including by urbanicity and minority ethnic groups; and (2) the role of multiple environmental and genetic risk factors, and their interactions, in the development of psychotic disorders.
Methods
Between 2010 and 2015, we identified 2774 incident cases of psychotic disorders during 12.9 million person-years at risk, across 17 sites in 6 countries (UK, The Netherlands, France, Spain, Italy, and Brazil). Of the 2774 incident cases, 1130 cases were assessed in detail and form the case sample for case–control analyses. Across all sites, 1497 controls were recruited and assessed. We collected data on an extensive range of exposures and outcomes, including demographic, clinical (e.g. premorbid adjustment), social (e.g. childhood and adult adversity, cannabis use, migration, discrimination), cognitive (e.g. IQ, facial affect processing, attributional biases), and biological (DNA via blood sample/cheek swab). We describe the methodology of the study and some descriptive results, including representativeness of the cohort.
Conclusions
This resource constitutes the largest and most extensive incidence and case–control study of psychosis ever conducted.
Although cannabis use after a first episode of psychosis has been associated with relapse, little is known about the determinants of this most preventable risk factor for relapse of psychosis. Here ...we aimed to study whether the effects on outcome vary depending on the type of cannabis consumed and usage pattern.
In this observational study, we prospectively recruited and followed up patients aged 18–65 years who presented with their first episode of psychosis to psychiatric services in south London, London, UK. Relapse of psychosis within 2 years after onset of psychosis was defined as risk of subsequent admission to hospital. We classified patients into different patterns of cannabis use based on continuity of use after onset of psychosis, potency of cannabis consumed, and frequency of use after the onset of their illness. We used multiple regression analyses (logistic or binominal) to compare the different cannabis use groups and propensity score analysis to validate the results.
Between April 12, 2002, and July 26, 2013, 256 patients presented with a first episode of psychosis. We did follow-up assessments for these patients until September, 2015. Simple analyses showed that former regular users of cannabis who stopped after the onset of psychosis had the most favourable illness course with regards to relapse. In multiple analysis, continued high-frequency users (ie, daily use in all 24 months) of high-potency (skunk-like) cannabis had the worst outcome, indexed as an increased risk for a subsequent relapse (odds ratio OR 3·28; 95% CI 1·22–9·18), more relapses (incidence rate ratio 1·77; 95% CI 0·96–3·25), fewer months until a relapse occurred (b −0·22; 95% CI −0·40 to −0·04), and more intense psychiatric care (OR 3·16; 95% CI 1·26–8·09) after the onset of psychosis.
Adverse effects associated with continued use of cannabis after the onset of a first episode of psychosis depend on the specific patterns of use. Possible interventions could focus on persuading cannabis-using patients with psychosis to reduce use or shift to less potent forms of cannabis.
National Institute for Health Research (NIHR).
Background
Psychosis rates are higher among some migrant groups. We hypothesized that psychosis in migrants is associated with cumulative social disadvantage during different phases of migration.
...Methods
We used data from the EUropean Network of National Schizophrenia Networks studying Gene-Environment Interactions (EU-GEI) case-control study. We defined a set of 3 indicators of social disadvantage for each phase: pre-migration, migration, and post-migration.
Results
249 cases and 219 controls were assessed. Pre-migration (OR 1.61, 95%CI 1.06-2.44, p=0.027) and postmigration social disadvantages (OR 1.89, 95%CI 1.02-3.51, p=0.044), along with expectations/achievements mismatch (OR 1.14, 95%CI 1.03-1.26, p=0.014) were all significantly associated with psychosis. We found a dose-response effect between number of adversities across all phases and odds of psychosis (≥6: OR 14.09, 95%CI 2.06-96-47, p=0.007).
Conclusions
The cumulative effect of social disadvantages before, during and after migration was associated with increased odds of psychosis in migrants, independently of ethnicity or length of stay in the country of arrival. Public health initiatives that address the social disadvantages that many migrants face during the whole migration process and post-migration psychological support may be reduce the excess of psychosis in migrants.
Disclosure of Interest
None Declared
Jumping to conclusions (JTC), which is the proneness to require less information before forming beliefs or making a decision, has been related to formation and maintenance of delusions. Using data ...from the National Institute of Health Research Biomedical Research Centre Genetics and Psychosis (GAP) case-control study of first-episode psychosis (FEP), we set out to test whether the presence of JTC would predict poor clinical outcome at 4 years.
One-hundred and twenty-three FEP patients were assessed with the Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF) and the probabilistic reasoning 'Beads' Task at the time of recruitment. The sample was split into two groups based on the presence of JTC bias. Follow-up data over an average of 4 years were obtained concerning clinical course and outcomes (remission, intervention of police, use of involuntary treatment - the Mental Health Act (MHA) - and inpatient days).
FEP who presented JTC at baseline were more likely during the follow-up period to be detained under the MHA adjusted OR 15.62, 95% confidence interval (CI) 2.92-83.54, p = 0.001, require intervention by the police (adjusted OR 14.95, 95% CI 2.68-83.34, p = 0.002) and have longer admissions (adjusted IRR = 5.03, 95% CI 1.91-13.24, p = 0.001). These associations were not accounted for by socio-demographic variables, IQ and symptom dimensions.
JTC in FEP is associated with poorer outcome as indicated and defined by more compulsion police intervention and longer periods of admission. Our findings raise the question of whether the implementation of specific interventions to reduce JTC, such as Metacognition Training, may be a useful addition in early psychosis intervention programmes.
Epidemiological and biological evidence support the association between heavy cannabis use and psychosis. However, it is unclear which cannabis users are susceptible to its psychotogenic effect. ...Therefore, understanding genetic factors contributing to this relationship might prove an important strategy to identify the mechanisms underlying cannabis-associated psychotic experiences. We aimed to determine how variation in AKT1, COMT and FAAH genotypes, and their interaction with three different groups (first episode psychosis (FEP) patients (n = 143), controls (n = 92) and young adult (YA) cannabis users n = 485)) influenced cannabis experiences, in those who had used cannabis at least once. We investigated the role of AKT1 (rs2494732), COMT Val158Met (rs4680) and FAAH (rs324420) on cannabis experiences by combining data from a large case-control study of FEP patients, with a naturalistic study of YA cannabis users (n = 720). Outcome measures were cannabis-induced psychotic-like experiences (cPLEs) and euphoric experiences (cEEs). We used linear mixed effects models to assess the effects of each genotype and their interaction with group, adjusting for age, sex, ethnicity, age of first cannabis use, years of use and frequency. cPLEs were more frequent in FEP patients than controls and YA cannabis users. cEEs were more prevalent in YA cannabis users than FEP patients or controls. Variation in AKT1, COMT or FAAH was not associated with cPLEs/cEEs. There was no interaction between genotype and group (FEP cases, controls and YA cannabis users) on cPLEs/cEEs. In conclusion, AKT1, COMT or FAAH did not modulate specific psychotomimetic response to cannabis and did not interact with group, contrary to previous research.
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