Background Cannabis use is associated with increased risk of later psychotic disorder but whether it affects incidence of the disorder remains unclear. We aimed to identify patterns of cannabis use with the strongest effect on odds of psychotic disorder across Europe and explore whether differences in such patterns contribute to variations in the incidence rates of psychotic disorder. Methods We included patients aged 18-64 years who presented to psychiatric services in 11 sites across Europe and Brazil with first-episode psychosis and recruited controls representative of the local populations. We applied adjusted logistic regression models to the data to estimate which patterns of cannabis use carried the highest odds for psychotic disorder. Using Europe-wide and national data on the expected concentration of Δ⁹-tetrahydrocannabinol (THC) in the different types of cannabis available across the sites, we divided the types of cannabis used by participants into two categories: low potency (THC <10%) and high potency (THC ≥10%). Assuming causality, we calculated the population attributable fractions (PAFs) for the patterns of cannabis use associated with the highest odds of psychosis and the correlation between such patterns and the incidence rates for psychotic disorder across the study sites. Findings Between May 1, 2010, and April 1, 2015, we obtained data from 901 patients with first-episode psychosis across 11 sites and 1237 population controls from those same sites. Daily cannabis use was associated with increased odds of psychotic disorder compared with never users (adjusted odds ratio [OR] 3•2, 95% CI 2•2-4•1), increasing to nearly five-times increased odds for daily use of high-potency types of cannabis (4•8, 2•5-6•3). The PAFs calculated indicated that if high-potency cannabis were no longer available, 12•2% (95% CI 3•0-16•1) of cases of first-episode psychosis could be prevented across the 11 sites, rising to 30•3% (15•2-40•0) in London and 50•3% (27•4-66•0) in Amsterdam. The adjusted incident rates for psychotic disorder were positively correlated with the prevalence in controls across the 11 sites of use of high-potency cannabis (r = 0•7; p=0•0286) and daily use (r = 0•8; p=0•0109). Interpretation Differences in frequency of daily cannabis use and in use of high-potency cannabis contributed to the striking variation in the incidence of psychotic disorder across the 11 studied sites. Given the increasing availability of high-potency cannabis, this has important implications for public health.

Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype.

Background/Objective: The heterogeneous clinical presentations of individuals with Autism Spectrum Disorders (ASD) pose a significant challenge for sample characterization. Therefore the main goal of DSM-5 must be to identify subgroups of ASD, including comorbidity disorders and severity. The main goal of this study is to explore the psychiatric comorbidities and the severity of symptoms that could be relevant for the phenotype characterization in ASD and also to compare these results according to the different classification criteria between the DSM-IV-TR and the DSM-5. Method: A comparative study of severity and psychiatric comorbidities was carried out between a sample of participants that only met criteria for Pervasive Developmental Disorder (PDD) according to the DSM-IV-TR and a sample of participants that also met ASD criteria according to DSM-5 classification. The recruitment of children was via educational (N = 123). The psychiatric symptoms, comorbid disorders and severity of symptoms were assessed through The Nisonger Child Behavior Rating Form, clinical interview and The Inventory of Autism Spectrum Disorder, respectively. The psychiatric comorbidities considered were: anxiety, eating behavioural problems, self-aggressiveness, hetero–aggressiveness, self-harm, obsessive compulsive disorder and attention deficit and hyperactivity disorder. Results: Statistically significant differences between both groups were found regarding obsessive compulsive disorder, eating behavioural problems and severity. Conclusions: The results support the hypothesis that patients who meet the DSM-5 criteria have more severe symptoms, not only regarding the core autistic symptoms but also in relation with psychiatric comorbidities.

The aims of this study were to examine the nature and extent of cognitive impairment in first-episode early-onset psychosis (FE-EOP) soon after their stabilisation and to search for potential differences according to specific diagnostic sub-groups of patients. As part of a Spanish multicentre longitudinal study, 107 FE-EOP patients and 98 healthy controls were assessed on the following cognitive domains: attention, working memory, executive functioning, and verbal learning and memory. Three diagnostic categories were established in the patient sample: schizophrenia (n = 36), bipolar disorder (n = 19), and other psychosis (n = 52). Patients performed significantly worse than controls in all cognitive domains. The three diagnostic sub-groups did not differ in terms of impaired/preserved cognitive functions or degree of impairment. FE-EOP patients show significant cognitive impairment that, during this early phase, seems to be non-specific to differential diagnosis.

To investigate the relationship between cognition and prior cannabis use in children and adolescents presenting a first episode of psychosis. A total of 107 patients with first episode of psychosis and 96 healthy controls, aged 9 to 17 years, were interviewed about their previous substance use and to assess their cognitive functions. Patients were assessed while not using cannabis by means of a comprehensive neuropsychological battery. They were divided into 2 groups depending on the history of prior cannabis use: cannabis users (CU) and cannabis nonusers (CNU). Significant differences were found in all areas evaluated between the 3 groups. Both CU and CNU patients obtained lower scores than controls on verbal learning and memory and working memory. Patients with prior cannabis use performed better on some tests of attention (Continuous performance test (CPT) number of correct responses, p = 0.002; CPT average reaction time, p < 0.001) and executive functions (Trail Making Test, part B (TMT-B) number of mistakes, p < 0.001; Wisconsin Card Sorting Test (WCST) number of categories completed, p < 0.001) than CNU patients. CU patients performed better than CNU subjects on some cognitive measures. This may indicate lower individual vulnerability for psychosis in CU patients in whom cannabis use can be a precipitating factor of psychotic episodes.

Despite the greater reduction of NSS in patients than in controls along the follow-up, patients still have more neurological signs than healthy controls; therefore, these signs may be considered a trait marker. NSS do not seem to be specific to schizophrenia as they are present in different EOPs.

NSS are more prevalent in Asperger syndrome than in healthy controls. The NSS profile was not disorder-specific in our samples of patients with Asperger syndrome and early-onset psychoses.

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