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The GAP multidisciplinary study carried out in South London, recruited 410 first episode of psychosis patients and 370 controls; the aim was to elucidate the multiple genetic and environmental factors influencing the onset and outcome of psychosis. The study demonstrated the risk increasing effect of adversity in childhood (especially parental loss, abuse, and bullying) on onset of psychosis especially positive symptoms. Adverse life events more proximal to onset, being from an ethnic minority, and cannabis use also played important roles; indeed, one quarter of new cases of psychosis could be attributed to use of high potency cannabis. The "jumping to conclusions" bias appeared to mediate the effect of lower IQ on vulnerability to psychosis. We confirmed that environmental factors operate on the background of polygenic risk, and that genetic and environment act together to push individuals over the threshold for manifesting the clinical disorder. The study demonstrated how biological pathways involved in the stress response (HPA axis and immune system) provide important mechanisms linking social risk factors to the development of psychotic symptoms. Further evidence implicating an immune/inflammatory component to psychosis came from our finding of complement dysregulation in FEP. Patients also showed an upregulation of the antimicrobial alpha-defensins, as well as differences in expression patterns of genes involved in NF-κB signaling and Cytokine Production. Being of African origin not only increased risk of onset but also of a more difficult course of illness. The malign effect of childhood adversity predicted a poorer outcome as did continued use of high potency cannabis., Competing Interests: Declaration of competing interest Robin Murray has received honoraria for lectures from Janssen, Lundbeck, Sunovian, Otsuka, Angelini., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aims: Cognitive impairment is a possible indicator of neurodevelopmental impairment, but not all psychotic patients are cognitively compromised. It has been suggested that heavy cannabis use may precipitate psychosis in those who show no such compromise. This study compares two samples of patients with first-episode psychosis and their respective non-psychotic controls, in London (UK) and Palermo (Italy), and examines whether different patterns of cannabis use are reflected in differences in IQ., Methods: The two studies used the same inclusion/exclusion criteria and instruments. The sample comprised 249 subjects from London (106 patients and 143 controls) and 247 subjects from Palermo (120 patients and 127 controls). ANCOVA was performed with IQ as the dependent variable and city and frequency of cannabis use as predictors. This was then repeated with the case group only, by adjusting for relevant confounders., Results: We found a greater amount of cannabis use in the London sample, compared to Palermo and patients from London had higher IQ than patients from Palermo, a difference that was more significant than that reflected between controls (F group*city (1, 402) = 7.6, p = 0.006). Once corrected for symptomatology and treatment, patients from London who had never used cannabis were similar to patients from Palermo regarding IQ. Thus the higher IQ of patients from London was mainly due to the subgroup of cannabis-using patients (F cannabis*city (2,145) = 4.6, p = 0.011)., Conclusions: We can speculate that a greater amount of cannabis-use may have contributed by precipitating psychosis in patients with a higher IQ in London but less so in patients from Palermo., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Aim: 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., Methods: Up to 231 individuals presenting for the first time to mental health services with psychotic disorders and 214 unaffected population controls from South London, United Kingdom, were recruited as part of the Genetics and Psychosis study. Information about history of cannabis use was collected using the Cannabis Experiences Questionnaire. Childhood physical and sexual abuse was assessed using the Childhood Experience of Care and Abuse Questionnaire., Results: Neither lifetime cannabis use nor reported exposure to childhood abuse was associated with psychotic disorder when the other environmental variable was taken into account. Although the combination of the two risk factors raised the odds for psychosis by nearly three times (adjusted OR = 2.94, 95% CI: 1.44-6.02, P = 0.003), no evidence of interaction was found (adjusted OR = 1.46, 95% CI: -0.54 to 3.46, P = 0.152). Furthermore, the association of high-potency cannabis and daily consumption with psychosis was at least partially independent of the effect of childhood abuse., Conclusions: The heavy use of high-potency cannabis increases the risk of psychosis but, in addition, smoking of traditional resin (hash) and less than daily cannabis use may increase the risk for psychosis when combined with exposure to severe childhood abuse., (© 2015 Wiley Publishing Asia Pty Ltd.)