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Background and Hypothesis: Despite the accepted link between childhood adversity (CA) and psychotic disorders, evidence on the relationship between CA and poor functional outcome remains less consistent and has never been reviewed quantitatively. The aim of this meta-analysis was to systematically examine the association between CA and functional outcomes in people with psychotic disorders., Study Design: The study protocol was registered on the International Prospective Register of Systematic Reviews (CRD42021254201). A search was conducted across EMBASE, MEDLINE, PsycINFO, and Cochrane Libraries (CENTRAL) using search terms related to psychosis; CA (general, sexual abuse, physical abuse, emotional abuse, physical neglect, and emotional neglect); and functional outcomes (social, occupational, and general functioning [GF]). We conducted random-effects models, sensitivity and heterogeneity analyses, meta-regressions, and we assessed quality., Study Results: Our meta-analysis comprised 35 studies, including 10 568 cases with psychosis. General CA was negatively associated with GF (28 studies; r = -0.109, 95%CI = -0.161 to -0.05, P < .001), with greater effects in prospective data (10 studies; r = -0.151, 95% CI = -0.236 to -0.063, P = .001). General CA was also associated with social functioning (r = -0.062, 95% CI = -0.120 to -0.004, P = .018) but not occupational outcomes. All CA subtypes except sexual abuse were significantly associated with GF, with emotional and physical neglect showing the largest magnitudes of effect (ranging from r = -0.199 to r = -0.250)., Conclusions: This meta-analysis provides evidence for a negative association between general CA, specific subtypes, and general and social functional outcomes in people with psychosis., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Cluster studies identified a subgroup of patients with psychosis whose premorbid adjustment deteriorates before the onset, which may reflect variation in genetic influence. However, other studies reported a complex relationship between distinctive patterns of cannabis use and cognitive and premorbid impairment that is worthy of consideration. We examined whether: (1) premorbid social functioning (PSF) and premorbid academic functioning (PAF) in childhood and adolescence and current intellectual quotient (IQ) define different clusters in 802 first-episode of psychosis (FEP) patients; resulting clusters vary in (2) polygenic risk scores (PRSs) for schizophrenia (SCZ&#95;PRS), bipolar disorder (BD&#95;PRS), major depression (MD&#95;PRS), and IQ (IQ&#95;PRS), and (3) patterns of cannabis use, compared to 1,263 population-based controls. Four transdiagnostic clusters emerged (BIC = 2268.5): (1) high-cognitive-functioning (n = 205), with the highest IQ (Mean = 106.1, 95% CI: 104.3, 107.9) and PAF, but low PSF. (2) Low-cognitive-functioning (n = 223), with the lowest IQ (Mean = 73.9, 95% CI: 72.2, 75.7) and PAF, but normal PSF. (3) Intermediate (n = 224) (Mean&#95;IQ = 80.8, 95% CI: 79.1, 82.5) with low-improving PAF and PSF. 4) Deteriorating (n = 150) (Mean&#95;IQ = 80.6, 95% CI: 78.5, 82.7), with normal-deteriorating PAF and PSF. The PRSs explained 7.9% of between-group membership. FEP had higher SCZ&#95;PRS than controls [F(4,1319) = 20.4, P < .001]. Among the clusters, the deteriorating group had lower SCZ&#95;PRS and was likelier to have used high-potency cannabis daily. Patients with FEP clustered according to their premorbid and cognitive abilities. Pronounced premorbid deterioration was not typical of most FEP, including those more strongly predisposed to schizophrenia, but appeared in a cluster with a history of high-potency cannabis use., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Background and Hypothesis: Evidence suggests that childhood maltreatment (ie, childhood abuse and childhood neglect) affects educational attainment and cognition. However, the association between childhood maltreatment and Intelligence Quotient (IQ) seems stronger among controls compared to people with psychosis. We hypothesised that: the association between childhood maltreatment and poor cognition would be stronger among community controls than among people with first-episode of psychosis (FEP); compared to abuse, neglect would show stronger associations with educational attainment and cognition; the association between childhood maltreatment and IQ would be partially accounted for by other risk factors; and the association between childhood maltreatment, educational attainment, and IQ would be stronger among patients with affective psychoses compared to those with nonaffective psychoses., Study Design: 829 patients with FEP and 1283 community controls from 16 EU-GEI sites were assessed for child maltreatment, education attainment, and IQ., Study Results: In both the FEP and control group, childhood maltreatment was associated with lower educational attainment. The association between childhood maltreatment and lower IQ was robust to adjustment for confounders only among controls. Whereas childhood neglect was consistently associated with lower attainment and IQ in both groups, childhood abuse was associated with IQ only in controls. Among both patients with affective and nonaffective psychoses, negative associations between childhood maltreatment and educational attainment were observed, but the crude association with IQ was only evident in affective psychoses., Conclusions: Our findings underscore the role of childhood maltreatment in shaping academic outcomes and cognition of people with FEP as well as controls., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Psychotic patients with a lifetime history of cannabis use generally show better cognitive functioning than other psychotic patients. Some authors suggest that cannabis-using patients may have been less cognitively impaired and less socially withdrawn in their premorbid life. Using a dataset comprising 948 patients with first-episode psychosis (FEP) and 1313 population controls across 6 countries, we examined the extent to which IQ and both early academic (Academic Factor [AF]) and social adjustment (Social Factor [SF]) are related to the lifetime frequency of cannabis use in both patients and controls. We expected a higher IQ and a better premorbid social adjustment in psychotic patients who had ever used cannabis compared to patients without any history of use. We did not expect such differences in controls. In both patients and controls, IQ was 3 points higher among occasional-users than in never-users (mean difference [Mdiff] = 2.9, 95% CI = [1.2, 4.7]). Both cases and control daily-users had lower AF compared to occasional (Mdiff = -0.3, 95% CI = [-0.5; -0.2]) and never-users (Mdiff = -0.4, 95% CI = [-0.6; -0.2]). Finally, patient occasional (Mdiff = 0.3, 95% CI = [0.1; 0.5]) and daily-users (Mdiff = 0.4, 95% CI = [0.2; 0.6]) had better SF than their never-using counterparts. This difference was not present in controls (Fgroup*frequency(2, 2205) = 4.995, P = .007). Our findings suggest that the better premorbid social functioning of FEP with a history of cannabis use may have contributed to their likelihood to begin using cannabis, exposing them to its reported risk-increasing effects for Psychotic Disorders., (© The Author(s) 2019. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., (© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.)