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Background The association between cannabis and psychosis is established, but the role of underlying genetics is unclear. We used data from the EU-GEI case-control study and UK Biobank to examine the independent and combined effect of heavy cannabis use and schizophrenia polygenic risk score (PRS) on risk for psychosis. Methods Genome-wide association study summary statistics from the Psychiatric Genomics Consortium and the Genomic Psychiatry Cohort were used to calculate schizophrenia and cannabis use disorder (CUD) PRS for 1098 participants from the EU-GEI study and 143600 from the UK Biobank. Both datasets had information on cannabis use. Results In both samples, schizophrenia PRS and cannabis use independently increased risk of psychosis. Schizophrenia PRS was not associated with patterns of cannabis use in the EU-GEI cases or controls or UK Biobank cases. It was associated with lifetime and daily cannabis use among UK Biobank participants without psychosis, but the effect was substantially reduced when CUD PRS was included in the model. In the EU-GEI sample, regular users of high-potency cannabis had the highest odds of being a case independently of schizophrenia PRS (OR daily use high-potency cannabis adjusted for PRS = 5.09, 95% CI 3.08–8.43, p = 3.21 × 10 −10). We found no evidence of interaction between schizophrenia PRS and patterns of cannabis use. Conclusions Regular use of high-potency cannabis remains a strong predictor of psychotic disorder independently of schizophrenia PRS, which does not seem to be associated with heavy cannabis use. These are important findings at a time of increasing use and potency of cannabis worldwide. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Recent findings suggest the incidence of first-episode psychotic disorders (FEP) varies according to setting-level deprivation and cannabis use, but these factors have not been investigated together. We hypothesized deprivation would be more strongly associated with variation in FEP incidence than the prevalence of daily or high-potency cannabis use between settings. Study Design We used incidence data in people aged 18–64 years from 14 settings of the EU-GEI study. We estimated the prevalence of daily and high-potency cannabis use in controls as a proxy for usage in the population at-risk; multiple imputations by chained equations and poststratification weighting handled missing data and control representativeness, respectively. We modeled FEP incidence in random intercepts negative binomial regression models to investigate associations with the prevalence of cannabis use in controls, unemployment, and owner-occupancy in each setting, controlling for population density, age, sex, and migrant/ethnic group. Study Results Lower owner-occupancy was independently associated with increased FEP (adjusted incidence rate ratio [aIRR]: 0.76, 95% CI: 0.61–0.95) and non-affective psychosis incidence (aIRR: 0.68, 95% CI: 0.55–0.83), after multivariable adjustment. Prevalence of daily cannabis use in controls was associated with the incidence of affective psychoses (aIRR: 1.53, 95% CI: 1.02–2.31). We found no association between FEP incidence and unemployment or high-potency cannabis use prevalence. Sensitivity analyses supported these findings. Conclusions Lower setting-level owner-occupancy and increased prevalence of daily cannabis use in controls independently contributed to setting-level variance in the incidence of different psychotic disorders. Public health interventions that reduce exposure to these harmful environmental factors could lower the population-level burden of psychotic disorders. [ABSTRACT FROM AUTHOR]

Background: A history of childhood adversity is associated with psychotic disorder, with an increase in risk according to the number of exposures. However, it is not known why only some exposed individuals go on to develop psychosis. One possibility is pre-existing polygenic vulnerability. Here, we investigated, in the largest sample of first-episode psychosis (FEP) cases to date, whether childhood adversity and high polygenic risk scores for schizophrenia (SZ-PRS) combine synergistically to increase the risk of psychosis, over and above the effect of each alone. Methods: We assigned a schizophrenia-polygenic risk score (SZ-PRS), calculated from the Psychiatric Genomics Consortium (PGC2), to all participants in a sample of 384 FEP patients and 690 controls from the case–control component of the EU-GEI study. Only participants of European ancestry were included in the study. A history of childhood adversity was collected using the Childhood Trauma Questionnaire (CTQ). Synergistic effects were estimated using the interaction contrast ratio (ICR) [odds ratio (OR)exposure and PRS − ORexposure − ORPRS + 1] with adjustment for potential confounders. Results: There was some evidence that the combined effect of childhood adversities and polygenic risk was greater than the sum of each alone, as indicated by an ICR greater than zero [i.e. ICR 1.28, 95% confidence interval (CI) −1.29 to 3.85]. Examining subtypes of childhood adversities, the strongest synergetic effect was observed for physical abuse (ICR 6.25, 95% CI −6.25 to 20.88). Conclusions: Our findings suggest possible synergistic effects of genetic liability and childhood adversity experiences in the onset of FEP, but larger samples are needed to increase precision of estimates. [ABSTRACT FROM AUTHOR]

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_PRS), bipolar disorder (BD_PRS), major depression (MD_PRS), and IQ (IQ_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_IQ = 80.8, 95% CI: 79.1, 82.5) with low-improving PAF and PSF. 4) Deteriorating (n  = 150) (Mean_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_PRS than controls [ F (4,1319) = 20.4, P  < .001]. Among the clusters, the deteriorating group had lower SCZ_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. [ABSTRACT FROM AUTHOR]

Background and Hypothesis Facial Emotion Recognition is a key domain of social cognition associated with psychotic disorders as a candidate intermediate phenotype. In this study, we set out to investigate global and specific facial emotion recognition deficits in first-episode psychosis, and whether polygenic liability to psychotic disorders is associated with facial emotion recognition. Study Design 828 First Episode Psychosis (FEP) patients and 1308 population-based controls completed assessments of the Degraded Facial Affect Recognition Task (DFAR) and a subsample of 524 FEP and 899 controls provided blood or saliva samples from which we extracted DNA, performed genotyping and computed polygenic risk scores for schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MD). Study Results A worse ability to globally recognize facial emotion expressions was found in patients compared with controls [ B = −1.5 (0.6), 95% CI −2.7 to −0.3], with evidence for stronger effects on negative emotions (fear [ B = −3.3 (1.1), 95% CI −5.3 to −1.2] and anger [ B = −2.3 (1.1), 95% CI −4.6 to −0.1]) than on happiness [ B = 0.3 (0.7), 95% CI −1 to 1.7]. Pooling all participants, and controlling for confounds including case/control status, facial anger recognition was associated significantly with Schizophrenia Polygenic Risk Score (SZ PRS) [ B = −3.5 (1.7), 95% CI −6.9 to −0.2]. Conclusions Psychosis is associated with impaired recognition of fear and anger, and higher SZ PRS is associated with worse facial anger recognition. Our findings provide evidence that facial emotion recognition of anger might play a role as an intermediate phenotype for psychosis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: Affecting more than 264 million people, depression is a systemic and multifactorial disorder that represents one of the leading causes of illness and disability worldwide. Several studies showed an inflammatory response in depressed patients, including the involvement of both chronic low-grade inflammatory response and activation of cell-mediated immunity. The present study aimed to verify the efficacy of a structured functional therapy program for patients with depressed mood, and to determine whether this program can significantly reduce levels of C-reactive protein. Method: 28 outpatients with depressed mood received 20 individual sessions of Functional therapy. Data about socio-demographic variables, depression, self-esteem, and quality of life were collected; moreover, blood specimens were collected before and after treatment, and CRP measurement was performed by immunoenzymatic method. All measures were administered at baseline, at the end of treatment (i.e., 3 months after baseline), and at follow-up (i.e., 6 months after baseline). Results: A repeated measures ANOVA showed a significant difference after treatment on depression levels, levels of self-esteem, and all dimensions of quality of life, such as physical, psychological, social relationships, and environment. Furthermore, a statistically significant difference on levels of CRP was found. Moreover, at follow-up, improvements were maintained. Conclusions: The study revealed initial evidence of the efficacy of a functional therapy program on treating depression and its psychological and inflammation-related markers. [ABSTRACT FROM AUTHOR]

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 (F group*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. [ABSTRACT FROM AUTHOR]

Competing Interests: There are no conflicts of interest.