Synergistic effects of childhood adversity and polygenic risk in first-episode psychosis: the EU-GEI study.

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.

Child maltreatment, migration and risk of first-episode psychosis: results from the multinational EU-GEI study.

BACKGROUND: Child maltreatment (CM) and migrant status are independently associated with psychosis. We examined prevalence of CM by migrant status and tested whether migrant status moderated the association between CM and first-episode psychosis (FEP). We further explored whether differences in CM exposure contributed to variations in the incidence rates of FEP by migrant status. METHODS: We included FEP patients aged 18-64 years in 14 European sites and recruited controls representative of the local populations. Migrant status was operationalized according to generation (first/further) and region of origin (Western/non-Western countries). The reference population was composed by individuals of host country's ethnicity. CM was assessed with Childhood Trauma Questionnaire. Prevalence ratios of CM were estimated using Poisson regression. We examined the moderation effect of migrant status on the odds of FEP by CM fitting adjusted logistic regressions with interaction terms. Finally, we calculated the population attributable fractions (PAFs) for CM by migrant status. RESULTS: We examined 849 FEP cases and 1142 controls. CM prevalence was higher among migrants, their descendants and migrants of non-Western heritage. Migrant status, classified by generation (likelihood test ratio:χ2 = 11.3, p = 0.004) or by region of origin (likelihood test ratio:χ2 = 11.4, p = 0.003), attenuated the association between CM and FEP. PAFs for CM were higher among all migrant groups compared with the reference populations. CONCLUSIONS: The higher exposure to CM, despite a smaller effect on the odds of FEP, accounted for a greater proportion of incident FEP cases among migrants. Policies aimed at reducing CM should consider the increased vulnerability of specific subpopulations.

Migration history and risk of psychosis: results from the multinational EU-GEI study.

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 three indicators of social disadvantage for each phase: pre-migration, migration and post-migration. We examined whether social disadvantage in the pre- and post-migration phases, migration adversities, and mismatch between achievements and expectations differed between first-generation migrants with first-episode psychosis and healthy first-generation migrants, and tested whether this accounted for differences in odds of psychosis in multivariable logistic regression models. RESULTS: In total, 249 cases and 219 controls were assessed. Pre-migration (OR 1.61, 95% CI 1.06-2.44, p = 0.027) and post-migration 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. Migration adversities (OR 1.18, 95% CI 0.672-2.06, p = 0.568) were not significantly related to the outcome. Finally, we found a dose-response effect between the 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 reduce the excess of psychosis in migrants.

The relationship of symptom dimensions with premorbid adjustment and cognitive characteristics at first episode psychosis: Findings from the EU-GEI study.

Premorbid functioning and cognitive measures may reflect gradients of developmental impairment across diagnostic categories in psychosis. In this study, we sought to examine the associations of current cognition and premorbid adjustment with symptom dimensions in a large first episode psychosis (FEP) sample. We used data from the international EU-GEI study. Bifactor modelling of the Operational Criteria in Studies of Psychotic Illness (OPCRIT) ratings provided general and specific symptom dimension scores. Premorbid Adjustment Scale estimated premorbid social (PSF) and academic adjustment (PAF), and WAIS-brief version measured IQ. A MANCOVA model examined the relationship between symptom dimensions and PSF, PAF, and IQ, having age, sex, country, self-ascribed ethnicity and frequency of cannabis use as confounders. In 785 patients, better PSF was associated with fewer negative (B = -0.12, 95% C.I. -0.18, -0.06, p < 0.001) and depressive (B = -0.09, 95% C.I. -0.15, -0.03, p = 0.032), and more manic (B = 0.07, 95% C.I. 0.01, 0.14, p = 0.023) symptoms. Patients with a lower IQ presented with slightly more negative and positive, and fewer manic, symptoms. Secondary analysis on IQ subdomains revealed associations between better perceptual reasoning and fewer negative (B = -0.09, 95% C.I. -0.17, -0.01, p = 0.023) and more manic (B = 0.10, 95% C.I. 0.02, 0.18, p = 0.014) symptoms. Fewer positive symptoms were associated with better processing speed (B = -0.12, 95% C.I. -0.02, -0.004, p = 0.003) and working memory (B = -0.10, 95% C.I. -0.18, -0.01, p = 0.024). These findings suggest that the negative and manic symptom dimensions may serve as clinical proxies of different neurodevelopmental predisposition in psychosis.

First-episode Psychosis and Migration in Italy: Results from a Study in the Italian Mental Health Services (Pep-Ita Study).

BACKGROUND: Migrants present high rates of psychosis. A better understanding of this phenomenon is needed. METHODS: We conducted a multicentre First-Episode Psychosis (FEP) prospective study over two years (January 2012-December 2013) to evaluate first-generation migrants presenting with FEP at the participating Community Mental Health Centers (CMHCs). RESULTS: 109 FEP migrants were identified. Almost half of them were highly educated, employed and in a stable affective relationship. The average age was 32.8 (± 9.8) years, and the average length of stay in Italy was 8.6 (± 8.8) years. About 2/3 of patients were referred to CMHCs following Emergency Department access or psychiatric admission. CONCLUSIONS: Our finding of a "high functioning portrait" of FEP migrants allow us to hypothesize that a high burden of negative psychosocial factors is likely to be needed for the FEP onset. Furtherly, mental health services should implement more appropriate resources and organizational methods to respond to migrants' health needs.

Childhood medical history and psychosis in adult life: Findings from the Bologna EU-GEI incidence and case-control study.

AIM: To estimate the association between the inpatient admissions and Emergency Department (ED) visits before age of 18 years and adulthood-onset first-episode psychosis (FEP). METHODS: We conducted a FEP incidence and case-control study and calculated the odds ratios (ORs) for incident FEP associated with inpatient admissions and ED visits prior to age of 18 years, adjusting our results for cannabis use, parental socio-economic class and childhood trauma. RESULTS: In multivariate logistic regression analysis, odds of FEP increased significantly if the participant had a history of at least one inpatient admission (OR = 3.52; 95% confidence interval [95%CI] 1.07-11.54; P = .04) or at least one ED visit (OR = 8.93; 95%CI 2.41-33.14; P = .001) before age of 18. The associations remained significant adjusting for cannabis use, education, parental socio-economic class and childhood trauma. CONCLUSION: Consistently with the socio-neurodevelopmental model, we found a significant association between a positive history of hospital care in childhood and adulthood-onset psychosis.

Multiplexed therapeutic drug monitoring of antipsychotics in dried plasma spots by LC-MS/MS.

In this work, a convenient method for the therapeutic monitoring of seven common antipsychotic drugs in "dried plasma spot" samples has been developed. It is based on the liquid chromatography tandem mass spectrometry technique, operating in multiple reaction monitoring mode, and a straightforward procedure for the simultaneous extraction of all antipsychotics in a single step, with high extraction yield. The method was fully validated with proper accuracy, precision, selectivity and sensitivity, for all the drugs. Limits of quantification were 0.12, 1.09, 1.46, 1.47, 5.70, 1.32, 1.33 µg/L for haloperidol, aripiprazole, olanzapine, quetiapine, clozapine, risperidone, and paliperidone, respectively. Accuracy, intra- and interday precision values were <10% for all drugs at all concentration levels examined. The method was tested in the analysis of 30 plasma samples from real patients for each drug. The proposed analytical approach, by combining practical and logistical advantages of microsampling with liquid chromatography tandem mass spectrometry analytical performance, could offer an ideal strategy for accurate and timely therapeutic drug monitoring of antipsychotic drugs in most clinical settings, even in remote centers and/or in out-patient settings, bringing so many potential improvements in psychiatric patient care.

Prevalence and effectiveness of psychiatric treatments for patients with IBD: A systematic literature review.

OBJECTIVES: Higher prevalence of psychiatric disorders, such as anxiety and depression, has been found in people with Crohn's disease and Ulcerative Colitis compared to the general population. Nowadays, international guidelines advocate psychotherapy and psycho-pharmacological treatments as playing an important role in IBD care. The main goal of this systematic literature review was summarize the evidence on the utilization and effectiveness of treatments for depression and anxiety in persons with IBD. METHODS: A systematic literature review was conducted using three different electronic databases: MEDLINE, PsychINFO, and EMBASE to identify studies reporting the prevalence and efficacy of psycho-pharmacological and psychotherapeutic treatments for IBD. A quality appraisal was conducted using several scales as appropriate for each study design. A narrative synthesis was also performed. RESULTS: Forty-three studies were included. Although a high rate of psychoactive drug use was found in people with IBD, a low proportion of IBD patients have access to psychiatric referral. 1/3 of the studies found that psychotherapy was effective for improving the quality of life, perception of stress, anxiety and depression as well as disease. Antidepressants proved effective in reducing disease activity, gastrointestinal symptoms, anxiety and depression. CONCLUSION: Our results suggest that psychiatric treatment should be implemented in IBD care. However, further studies are needed to confirm the findings of our systematic review.