Obstetric complications and psychopathology in schizophrenia: A systematic review and meta-analysis.

Schizophrenia (SZ) is a severe mental health condition involving gene-environment interactions, with obstetric complications (OCs) conferring an elevated risk for the disease. Current research suggests that OCs may exacerbate SZ symptoms. This study conducted a systematic review and meta-analysis to comprehensively evaluate differences in psychopathology between individuals with and without exposure to OCs in relation to SZ and related disorders. We systematically searched PubMed, PsycINFO, and SCOPUS to identify eligible studies. A total of 4,091 records were retrieved through systematic and citation searches. 14 studies were included in the review, and 12 met the criteria for meta-analysis, involving 2,992 patients. The analysis revealed that SZ patients who had been exposed to OCs exhibited significantly higher levels of positive symptoms (SMD=0.10, 95%CI=0.01,0.20; p=0.03), general psychopathology (SMD=0.37, 95%CI=0.22,0.52; p<0.001), total clinical symptomatology (SMD=0.44, 95%CI=0.24,0.64; p<0.001) and depressive symptoms (SMD=0.47, 95%CI=0.09,0.84; p=0.01). No significant differences were found in negative symptomatology and functioning. Our results suggest that OCs are not only associated with an increased risk of developing psychosis but with more severe symptomatology.

Individualized pretest risk estimates to guide treatment decisions in patients with clinical high risk for psychotic disorders.

INTRODUCTION: Clinical high risk for psychosis (CHR) states are associated with an increased risk of transition to psychosis. However, the predictive value of CHR screening interviews is dependent on pretest risk enrichment in referred patients. This poses a major obstacle to CHR outreach campaigns since they invariably lead to risk dilution through enhanced awareness. A potential compensatory strategy is to use estimates of individual pretest risk as a 'gatekeeper' for specialized assessment. We aimed to test a risk stratification model previously developed in London, UK (OASIS) and to train a new predictive model for the Swiss population. METHOD: The sample was composed of 513 individuals referred for CHR assessment from six Swiss early psychosis detection services. Sociodemographic variables available at referral were used as predictors whereas the outcome variable was transition to psychosis. RESULTS: Replication of the risk stratification model developed in OASIS resulted in poor performance (Harrel's c=0.51). Retraining resulted in moderate discrimination (Harrel's c=0.67) which significantly differentiated between different risk groups. The lowest risk group had a cumulative transition incidence of 6.4% (CI: 0-23.1%) over two years. CONCLUSION: Failure to replicate the OASIS risk stratification model might reflect differences in the public health care systems and referral structures between Switzerland and London. Retraining resulted in a model with adequate discrimination performance. The developed model in combination with CHR assessment result, might be useful for identifying individuals with high pretest risk, who might benefit most from specialized intervention.

Statistical implication analysis: a novel approach to understand the reciprocal relationships between outcomes in early psychosis.

BACKGROUND: Patients can respond differently to intervention in the early phase of psychosis. Diverse symptomatic and functional outcomes can be distinguished and achieving one outcome may mean achieving another, but not necessarily the other way round, which is difficult to disentangle with cross-sectional data. The present study's goal was to evaluate implicative relationships between diverse functional outcomes to better understand their reciprocal dependencies in a cross-sectional design, by using statistical implication analysis (SIA). METHODS: Early psychosis patients of an early intervention program were evaluated for different outcomes (symptomatic response, functional recovery, and working/living independently) after 36 months of treatment. To determine which positive outcomes implied other positive outcomes, SIA was conducted by using the Iota statistical implication index, a newly developed approach allowing to measure asymmetrical bidirectional relationships between outcomes. RESULTS: Two hundred and nineteen recent onset patients with early psychosis were assessed. Results at the end of the three-years in TIPP showed that working independently statistically implied achieving all other outcomes. Symptomatic and functional recovery reciprocally implied one another. Living independently weakly implied symptomatic and functional recovery and did not imply independent working. CONCLUSIONS: The concept of implication is an interesting way of evaluating dependencies between outcomes as it allows us to overcome the tendency to presume symmetrical relationships between them. We argue that a better understanding of reciprocal dependencies within psychopathology can provide an impetus to tailormade treatments and SIA is a useful tool to address this issue in cross-sectional designs.

Winter birth: A factor of poor functional outcome in a Swiss early psychosis cohort.

OBJECTIVE: Winter birth has consistently been identified as a risk factor for schizophrenia. This study aimed to determine whether individuals born during this season are also at higher risk for early psychosis and whether this is associated with distinct functional and clinical outcomes. METHODS: We conducted a prospective study on 222 patients during their early phase of psychosis in Switzerland, nested in the Treatment and Early Intervention in Psychosis (TIPP) cohort. We compared the birth trimesters of these patients with those of the general Swiss population. Additionally, we evaluated the Global Assessment of Functioning scale (GAF) and the Positive and Negative Syndrome Scale (PANSS) scores among patients born in winter (January to March) versus those born during the rest of the year during a three-year follow-up period. RESULTS: A significantly higher proportion of patients experiencing early psychosis were born in winter compared to the general Swiss population. Patients born in winter had significantly lower GAF scores at 6 months, 24 months, and 36 months of follow-up, compared to patients born during the rest of the year. They also manifested fewer positive symptoms, as indicated by the PANSS positive subscale. CONCLUSION: Birth in winter appears to be associated with a lower functional outcome and potentially distinct symptomatology in the early phase of psychosis.

Gender differences in first episode psychosis: Some arguments to develop gender specific treatment strategies.

INTRODUCTION: Some aspects of gender differences in patients with schizophrenia spectrum disorders (SSD) have been studied, especially in cross-sectional designs and with a short-term follow-up. However, only a few studies have considered the evolution during the follow-up of SSD patients according to their gender. In this study, we explore gender differences from the time of entry in an early intervention program for psychosis, up to three years follow-up. METHODS: We conducted a prospective study including a cohort of 474 patients treated at the Treatment and Early Intervention in Psychosis (TIPP) program, 319 men and 155 women, having presented a first episode of psychosis (FEP). Data regarding premorbid and baseline sociodemographic, psychopathological and patient functioning, were collected. These data were reassessed longitudinally after 2, 6, 12, 18, 24, 30 and 36 months after entry in TIPP. RESULTS: Regarding premorbid and baseline characteristics, woman developed threshold symptoms of a FEP 1 year later than men on average. Women were more likely to be married, men were more likely to live in pension or care home facility or to be homeless. Women displayed a higher rate of history of suicide attempts and exposure to childhood trauma, while men were more likely to have a forensic history, a history of abuse of alcohol and cannabis as well as a dependency to cannabis at the time of entry in TIPP. Regarding evolution, men were more prone to violent acts and were less likely to decrease their usage of substances. The longitudinal analysis highlighted that men displayed greater negative symptoms over the entire treatment period, lower functioning after 6 months and on all assessment points after. Both genders displayed similar rate of improvement in these 3 dimensions over time. CONCLUSION: Our study confirms that there are some gender differences in the early phase of psychosis that may require differentiation of assessment and treatment to improve recovery.

Pathways to care in youth and young adults at clinical high risk for psychosis in Switzerland: Current situation and clinical implementation of the PsyYoung project.

AIM: We aim to give an insight into the current situation in Switzerland concerning the pathways to care of young people with clinical high risk of psychosis. In a second step we propose a procedure of optimizing pathways to care developed within the project PsyYoung. METHODS: A qualitative survey derived and adapted from Kotlicka-Antczak et al. (2020) was conducted in large early detection services of three Swiss cantons (Geneva, Basel-Stadt, Vaud) focusing on pathways to care. More specifically, using questionnaires delivered to the heads of participating services, information was collected on referral sources, on activities to implement outreach campaigns and on the use of a pre-screening tool. RESULTS: Main results on referral source indicated that sources were variable but seemed to come primarily from the medical sector and more so from the psychiatric sector. Very few referrals came from non-medical sectors. Outreach activities included the contact to other clinics as well as through brochures and posters. All services but one used the Prodromal Questionnaire - 16 as pre-screening tool. CONCLUSIONS: All in all, the results indicate a referral and care pathway system implemented mostly within the medical and particularly mental health sector. Accordingly, the PsyYoung project proposes a procedure for pathways to care which could help overcome the obstacle of referrals being restrained to a narrow field of mental health and to harmonize the referral process within services dedicated to the same aim of helping young people at high risk of developing a psychosis.

Duration of Untreated Psychosis and Outcomes in First-Episode Psychosis: Systematic Review and Meta-analysis of Early Detection and Intervention Strategies.

BACKGROUND: The role of duration of untreated psychosis (DUP) as an early detection and intervention target to improve outcomes for individuals with first-episode psychosis is unknown. STUDY DESIGN: PRISMA/MOOSE-compliant systematic review to identify studies until February 1, 2023, with an intervention and a control group, reporting DUP in both groups. Random effects meta-analysis to evaluate (1) differences in DUP in early detection/intervention services vs the control group, (2) the efficacy of early detection strategies regarding eight real-world outcomes at baseline (service entry), and (3) the efficacy of early intervention strategies on ten real-world outcomes at follow-up. We conducted quality assessment, heterogeneity, publication bias, and meta-regression analyses (PROSPERO: CRD42020163640). STUDY RESULTS: From 6229 citations, 33 intervention studies were retrieved. The intervention group achieved a small DUP reduction (Hedges' g = 0.168, 95% CI = 0.055-0.283) vs the control group. The early detection group had better functioning levels (g = 0.281, 95% CI = 0.073-0.488) at baseline. Both groups did not differ regarding total psychopathology, admission rates, quality of life, positive/negative/depressive symptoms, and employment rates (P > .05). Early interventions improved quality of life (g = 0.600, 95% CI = 0.408-0.791), employment rates (g = 0.427, 95% CI = 0.135-0.718), negative symptoms (g = 0.417, 95% CI = 0.153-0.682), relapse rates (g = 0.364, 95% CI = 0.117-0.612), admissions rates (g = 0.335, 95% CI = 0.198-0.468), total psychopathology (g = 0.298, 95% CI = 0.014-0.582), depressive symptoms (g = 0.268, 95% CI = 0.008-0.528), and functioning (g = 0.180, 95% CI = 0.065-0.295) at follow-up but not positive symptoms or remission (P > .05). CONCLUSIONS: Comparing interventions targeting DUP and control groups, the impact of early detection strategies on DUP and other correlates is limited. However, the impact of early intervention was significant regarding relevant outcomes, underscoring the importance of supporting early intervention services worldwide.

The role of interpersonal trauma and substance use in mental health: A large population-based study.

Both interpersonal trauma (IPT) and substance use are linked to mental health problems, however their interplay is understudied. This study will investigate the relationship between IPT, substance use and mental health in a large population-based sample. Participants included 3756 individuals, mainly young university students using a snowball sampling method. History of IPT was collected retrospectively using the Traumatic Experiences Checklist. Substance use was examined using the World Health Organization's Alcohol, Smoking and Substance Involvement Screening Test. Mental health symptoms were assessed by the DSM-5 Level 1 Cross-Cutting Symptom Measure. Moderation analyses were performed investigating the relationship between IPT, substance use, and mental health symptoms. Participants exposed to IPT had a higher prevalence of substance use (cannabis, alcohol, tobacco) and had more severe mental health problems than people without IPT. Substance use was associated with a blunted increase of depression, anxiety, and anger in trauma victims. A history of abuse was more strongly linked to substance use than neglect. Moderation analyses further revealed that cannabis use increased psychotic symptoms and psychotic symptoms increased cannabis use in participants with high levels of IPT. Our findings indicate that substance use worsens psychotic symptoms in IPT victims whilst dampening other mental health symptoms.

Proxy measures for the assessment of psychotic and affective symptoms in studies using electronic health records.

BACKGROUND: There is a lack of standardised psychometric data in electronic health record (EHR)-based research. Proxy measures of symptom severity based on patients' clinical records may be useful surrogates in mental health EHR research. AIMS: This study aimed to validate proxy tools for the short versions of the Positive and Negative Syndrome Scale (PANSS-6), Young Mania Rating Scale (YMRS-6) and Montgomery-Åsberg Depression Rating Scale (MADRS-6). METHOD: A cross-sectional, multicentre study was conducted in a sample of 116 patients with first-episode psychosis from 12 public hospitals in Spain. Concordance between PANSS-6, YMRS-6 and MADRS-6 scores and their respective proxies was evaluated based on information from EHR clinical notes, using a variety of statistical procedures, including multivariate tests to adjust for potential confounders. Bootstrapping techniques were used for internal validation, and an independent cohort from the Treatment and Early Intervention in Psychosis Program (TIPP-Lausanne, Switzerland) for external validation. RESULTS: The proxy versions correlated strongly with their respective standardised scales (partial correlations ranged from 0.75 to 0.84) and had good accuracy and discriminatory power in distinguishing between patients in and not in remission (percentage of patients correctly classified ranged from 83.9 to 91.4% and bootstrapped optimism-corrected area under the receiver operating characteristic curve ranged from 0.76 to 0.89), with high interrater reliability (intraclass correlation coefficient of 0.81). The findings remained robust in the external validation data-set. CONCLUSIONS: The proxy instruments proposed for assessing psychotic and affective symptoms by reviewing EHR provide a feasible and reliable alternative to traditional structured psychometric procedures, and a promising methodology for real-world practice settings.

What is the duration of untreated psychosis worldwide? - A meta-analysis of pooled mean and median time and regional trends and other correlates across 369 studies.

Duration of untreated psychosis (DUP) has been associated with poor mental health outcomes. We aimed to meta-analytically estimate the mean and median DUP worldwide, evaluating also the influence of several moderating factors. This PRISMA/MOOSE-compliant meta-analysis searched for non-overlapping individual studies from inception until 9/12/2022, reporting mean ± s.d. or median DUP in patients with first episode psychosis (FEP), without language restrictions. We conducted random-effect meta-analyses, stratified analyses, heterogeneity analyses, meta-regression analyses, and quality assessment (PROSPERO:CRD42020163640). From 12 461 citations, 369 studies were included. The mean DUP was 42.6 weeks (95% confidence interval (CI) 40.6-44.6, k = 283, n = 41 320), varying significantly across continents (p < 0.001). DUP was (in descending order) 70.0 weeks (95% CI 51.6-88.4, k = 11, n = 1508) in Africa; 48.8 weeks (95% CI 43.8-53.9, k = 73, n = 12 223) in Asia; 48.7 weeks (95% CI 43.0-54.4, k = 36, n = 5838) in North America; 38.6 weeks (95% CI 36.0-41.3, k = 145, n = 19 389) in Europe; 34.9 weeks (95% CI 23.0-46.9, k = 11, n = 1159) in South America and 28.0 weeks (95% CI 20.9-35.0, k = 6, n = 1203) in Australasia. There were differences depending on the income of countries: DUP was 48.4 weeks (95% CI 43.0-48.4, k = 58, n = 5635) in middle-low income countries and 41.2 weeks (95% CI 39.0-43.4, k = 222, n = 35 685) in high income countries. Longer DUP was significantly associated with older age (ß = 0.836, p < 0.001), older publication year (ß = 0.404, p = 0.038) and higher proportion of non-White FEP patients (ß = 0.232, p < 0.001). Median DUP was 14 weeks (Interquartile range = 8.8-28.0, k = 206, n = 37 215). In conclusion, DUP is high throughout the world, with marked variation. Efforts to identify and intervene sooner in patients with FEP, and to promote global mental health and access to early intervention services (EIS) are critical, especially in developing countries.

Cannabis use as a potential mediator between childhood adversity and first-episode psychosis: results from the EU-GEI case-control study.

BACKGROUND: Childhood adversity and cannabis use are considered independent risk factors for psychosis, but whether different patterns of cannabis use may be acting as mediator between adversity and psychotic disorders has not yet been explored. The aim of this study is to examine whether cannabis use mediates the relationship between childhood adversity and psychosis. METHODS: Data were utilised on 881 first-episode psychosis patients and 1231 controls from the European network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study. Detailed history of cannabis use was collected with the Cannabis Experience Questionnaire. The Childhood Experience of Care and Abuse Questionnaire was used to assess exposure to household discord, sexual, physical or emotional abuse and bullying in two periods: early (0-11 years), and late (12-17 years). A path decomposition method was used to analyse whether the association between childhood adversity and psychosis was mediated by (1) lifetime cannabis use, (2) cannabis potency and (3) frequency of use. RESULTS: The association between household discord and psychosis was partially mediated by lifetime use of cannabis (indirect effect coef. 0.078, s.e. 0.022, 17%), its potency (indirect effect coef. 0.059, s.e. 0.018, 14%) and by frequency (indirect effect coef. 0.117, s.e. 0.038, 29%). Similar findings were obtained when analyses were restricted to early exposure to household discord. CONCLUSIONS: Harmful patterns of cannabis use mediated the association between specific childhood adversities, like household discord, with later psychosis. Children exposed to particularly challenging environments in their household could benefit from psychosocial interventions aimed at preventing cannabis misuse.

Risk and protective factors for recovery at 3-year follow-up after first-episode psychosis onset: a multivariate outcome approach.

PURPOSE: Recovery in people with first-episode psychosis (FEP) remains a major issue. When risk factors are studied in relation to the disorder, potential protective factors should also be considered since they can modulate this relationship. This study is aimed at exploring which premorbid and baseline characteristics are associated with a good and poor global recovery in patients with FEP at 3-year follow-up. METHODS: We categorized patients' outcome by using a Latent Class Analysis (LCA) considering a multimodal set of symptomatic and functional outcomes. A Mixed effects Models Repeated Measures analysis of variance (MMRM) was used to highlight group differences over time on symptomatic and functional outcomes assessed during the 3-year follow-up. RESULTS: A total of 325 patients with FEP aged between 18 and 35 years were included. Two groups were identified. A total of 187 patients (57.5%) did not achieve recovery, and 138 patients (42.5%) achieved recovery. Recovered patients had generally a better premorbid and baseline profile in comparison with non-recovered patients (as among which shorter duration of untreated psychosis (DUP), higher degree of insight, better functional level and lower illness severity at baseline). The trajectories for the psychopathological and functional outcomes over 36 months differed between the non-recovered and the recovered group of patients. CONCLUSIONS: Our results pointed to some variables associated with recovery, acting as potential protective factors. These should be considered for early intervention programs to promote psychological resilience specifically in those with a worse prognosis in order to mitigate the effects of the variables that make them more vulnerable to poorer outcome.

A better understanding of the impact of childhood trauma on depression in early psychosis: A differential item functioning approach.

BACKGROUND: Childhood trauma (CT) has been shown to impact depressive symptoms measured broadly in early psychosis patients. Beyond the broad intensity of such impact, less is known about which depressive features are more impacted. METHODS: Patients of a specialized early intervention programme were evaluated after the first two and six months of treatment with the Montgomery-Asberg Depression Rating Scale (MADRS). We used the first assessment available. We estimated an Item-response model to reveal potential differential item functioning (DIF) in order to highlight depressive features that could be impacted differently than others by experiences of abuse (sexual physical and emotional) and neglect (physical and emotional). RESULTS: Two hundred and sixty-two recent onset patients with psychosis were assessed. Results at the beginning of the Treatment and Early Intervention in Psychosis Program (TIPP) showed that abuse but not neglect was associated with more severe depression levels, measured at a global MADRS score. Concerning specific depressive symptoms, concentration difficulties were left largely unaffected by abuse in contrast with other aspects of depression. CONCLUSIONS: The cognitive item of the depressive dimension assessed by the MADRS was not impacted by experiences of abuse, while the remaining subdomains involving anxiety, suicidality, somatic symptoms, and anhedonia were. Trials focusing on improving the impact of depression in traumatised individuals should account for the possible diluting effect of concentration when measuring the depression broadly. DIF is a promising method to better understand the impact many variables may have on various psychological dimensions at the item level.

[Diagnostic of a first psychotic episode : role of the general practitioner]. / Diagnostic d'un premier épisode psychotique : le rôle clé du médecin généraliste.

As psychoses can have a long-term impact, they need to be diagnosed as quickly as possible in order to provide appropriate care and avoid the onset of comorbid complications. As general practitioners are often the first to be approached, it is important that they think about this diagnosis in young patients, even if the manifestations are often atypical or if patients are reluctant to talk about it. Specialized programs have sprung up all over the world, staffed by mobile teams and professionals specialized in this type of treatment, with far superior results at a lower overall cost than the usual treatments. In the absence of a clear national policy in this area, Switzerland remains poorly equipped, although successful programs do exist in some regions.

Les psychoses pouvant avoir un impact à long terme, les diagnostiquer aussi rapidement que possible permet d'offrir des soins adaptés aux patients et d'éviter la survenue de complications comorbides. Les médecins généralistes étant souvent sollicités en premier, il est important qu'ils pensent à ce diagnostic chez des patients jeunes, même si les manifestations sont souvent atypiques ou les patients réticents à en parler. Des programmes spécialisés se sont développés dans le monde entier, dotés d'équipes mobiles et de professionnels spécialisés dans ce type de traitements, avec des résultats nettement supérieurs à un coût global moindre que ceux habituels. En l'absence d'une politique nationale claire à cet égard, la Suisse reste mal dotée dans ce domaine bien que des programmes performants existent dans quelques régions.

Examining associations, moderators and mediators between childhood maltreatment, social functioning, and social cognition in psychotic disorders: a systematic review and meta-analysis.

Childhood maltreatment (CM) has been related to social functioning and social cognition impairment in people with psychotic disorders (PD); however, evidence across different CM subtypes and social domains remains less clear. We conducted a systematic review and meta-analysis to quantify associations between CM, overall and its different subtypes (physical/emotional/sexual abuse, physical/emotional neglect), and domains of social functioning and social cognition in adults with PD. We also examined moderators and mediators of these associations. A PRISMA-compliant systematic search was performed on 24 November 2022 (PROSPERO CRD42020175244). Fifty-three studies (N = 13 635 individuals with PD) were included in qualitative synthesis, of which 51 studies (N = 13 260) with 125 effects sizes were pooled in meta-analyses. We found that CM was negatively associated with global social functioning and interpersonal relations, and positively associated with aggressive behaviour, but unrelated to independent living or occupational functioning. There was no meta-analytic evidence of associations between CM and social cognition. Meta-regression analyses did not identify any consistent moderation pattern. Narrative synthesis identified sex and timing of CM as potential moderators, and depressive symptoms and maladaptive personality traits as possible mediators between CM and social outcomes. Associations were of small magnitude and limited number of studies assessing CM subtypes and social cognition are available. Nevertheless, adults with PD are at risk of social functioning problems after CM exposure, an effect observed across multiple CM subtypes, social domains, diagnoses and illness stages. Maltreated adults with PD may thus benefit from trauma-related and psychosocial interventions targeting social relationships and functioning.

Improving Pathways to Care for Patients at High Psychosis Risk in Switzerland: PsyYoung Study Protocol.

AIMS: Psychotic disorders are one of the main causes of chronic disability in young people. An at-risk mental state (ARMS) is represented by subclinical symptoms that precede the first episode of psychosis (FEP). The PsyYoung project aims to optimize the detection of an ARMS while reducing unnecessary psychiatric treatments. It investigates the effects of service changes on the referrals and outcomes of young people with ARMS or a FEP. METHODS: Six psychiatric outpatient clinics in three cantons (Basel-Stadt, Vaud, and Geneva) participated in the project. They passed through an implementation phase including service changes and the adaptation of a standardized stepped care model for diagnosis and assessment, in addition to measures for increasing the awareness, networking and training of local professionals. PRELIMINARY RESULTS: All participating cantons had entered the implementation phase. By March 2023, there were 619 referrals to participating sites. A total of 163 patients (37% FEP and 31% ARMS) and 15 close relatives had participated in individual longitudinal assessments, and 26 patients participated in qualitative interviews. CONCLUSION: This national collaborative project addresses the issue of early intervention for emerging psychoses, and creates spaces for fruitful reflections and collaboration in Switzerland. The ultimate aim of PsyYoung is to harmonize clinical practices in early intervention of psychosis on a national level.

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.

The relationship between genetic liability, childhood maltreatment, and IQ: findings from the EU-GEI multicentric case-control study.

This study investigated if the association between childhood maltreatment and cognition among psychosis patients and community controls was partially accounted for by genetic liability for psychosis. Patients with first-episode psychosis (N = 755) and unaffected controls (N = 1219) from the EU-GEI study were assessed for childhood maltreatment, intelligence quotient (IQ), family history of psychosis (FH), and polygenic risk score for schizophrenia (SZ-PRS). Controlling for FH and SZ-PRS did not attenuate the association between childhood maltreatment and IQ in cases or controls. Findings suggest that these expressions of genetic liability cannot account for the lower levels of cognition found among adults maltreated in childhood.

The association between reasons for first using cannabis, later pattern of use, and risk of first-episode psychosis: the EU-GEI case-control study.

BACKGROUND: While cannabis use is a well-established risk factor for psychosis, little is known about any association between reasons for first using cannabis (RFUC) and later patterns of use and risk of psychosis. METHODS: We used data from 11 sites of the multicentre European Gene-Environment Interaction (EU-GEI) case-control study. 558 first-episode psychosis patients (FEPp) and 567 population controls who had used cannabis and reported their RFUC.We ran logistic regressions to examine whether RFUC were associated with first-episode psychosis (FEP) case-control status. Path analysis then examined the relationship between RFUC, subsequent patterns of cannabis use, and case-control status. RESULTS: Controls (86.1%) and FEPp (75.63%) were most likely to report 'because of friends' as their most common RFUC. However, 20.1% of FEPp compared to 5.8% of controls reported: 'to feel better' as their RFUC (χ2 = 50.97; p < 0.001). RFUC 'to feel better' was associated with being a FEPp (OR 1.74; 95% CI 1.03-2.95) while RFUC 'with friends' was associated with being a control (OR 0.56; 95% CI 0.37-0.83). The path model indicated an association between RFUC 'to feel better' with heavy cannabis use and with FEPp-control status. CONCLUSIONS: Both FEPp and controls usually started using cannabis with their friends, but more patients than controls had begun to use 'to feel better'. People who reported their reason for first using cannabis to 'feel better' were more likely to progress to heavy use and develop a psychotic disorder than those reporting 'because of friends'.