Search

Previously, we established an estimated exposome score for schizophrenia (ES-SCZ) as a cumulative measure of environmental liability for schizophrenia to use in gene–environment interaction studies and for risk stratification in population cohorts. Hereby, we examined the discriminative function of ES-SCZ for identifying individuals diagnosed with schizophrenia spectrum disorder in the general population by measuring the area under the receiver operating characteristic curve (AUC). Furthermore, we compared this ES-SCZ method to an environmental sum score (Esum-SCZ) and an aggregate environmental score weighted by the meta-analytical estimates (Emet-SCZ). We also estimated ORs and Nagelkerke’s R2 for ES-SCZ in association with psychiatric diagnoses and other medical outcomes. ES-SCZ showed a good discriminative function (AUC = 0.84) and statistically significantly performed better than both Esum-SCZ (AUC = 0.80) and Emet-SCZ (AUC = 0.80). At optimal cut point, ES-SCZ showed similar performance in ruling out (LR− = 0.20) and ruling in (LR+ = 3.86) schizophrenia. ES-SCZ at optimal cut point showed also a progressively greater magnitude of association with increasing psychosis risk strata. Among all clinical outcomes, ES-SCZ was associated with schizophrenia diagnosis with the highest OR (2.76, P < .001) and greatest explained variance (R2 = 14.03%), followed by bipolar disorder (OR = 2.61, P < .001, R2 = 13.01%) and suicide plan (OR = 2.44, P < .001, R2 = 12.44%). Our findings from an epidemiologically representative general population cohort demonstrate that an aggregate environmental exposure score for schizophrenia constructed using a predictive modeling approach—ES-SCZ—has the potential to improve risk prediction and stratification for research purposes and may help gain insight into the multicausal etiology of psychopathology.

The polygenic risk score (PRS) allows for quantification of the relative contributions of genes and environment in population-based studies of mental health. We analyzed the impact of transdiagnostic schizophrenia PRS and measures of familial and environmental risk on the level of and change in general mental health (Short-Form-36 mental health) in the Netherlands Mental Health Survey and Incidence Study-2 general population sample, interviewed 4 times over a period of 9 years, yielding 8901 observations in 2380 individuals. Schizophrenia PRS, family history, somatic pain, and a range of environmental risks and social circumstances were included in the regression model of level of and change in mental health. We calculated the relative contribution of each (group of) risk factor(s) to the variance in (change in) mental health. In the combined model, familial and environmental factors explained around 17% of the variance in mental health, of which around 5% was explained by age and sex, 30% by social circumstances, 16% by pain, 22% by environmental risk factors, 24% by family history, and 3% by PRS for schizophrenia (PRS-SZ). Results were similar, but attenuated, for the model of mental health change over time. Childhood trauma and gap between actual and desired social status explained most of the variance. PRS for bipolar disorder, cross-disorder, and depression explained less variance in mental health than PRS-SZ. Polygenic risk for mental suffering, derived from significance-testing in massive samples, lacks impact in analyses focusing on prediction in a general population epidemiological setting. Social-environmental circumstances, particularly childhood trauma and perceived status gap, drive most of the attributable variation in population mental health.

Background: The observed link between positive psychotic experiences (PE) and psychosis spectrum disorder (PSD) may be stronger depending on concomitant presence of PE with other dimensions of psychopathology. We examined whether the effect of common risk factors for PSD on PE is additive and whether the impact of risk factors on the occurrence of PE depends on the co-occurrence of other symptom dimensions (affective dysregulation, negative symptoms, and cognitive alteration).Method: Data from the Netherlands Mental Health Survey and Incidence Study 2 were used. Risk factors included childhood adversity, cannabis use, urbanicity, foreign born, hearing impairment, and family history of affective disorders. Logistic regression models were applied to test (1) the additive effect of risk factors (4 levels) on PE and (2) the moderating effects of symptom dimensions on the association between risk factors (present/absent) and PE, using additive interaction, expressed as the interaction contrast ratio.Results: Risk factors were additive: the greater the number of risk factors, the greater the odds of PE. Furthermore, concomitant presence of the other symptom dimensions all increased the impact of risk factors on PE. After controlling for age, sex, and education, only affective dysregulation and negative symptoms remained significant moderators; only affective dysregulation remained a significant moderator if all dimensions were adjusted for each other.Conclusions: Risk factors may not be directly associated with PE but additively give rise to a multidimensional subthreshold state anticipating the multidimensional clinical syndrome. Early motivational and cognitive impairments in the context of PE may be reducible to affective dysregulation.

Background: Different psychological models of trauma-induced psychosis have been postulated, often based on the observation of specific associations between particular types of childhood trauma (CT) and particular psychotic symptoms or the co-occurrence of delusions and hallucinations. However, the actual specificity of these associations remains to be tested. Methods: In 2 population-based studies with comparable methodology (Netherlands Mental Health Survey and Incidence Study-1 [NEMESIS-1] and NEMESIS-2, N 13 722), trained interviewers assessed CT, psychotic symptoms, and other psychopathology. Specificity of associations was assessed with mixed-effects regression models with multiple outcomes, a statistical method suitable to examine specificity of associations in case of multiple correlated outcomes. Results: Associations with CT were strong and significant across the entire range of psychotic symptoms, without evidence for specificity in the relationship between particular trauma variables and particular psychotic experiences (PEs). Abuse and neglect were both associated with PEs (ORabuse: 2.12, P

Background There is robust evidence that reasoning biases such as a tendency of jumping to conclusions (JTC) as well as cognitive deficits are associated with psychosis, but evidence on their association with affective disturbances remains inconclusive. Recent findings also suggest a transdiagnostic phenotype of co-occurring affective disturbances and psychotic experiences. This study aimed to investigate whether JTC bias and decreased working memory performance are associated with the co-occurrence of affective disturbances, psychotic experiences (PEs), and psychosis-related help-seeking behaviour (HS) in the general population. Methods The second Netherlands Mental Health Survey and Incidence Study (NEMESIS-2). Trained interviewers administered the Composite International Diagnostic Interview (CIDI) at three time points in a representative general population sample, with N=4.596 individuals who completed all assessments. The beads task and digit-span task were completed to assess JTC bias and working memory performance, respectively. CIDI was used to measure affective disturbances (i.e. depression, anxiety, mania) and an add-on instrument to measure PEs and HS. Results We found that, compared to individuals with neither affective disturbances nor PEs, JTC bias was more likely to be present in individuals with co-occurring affective disturbances, PEs, and HS (moderate psychosis [1–2 PEs]: relative risk ratio [RRR]=1.23, 95% CI 1.03 – 1.48, p=0.023; high psychosis [3 or more PEs or HS]: RRR=1.66, 95% CI 1.26 – 2.19, p

BACKGROUND: Early intervention of psychosis is an active area of investigation. Guided by the ultra-high-risk framework, clinical research has thus far focused largely on the positive psychotic symptoms. However, findings from the general population—and recently from clinical samples such as Headspace Australia— suggest that psychotic symptoms might be bidirectionally and non-causally associated with the severity of multidimensional psychopathology and indicate poor outcome. Data on progression of psychotic symptoms in the general population are scarce. Therefore, in this longitudinal study, we aimed to explore the “risk” and “transition” in the general population by evaluating the incidence and transition rates in different categorical risk states with a focus on the presence and severity of psychotic experiences (PE), estimating the population attributable fraction of transition (PAF; the proportion of transition that would not have occurred when the risk was decreased), and assessing preceding affective symptomatology. METHODS: Data (n = 6071) from three waves of the Netherlands Mental Health Survey and Incidence Study-II (NEMESIS-II), a prospective survey in the Dutch general population aged 18 – 64, was used. Participants with life-time diagnosis of schizophrenia and related disorders at baseline were excluded. The baseline data (T0) of NEMESIS-II were collected from 2007 to 2009 and were followed up at year 3 (T1) and year 6 (T2). PE were assessed with a modified version (i.e. 20 items with “yes” vs “no” responses) of the CIDI 1.1; and later confirmed by a clinician on telephone interview. The categorical risk strata were defined as no risk (No PE), low-risk (single PE), moderate-risk (multiple PE), and high-risk (at least 1 PE + help seeking behaviour). Transition to psychosis was defined as antipsychotic treatment or clinical admission for psychotic symptoms. RESULTS: The incidence rates were low across the study period (low-risk: 0.9%, moderate-risk: 0.3%, high-risk: 0.5%, and transition to psychosis: 0.07%), with low annual transition rates (no-risk: 0.03%, low-risk: 0.1%, moderate-risk: 0.1%, high-risk:1.2%). The PAF was 7% for the low-risk, 3% for the moderate-risk, and 49% for the high-risk strata. Preceding affective symptomatology was frequent in all risk states and increased as a function of the risk strata: no-risk (55%), low-risk (75%), moderate-risk (77%), high-risk (90%), and psychosis transition (97%). DISCUSSION: Although individuals at high-risk are more likely to transition and almost half of those cases could be prevented if risk is successfully eliminated, low incidence and transition rates indicate that the high-risk approach would have a low public health impact in the general population. Our findings showing frequent preceding affective symptomatology also suggest that shifting the focus to multidimensional psychopathology may add valuable knowledge to preventive research.

Rates of self-reported psychotic experiences (SRPEs) in general population samples are high; however the reliability against interview-based assessments and the clinical significance of false-positive (FP) ratings remain unclear. Design: The second Netherlands Mental Health Survey and Incidence Study-2, a general population study.Methods:Trained lay interviewers administered a structured interview assessing psychopathology and psychosocial characteristics in 6646 participants. Participants with at least one SRPE (N = 1084) were reassessed by clinical telephone interview.Results:Thirty-six percent of participants with SRPEs were confirmed by clinical interview as true positive (TP). SPREs not confirmed by clinical interview (FP group) generated less help-seeking behavior and occurred less frequently compared with TP experiences (TP group). However, compared with controls without psychotic experiences, the FP group more often displayed mood disorder (relative risk [RR] 1.7, 1.4–2.2), substance use disorder (RR 2.0, 1.6–2.6), cannabis use (RR 1.5, 1.2–1.9), higher levels of neuroticism (RR 1.8, 1.5–2.2), affective dysregulation, and social dysfunction. The FP group also experienced more sexual (RR 2.0, 1.5–2.8) and psychological childhood trauma (RR 2.1, 1.7–2.6) as well as peer victimization (RR 1.5, 1.2–2.0) and recent life events (RR 2.0, 1.6–2.4) than controls without psychotic experiences. Differences between the FP group and the TP group across these domains were much smaller and less conclusive.Discussion:SRPEs not confirmed by clinical interview may epresent the softest expression of an extended psychosis phenotype that is phenotypically continuous with clinical psychosis but discontinuous in need for care.