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Objective: To test whether polygenic risk score for schizophrenia (PRS‐S) interacts with childhood adversity and daily‐life stressors to influence momentary mental state domains (negative affect, positive affect, and subtle psychosis expression) and stress‐sensitivity measures. Methods: The data were retrieved from a general population twin cohort including 593 adolescents and young adults. Childhood adversity was assessed using the Childhood Trauma Questionnaire. Daily‐life stressors and momentary mental state domains were measured using ecological momentary assessment. PRS‐S was trained on the latest Psychiatric Genetics Consortium schizophrenia meta‐analysis. The analyses were conducted using multilevel mixed‐effects tobit regression models. Results: Both childhood adversity and daily‐life stressors were associated with increased negative affect, decreased positive affect, and increased subtle psychosis expression, while PRS‐S was only associated with increased positive affect. No gene–environment correlation was detected. There is novel evidence for interaction effects between PRS‐S and childhood adversity to influence momentary mental states [negative affect (b = 0.07, P = 0.013), positive affect (b = −0.05, P = 0.043), and subtle psychosis expression (b = 0.11, P = 0.007)] and stress‐sensitivity measures. Conclusion: Exposure to childhood adversities, particularly in individuals with high PRS‐S, is pleiotropically associated with emotion dysregulation and psychosis proneness. [ABSTRACT FROM AUTHOR]

Objective Altered social reward functioning is associated with psychosis irrespective of stage and severity. Examining the role of social reward functioning prospectively in relation to psychotic experiences before these become persistent and potentially disabling can aid in elucidating social mechanisms that induce shifts toward more severe psychotic states, without the confounding effects of clinical disorder. Method In a longitudinal general population sample ( N = 566), the experience sampling method (repetitive random sampling of momentary emotions and social context) was used to assess daily life social functioning at baseline. Persistence of subclinical psychotic experiences was based on the Community Assessment of Psychic Experiences assessed three times over 14 months. Analyses examined to what degree i) social context and ii) appreciation thereof differentiated between those who did and did not develop persistent psychotic experiences. Results Although individuals with persistent psychotic experiences did not differ in overall level of positive effect, the amount of time spent alone or the level of social satisfaction compared to individuals without persistent psychotic experiences, they were more sensitive to the rewarding effects of social company. Conclusion Alterations in social reward experience may form one of the mechanisms that precede the development of the extended psychosis phenotype over time. [ABSTRACT FROM AUTHOR]

Peerbooms O, Rutten BPF, Collip D, Lardinois M, Lataster T, Thewissen V, Mafi Rad S, Drukker M, Kenis G, van Os J, Myin-Germeys I, van Winkel R. Evidence that interactive effects of COMT and MTHFR moderate psychotic response to environmental stress. Objective: A functional interaction between Catechol-O-Methyltransferase (COMT) Val158Met and methylenetetrahydrofolate reductase (MTHFR) C677T has been shown to differentially affect cognition in patients with schizophrenia and healthy controls; the effect of COMT Val158Met × MTHFR interaction on resilience to stress in patients and controls remains to be examined. Method: A total of 98 patients with non-affective psychotic disorder and 118 controls were genotyped for MTHFR C677T, MTHFR A1298C, and COMTVal158Met. Daily life reactivity to stress, modelled as the effect of daily life stress on psychotic experiences, was measured using the experience sampling method (ESM). Results: The MTHFR C677T genotype moderated the interaction between COMT Val158Met genotype and stress in patients ( P < 0.0001), but not in controls ( P = 0.68). Further examination of this interaction revealed that in patients with the MTHFR 677 T-allele, COMT Met/Met individuals displayed the largest increases in psychotic symptoms in reaction to ESM stress [χ2(2) = 29.51; P < 0.0001], whereas in patients with the MTHFR 677 C/C genotype no significant COMT Val158Met × ESM stress interaction was apparent [χ2(2) = 3.65; P = 0.16]. No moderating effect of MTHFR A1298C was found. Conclusion: Stress reactivity associated with COMT Val158Met in patients with psychosis may crucially depend on MTHFR C677T genotype. [ABSTRACT FROM AUTHOR]

Lataster T, Collip D, Lardinois M, van Os J, Myin-Germeys I. Evidence for a familial correlation between increased reactivity to stress and positive psychotic symptoms. Objective: This study tested the hypothesis that stress-reactivity may represent an intermediary phenotype underlying positive psychotic symptoms. It was examined whether: (i) stress-reactivity clusters within families of psychotic patients and (ii) stress-reactivity in relatives cosegregates with positive symptoms in patients. Method: The sample consisted of 40 patients and 47 siblings of these patients . The Experience Sampling Method (ESM - a structured diary technique) was used to measure stress-reactivity. Positive symptoms in patients were measured with the Comprehensive Assessment of Symptoms and History. Results: Within-trait, cross-sib associations showed a significant association between stress-reactivity in the patient and stress-reactivity in their siblings. Significant cross-trait, cross-sib associations were established showing a significant association between positive psychotic symptoms in the patient and stress-reactivity in the sibling. Conclusion: The findings show familial clustering of increased stress-reactivity, suggesting common aetiological influences, probably both genetic and environmental, underlying stress-reactivity in the siblings and patients. In addition, the results underscore the hypothesis that increased stress-reactivity is an unconfounded mechanism of risk underlying the positive symptoms of psychotic disorders. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the longitudinal relationship between subclinical psychotic symptoms and social functioning in a representative general population sample of adolescents., Method: Data were derived from a routine general health screening of 1909 adolescents in a circumscribed region. Baseline measurement was in the second grade of secondary school (T0), and follow-up occurred approximately 2 years later (T1). Social functioning and subclinical psychotic symptoms of hallucinations and delusions were assessed at both time points., Results: Baseline (T0) social problems preceded follow-up (T1) subclinical delusions, but not T1 subclinical hallucinations. Similarly, T0 delusions preceded social problems at T1, but T0 hallucinations did not., Conclusion: This longitudinal general population study demonstrated a bidirectional association between social problems and delusions, but found no link between social problems and hallucinations. This may reflect a downward negative spiral where delusional thoughts and social problems reinforce each other., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: The interplay between the catechol-O-methyltransferase (COMT) Val158Met polymorphism and environmental stress may have etiological relevance for psychosis, but differential effects have been reported in healthy control and patient groups, suggesting that COMT Val158Met interactions with stress may be conditional on background genetic risk for psychotic disorder., Methods: Patients with a nonaffective psychotic disorder (n = 86) and control participants (n = 109) were studied with the experience sampling method (a structured diary technique) in order to assess stress, negative affect and momentary psychotic symptoms in the flow of daily life., Results: Multilevel analyses revealed significant three-way interactions between group status (patient or control), COMT genotype and stress in the model of negative affect (χ(2)(2) = 13.26, P < 0.01) as well as in the model of momentary psychotic symptoms (χ(2)(2) = 6.92, P < 0.05). Exploration of the three-way interaction revealed that in patients, COMT genotype moderated the association between stress and negative affect (χ(2)(4) = 11.50, P < 0.005), as well as the association between stress and momentary psychosis (χ(2)(4) = 12.79, P < 0.005). Met/Met genotype patients showed significantly increased psychotic and affective reactivity to stress in comparison to the Val/Met and Val/Val genotypes. In contrast, healthy controls did not display large or significant COMT Val158Met X stress interactions., Conclusions: Important differences exist in the effect of COMT Val158Met on stress reactivity, which may depend on background risk for psychotic disorder. Differential sensitivity to environmental stress occasioned by COMT Val158Met may be contingent on higher order interactions with genetic variation underlying psychotic disorder., (© 2010 Blackwell Publishing Ltd.)

The recent advent of genome-wide mass-marker technology has resulted in renewed optimism to unravel the genetic architecture of psychotic disorders. Genome-wide association studies have identified a number of common polymorphisms robustly associated with schizophrenia, in ZNF804A, transcription factor 4, major histocompatibility complex, and neurogranin. In addition, copy number variants (CNVs) in 1q21.1, 2p16.3, 15q11.2, 15q13.3, 16p11.2, and 22q11.2 were convincingly implicated in schizophrenia risk. Furthermore, these studies have suggested considerable genetic overlap with bipolar disorder (particularly for common polymorphisms) and neurodevelopmental disorders such as autism (particularly for CNVs). The influence of these risk variants on relevant intermediate phenotypes needs further study. In addition, there is a need for etiological models of psychosis integrating genetic risk with environmental factors associated with the disorder, focusing specifically on environmental impact on gene expression (epigenetics) and convergence of genes and environment on common biological pathways bringing about larger effects than those of genes or environment in isolation (gene-environment interaction). Collaborative efforts that bring together expertise in statistics, genetics, epidemiology, experimental psychiatry, brain imaging, and clinical psychiatry will be required to succeed in this challenging task., (© 2010 Blackwell Publishing Ltd.)