Are genetic risk factors for psychosis also associated with dimension-specific psychotic experiences in adolescence?

Psychosis has been hypothesised to be a continuously distributed quantitative phenotype and disorders such as schizophrenia and bipolar disorder represent its extreme manifestations. Evidence suggests that common genetic variants play an important role in liability to both schizophrenia and bipolar disorder. Here we tested the hypothesis that these common variants would also influence psychotic experiences measured dimensionally in adolescents in the general population. Our aim was to test whether schizophrenia and bipolar disorder polygenic risk scores (PRS), as well as specific single nucleotide polymorphisms (SNPs) previously identified as risk variants for schizophrenia, were associated with adolescent dimension-specific psychotic experiences. Self-reported Paranoia, Hallucinations, Cognitive Disorganisation, Grandiosity, Anhedonia, and Parent-rated Negative Symptoms, as measured by the Specific Psychotic Experiences Questionnaire (SPEQ), were assessed in a community sample of 2,152 16-year-olds. Polygenic risk scores were calculated using estimates of the log of odds ratios from the Psychiatric Genomics Consortium GWAS stage-1 mega-analysis of schizophrenia and bipolar disorder. The polygenic risk analyses yielded no significant associations between schizophrenia and bipolar disorder PRS and the SPEQ measures. The analyses on the 28 individual SNPs previously associated with schizophrenia found that two SNPs in TCF4 returned a significant association with the SPEQ Paranoia dimension, rs17512836 (p-value=2.57x10-4) and rs9960767 (p-value=6.23x10-4). Replication in an independent sample of 16-year-olds (N=3,427) assessed using the Psychotic-Like Symptoms Questionnaire (PLIKS-Q), a composite measure of multiple positive psychotic experiences, failed to yield significant results. Future research with PRS derived from larger samples, as well as larger adolescent validation samples, would improve the predictive power to test these hypotheses further. The challenges of relating adult clinical diagnostic constructs such as schizophrenia to adolescent psychotic experiences at a genetic level are discussed

Micro-Level Affect Dynamics in Psychopathology Viewed From Complex Dynamical System Theory

© 2015 ISRE and SAGE. This article discusses the role of moment-to-moment affect dynamics in mental disorder and aims to integrate recent literature on this topic in the context of complex dynamical system theory. First, we will review the relevance of temporal and contextual aspects of affect dynamics in relation to psychopathology. Related to this, we will discuss recent insights resulting from a network view on affect dynamics in psychopathology. Next, we explore how we can reconcile literature findings from a perspective of complex dynamical system theory. Finally, future directions with regard to personalized assessment of risk and diagnostic use are discussed.status: publishe

Early trauma and familial risk in the development of the extended psychosis phenotype in adolescence

Both genetic and environmental factors are thought to play a role in the development of psychotic outcomes; however, their respective contributions over time, including possible developmental interactions, remain largely unknown.status: publishe

Early trauma and familial risk in the development of the extended psychosis phenotype in adolescence

Wigman JTW, van Winkel R, Ormel J, Verhulst FC, van Os J, Vollebergh WAM. Early trauma and familial risk in the development of the extended psychosis phenotype in adolescence. Objective: Both genetic and environmental factors are thought to play a role in the development of psychotic outcomes; however, their respective contributions over time, including possible developmental interactions, remain largely unknown. Method: The contribution of parental general and psychotic psychopathology as proxies of genetic risk to the development of subthreshold psychosis and its hypothesized interaction with childhood trauma were studied in a general population sample of 2230 adolescents, followed from age 1016 years. Outcome measures were: i) level of psychotic experiences at age 16 years and ii) persistence of such experiences over the total follow-up period. Results: General parental psychopathology was associated with CAPE score (OR = 1.08; P < 0.043 for highest quintile) and suggestively predicted psychosis persistence (OR, 1.16; P < 0.072). Psychotic parental psychopathology was suggestively associated with CAPE score (OR, 2.25; P < 0.063 for highest quintile), predicted membership of the Persistent group (OR, 3.72; P < 0.039) and suggestively predicted membership of the Decreasing group (OR 2.04; P < 0.051). Childhood trauma was associated with CAPE score and with all developmental trajectories of subclinical psychosis. No evidence was found for an interaction between trauma and parental psychopathology. Conclusion: The development and persistence of subthreshold psychotic symptoms may be conditional on non-interacting proxy genetic and environmental influences

The Structure of The Extended Psychosis Phenotype in Early Adolescence-A Cross-sample Replication

The extended psychosis phenotype, or the expression of nonclinical positive psychotic experiences, is already prevalent in adolescence and has a dose-response risk relationship with later psychotic disorder. In 2 large adolescent general population samples (n = 5422 and n = 2230), prevalence and structure of the extended psychosis phenotype was investigated. Positive psychotic experiences, broadly defined, were reported by the majority of adolescents. Exploratory analysis with Structural Equation Modelling (Exploratory Factor Analysis followed by Confirmatory Factor Analysis [CFA]) in sample 1 suggested that psychotic experiences were best represented by 5 underlying dimensions; CFA in sample 2 provided a replication of this model. Dimensions were labeled Hallucinations, Delusions, Paranoia, Grandiosity, and Paranormal beliefs. Prevalences differed strongly, Hallucinations having the lowest and Paranoia having the highest rates. Girls reported more experiences on all dimensions, except Grandiosity, and from age 12 to 16 years rates increased. Hallucinations, Delusions, and Paranoia, but not Grandiosity and Paranormal beliefs, were associated with distress and general measures of psychopathology. Thus, only some of the dimensions of the extended psychosis phenotype in young people may represent a continuum with more severe psychopathology and predict later psychiatric disorder

Evidence for a persistent, environment-dependent and deteriorating subtype of subclinical psychotic experiences: a 6-year longitudinal general population study

Research suggests that subclinical psychotic experiences during adolescence represent the behavioral expression of liability for psychosis. Little is known, however, about the longitudinal trajectory of liability in general population samples.status: publishe

Exploring the underlying structure of mental disorders: cross-diagnostic differences and similarities from a network perspective using both a top-down and a bottom-up approach

It has been suggested that the structure of psychopathology is best described as a complex network of components that interact in dynamic ways. The goal of the present paper was to examine the concept of psychopathology from a network perspective, combining complementary top-down and bottom-up approaches using momentary assessment techniques.status: publishe