Identifying Gene-Environment Interactions in Schizophrenia: Contemporary Challenges for Integrated, Large-scale Investigations

Abstract

Recent years have seen considerable progress in epidemiological and molecular genetic research into environmental and genetic factors in schizophrenia, but methodological uncertainties remain with regard to validating environmental exposures, and the population risk conferred by individual molecular genetic variants is small. There are now also a limited number of studies that have investigated molecular genetic candidate gene-environment interactions (G × E), however, so far, thorough replication of findings is rare and G × E research still faces several conceptual and methodological challenges. In this article, we aim to review these recent developments and illustrate how integrated, large-scale investigations may overcome contemporary challenges in G × E research, drawing on the example of a large, international, multi-center study into the identification and translational application of G × E in schizophrenia. While such investigations are now well underway, new challenges emerge for G × E research from late-breaking evidence that genetic variation and environmental exposures are, to a significant degree, shared across a range of psychiatric disorders, with potential overlap in phenotype.

IgG dynamics of dietary antigens point to cerebrospinal fluid barrier or flow dysfunction in first-episode schizophrenia

“…Although schizophrenia has a strong heritable component, it is a disorder thought to result from an interaction of both genetic and environmental factors (Demjaha et al, 2012; Modinos et al, 2013; Tsuang, 2000; van Os et al, 2014). A replicated susceptibility locus that is consistent with a gene by environment etiology of schizophrenia is the 6p21 region encoding the major histocompatibility complex and human leukocyte antigen genes (Corvin and Morris, 2014; Purcell et al, 2009; Shi et al, 2009; Stefansson et al, 2009).…”

Psychological processes underlying the association between childhood trauma and psychosis in daily life: an experience sampling study

“…ARMS, At-Risk Mental State for psychosis; CAARMS, Comprehensive Assessment of At-Risk Mental States; FEP, first-episode psychosis; OPCRIT, Operational CRITeria system; SCID, Structured Clinical Interview for DSM Disorders; SOFAS, Social and Occupational Functioning Assessment Scale; SPI-A, Schizophrenia Proneness Instrument – Adult version; WAIS, Wechsler Adult Intelligence Scale.aARMS criteria based on the CAARMS (Yung et al 2005; EU-GEI, 2014): Schizotypal personality disorder plus a recent decline in function [defined as (i) a 30% drop in the SOFAS score (Goldman et al 1992) from premorbid level, sustained for 1 month, and occurring within past 12 months; or (ii) a SOFAS score of ⩽50 for past ⩾12 months].First-degree relative with psychosis plus a recent decline in function (see above).‘Attenuated’ positive psychotic symptoms.Brief psychotic episode of less than one week duration that resolves without antipsychotic medication.…”

Impact of early life adversity on EMG stress reactivity of the trapezius muscle

“…[37] The Childhood Experiences of Care and Abuse questionnaire comprises 15 questions on adverse childhood events, like the divorce of parents, the presence of financial problems, the occurrence of sexual abuse, and so on.…”