Animal models of gene–environment interaction in schizophrenia: A dimensional perspective

Abstract

Schizophrenia has long been considered as a disorder with multifactorial origins. Recent discoveries have advanced our understanding of the genetic architecture of the disease. However, even with the increase of identified risk variants, heritability estimates suggest an important contribution of non-genetic factors. Various environmental risk factors have been proposed to play a role in the etiopathogenesis of schizophrenia. These include season of birth, maternal infections, obstetric complications, adverse events at early childhood, and drug abuse. Despite the progress in identification of genetic and environmental risk factors, we still have a limited understanding of the mechanisms whereby gene-environment interactions (GxE) operate in schizophrenia and psychoses at large. In this review we provide a critical analysis of current animal models of GxE relevant to psychotic disorders and propose that dimensional perspective will advance our understanding of the complex mechanisms of these disorders.

Predicting brain structure in population‐based samples with biologically informed genetic scores for schizophrenia

“…Separating these genetic from environmental influences is quite difficult. Most co‐factors may be environmental in nature, and include effects of stressful life events, prenatal infections, perinatal hypoxia, or substance abuse which are known risk factors for schizophrenia [van Os et al, ; Schmidt‐Kastner et al, ; Ayhan et al, ]. Also genetic epistasis between variants may be a relevant factor [Sadee et al, ].…”

Maternal immune activation: Implications for neuropsychiatric disorders

“…MIA appears to act as a “disease primer”(14) to make an individual more susceptible to the effects of genetic mutations and environmental exposures in triggering disease-related symptoms later in life(41). Consistent with this idea, the incidence of both ASD and SZ is much higher in families with autoimmune disorders(2, 6) and the effect of maternal infection in increasing SZ risk is greater in families with a history of SZ(3).…”

Maternal immune activation in neurodevelopmental disorders

“…Intriguingly, an analysis in a relatively small cohort of the interaction between polymorphism in sialyltransferase (ST8SIA2), a susceptibility gene for schizophrenia, and the incidence of stressful life events showed a trend toward a certain amount of stress being protective against the disorder (Mandelli et al, 2016). An increasing number of human and animal studies have found interacting effects of genetic mutations and environmental factors (including MIA) on the manifestation of schizophrenialike symptoms (Ayhan et al, 2016). An increasing number of human and animal studies have found interacting effects of genetic mutations and environmental factors (including MIA) on the manifestation of schizophrenialike symptoms (Ayhan et al, 2016).…”

“…A recent study showed a genetic association of schizophrenia with allelic variants of complement component C4, a protein involved in an innate immune system pathway that rapidly recognizes and eliminates pathogens and cellular debris (Sekar et al, 2016). An increasing number of human and animal studies have found interacting effects of genetic mutations and environmental factors (including MIA) on the manifestation of schizophrenialike symptoms (Ayhan et al, 2016).…”