Childhood trauma and genetic factors in familial schizophrenia associated with the NOS1AP gene

Abstract

There is some evidence that childhood adversity may be associated with the expression of schizophrenia but whether genetic risk affects this finding is unknown. We investigated the history of early trauma in 194 subjects from 24 multiply affected families where schizophrenia was previously shown to be associated with a functional allele in the NOS1AP gene. In subjects with schizophrenia (n=79), only events prior to the onset of psychosis were considered. Generalized estimating equation models that adjusted for familial clustering were used to estimate odds ratios (ORs) and 95% confidence intervals (CI). Subjects with narrowly defined schizophrenia were more likely than their unaffected family members to have a history of early trauma (adjusted OR=4.17, 95% CI=1.52, 11.44). The results were similar after adjusting for the NOS1AP risk genotype (adjusted OR=3.57, 95% CI=1.32, 9.65) and for maternal or paternal history of schizophrenia (adjusted ORs=3.27, 95% CI=1.45, 7.38; 4.38, 95% CI=1.61, 11.91, respectively). The results suggest that childhood trauma is associated with expression of schizophrenia independent of measured genetic susceptibility and may be a candidate for gene-environment research using genetic variants.

The genetic contribution of the NO system at the glutamatergic post-synapse to schizophrenia: Further evidence and meta-analysis

“…To this end, a Pub Med search was carried out using the keywords "(NOS1AP OR CAPON) AND schizophrenia" as well as "NOS1 AND schizophrenia", to identify all genetic studies on NOS1AP (n=24 retrieved studies) or NOS1 (n=42 retrieved) and schizophrenic disorders. Titles and abstracts were scrutinized to exclude non-genetic studies, reducing the number of included studies to Costain et al, 2010;Fang et al, 2008;Greenwood et al, 2011;Husted et al, 2010;Kremeyer et al, 2009;Miranda et al, 2006;Nicodemus et al, 2008;Wratten et al, 2009) and one on NOS1 (Fallin et al, 2005), presented family-based, but not case-control data and were therefore not integrated in the meta-analysis for methodological reasons. The remaining studies on NOS1AP (n=6; (Aberg et al, 2010;Delorme et al, 2010;Nicodemus et al, 2010;Puri et al, 2007;Puri et al, 2006;Zheng et al, 2005)) and NOS1 (n=14; (Cui et al, 2010;Donohoe et al, 2009;Kawohl et al, 2008;Nicodemus et al, 2010;O'Donoghue et al, 2012;Okumura et al, 2009;Reif et al, 2006;Reif et al, 2011;Riley et al, 2010;Rose et al, 2012;Shinkai et al, 2002;Silberberg et al, 2010;Tang et al, 2008;Wang et al, 2012)) reported on case-control association data and were scrutinized in greater detailed.…”

Childhood trauma, antisocial personality typologies and recent violent acts among inpatient males with severe mental illness: Exploring an explanatory pathway

“…Individuals with severe mental illness (SMI) report elevated rates of traumatic experiences compared to the general population (Spidel et al, 2010) with estimates of lifetime interpersonal trauma exposure ranging between 16% and 98% (Morgan and Fisher, 2007;Husted et al, 2010;Bebbington et al, 2011;Subica et al, 2012). Trauma has been associated with more complex presentations and poorer prognoses among persons with SMI (Alvarez et al, 2011).…”

The effects of childhood abuse on self-reported psychotic symptoms in severe mental illness: Mediating effects of posttraumatic stress symptoms

“…The risk for developing SMI increases up to 33% following childhood abuse (Kessler et al, 2010) and this significant role of childhood abuse remains even after controlling for the presence of psychiatric illness in the parent (Husted et al, 2010). A meta-analysis of 10 prospective studies indicates that exposure to childhood abuse significantly increases the risk for the development of psychosis (Varese et al, 2012).…”