Abstract
IntroductionPrevious research has indicated that variation in genes encoding catechol‐O‐methyltransferase (COMT) and dopamine receptor D2 (DRD2) may influence cognitive function and that this may confer vulnerability to the development of mental health disorders such as schizophrenia. However, increasing evidence suggests environmental factors such as early life stress may interact with genetic variants in affecting these cognitive outcomes. This study investigated the effect of COMT Val158Met and DRD2 C957T polymorphisms on executive function and the impact of early life stress in healthy adults.MethodsOne hundred and twenty‐two healthy adult males (mean age 35.2 years, range 21–63) were enrolled in the study. Cognitive function was assessed using Cambridge Neuropsychological Test Automated Battery and early life stress was assessed using the Childhood Traumatic Events Scale (Pennebaker & Susman, 1988).Results DRD2 C957T was significantly associated with executive function, with CC homozygotes having significantly reduced performance in spatial working memory and spatial planning. A significant genotype–trauma interaction was found in Rapid Visual Information Processing test, a measure of sustained attention, with CC carriers who had experienced early life stress exhibiting impaired performance compared to the CC carriers without early life stressful experiences. There were no significant findings for COMT Val158Met.ConclusionsThis study supports previous findings that DRD2 C957T significantly affects performance on executive function related tasks in healthy individuals and shows for the first time that some of these effects may be mediated through the impact of childhood traumatic events. Future work should aim to clarify further the effect of stress on neuronal systems that are known to be vulnerable in mental health disorders and more specifically what the impact of this might be on cognitive function.
Highlights
Previous research has indicated that variation in genes encoding catechol-O-methyltransferase (COMT) and dopamine receptor D2 (DRD2) may influence cognitive function and that this may confer vulnerability to the development of mental health disorders such as schizophrenia
It has been proposed that individual vulnerability and sensitization to the later development of mental health disorders may partly be regulated through variation in genes encoding proteins that impact on neurotransmitter and hormone systems such as those involved in dopamine, serotonin, and cortisol function (Caspi & Moffitt, 2006; Collip, Myin-Germeys, & Van Os, 2008; van Winkel, Stefanis, & Myin- Germeys, 2008; van Winkel, van Nierop, Myin-Germeys, & van Os, 2013)
Results from two-way analysis of covariance (ANCOVA) with DRD2 C957T genotype and childhood trauma category as fixed factors and age and education as covariates showed that DRD2 C957T polymorphism had a significant main effect on the number of errors made in the spatial working memory (SWM) test (F2,114 = 4.664, p = .011, partial η2 = .076)
Summary
Ever since the mapping of the human genome, identification of genetic determinants of complex psychiatric disorders such as schizophrenia, major depression or bipolar disorder has proven challenging (Allen et al, 2008). Understanding how certain genetic vulnerabilities might affect or impair cognitive processes mediated by the prefrontal cortex (PFC) is of great importance given the functional abnormalities of the PFC present in schizophrenia and bipolar disorder (Pennington et al, 2008). The genetic studies looking at the association of DRD2 C957T with cognitive function have generally shown that CC homozygosity is associated with poorer performance on tests of executive function and working memory in the general population (Rodriguez-Jimenez et al, 2006; Xu et al, 2007), decreased general cognitive ability in elderly healthy males and females (Bolton et al, 2010), impaired executive function and cognitive flexibility in HIV-infected individuals who abuse alcohol (Villalba, Devieux, Rosenberg, & Cadet, 2015), and poorer performance in an attentional switching task in CC homozygotic females (Gurvich & Rossell, 2015). Prefrontal cortical D2 receptors are proposed to affect responsivity to stress via subcortical projections by attenuating dopamine release in the midbrain via a negative feedback system (Deutch, 1993)
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