Genetic Influences on cortical and subcortical function

This line of research investigates individual differences in cortical and subcortical function from a genetics perspective. Recent advances in the field of genetics have identified a number of common functional polymorphisms in genes influencing neurotransmission that impact upon monoamine modulation of cortical and subcortical function. For example, a common val 158 met polymorphism in the catechol-O-methyltransferase (COMT) gene impacts strongly upon dopamine metabolism in prefrontal regions while a polymorphism in the promoter region of the serotonin transporter gene (5HTT-LPR) has been shown to modulate amygdala function.

In an initial study combining genetic and neuroimaging techniques, we tested the hypothesis that the COMT val 158 met polymorphism would modulate prefrontal function during attentional control over threat-related distractors. This follows findings that the 'met' allele is over-expressed in clinically anxious populations and that individuals with the 'val' allele show more robust recruitment of prefrontal mechanisms during other tasks tapping executive function (working memory). In line with our predictions, COMT val allele load was positively associated with activity in prefrontal control-related regions and activity in regions supporting the representation of task-related stimuli during conditions requiring attentional regulation of threat-related distractors. [Bishop et al. 2006 CABN] Following this initial work, a number of projects are now underway looking at the effects of the COMT val 158 met polymorphism upon prefrontal cortical function [e.g. Bishop et al, 2008, Cerebral Cortex] and at the 5HTT-LPR, BDNF val 66 met and OTR polymorphisms upon neural mechanisms supporting various aspects of emotional and social processing. We are also interested in novel approaches to reducing dimensionality in both genetic and brain data, or in other ways constraining the multiple comparison problem, in order to allow for largescale (e.g. 50,000 SNP) investigations of genetic influences upon brain function.

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