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Depression is a serious, costly, and heterogeneous disorder for which no one genetic determinant has been identified. Research has shown that stress, and subsequent hypothalamic-pituitary-adrenal (HPA) axis dysregulation, is a significant predictor of depression, and one particular stressor that has been linked to vulnerability to depression and HPA axis dysregulation is early life trauma. Due to the heterogeneity and complexity of depression, it is likely that specific gene-environment interactions play a role in the development of depression. Interaction between catechol-O-methyltransferase (COMT) Val158Met variants with specific environmental factors can potentially increase vulnerability to depression. The present proposed experiment examines the interaction between COMT genotype and the effects of early life stress in a maternal separation paradigm on behavioral and neurological factors in a rodent model of depression. Outcome measures include anhedonia-like behavior, as indexed by performance on a sucrose consumption test, and striatal dopamine concentration, a neurological measure of depression. I hypothesize that across genotype, stress leads to decreased sucrose consumption and decreased striatal dopamine concentrations. However, the functional COMT Val158Met polymorphism will interact with stress such that these results are most pronounced among stressed Met/Met rats, as compared to Val/Met rats and Val/Val rats. These results may have implications for treatment of depression in COMT polymorphic individuals, who appear to be more sensitive to stress and more vulnerable to developing depression.
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Cole, Sally Lauren, "Effects of Early Life Stress on Anhedonia and Striatal Dopamine Concentration Depends on Variation in catechol-O-methyltransferase (COMT) Genotype" (2016). Senior Projects Spring 2016. 232.