Dopamine Genetic Risk Score Predicts Depressive Symptoms in Healthy Adults and Adults with Depression
Pearson-Fuhrhop, Kristin M.
Devan, William J.
Cramer, Steven C.Note: Order does not necessarily reflect citation order of authors.
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CitationPearson-Fuhrhop, K. M., E. C. Dunn, S. Mortero, W. J. Devan, G. J. Falcone, P. Lee, A. J. Holmes, et al. 2014. “Dopamine Genetic Risk Score Predicts Depressive Symptoms in Healthy Adults and Adults with Depression.” PLoS ONE 9 (5): e93772. doi:10.1371/journal.pone.0093772. http://dx.doi.org/10.1371/journal.pone.0093772.
AbstractBackground: Depression is a common source of human disability for which etiologic insights remain limited. Although abnormalities of monoamine neurotransmission, including dopamine, are theorized to contribute to the pathophysiology of depression, evidence linking dopamine-related genes to depression has been mixed. The current study sought to address this knowledge-gap by examining whether the combined effect of dopamine polymorphisms was associated with depressive symptomatology in both healthy individuals and individuals with depression. Methods: Data were drawn from three independent samples: (1) a discovery sample of healthy adult participants (n = 273); (2) a replication sample of adults with depression (n = 1,267); and (3) a replication sample of healthy adult participants (n = 382). A genetic risk score was created by combining functional polymorphisms from five genes involved in synaptic dopamine availability (COMT and DAT) and dopamine receptor binding (DRD1, DRD2, DRD3). Results: In the discovery sample, the genetic risk score was associated with depressive symptomatology (β = −0.80, p = 0.003), with lower dopamine genetic risk scores (indicating lower dopaminergic neurotransmission) predicting higher levels of depression. This result was replicated with a similar genetic risk score based on imputed genetic data from adults with depression (β = −0.51, p = 0.04). Results were of similar magnitude and in the expected direction in a cohort of healthy adult participants (β = −0.86, p = 0.15). Conclusions: Sequence variation in multiple genes regulating dopamine neurotransmission may influence depressive symptoms, in a manner that appears to be additive. Further studies are required to confirm the role of genetic variation in dopamine metabolism and depression.
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