|Publication Type||Journal Article|
|Year of Publication||2014|
|Authors||Pearson-Fuhrhop, KM, Dunn, EC, Mortero, S, Devan, WJ, Falcone, GJ, Lee, P, Holmes, AJ, Hollinshead, MO, Roffman, JL, Smoller, JW, Rosand, J, Cramer, SC|
|Keywords||Adult, Catechol O-Methyltransferase, Depression, Dopamine Plasma Membrane Transport Proteins, Genetic Variation, Genotype, Humans, Linear Models, Phenotype, Receptors, Dopamine, Risk Assessment|
BACKGROUND: 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.
|Alternate Journal||PLoS ONE|
|PubMed Central ID||PMC4023941|
|Grant List||K24 MH094614 / MH / NIMH NIH HHS / United States |
K99 MH101367 / MH / NIMH NIH HHS / United States
5M011 RR-00827-29 / RR / NCRR NIH HHS / United States
K01MH099232 / MH / NIMH NIH HHS / United States
R01 NS058755 / NS / NINDS NIH HHS / United States
K24 HD074722 / HD / NICHD NIH HHS / United States
UL1 TR000153 / TR / NCATS NIH HHS / United States
K01 MH099232 / MH / NIMH NIH HHS / United States