期刊
PLOS ONE
卷 9, 期 5, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0093772
关键词
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资金
- NIH [R01 NS058755, 5M011 RR-00827-29]
- American Heart Association
- Science of Health and Development Initiative at the Center on the Developing Child at Harvard University
- NIMH [K24 MH094614, K01MH099232]
- National Center for Research Resources
- National Center for Advancing Translational Sciences, National Institutes of Health [UL1 TR000153]
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 (beta = -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 (beta = -0.51, p = 0.04). Results were of similar magnitude and in the expected direction in a cohort of healthy adult participants (beta = -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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