Format

Send to

Choose Destination
PLoS One. 2014 May 16;9(5):e93772. doi: 10.1371/journal.pone.0093772. eCollection 2014.

Dopamine genetic risk score predicts depressive symptoms in healthy adults and adults with depression.

Author information

1
Department of Anatomy and Neurobiology, University of California Irvine, Irvine, California, United States of America.
2
Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States of America; Stanley Center for Psychiatric Research, The Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America.
3
Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America.
4
Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States of America; Department of Psychology, Yale University, New Haven, Connecticut, United States of America.
5
Department of Psychology, Center for Brain Science, Harvard University, Cambridge, Massachusetts, United States of America.
6
Department of Psychiatry, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States of America.
7
Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, United States of America; Department of Neurology, Massachusetts General Hospital/Harvard Medical School, Boston, Massachusetts, United States of America; Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, Massachusetts, United States of America.
8
Department of Anatomy and Neurobiology, University of California Irvine, Irvine, California, United States of America; Department of Neurology, University of California Irvine, Irvine, California, United States of America.

Abstract

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.

PMID:
24834916
PMCID:
PMC4023941
DOI:
10.1371/journal.pone.0093772
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center