Positive
association between the dopamine D4 receptor
gene (DRD4) and mood disorders
Dopamine
neurotransmission is altered in mood disorders
and the dopamine D4 receptor gene (DRD4) has
been suggested to be a candidate gene for
depression. Some studies have reported
associations between DRD4
alleles and unipolar depressive disorder (UP)
and bipolar depressive disorder (BP), while
others have failed to confirm these findings,
possibly due to their small sample size. A
meta-analysis was conducted to re-evaluate the
role of the DRD4 gene 48-base-pair-repeat
polymorphism in UP or BP.
The analysis, based on Medline search for
publications, was limited to studies using a
patient-control design and studies that reported
allele frequencies. There were three groups of
patients, UP, BP, and both combined. The data
from 12 studies of 917 patients and 1164 control
individuals were pooled. The effects of the
three most prevalent alleles: two-repeat
(DRD4.2), four-repeat (DRD4.4), and seven-repeat
(DRD4.7) were examined. In addition, the
association of mood disorders with short
(one-repeat to four-repeat) versus long alleles
(five-repeat to ten-repeat) was also
determined.
There was an association between DRD4.2 and all
mood disorder groups. The link between DRD4.2
and BP lost significance when multiple testing
was corrected, however an association between
the DRD4.2 allele and UP and the combined group
remained evident. No association was found with
the other alleles tested or when divided into
short and long alleles.
The association between DRD4.2 allele and two
groups, UP and UP and BP combined, suggests that
the DRD4.2 allele is a risk allele for
depression symptomatology confirming that the
DRD4 gene does represents a susceptibility gene
for mood disorders. These findings also show
that meta-analyses are useful for association
studies in psychiatric genetics compared to
small sample sized studies which lack
statistical power. Lopez
Leon S, Croes EA, Sayed-Tabatabaei FA, Claes S,
Van Broeckhoven C, van Duijn CM. The dopamine D4
receptor gene 48-base-pair-repeat polymorphism
and mood disorders: a meta-analysis. Biol
Psychiatry 2005, 57:999-1003.