Association of a dopamine beta-hydroxylase gene variant with depression in elderly women possibly reflecting noradrenergic dysfunction.
BACKGROUND
Depression has a multifactorial etiology which involves genetic factors and comorbid diseases.


METHODS
A cross-sectional sample of 1371 elderly women (mean age=69.2 years) was examined. Detailed information on their health was obtained. Cognitive functions were assessed by the Short Blessed Test and the Animal Naming Task. A 19 bp insertion/deletion polymorphism in the dopamine beta-hydroxylase (DBH) gene, the apolipoprotein (APOE) epsilon2/epsilon3/epsilon4 variation and 5-HTTLPR in the serotonin transporter gene were genotyped.


RESULTS
Depression was univariately associated with homozygosity for the DBH gene 19 bp deletion allele (odds ratio [OR]=1.96, 95% confidence intervals [95% CI]=1.17-3.29, p=0.01), family history of depression (OR=3.86, 95% CI=1.85-8.06, p=0.0003), a composite measure of cardiovascular diseases (OR=1.96, 95% CI=1.11-3.47, p=0.02), cognitive impairment assessed by the Short Blessed Test (OR=3.88, 95% CI=1.29-11.64, p=0.02) and performance on the Animal Naming Task (OR=0.74, 95% CI=0.59-0.93, p=0.01). The strength of the association of DBH genotype with depression essentially remained unchanged after correction for other variables in a multivariate model. This association may reflect noradrenaline dysfunction in the brain.
Togsverd
Mads
M
Research Institute of Biological Psychiatry, Sct. Hans Hospital, Roskilde, Copenhagen University, Denmark.
Werge
Thomas M
TM
Tankó
Laszlo B
LB
Bagger
Yu Z
YZ
Hansen
Thomas
T
Qin
Gerong
G
Christiansen
Claus
C
Rasmussen
Henrik B
HB
D000368:Aged; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics; D002318:Cardiovascular Diseases / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D015897:Comorbidity; D003430:Cross-Sectional Studies; D003704:Dementia / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics; D003718:Denmark; D003866:Depressive Disorder / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D004299:Dopamine beta-Hydroxylase / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics*; D008875:Middle Aged; D009638:Norepinephrine / Q000502:physiology*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies; D012307:Risk Factors; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics
D001057:Apolipoproteins E; C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D004299:Dopamine beta-Hydroxylase; D009638:Norepinephrine