Lack of influence of DAT1 and DRD2 gene variants on antidepressant response in generalized anxiety disorder.
OBJECTIVE
Although antidepressant drugs are used as first-line intervention to treat patients with generalized anxiety disorder (GAD), only one-third of patients respond positively to treatment. In our study, we investigated whether functional genetic polymorphisms in the dopamine active transporter 1 (DAT1) and dopamine receptor D2 (DRD2) may play a role in antidepressant treatment response in GAD.


METHODS
We examined 156 patients diagnosed with GAD who received venlafaxine Extended-Release (XR) treatment as part of an 18-month relapse-prevention study to determine whether variation in these genes had an effect on treatment response after 6 months of open-label treatment. Genotypes were obtained for rs1076560 (DRD2), rs1800497 (DRD2), rs2550948 (DAT1), and a variable number tandem repeat in the 3' untranslated region of the DAT1 gene using standard methods.


RESULTS
Results show that none of the tested variants were associated with treatment response to venlafaxine XR in GAD. Genotype and allele frequencies did not differ statistically significantly between responders and non-responders using either the Hamilton Anxiety or Clinical Global Impressions of Improvement Scale at 6 months.


CONCLUSIONS
Although we detected no association in our sample, future studies using larger samples and more comprehensive gene coverage are needed to evaluate potential effects of dopaminergic variants on antidepressant treatment response in anxiety disorders.
Psychiatric Pharmacogenetics Laboratory, Center for Neurobiology and Behavior, Department of Psychiatry, University of Pennsylvania School of Medicine, Philadelphia, PA, USA.
Wint Thu
WT
Saung
Sneha
S
Narasimhan
Falk W
FW
Lohoff
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000235:genetics*; D003511:Cyclohexanols / Q000008:administration & dosage*; D003692:Delayed-Action Preparations; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D004311:Double-Blind Method; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D016896:Treatment Outcome; D000069470:Venlafaxine Hydrochloride; D055815:Young Adult
D000928:Antidepressive Agents; D003511:Cyclohexanols; C581293:DRD2 protein, human; D003692:Delayed-Action Preparations; D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; D000069470:Venlafaxine Hydrochloride
DAT1; DRD2; antidepressant treatment response; anxiety disorders; dopamine; pharmacogenetics