Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/71279
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Type: Journal article
Title: Dopamine D₃ receptor gene variation: impact on electroconvulsive therapy response and ventral striatum responsiveness in depression
Other Titles: Dopamine D(3) receptor gene variation: impact on electroconvulsive therapy response and ventral striatum responsiveness in depression
Author: Dannlowski, U.
Domschke, K.
Birosova, E.
Lawford, B.
Young, R.
Voisey, J.
Morris, P.
Suslow, T.
Konrad, C.
Kugel, H.
Ohrmann, P.
Bauer, J.
Schoning, S.
Zavorotnyy, M.
Diemer, J.
Arolt, V.
Baune, B.
Zwanzger, P.
Citation: International Journal of Neuropsychopharmacology, 2013; 16(7):1443-1459
Publisher: Cambridge Univ Press
Issue Date: 2013
ISSN: 1461-1457
1469-5111
Statement of
Responsibility: 
Udo Dannlowski, Katharina Domschke, Eva Birosova, Bruce Lawford, Ross Young, Joanne Voisey, C. Phillip Morris, Thomas Suslow, Carsten Konrad, Harald Kugel, Patricia Ohrmann, Jochen Bauer, Sonja Schöning, Maxim Zavorotnyy, Julia Diemer, Volker Arolt, Bernhard T. Baune and Peter Zwanzger
Abstract: Dysfunction of dopamine D₃ receptors, particularly in the mesocorticolimbic system, has been linked to the pathogenesis of major depression. Preclinical data show enhanced D₃ receptor binding in the striatum upon antidepressant medication and electroconvulsive therapy (ECT). Thus, the potential impact of dopamine D₃ receptor gene (DRD3) variation on ECT outcome in treatment-resistant major depression was evaluated by applying a combined molecular and imaging genetic approach. Altogether, 10 representative variants covering 95.4% of DRD3 gene variation were investigated for association with response to ECT in a sample of 104 (71 female, 33 male) Caucasian patients with pharmacorefractory major depression. Additionally, ventral striatum responsiveness to happy faces was assessed in two independent samples of depressed patients (total N=54) by means of functional magnetic resonance imaging at 3 T. Significant association of DRD3 rs3732790, rs3773679 and rs9817063 variants with response (uncorrected p=0.02-0.03) and remission (uncorrected p=0.01) after ECT was discerned. Logistic regression analyses revealed association of rs3732790 (uncorrected p=0.009; corrected p=0.045) and rs3773679 (uncorrected p=0.009; corrected p=0.045) with remission when applying a recessive model of inheritance. The rs3732790T allele conferring a more favourable treatment response was furthermore found to be associated with stronger striatal responsiveness to happy facial expressions (sample 1: cluster-corrected p=0.002; sample 2: p=0.023). In summary, the present study suggests some impact of DRD3 gene variation on ECT response, potentially mediated by alteration of striatal engagement during the processing of emotionally rewarding stimuli.
Keywords: Depression; DRD₃; electroconvulsive therapy; pharmacogenetics; ventral striatum.
Rights: © CINP 2011
RMID: 0020118590
DOI: 10.1017/S1461145711001659
Appears in Collections:Psychiatry publications

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