Dopamine D3 receptor gene variation: impact on electroconvulsive therapy response and ventral striatum responsiveness in depression

Dannlowski, Udo, Domschke, Katharina, Birosova, Eva, Lawford, Bruce, Young, Ross, Voisey, Joanne, Morris, Phillip, Suslow, Thomas, Konrad, Carston, Kugel, Harald, Ohrmann, Patricia, Bauer, Jochen, Schoning, Sonja, Zavorotnyy, Maxim, Diemer, Julia, Arolt, Volker, Baune, Bernard, & Zwanzger, Peter (2013) Dopamine D3 receptor gene variation: impact on electroconvulsive therapy response and ventral striatum responsiveness in depression. International Journal of Neuropsychopharmacology, 16(7), pp. 1443-1459.

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Abstract

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.

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ID Code: 52168
Item Type: Journal Article
Refereed: Yes
Additional Information: Articles free to read on journal website
Keywords: Depression, DRD3, electroconvulsive therapy, Pharmacogenetics, Ventral striatum
DOI: 10.1017/S1461145711001659
ISSN: 1461-1457
Subjects: Australian and New Zealand Standard Research Classification > BIOLOGICAL SCIENCES (060000) > GENETICS (060400) > Neurogenetics (060410)
Australian and New Zealand Standard Research Classification > PSYCHOLOGY AND COGNITIVE SCIENCES (170000) > PSYCHOLOGY (170100) > Biological Psychology (Neuropsychology Psychopharmacology Physiological Psychology) (170101)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Current > Institutes > Institute of Health and Biomedical Innovation
Deposited On: 19 Jul 2012 06:28
Last Modified: 07 Apr 2017 06:21

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