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, C. Phillip, Suslow, Thomas, Konrad, Carsten, Kugel, Harald, Ohrmann, Patricia, Bauer, Jochen, Schöning, Sonja, Zavorotnyy, Maxim, Diemer, Julia, Arolt, Volker, Baune, Bernhard T., and 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

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.

Item ID: 32148
Item Type: Article (Refereed Research - C1)
Keywords: depression, DRD3, electroconvulsive therapy, pharmacogenetics, ventral striatum
ISSN: 1469-5111
Funders: Deutsche Forschungsgemeinschaft (DFG), Innovative Medizinische Forschung, Rolf-Dierichs-Stiftung, National Health and Medical Research Council (NHMRC)
Projects and Grants: DFG (SFB-TRR-58), Innovative Medizinische Forschung (IMF DA120309), Rolf-Dierichs-Stiftung (ZUW80037), NHMRC (ID 512381, ID 510124, ID 512672, APP 1003788)
Date Deposited: 29 Apr 2014 00:38
FoR Codes: 11 MEDICAL AND HEALTH SCIENCES > 1109 Neurosciences > 110999 Neurosciences not elsewhere classified @ 100%
SEO Codes: 92 HEALTH > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions) > 920111 Nervous System and Disorders @ 100%
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