Dopamine D-3 receptor gene variation: impact on electroconvulsive therapy response and ventral striatum responsiveness in depression

作者：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; Schoening Sonja; Zavorotnyy Maxim; Diemer Julia; Arolt Volker; Baune Bernhard T; Zwanzger Peter

来源：International Journal of Neuropsychopharmacology, 2013, 16(7): 1443-1459.

DOI：10.1017/S1461145711001659

• Depression
• DRD3
• electroconvulsive therapy
• pharmacogenetics
• ventral striatum

Dysfunction of dopamine D-3 receptors, particularly in the mesocorticolimbic system, has been linked to the pathogenesis of major depression. Preclinical data show enhanced D-3 receptor binding in the striatum upon antidepressant medication and electroconvulsive therapy (ECT). Thus, the potential impact of dopamine D-3 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.

• 出版日期2013-8