title: Dopamine D₃ receptor gene variation: impact on electroconvulsive therapy response and ventral striatum responsiveness in depression.
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.
authors.affiliation: Department of Psychiatry, University of Muenster, Germany.
authors.forename: Udo
authors.initials: U
authors.lastname: Dannlowski
authors.forename: Katharina
authors.initials: K
authors.lastname: Domschke
authors.forename: Eva
authors.initials: E
authors.lastname: Birosova
authors.forename: Bruce
authors.initials: B
authors.lastname: Lawford
authors.forename: Ross
authors.initials: R
authors.lastname: Young
authors.forename: Joanne
authors.initials: J
authors.lastname: Voisey
authors.forename: C Phillip
authors.initials: CP
authors.lastname: Morris
authors.forename: Thomas
authors.initials: T
authors.lastname: Suslow
authors.forename: Carsten
authors.initials: C
authors.lastname: Konrad
authors.forename: Harald
authors.initials: H
authors.lastname: Kugel
authors.forename: Patricia
authors.initials: P
authors.lastname: Ohrmann
authors.forename: Jochen
authors.initials: J
authors.lastname: Bauer
authors.forename: Sonja
authors.initials: S
authors.lastname: Schöning
authors.forename: Maxim
authors.initials: M
authors.lastname: Zavorotnyy
authors.forename: Julia
authors.initials: J
authors.lastname: Diemer
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.forename: Bernhard T
authors.initials: BT
authors.lastname: Baune
authors.forename: Peter
authors.initials: P
authors.lastname: Zwanzger
mesh_terms: D000328:Adult; D000368:Aged; D001479:Basal Ganglia / Q000098:blood supply / Q000503:physiopathology*; D003865:Major Depressive Disorder / Q000235:genetics* / Q000628:therapy*; D004565:Electroconvulsive Therapy / Q000379:methods*; D005145:Face; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010100:Oxygen / Q000097:blood; D010364:Pattern Recognition, Visual / Q000502:physiology; D010775:Photic Stimulation; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D050637:Receptors, Dopamine D3 / Q000235:genetics*
chemical_list: D050637:Receptors, Dopamine D3; D010100:Oxygen