title: DRD2/ANKK1 Taq1A polymorphism (rs1800497) has opposing effects on D2/3 receptor binding in healthy controls and patients with major depressive disorder.
abstract: The A1 allele of the DRD2/ANKK1 Taq1A polymorphism (rs1800497) is associated with reduced striatal D(2/3) receptor binding in healthy individuals (Con) as well as depression and addiction. However, the effect of rs1800497 on D(2/3) receptor binding in depressed patients as well as the SNP's effect on D(2/3) binding during reward-associated dopamine release is unknown. Twelve unmedicated patients with major depressive disorder (MDD) and 24 Con completed PET scans with [(11)C]raclopride, once without receiving monetary rewards (baseline) and once while winning money. In Con, the A1 allele was associated with reduced baseline binding potential (BP(ND)) in the middle caudate and ventral striatum. However, in MDD patients the A1 allele was associated with increased baseline BP(ND) in these regions. There were no significant associations between rs1800497 and change in BP(ND) during reward-associated dopamine release. Conceivably, the A1 allele predisposes to depression and addiction via its effect on the post-synaptic D(2) receptor.
authors.affiliation: Laureate Institute for Brain Research, Tulsa, OK 74136, USA. jonathansavitz@hotmail.com
authors.forename: Jonathan
authors.initials: J
authors.lastname: Savitz
authors.forename: Colin A
authors.initials: CA
authors.lastname: Hodgkinson
authors.forename: Chantal
authors.initials: C
authors.lastname: Martin-Soelch
authors.forename: Pei-Hong
authors.initials: PH
authors.lastname: Shen
authors.forename: Joanna
authors.initials: J
authors.lastname: Szczepanik
authors.forename: Allison C
authors.initials: AC
authors.lastname: Nugent
authors.forename: Peter
authors.initials: P
authors.lastname: Herscovitch
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Grace
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.forename: Wayne C
authors.initials: WC
authors.lastname: Drevets
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D016022:Case-Control Studies; D003865:Major Depressive Disorder / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism* / Q000523:psychology; D018492:Dopamine Antagonists / Q000378:metabolism; D005260:Female; D005715:Gambling; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D049268:Positron-Emission Tomography; D020891:Raclopride / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000235:genetics* / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*; D012201:Reward
chemical_list: C581293:DRD2 protein, human; C493593:DRD3 protein, human; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D020891:Raclopride