Laureate Institute for Brain Research, Tulsa, OK 74136, USA.
Int J Neuropsychopharmacol. 2013 Oct;16(9):2095-101. doi: 10.1017/S146114571300045X. Epub 2013 May 20.
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.
DRD2/ANKK1 Taq1A 多态性(rs1800497)的 A1 等位基因与健康个体(对照组)的纹状体 D2/3 受体结合减少以及抑郁和成瘾有关。然而,rs1800497 对抑郁患者的 D2/3 受体结合的影响以及该 SNP 在与奖励相关的多巴胺释放期间对 D2/3 结合的影响尚不清楚。12 名未经药物治疗的重度抑郁症(MDD)患者和 24 名对照组完成了 [(11)C]raclopride 的 PET 扫描,一次是在没有获得金钱奖励的情况下(基线),一次是在赢得金钱时。在对照组中,A1 等位基因与中尾状核和腹侧纹状体的基线结合潜能(BP(ND))降低有关。然而,在 MDD 患者中,A1 等位基因与这些区域的基线 BP(ND)增加有关。rs1800497 与与奖励相关的多巴胺释放期间 BP(ND)变化之间没有显著关联。可以想象,A1 等位基因通过对突触后 D2 受体的影响,导致抑郁和成瘾。