Richter Anni, Barman Adriana, Wüstenberg Torsten, Soch Joram, Schanze Denny, Deibele Anna, Behnisch Gusalija, Assmann Anne, Klein Marieke, Zenker Martin, Seidenbecher Constanze, Schott Björn H
Leibniz Institute for NeurobiologyMagdeburg, Germany.
Department of Psychiatry and Psychotherapy, Charité University HospitalBerlin, Germany.
Front Psychol. 2017 May 1;8:654. doi: 10.3389/fpsyg.2017.00654. eCollection 2017.
Dopamine is critically important in the neural manifestation of motivated behavior, and alterations in the human dopaminergic system have been implicated in the etiology of motivation-related psychiatric disorders, most prominently addiction. Patients with chronic addiction exhibit reduced dopamine D2 receptor (DRD2) availability in the striatum, and the TaqIA (rs1800497) and C957T (rs6277) genetic polymorphisms have previously been linked to individual differences in striatal dopamine metabolism and clinical risk for alcohol and nicotine dependence. Here, we investigated the hypothesis that the variants of these polymorphisms would show increased reward-related memory formation, which has previously been shown to jointly engage the mesolimbic dopaminergic system and the hippocampus, as a potential intermediate phenotype for addiction memory. To this end, we performed functional magnetic resonance imaging (fMRI) in 62 young, healthy individuals genotyped for TaqIA and C957T variants. Participants performed an incentive delay task, followed by a recognition memory task 24 h later. We observed effects of both genotypes on the overall recognition performance with carriers of low-expressing variants, namely TaqIA A1 carriers and C957T C homozygotes, showing better performance than the other genotype groups. In addition to the better memory performance, C957T C homozygotes also exhibited a response bias for cues predicting monetary reward. At the neural level, the C957T polymorphism was associated with a genotype-related modulation of right hippocampal and striatal fMRI responses predictive of subsequent recognition confidence for reward-predicting items. Our results indicate that genetic variations associated with DRD2 expression affect explicit memory, specifically for rewarded stimuli. We suggest that the relatively better memory for rewarded stimuli in carriers of low-expressing variants may reflect an intermediate phenotype of addiction memory.
多巴胺在动机性行为的神经表现中至关重要，人类多巴胺能系统的改变与动机相关精神疾病的病因有关，其中最突出的是成瘾。慢性成瘾患者纹状体中多巴胺D2受体（DRD2）的可用性降低，而TaqIA（rs1800497）和C957T（rs6277）基因多态性先前已与纹状体多巴胺代谢的个体差异以及酒精和尼古丁依赖的临床风险相关联。在此，我们研究了这样一个假设，即这些多态性的变体将显示出与奖励相关的记忆形成增加，此前已表明这种记忆形成会共同激活中脑边缘多巴胺能系统和海马体，作为成瘾记忆的潜在中间表型。为此，我们对62名年轻健康个体进行了功能磁共振成像（fMRI），这些个体对TaqIA和C957T变体进行了基因分型。参与者执行了一项激励延迟任务，随后在24小时后进行了一项识别记忆任务。我们观察到两种基因型对总体识别表现都有影响，低表达变体的携带者，即TaqIA A1携带者和C957T C纯合子，表现优于其他基因型组。除了更好的记忆表现外，C957T C纯合子还对预测金钱奖励的线索表现出反应偏差。在神经层面，C957T多态性与右侧海马体和纹状体fMRI反应的基因型相关调节有关，这种调节可预测随后对奖励预测项目的识别信心。我们的结果表明，与DRD2表达相关的基因变异会影响外显记忆，但对奖励刺激的记忆影响尤为明显。我们认为，低表达变体携带者对奖励刺激相对更好的记忆可能反映了成瘾记忆的一种中间表型。
