Striatal Response to Reward Anticipation Evidence for a Systems-Level Intermediate Phenotype for Schizophrenia
Striatal Response to Reward Anticipation Evidence for a Systems-Level Intermediate Phenotype for Schizophrenia
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DOI：
10.1001/jamapsychiatry.2014.9
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发表时间：
2014-05-01
期刊：
影响因子：
25.8
通讯作者：
Meyer-Lindenberg, Andreas
中科院分区：
文献类型：
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作者：
Grimm, Oliver;Heinz, Andreas;Meyer-Lindenberg, Andreas
重要性奖励预期期间腹侧纹状体反应减弱是精神分裂症的核心特征，常见于前驱期、药物初治和慢性精神分裂症患者。精神分裂症是高度遗传性的，提高了这种表型的可能性是相关的遗传风险disorder.Objective检查一个大样本的健康的一级亲属的精神分裂症患者和比较他们的神经反应奖励预期与那些仔细匹配的控制没有家族精神病史。为了进一步支持这种表型的实用性，我们通过荟萃分析研究了其重测信度、潜在的脑结构贡献以及与精神分裂症相关的神经调节蛋白1（NRG 1）保护性错义变体的作用（即，rs 10503929）。设计、环境、A.对妇女和女童的教育在大学医院功能性磁共振成像期间建立金钱奖励预期范式;基于体素的形态测量;在25名健康参与者的独立样本中，用相同的任务扫描两次，对纹状体激活进行重测信度分析;以及对照组的成像遗传学分析。共54名精神分裂症患者的健康一级亲属和80名对照者的人口学、心理学、临床和任务绩效特征进行了研究。主要结果和指标：奖励预期期间的血氧水平依赖性反应，功能对比的组内相关分析，以及纹状体灰质体积与NRG 1基因型之间的关联。健康的一级亲属在奖励预期过程中腹侧纹状体激活显著降低（家庭误差校正P . 05），并受NRG 1基因型的影响（具有保护性rs 10503929 C等位基因的对照组纹状体反应更高;家族误差校正P
IMPORTANCE Attenuated ventral striatal response during reward anticipation is a core feature of schizophrenia that is seen in prodromal, drug-naive, and chronic schizophrenic patients. Schizophrenia is highly heritable, raising the possibility that this phenotype is related to the genetic risk for the disorder.OBJECTIVE To examine a large sample of healthy first-degree relatives of schizophrenic patients and compare their neural responses to reward anticipation with those of carefully matched controls without a family psychiatric history. To further support the utility of this phenotype, we studied its test-retest reliability, its potential brain structural contributions, and the effects of a protective missense variant in neuregulin 1 (NRG1) linked to schizophrenia by meta-analysis (ie, rs10503929).DESIGN, SETTING, AND PARTICIPANTS Examination of awell-established monetary reward anticipation paradigm during functional magnetic resonance imaging at a university hospital; voxel-based morphometry; test-retest reliability analysis of striatal activations in an independent sample of 25 healthy participants scanned twice with the same task; and imaging genetics analysis of the control group. A total of 54 healthy first-degree relatives of schizophrenic patients and 80 controls matched for demographic, psychological, clinical, and task performance characteristics were studied.MAIN OUTCOMES AND MEASURES Blood oxygen level-dependent response during reward anticipation, analysis of intraclass correlations of functional contrasts, and associations between striatal gray matter volume and NRG1 genotype.RESULTS Compared with controls, healthy first-degree relatives showed a highly significant decrease in ventral striatal activation during reward anticipation (familywise error-corrected P . 05), and affected by the NRG1 genotype (higher striatal responses in controls with the protective rs10503929 C allele; familywise error-corrected P