Unsuppressed Striatal Activity and Genetic Risk for Schizophrenia Associated With Individual Cognitive Performance Under Social Competition.

Unsuppressed Striatal Activity and Genetic Risk for Schizophrenia Associated With Individual Cognitive Performance Under Social Competition.
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不受抑制的纹状体活动和精神分裂症的遗传风险与社会竞争下的个人认知表现相关。

DOI:
10.1093/schbul/sbac010
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发表时间:
2022
影响因子:
6.6
通讯作者:
Yan,Hao
Yan,Hao
中科院分区:
医学1区
文献类型:
--
作者:
Zhang,Yuyanan;Li,Mingzhu;Zhang,Xiao;Zhang,Dai;Tan,Hao-Yang;Yue,Weihua;Yan,Hao

文献摘要

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背景与假设社会竞争通过诱发心理社会压力影响人类行为。在竞争环境中,个体对压力情境的认知行为反应差异的神经和遗传机制尚不清楚。我们假设,在压力相关的大脑激活和遗传异质性与精神疾病的变化可能会发挥作用,对个别差异反应下stress.Study DesignA共419名健康受试者和66例精神分裂症患者进行了功能磁共振成像检查工作记忆任务,包括社会竞争的压力。我们探讨了压力诱导的大脑活动和个人工作记忆表现之间的相关性。采用偏最小二乘回归方法分析了艾伦人脑图谱中应激相关活动与基因表达之间的遗传相关性。研究结果在社会竞争条件下,双侧纹状体活性抑制程度越大,工作记忆操作的行为改善越好(左:rPearson=-0.245,P = 4.0 × 10−6,右:rPearson=-0.234,P = 1.0 × 10−5)。与应激诱导的激活相关的转录基因与精神分裂症的遗传风险相关(PFDR< 0.005)。在社会竞争中准确性降低的被试,精神分裂症患者的PRS水平较高(t= 2.328,P = .021)。精神分裂症患者在社会应激条件下纹状体活性受抑制程度较低(F= 13.493,P= 3.5 × 10−4)。结论精神分裂症患者纹状体活性的改变和遗传风险可能是应激条件下工作记忆操作个体行为差异的重要原因。
Background and HypothesisSocial competition affects human behaviors by inducing psychosocial stress. The neural and genetic mechanisms of individual differences of cognitive-behavioral response to stressful situations in a competitive context remain unknown. We hypothesized that variation in stress-related brain activation and genetic heterogeneity associated with psychiatric disorders may play roles towards individually differential responses under stress.Study DesignA total of 419 healthy subjects and 66 patients with schizophrenia were examined functional magnetic resonance imaging during working memory task including social competition stressors. We explored the correlation between stress-induced brain activity and individual working memory performance. The partial least squares regression was performed to examine the genetic correlates between stress-related activity and gene expression data from Allen Human Brain Atlas. Polygenic risk score (PRS) was used to assess individual genetic risk for schizophrenia.Study ResultsGreater suppression of bilateral striatal activity was associated with better behavioral improvement in working memory manipulation under social competition (left:rPearson= −0.245,P= 4.0 × 10−6, right:rPearson= −0.234,P= 1.0 × 10−5). Genes transcriptionally related to stress-induced activation were linked to genetic risk for schizophrenia (PFDR< 0.005). Participants with decreased accuracy under social competition exhibited higher PRS of schizophrenia (t= 2.328,P= .021). Patients with schizophrenia showed less suppressed striatal activity under social stress (F= 13.493, P= 3.5 × 10−4).ConclusionsStriatal activity change and genetic risk for schizophrenia might play a role in the individually behavioral difference in working memory manipulation under stress.