Lewis Center for Neuroimaging, University of Oregon, Eugene, Oregon.
Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, California.
Brain Behav. 2018 Jun;8(6):e00988. doi: 10.1002/brb3.988. Epub 2018 Apr 25.
Working Memory and Task-Switching are essential components of cognitive control, which underlies many symptoms evident across multiple neuropsychiatric disorders, including psychotic and mood disorders. Vulnerability to these disorders has a substantial genetic component, suggesting that clinically unaffected first-degree relatives may carry some vulnerability-related traits. Converging evidence from animal and human studies demonstrates that dopamine transmission, striatal and frontal brain regions, and attention and switching behaviors are essential components of a multilevel circuit involved in salience, and disruptions in that circuit may lead to features of psychosis. Yet, it is possible that unaffected relatives may also possess characteristics that protect against development of illness. We hypothesized that reduced switch cost in a cued task-switching task, may be a behavioral expression of this "resilience" phenotype that will be observable in unaffected relatives.
We tested a large community sample (n = 536) via the web, to assess different subcomponents of cognitive control, including task-switching and working memory, as well as risk-taking, among individuals who report having an affected relative with a psychotic or mood disorder.
Healthy individuals with suspected genetic risk due to a self-reported familial history of a psychotic disorder demonstrated better task-switching performance compared to healthy people without a psychiatrically ill relative and those with a relative with a mood disorder. This result was specific to illness status and task domain, in that individuals with a personal history of depression or anxiety did not show improved task-switching performance, and this improvement was selective to task-switching and not seen in other putative cognitive control domains (working memory or risk taking).
Although this study has limitations and independent replication is needed, these preliminary findings suggest a potential avenue for understanding susceptibility to these disorders by highlighting possible protective as well as vulnerability-related aspects of risk phenotypes.
工作记忆和任务转换是认知控制的基本组成部分,认知控制是多种神经精神疾病(包括精神病和心境障碍)的许多症状的基础。这些疾病的易感性有很大的遗传成分,这表明未受临床影响的一级亲属可能具有一些与易感性相关的特征。动物和人类研究的综合证据表明,多巴胺传递、纹状体和额叶脑区以及注意力和转换行为是参与突显的多层次回路的重要组成部分,该回路的中断可能导致精神病的特征。然而,未受影响的亲属也可能具有保护其免受疾病发展影响的特征。我们假设,在提示任务转换任务中减少转换成本,可能是这种“弹性”表型的行为表达,在未受影响的亲属中是可以观察到的。
我们通过网络测试了一个大型社区样本(n=536),以评估认知控制的不同子成分,包括任务转换和工作记忆,以及风险承担,这些都在报告有精神病或心境障碍的受影响亲属的个体中进行评估。
由于有自我报告的精神病家族史而有遗传风险的健康个体,与没有精神病亲属的健康个体和有心境障碍亲属的健康个体相比,表现出更好的任务转换表现。这一结果特定于疾病状态和任务领域,即有抑郁或焦虑个人病史的个体没有表现出改善的任务转换表现,并且这种改善是选择性的,不能在其他假定的认知控制领域(工作记忆或风险承担)中看到。
尽管这项研究存在局限性,需要独立复制,但这些初步发现表明了通过突出风险表型的可能保护和易感性相关方面来理解对这些疾病的易感性的潜在途径。