Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, USA.
Department of Psychology, Stanford University, Stanford, USA.
Transl Psychiatry. 2018 Jan 10;8(1):5. doi: 10.1038/s41398-017-0051-0.
Corticotropin-releasing factor signaling through CRF receptor type 1 (CRF) has been shown to contribute to learning and memory function. A haplotype of alleles T-A-T in a set of common polymorphisms in the gene encoding for CRF (CRHR1) has been associated with both depression vulnerability and alterations in cognitive functioning. The present study investigated the relations between the TAT haplotype and specific symptoms of depression, self-reported ruminative behaviors, and neuropsychological performance on a learning and memory task. Participants were adults with major depression with and without psychotic features (N = 406). Associations were examined between TAT haplotype and endorsement of depression symptoms from diagnostic interviews, scores on the rumination response scale (RRS), and verbal memory performance on the California Verbal Learning Test-II (CVLT-II). All analyses included depression subtype, age, and sex as covariates; CVLT-II analyses also included evening cortisol levels. Across the entire sample, carriers of more copies of the TAT haplotype reported greater endorsement of the symptom describing difficulty concentrating and making decisions. In separate subsamples, TAT homozygotes had higher rumination scores on the RRS, both brooding and reflection subscales, and more TAT copies were associated with poorer CVLT-II performance in both total learning and free recall trials. These data demonstrate that the CRHR1 TAT haplotype is associated with cognitive features of depression including difficulty with decision-making, higher rumination, and poorer learning and memory. It will be important in future research to identify the specific molecular mechanisms for CRF signaling that contribute to depression-related cognitive dysfunction.
促肾上腺皮质释放因子通过 CRF 受体 1 型（CRF1）的信号转导已被证明有助于学习和记忆功能。在编码 CRF（CRHR1）的基因中的一组常见多态性中，T-A-T 等位基因的单倍型与抑郁易感性和认知功能改变有关。本研究调查了 TAT 单倍型与特定抑郁症状、自我报告的沉思行为以及学习和记忆任务中的神经心理学表现之间的关系。参与者为有或无精神病特征的成年重性抑郁症患者（N=406）。在诊断访谈中，评估 TAT 单倍型与抑郁症状的关联，评估沉思反应量表（RRS）的评分，以及加利福尼亚语言学习测验-第二版（CVLT-II）的言语记忆表现。所有分析均包括抑郁亚型、年龄和性别作为协变量；CVLT-II 分析还包括傍晚皮质醇水平。在整个样本中，携带更多 TAT 单倍型的个体报告了更多描述注意力集中和决策困难的症状。在单独的亚样本中，TAT 纯合子在 RRS 的沉思得分更高，无论是沉思还是反思子量表，而且更多的 TAT 拷贝与 CVLT-II 总学习和自由回忆试验中的表现更差相关。这些数据表明，CRHR1 TAT 单倍型与抑郁的认知特征有关，包括决策困难、更高的沉思和更差的学习和记忆。在未来的研究中，确定与抑郁相关的认知功能障碍有关的 CRF 信号的特定分子机制将非常重要。
