年轻人中抑郁症的多基因风险与膝下前扣带回皮质的静息态功能连接性
Polygenic risk for depression and resting-state functional connectivity of subgenual anterior cingulate cortex in young adults.
作者信息
Chen Yu, Li Huey-Ting, Luo Xingguang, Li Guangfei, Ide Jaime S, Li Chiang-Shan R
机构信息
From the Department of Psychiatry, Yale University School of Medicine, New Haven, Conn., USA (Chen, Luo, Ide, C.-S. Li); Yale University, New Haven, Conn., USA (H.-T. Li); the Department of Biomedical Engineering, College of Chemistry and Life Science, Beijing University of Technology, Beijing, China (G. Li); the Beijing International Science and Technology Cooperation Base for Intelligent Physiological Measurement and Clinical Transformation, Beijing, China (G. Li); the Department of Neuroscience, Yale University School of Medicine, New Haven, Conn., USA (C.-S Li); the Interdepartment Neuroscience Program, Yale University, New Haven, Conn., USA (C.-S. Li); the Wu Tsai Institute, Yale University, New Haven, Conn., USA (C.-S. Li)
From the Department of Psychiatry, Yale University School of Medicine, New Haven, Conn., USA (Chen, Luo, Ide, C.-S. Li); Yale University, New Haven, Conn., USA (H.-T. Li); the Department of Biomedical Engineering, College of Chemistry and Life Science, Beijing University of Technology, Beijing, China (G. Li); the Beijing International Science and Technology Cooperation Base for Intelligent Physiological Measurement and Clinical Transformation, Beijing, China (G. Li); the Department of Neuroscience, Yale University School of Medicine, New Haven, Conn., USA (C.-S Li); the Interdepartment Neuroscience Program, Yale University, New Haven, Conn., USA (C.-S. Li); the Wu Tsai Institute, Yale University, New Haven, Conn., USA (C.-S. Li).
出版信息
J Psychiatry Neurosci. 2025 Jan 14;50(1):E31-E44. doi: 10.1503/jpn.240087. Print 2025 Jan-Feb.
BACKGROUND
Genetic variants may confer risk for depression by modulating brain structure and function; evidence has underscored the key role of the subgenual anterior cingulate cortex (sgACC) in depression. We sought to examine how the resting-state functional connectivity (rsFC) of the sgACC was associated with polygenic risk for depression in a subclinical population.
METHODS
Following published protocols, we computed seed-based whole-brain sgACC rsFC and calculated polygenic risk scores (PRS) using data from healthy young adults from the Human Connectome Project. We performed whole-brain regression against PRS and severity of depression symptoms in a single model for all participants and by sex, controlling for age, sex, race or ethnicity, alcohol use severity, and household income. We evaluated the results at a corrected threshold.
RESULTS
We included data for 717 healthy young adults. We found lower rsFC between the sgACC and the default mode network and frontal regions in association with PRS and lower sgACC-cerebellar rsFC in association with depression severity. We also noted differences by sex in the connectivity correlates of PRS and depression severity. In an additional set of analyses, we observed a significant correlation between PRS and somatic complaints, as well as altered sgACC-somatosensory cortical connectivity in association with the severity of somatic complaints.
LIMITATIONS
The current findings should be considered specific to subclinical depression and may not generalize to patients with depressive disorders.
CONCLUSION
Our findings highlight the pivotal role of distinct sgACC-based networks in the genetic predisposition for depression and the manifestation of depression among young adults with subclinical depression. Distinguishing the risk from severity markers of depression may have implications in developing early and effective treatments for people at risk for depression.
背景
基因变异可能通过调节大脑结构和功能来增加患抑郁症的风险；有证据强调了膝下前扣带回皮质（sgACC）在抑郁症中的关键作用。我们试图研究sgACC的静息态功能连接（rsFC）如何与亚临床人群的抑郁症多基因风险相关联。
方法
按照已发表的方案，我们计算了基于种子点的全脑sgACC rsFC，并使用来自人类连接组计划的健康年轻成年人的数据计算多基因风险评分（PRS）。我们在一个单一模型中针对所有参与者并按性别进行全脑回归，以PRS和抑郁症状严重程度为自变量，同时控制年龄、性别、种族或民族、酒精使用严重程度和家庭收入。我们在校正阈值下评估结果。
结果
我们纳入了717名健康年轻成年人的数据。我们发现sgACC与默认模式网络和额叶区域之间的rsFC较低与PRS相关，sgACC与小脑之间的rsFC较低与抑郁严重程度相关。我们还注意到在PRS和抑郁严重程度的连接相关性方面存在性别差异。在另一组分析中，我们观察到PRS与躯体主诉之间存在显著相关性，以及与躯体主诉严重程度相关的sgACC与躯体感觉皮层连接的改变。
局限性
目前的研究结果应被视为特定于亚临床抑郁症，可能不适用于抑郁症患者。
结论
我们的研究结果突出了基于sgACC的不同网络在抑郁症遗传易感性以及亚临床抑郁症年轻成年人中抑郁症表现方面的关键作用。区分抑郁症的风险和严重程度标志物可能对为有抑郁症风险的人开发早期有效治疗方法具有启示意义。
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