Mental Health Center and Psychiatric Laboratory, the State Key Laboratory of Biotherapy, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
Affiliated Mental Health Center and Hangzhou Seventh People's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
J Affect Disord. 2022 Feb 1;298(Pt A):472-480. doi: 10.1016/j.jad.2021.10.125. Epub 2021 Nov 1.
Objectives The current study aimed to identify shared and distinct brain structure abnormalities and their relationships with the expression of circadian genes in patients with bipolar or unipolar depression. Method A total of 93 subjects participated in this study, including 32 patients with bipolar depression (BDP), 26 patients with unipolar depression (UDP) and 35 age- and sex-matched healthy controls. Brain structural magnetic resonance imaging scans were obtained, and optimized voxel-based morphometry was used to explore group differences in regional gray matter volume (GMV). The mRNA expression levels of circadian genes in peripheral blood were measured using reverse transcription quantitative real-time polymerase chain reaction. Results Our results showed that the GMV in brain regions in the thalamus-limbic pathways had significantly increased in the BDP patients compared to controls, while the increased GMV in UDP patients compared to controls was limited to the thalamus. The mRNA expression levels of circadian-related genes decreased significantly in patients with BDP, but increased in patients with UDP, compared to controls. In addition, the GMV in the right thalamus in the patients with UDP was positively associated with mRNA levels of CRY2, while the GMV in the right hippocampus in the patients with BDP was negatively associated with mRNA levels of PER3. Conclusion Our study suggested that patients with BDP or MDD shared GMV abnormalities in the right thalamus. The PER3 and CRY2 genes might be critical to right hippocampal dysfunction in BDP and right thalamic dysfunction in UDP, respectively. The result provided potentially important molecular targets for the treatment of mood disorders.
目的 本研究旨在识别双相或单相抑郁患者中存在的共享和独特的大脑结构异常及其与昼夜节律基因表达的关系。
方法 共有 93 名受试者参与了这项研究,包括 32 名双相抑郁患者(BDP)、26 名单相抑郁患者(UDP)和 35 名年龄和性别匹配的健康对照者。获得脑结构磁共振成像扫描,并采用优化的体素基形态计量学方法来探讨区域灰质体积(GMV)的组间差异。使用反转录定量实时聚合酶链反应测量外周血中昼夜节律基因的 mRNA 表达水平。
结果 我们的研究结果表明,BDP 患者的丘脑-边缘通路脑区 GMV 显著增加,而 UDP 患者与对照组相比,GMV 增加仅限于丘脑。与对照组相比,BDP 患者的昼夜节律相关基因的 mRNA 表达水平显著降低,而 UDP 患者的表达水平升高。此外,UDP 患者右侧丘脑的 GMV 与 CRY2 的 mRNA 水平呈正相关,而 BDP 患者右侧海马的 GMV 与 PER3 的 mRNA 水平呈负相关。
结论 本研究表明,BDP 或 MDD 患者共享右侧丘脑 GMV 异常。PER3 和 CRY2 基因可能分别是 BDP 右侧海马功能障碍和 UDP 右侧丘脑功能障碍的关键。研究结果为治疗心境障碍提供了潜在的重要分子靶点。