Department of Neurology, Affiliated ZhongDa Hospital, School of Medicine, Institution of Neuropsychiatry, Southeast University, Nanjing, Jiangsu 210009, China.
Department of Psychology, Xinxiang Medical University, Xinxiang, Henan 453003, China.
EBioMedicine. 2021 Apr;66:103337. doi: 10.1016/j.ebiom.2021.103337. Epub 2021 Apr 13.
circular RNAs (circRNAs) are expressed abundantly in the brain and are implicated in the pathophysiology of neuropsychiatric disease. However, the potential clinical value of circRNAs in major depressive disorder (MDD) remains unclear.
RNA sequencing was conducted in whole-blood samples in a discovery set (7 highly homogeneous MDD patients and 7 matched healthy controls [HCs]). The differential expression of circRNAs was verified in an independent validation set. The interventional study was conducted to assess the potential effect of the antidepressive treatment on the circRNA expression.
in the validation set, compared with 52 HCs, significantly decreased circFKBP8 levels (Diff: -0.24; [95% CI -0.39 ~ -0.09]) and significantly elevated circMBNL1 levels (Diff: 0.37; [95% CI 0.09 ~ 0.64]) were observed in 53 MDD patients. The expression of circMBNL1 was negatively correlated with 24-item Hamilton Depression Scale (HAMD-24) scores in 53 MDD patients. A mediation model indicated that circMBNL1 affected HAMD-24 scores through a mediator, serum brain-derived neurotrophic factor. In 53 MDD patients, the amplitude of low-frequency fluctuations in the right orbital part middle frontal gyrus was positively correlated with circFKBP8 and circMBNL1 expression. Furthermore, the interventional study of 53 MDD patients demonstrated that antidepressive treatment partly increased circFKBP8 expression and the change in expression of circFKBP8 was predictive of further reduced HAMD-24 scores.
whole-blood circFKBP8 and circMBNL1 may be potential biomarkers for the diagnosis of MDD, respectively, and circFKBP8 may show great potential for the antidepressive treatment.
环状 RNA（circRNAs）在大脑中表达丰富，与神经精神疾病的病理生理学有关。然而，circRNAs 在重度抑郁症（MDD）中的潜在临床价值尚不清楚。
在一个发现集（7 名高度同质的 MDD 患者和 7 名匹配的健康对照者[HCs]）中进行全血样本的 RNA 测序。在一个独立的验证集中验证 circRNAs 的差异表达。进行干预研究以评估抗抑郁治疗对 circRNA 表达的潜在影响。
在验证集中，与 52 名 HCs 相比，在 53 名 MDD 患者中观察到 circFKBP8 水平显著降低（差异：-0.24；[95%CI -0.39-0.09]），circMBNL1 水平显著升高（差异：0.37；[95%CI 0.090.64]）。53 名 MDD 患者中，circMBNL1 的表达与 24 项汉密尔顿抑郁量表（HAMD-24）评分呈负相关。中介模型表明，circMBNL1 通过血清脑源性神经营养因子影响 HAMD-24 评分。在 53 名 MDD 患者中，右侧眶额中额回低频波动幅度与 circFKBP8 和 circMBNL1 的表达呈正相关。此外，对 53 名 MDD 患者的干预研究表明，抗抑郁治疗部分增加了 circFKBP8 的表达，circFKBP8 表达的变化可预测 HAMD-24 评分的进一步降低。
全血 circFKBP8 和 circMBNL1 可能分别是 MDD 诊断的潜在生物标志物，circFKBP8 可能具有很大的抗抑郁治疗潜力。
