The Role of the Complement C3-Hippocampus Pathway in Relation With Mood Symptoms in Offspring of Parents With Bipolar Disorder

IF 4.5 2区医学 Q1 CLINICAL NEUROLOGY

Bipolar Disorders Pub Date : 2025-09-01 DOI:10.1111/bdi.70056

Shiyun Wu, Zhongwan Liu, Robin Shao, Wenjin Zou, Xiaoyue Li, Weicong Lu, Jinyong Chen, Suk-Yu Yau, Kangguang Lin

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引用次数: 0

Abstract

Objective

Accumulative research indicates key roles of the peripheral inflammation system and hippocampal function in major mood disorders. The complement system modulates inflammatory function and is abnormal in mood disorders, but its precise neural pathway remains unclear. This study investigates the interrelations among complement component 3 (C3) levels, hippocampal function, and mood symptoms among offspring of bipolar disorder (BD) parents who carry familial risk of mood disorders.

Method

We recruited unaffected BD offspring with (symptomatic offspring, SO, N = 31) or without (asymptomatic offspring, AO, N = 39) subthreshold symptoms, and matched healthy controls (HC, N = 41). Peripheral C3 levels were measured, and resting-state fMRI was conducted to assess hippocampal functional connectivity (FC). Spectral dynamic causal modeling (spDCM) was conducted to verify the directionality of the hippocampal FC.

Results

The SO group exhibited significantly lower peripheral C3 levels (F_2,108 = 23.651, p < 0.001) and reduced left hippocampus-left cerebellum FC (F_2,108 = 8.541, p < 0.001) compared to both the AO and HC groups. Furthermore, the left hippocampus-left cerebellum FC partially mediated the relationship between C3 levels and depressive symptoms in the SO group (bootstrapping 95% CI = −4.1168 to −0.1569), but not in AO (bootstrapping 95% CI = −0.3479 to 0.1317) or HC (bootstrapping 95% CI = −0.3297 to 0.0885). The left hippocampus-left cerebellum FC was bidirectional in all 3 groups.

Conclusion

Our findings indicate a C3-hippocampus-depressive symptom pathway might underpin the particular high vulnerability of individuals with both familial and symptomatic risks of mood disorders. This evidence provides new neuroinflammatory markers and targets for early identification and intervention of these individuals.

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补体c3 -海马通路在双相情感障碍父母后代情绪症状中的作用

目的：研究表明外周炎症系统和海马功能在重大情绪障碍中的关键作用。补体系统调节炎症功能，在情绪障碍中异常，但其确切的神经通路尚不清楚。本研究探讨了具有情绪障碍家族风险的双相情感障碍（BD）父母后代补体成分3 （C3）水平、海马功能和情绪症状之间的相互关系。方法：我们招募了未受影响的双相障碍后代（有症状的后代，SO, N = 31）或没有（无症状的后代，AO, N = 39）阈下症状，并匹配健康对照（HC, N = 41）。测量外周C3水平，静息状态fMRI评估海马功能连通性（FC）。采用频谱动态因果模型（spDCM）验证海马FC的方向性。结果：SO组外周血C3水平明显降低（f2108 = 23.651, p 2108 = 8.541, p）。结论：C3-海马-抑郁症状通路可能是具有家族性和症状性情绪障碍风险个体特别高易感性的基础。这一证据为这些个体的早期识别和干预提供了新的神经炎症标志物和靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Bipolar Disorders 医学-精神病学

CiteScore

8.20

自引率

7.40%

发文量

审稿时长

6-12 weeks

期刊介绍： Bipolar Disorders is an international journal that publishes all research of relevance for the basic mechanisms, clinical aspects, or treatment of bipolar disorders and related illnesses. It intends to provide a single international outlet for new research in this area and covers research in the following areas: biochemistry physiology neuropsychopharmacology neuroanatomy neuropathology genetics brain imaging epidemiology phenomenology clinical aspects and therapeutics of bipolar disorders Bipolar Disorders also contains papers that form the development of new therapeutic strategies for these disorders as well as papers on the topics of schizoaffective disorders, and depressive disorders as these can be cyclic disorders with areas of overlap with bipolar disorders. The journal will consider for publication submissions within the domain of: Perspectives, Research Articles, Correspondence, Clinical Corner, and Reflections. Within these there are a number of types of articles: invited editorials, debates, review articles, original articles, commentaries, letters to the editors, clinical conundrums, clinical curiosities, clinical care, and musings.