Association of the plasma complement system with brain volume deficits in bipolar and major depressive disorders

• Published in: Psychological medicine 2023-10, Vol.53 (13), p.6102-6112
• Main Authors: Yu, Hua, Ni, Peiyan, Tian, Yang, Zhao, Liansheng, Li, Mingli, Li, Xiaojing, Wei, Wei, Wei, Jinxue, Du, Xiangdong, Wang, Qiang, Guo, Wanjun, Deng, Wei, Ma, Xiaohong, Coid, Jeremy, Li, Tao
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Anatomy; Antigens; Biomarkers; Bipolar disorder; Brain; Brain architecture; Brain injuries; Cingulum; Complement system; Cortex; Cortex (frontal); Depressive personality disorders; Emotional disorders; Frontal gyrus; Illnesses; Immunology; Inflammation; Intellectual disabilities; Mental depression; Mental disorders; Mood; Mood disorders; Neuropathology; Original Article; Pathogenesis; Pathophysiology; Precentral gyrus; Properdin; Schizophrenia; Substance abuse treatment; Substantia grisea; Suicides & suicide attempts
• ISSN: 0033-2917; 1469-8978
• DOI: 10.1017/S0033291722003282

BackgroundInflammation plays a crucial role in the pathogenesis of major depressive disorder (MDD) and bipolar disorder (BD). This study aimed to examine whether the dysregulation of complement components contributes to brain structural defects in patients with mood disorders.MethodsA total of 52 BD patients, 35 MDD patients, and 53 controls were recruited. The human complement immunology assay was used to measure the levels of complement factors. Whole brain-based analysis was performed to investigate differences in gray matter volume (GMV) and cortical thickness (CT) among the BD, MDD, and control groups, and relationships were explored between neuroanatomical differences and levels of complement components.ResultsGMV in the medial orbital frontal cortex (mOFC) and middle cingulum was lower in both patient groups than in controls, while the CT of the left precentral gyrus and left superior frontal gyrus were affected differently in the two disorders. Concentrations of C1q, C4, factor B, factor H, and properdin were higher in both patient groups than in controls, while concentrations of C3, C4 and factor H were significantly higher in BD than in MDD. Concentrations of C1q, factor H, and properdin showed a significant negative correlation with GMV in the mOFC at the voxel-wise level.ConclusionsBD and MDD are associated with shared and different alterations in levels of complement factors and structural impairment in the brain. Structural defects in mOFC may be associated with elevated levels of certain complement factors, providing insight into the shared neuro-inflammatory pathogenesis of mood disorders.