Association of Plasma Complement System With Brain Structure Deficits in Bipolar and Major Depressive Disorders

Abstract Objective Inflammation plays a crucial role in the pathogenesis of major depressive disorder (MDD) and bipolar disorder (BD). However, the underlying neurobiological mechanisms are poorly understood. This study aimed to examine whether the dysregulation of complement components contributes to brain structure deficits in BD and MDD patients. Methods A total of 52 BD patients, 35 MDD patients, and 53 mentally healthy controls were recruited from the inpatient and outpatient departments of West China Hospital of Sichuan University. The human complement panel 2-immunology multiplex assay was used to measure the levels of complement C1q, C3, C3b, C4, factor B, factor H, and properdin. Whole brain-based comparison was performed to investigate differences in gray matter volume and cortical thickness among the BD, MDD, and control groups, and relationships were explored between neuroanatomical differences and levels of complement components.Results The gray matter volume in the medial orbital frontal cortex (mOFC) and middle cingulum decreased in both patient groups, while the cortical thickness of the left precentral and left superior frontal gyrus was affected differently. Log10-transformed concentrations of C1q, C4, factor B, factor H, and properdin were higher in both patient groups than in controls, while levels of C1q, factor H, and properdin showed a significant negative correlation with gray matter volume in the mOFC at the voxel-wise level.Conclusion Greater inflammation in mOFC was observed in BD and MDD patients than in controls. Structural deficits in both patient groups were associated with elevated levels of certain complement factors, providing insight into the neuro-inflammatory pathogenesis of mood disorders.