The mediating effect of circulating C-reactive protein on the association between depression and brain cortical dysconnectivity.

Abstract

Chronic low grade systemic inflammation is associated in the pathophysiology of major depressive disorder (MDD). However, the specific cortical structural connectivity changes associated with peripheral inflammation in MDD remains poorly understood. In this case-control study, 113 MDD patients and 107 healthy controls underwent 3T MRI and measurement of high sensitivity C-reactive protein (CRP). Fiber connectivity density (FiCD) mapping, a data driven whole-cortex pipeline combining cortical surface reconstruction with diffusion tractography, was used to examine depression and CRP interaction effects on cortical connectivity. A subgroup of MDD patients completed a six-week antidepressant follow-up with repeat MRI. A significant interaction between depression and CRP was identified in the left rostral middle frontal cortex (LRMF). FiCD in the LRMF was significantly lower in MDD patients than controls and negatively correlated with CRP in patients but not controls. Following six weeks of antidepressant treatment, FiCD in LRMF increased significantly, and this increase was negatively correlated with baseline. Peripheral inflammation is possibly associated with disrupted cortical connectivity in MDD and disturbs the brain structural recovery process during antidepressant treatment. The left rostral middle frontal cortex possibly serves as an important target.