Higher Levels of C-reactive Protein Are Associated With Higher Cortical Surface Area and Lower Cortical Thickness in Youth With Bipolar Disorder

Abstract

Background: Inflammation is implicated in the neuropathology of bipolar disorder (BD). The association of C-reactive protein (CRP) with brain structure has been examined in relation to BD among adults but not youth. Methods: Participants included 101 youth (BD, n = 55; control group [CG], n = 46; aged 13-20 years). Blood samples were assayed for levels of CRP. T1-weighted brain images were acquired to obtain cortical surface area (SA), volume, and thickness for 3 regions of interest (ROI; whole-brain cortical gray matter, prefrontal cortex, orbitofrontal cortex [OFC]) and for vertex-wise analyses. Analyses included CRP main effects and interaction effects controlling for age, sex, and intracranial volume. Results: In ROI analyses, higher CRP was associated with higher whole-brain SA (β = 0.16; P =. 03) and lower whole-brain (β = -0.31; P =. 03) and OFC cortical thickness (β = -0.29; P =. 04) within the BD group and was associated with higher OFC SA (β = 0.17; P =. 03) within the CG. In vertex-wise analyses, higher CRP was associated with higher SA and lower cortical thickness in frontal and parietal regions within BD. A significant CRP-by-diagnosis interaction was found in frontal and temporal regions, whereby higher CRP was associated with lower neurostructural metrics in the BD group but higher neurostructural metrics in CG. Conclusions: This study found that higher CRP among youth with BD is associated with higher SA but lower cortical thickness in ROI and vertex-wise analyses. The study identified 2 regions in which the association of CRP with brain structure differs between youth with BD and the CG. Future longitudinal, repeated-measures studies incorporating additional inflammatory markers are warranted.