Higher Levels of C-reactive Protein are Associated with Higher Cortical Surface Area and Lower Cortical Thickness in Youth with Bipolar Disorder.

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 three regions of interest (ROI; whole-brain cortical gray matter, prefrontal cortex (PFC), 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=0.03), lower whole-brain (β=-0.31; p=0.03) and OFC cortical thickness (β=-0.29; p=0.04) within the BD group, and was associated with higher OFC SA (β=0.17; p=0.03) within 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 two regions in which the association of CRP with brain structure differs between youth with BD vs. CG. Future longitudinal, repeated-measures studies incorporating additional inflammatory markers are warranted.