The Link between High-Sensitivity C-Reactive Protein and Orbitofrontal Cortex in Euthymic Bipolar Disorder

Objective: C-reactive protein (CRP), a marker of underlying low-grade inflammation, has been associated with the pathophysiology of bipolar disorder. Additionally, bipolar disorder may be accompanied by functional or structural cerebral alterations. We attempted to discover whether serum high-sensitivity CRP (hs-CRP) levels are linked to the structural volume change of a specific brain region along with cognitive performance. Methods: We recruited 17 physically healthy patients with bipolar I disorder (DSM-IV), aged 18-45 years and euthymic, to undergo the Wisconsin Card Sorting Test (WCST) and volumetric magnetic resonance imaging at 1.5 T. The analytic method was based on the hidden Markov random field model with an expectation-maximization algorithm, and the volume of each brain region was presented as a percentage of the total intracranial volume. Results: Among the various regions, only the orbitofrontal cortex had a significantly negative correlation with serum hs-CRP levels after adjustment for age and gender (left and right orbitofrontal cortex: r = -0.62, p <0.01, and r = -0.67, p <0.005, respectively). Regarding cognitive function, poor WCST performance was also associated with certain subregions of the orbitofrontal cortex. Conclusion: Elevation of serum hs-CRP levels, an indicator of inflammation, may be associated with reduced volume of the orbitofrontal cortex. Persistent inflammation in the euthymic phase of bipolar disorder may involve the pathogenesis or pathophysiology of alteration of the frontal pathway.