Association of total peripheral inflammation with lower frontal and temporal lobe volumes in early-stage bipolar disorder: A proof-of-concept study

Background: We previously reported that in early-stage bipolar disorder (BD), frontal and temporal lobe volume reductions were more pronounced in patients with elevated BMI and more rapidly progressive in patients with additional weight gain. Elevated BMI is a pro-inflammatory state, and inflammation may contribute to brain volume reductions in BD. However, few studies have investigated the relationship between inflammation and brain volumes. Methods: We conducted a proof-of-concept analysis to investigate whether a composite measure of total peripheral inflammation derived from 9 cytokines predicted lower frontal and temporal lobe volumes, measured with 3 T MRI, in early-stage BD. Results: In 25 early-stage patients, linear regression models showed that greater total inflammation predicted lower white matter (WM) volumes in the left frontal lobe (β = −0.691, p = 0.001) and bilateral temporal lobes (left: β = −0.617, p = 0.003; right: β = −0.636, p = 0.001). Greater inflammation also predicted lower right frontal WM, although this did not survive correction for multiple comparisons (β = −0.557, p = 0.020). It did not predict frontal or temporal GM. Total inflammation was a stronger predictor of lower WM volumes than were individual cytokines. Limitations: Although the magnitude of the association between total inflammation and lower WM volumes was large, our sample was small. Our findings require confirmation in further studies, with samples large enough to determine whether inflammation mediates the relationship between elevated BMI and brain volumes. Conclusions: This study supports the hypothesis that inflammation contributes to brain volume reductions in BD and suggests that total inflammatory burden best captures the impact of inflammation on the brain.