ABSTRACT Objectives This study aimed to investigate: (1) whether Body Mass Index (BMI) and peripheral inflammation are associated with cognitive performance in bipolar disorder (BD) and healthy controls (HCs), and (2) the potential mediating role of inflammation in the BMI‐cognition link. Methods As part of an ongoing study, 127 participants (79 BD, 48 HCs) completed the MATRICS Consensus Cognitive Battery. C‐reactive protein (CRP), interleukin (IL)‐6, and tumor necrosis factor (TNF)‐α levels were quantified in blood, and a composite inflammation index was created and utilized in primary analyses. Regression and mediation analyses were conducted using SAS. Results The BD group had higher inflammation compared to HCs ( p < 0.05). In the entire sample of BD individuals and HCs, higher BMI was associated with worse global cognitive performance, controlling for age, sex, diagnosis, education and medical comorbidity (beta = −0.22, p = 0.006). This association remained evident in the BD group, controlling for additional clinical factors ( p < 0.05). Higher inflammation was associated with worse global cognition, controlling for relevant covariates in the entire sample (beta = −0.19, p = 0.024); however, this association was no longer significant in the BD group after controlling for additional clinical factors ( p = 0.09). The indirect effect of BMI on global cognition through IL‐6 was statistically different from zero (ab: beta = −0.09, CI = −0.18, −0.01) in the entire sample, holding age and sex constant, suggesting that IL‐6 partially accounts for the association between BMI and cognitive performance. However, this finding should be interpreted cautiously, given the modest sample size and exploratory analyses suggesting that the indirect effect may differ by diagnostic group. Conclusions BMI may serve as a potential biomarker and treatment target for obesity‐related cognitive impairment in both BD and the general population, with IL‐6 potentially contributing to this association.
Majd et al. (Fri,) studied this question.