Abstract
BACKGROUND: Cognitive deficits are common in individuals with bipolar disorder (BD), but there is considerable variability in cognitive functioning. Childhood maltreatment (CM), which is frequently reported in BD, has been linked to poorer cognitive performance, potentially through mechanisms such as inflammation. However, the relationship between CM and global cognition and the mediating role of inflammation in BD warrant further investigation. METHODS: The study sample consisted of 112 BD individuals and 83 healthy controls (HCs). Participants completed the MATRICS Consensus Cognitive Battery (MCCB), the Wisconsin Card Sorting Test, and the Childhood Trauma Questionnaire (CTQ). A composite inflammation index was created using blood levels of C-reactive protein (CRP), interleukin (IL)-6, and tumor necrosis factor (TNF)-α, and was used in primary analyses. RESULTS: The BD group, compared to HC, showed higher levels of inflammation and CM. Across the entire sample, higher total CM was associated with poorer global cognitive performance, with a medium effect size, even after accounting for diagnostic status. The associations were evident across all CM subscales. Specific cognitive domains affected included speed of processing, working memory, visual learning, and reasoning and problem solving. The association between CM and poorer global cognitive performance was partially mediated by inflammation (indirect effect: β = -0.048, CI = -0.10, -0.009). Within the BD group, higher total CM was similarly associated with worse global cognitive performance. The associations were evident across all CM subscales, except for physical neglect. Significant associations were observed between total CM and MCCB domains of speed of processing, attention and vigilance, working memory, visual learning, reasoning and problem solving, as well as cognitive flexibility. Within the HC group, only emotional neglect and physical neglect were associated with poorer global cognition. CONCLUSIONS: This study provides evidence that total CM and its subscales are associated with poorer global cognitive performance in a sample of individuals with BD and HC, with stronger associations found within the BD group. In addition, inflammation partially mediated the relationship between CM and global cognition. These findings highlight the importance of trauma-informed and cognition-focused interventions aimed at enhancing cognitive outcomes and slowing cognitive decline in individuals with BD who have a history of CM. Furthermore, the results suggest that while inflammation plays a role in the CM-cognition link, its effects are complex and likely interact with other biological and environmental factors.