Brain atrophy and cognitive decline in bipolar disorder: Influence of medication use, symptomatology and illness duration.

Bipolar disorder (BPD) is a chronic condition characterized by recurrent episodes of mania and depression. To date, the association of biological and psychopathological processes in BPD has not been extensively studied on a cognitive and cortical basis at the same time. We investigated whether brain atrophy (in prefrontal, temporal and occipital cortices) was associated with cognitive, biological and clinical processes in patients with BPD and healthy controls (HCs). A total of 104 participants (56 with BPD) completed tasks that measured attention, memory, information processing speed, inhibitory control, visuospatial working memory and cognitive flexibility. In addition, structural brain scans were obtained using high-resolution MRI. Outcomes of the measurements were examined using robust multiple mediation analyses. BPD patients showed greater cortical atrophy across all regions of interest when compared to HCs, linked to cognitive decline. BPD patients had slower reaction times and markedly increased errors of commission on the tasks. The outcomes were significantly influenced by medication use, symptomatology and illness duration. The findings showcase the complexity of brain structures and networks as well as the physiological mechanisms underlying diverse BPD symptomatology and endophenotypes. These differences were pronounced in patients with BPD, motivating further investigations of pathophysiological mechanisms involved in brain atrophy and cognitive decline.