Aging of the brain in bipolar disorder: Illness- and onset-related effects in cortical thickness and subcortical gray matter volume

Background: Older adults with bipolar disorder (BD) have received little study, although they often have severe symptoms, treatment resistance and high suicide risk. Furthermore, a subset develops cognitive dysfunction for unknown reasons.Methods: Here, cortical thickness and subcortical gray matter volume were compared across individuals ages 40-79y: 103 with BD ("later-onset" at ages >= 25y, n = 21; "early-onset" < 25y, n = 82) and healthy controls (HCs, n = 98).Results: Overall, those with BD showed lower prefrontal, cingulate, sensorimotor, parahippocampal, insula, temporal, parietal, and occipital cortical thickness (Cohen's d: 0.4 to 0.8) and hippocampal, amygdalar, thalamic, and striatal gray matter volume (d: 0.6 to 0.8). Later-onset BD showed negative relationships between age and parahippocampal, insular, temporal, parietal, and occipital cortical thickness, and hippocampal, thalamic and striatal volume (r:-0.7 to-0.4). Suicide attempt history was associated with lower dorsolateral prefrontal cortical thickness (d = 0.5). Limitations: The study used a cross-sectional design and the sample of those with a later-onset of BD was relatively modest. Conclusions: Results support widespread gray matter decreases in older adults with BD, and also suggest a separable later-onset phenotype characterized by age-related gray matter reductions in regions subserving cognitive, emotional and perceptual processes. Moreover, the results are the first to demonstrate structural brain differences associated with a history of suicide attempts in older adults with BD.