Transdiagnostic Domain-specific Cognitive Impairment in Inter-episode Mood Disorders and its Relationship with Rest-Activity Phenotypes

Abstract

Introduction: Cognitive impairment and disturbed rest-activity patterns often persist between episodes of major depressive disorder (MDD) and bipolar disorder (BD). Whether these deficits are disorder-specific or transdiagnostic remains unclear, as does the existence of a link between rest-activity phenotypes and cognitive performance. Methods: Using the All of Us Research Program, we derived normative deviation scores across four cognitive domains (sustained attention, inhibitory control, reward-based impulsivity, social cognition) from non-clinical controls (NCC), then compared deviations in MDD and BD. MDD was adequately powered to regress deviation scores on four 90-day Fitbit-derived phenotypes (step count, sleep duration, wakefulness after sleep onset, sleep timing variability); the same analysis was run on NCC as a sensitivity check. Results: Samples were substantially larger than prior works (MDD 5,087-6,536; BD 545-739; NCC 40,589-51,491). Relative to NCC, MDD and BD exhibited worse sustained attention (Delta Glass = -0.081 vs. -0.187) and higher impulsivity (Delta Glass = 0.092 vs. 0.240), with deficits more pronounced in BD. No wearable phenotype was significantly associated with cognitive performance in MDD (R2< 0.01); NCC associations, though significant, were of negligible magnitude (R2 <= 1.2%). Discussion: Inter-episode cognitive impairment was domain-selective rather than global, with a gradient BD > MDD. Despite adequate power, wearable rest-activity phenotypes were not associated with cognition in MDD. Whether this extends to BD, where deficits were largest, could not be tested due to limited power. Community-dwelling samples likely underestimate impairment relative to clinical cohorts.