White matter microstructure mediates the link between rest-activity rhythm instability and mania symptoms in individuals at risk for bipolar disorder.

Instability in sleep and rest-activity rhythms is associated with elevated risk for bipolar disorder, yet little is known about the neural correlates of this vulnerability.

We evaluated whether the links between actigraphy-derived sleep duration variability, sleep onset variability, and Circadian Function Index (CFI; index of circadian rhythm robustness) and white matter Orientation Dispersion Index were moderated by baseline mania vulnerability, and tested whether baseline Orientation Dispersion Index predicted 6-month mood symptoms.