Report from a randomized control trial: improved alignment between circadian biology and sleep-wake behavior as a mechanism of depression symptom improvement in evening-type adolescents with depressive symptoms.

Study Objectives: An evening circadian preference is common among adolescents. It is characterized by a behavioral predilection for later sleep and wake timing and is associated with higher rates of Major Depressive Disorder (MDD). The present study aims to (a) test the effectiveness of a cognitive behavioral sleep intervention (Transdiagnostic Sleep and Circadian Intervention; TranS-C) in a sample of adolescents with an evening circadian preference and clinically significant depressive symptoms and (b) evaluate improved alignment between circadian biology and sleep-wake behavior as a potential mechanism in the relationship between sleep and depression symptom improvement.

Methods: Adolescents with an evening circadian preference and clinically significant depressive symptoms were randomized to receive TranS-C (n = 24) or a psychoeducation condition (PE; n = 18). Alignment between circadian biology and sleep-wake behavior was measured using objective biological measurement. Measures of sleep and circadian rhythm were taken at pre- and posttreatment, and depression symptoms were measured at pre- and posttreatment and 6- and 12-month follow-up.

Results: Mixed effects modeling revealed that compared with an active control condition, TranS-C resulted in a significant reduction in MDD severity at 12-month follow-up. A MacArthur mediation analysis conducted to explore alignment between circadian biology and sleep-wake behavior as a mediator of depression severity reduction through 12-month follow-up revealed a significant interaction between change in alignment between circadian biology and sleep-wake behavior and treatment arm, indicating that improved alignment between circadian biology and sleep-wake behavior at posttreatment was associated with improvements in depression outcomes at 12-month follow-up under the treatment condition.

Conclusions: These results provide novel evidence for improved alignment between circadian biology and sleep-wake behavior as a specific mechanism of depression improvement, provide key clues into the complex relationship between sleep and depression, and have significant clinical implications for adolescents with depression.