Neuroimaging insights on sleep disturbances and risk for major depressive disorder in youth: A systematic review

Background Sleep is critical for brain function and cognitive development, especially in children and adolescents. Sleep disturbances or insufficient sleep may pose a risk for poor long-term health outcomes, including major depressive disorder (MDD). This systematic review sought to the neurobiological relationship between sleep and risk for future depressive disorders or symptoms. Methods A pre-registered, systematic search was conducted using MEDLINE, PsychInfo, and Embase databases from January 2000 to February 2025. Studies included investigated neurobiological changes related to sleep in predicting subsequent risk for first episode MDD or depressive symptoms in children, adolescents, and young adults (mean age < 30 years). We narratively synthesized the results and completed a quality assessment using a modified Newcastle-Ottawa scale. Results The search yielded four cross-sectional studies comparing high and low MDD risk individuals, and seven longitudinal studies predicting risk of future depressive symptoms. Sleep neurophysiological markers like rapid eye movement latency and sleep spindle density, white matter integrity in the cingulum bundle and superior longitudinal fasciculus, and activity within the salience network and dorsomedial prefrontal cortex associated with sleep quality and differed in individuals with an increased risk for MDD. A low-to-moderate risk of bias was detected among all studies. Conclusions Due to the limited number of studies and methodological heterogeneity, the highlighted evidence remains preliminary. This review emphasizes the importance of addressing sleep problems in youth before they potentially contribute to lasting changes in emotional and mental health, as well as the need to further study the relationship between sleep disturbances and risk for MDD.