Developmental Trajectories of Sleep EEG Biomarkers and Risk of Psychopathology Through Young Adulthood

Project Summary The brain undergoes anatomical and physiological changes with the onset of puberty, of which synaptic pruning and increased myelination in a posterior-to-anterior gradient are hallmarks. These neural changes are reflected in the sleep electroencephalogram (EEG), with sleep intensity and depth sharply declining and sleep integrity plateauing during adolescence. Supported by R01 MH118308, we leveraged sleep EEG data from a population- based cohort of children followed-up as adolescents with which we studied the age-related trajectories of slow wave activity (SWA), sleep spindle density (SSD) and odds ratio product (ORP), three EEG biomarkers of sleep intensity, integrity and depth, respectively. We showed that each followed distinct maturational trajectories, differentially depending upon sex and pubertal development. In addition, we showed that, compared to typically developing youth, those with unmedicated attention/learning disorders had a maturational disruption in SWA during childhood and greater ORP levels in adolescence, while those with unmedicated internalizing disorders showed a lower loss of frontal SWA in the transition to adolescence but greater ORP when medicated with antidepressants. The lack of young adult data did not permit unveiling whether those developmental trajectories were predictive of mental health outcomes at ages 20 to 30, a lifespan period critical for increased severity of psychopathology. Federal research priorities include understanding the developmental trajectories of mental health disorders across the lifespan and their underlying brain mechanisms. Hence, in this application, we propose to study the association of SWA, SSD and ORP with young adult psychopathology by leveraging sleep EEG data from the 15-year follow-up of a unique population-based child cohort, studied under our prior R01 MH118308 for their child (median 9y) and adolescent (median 16y) data and who are being recruited under R01 HL136587 for their young adult data (median 25y). We aim to leverage data from these subjects at age 20 years or older and assessed for their sleep EEG and clinically-meaningful psychopathology outcomes. We will study the longitudinal association between the trajectories of SWA, SSD and ORP with internalizing symptoms and suicidality (Aim 1) and externalizing behaviors and working memory (Aim 2), and how these sleep EEG trajectories may play a mechanistic role in the increased coexistence of internalizing and externalizing psychopathology in young adulthood (Aim 3). Given the known sex differences in brain maturation, we will test whether the associations in Aims 1-3 differ between males and females (Aim 4). This study will help better understand the developmental trajectories of psychopathology as they relate to altered brain maturation and sleep disruption at different life stages. Findings from this study will inform novel biomarkers for clinical trials that aim at improving the pathophysiology and long-term prognosis of diverse forms of psychopathology across the life span by targeting the sleeping brain.