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Changing sleep rhythms in adolescents often lead to sleep deficits and increased variability in sleep schedules. The adolescent brain, and in particular the rapidly developing structures involved in emotional control, are vulnerable to external and internal factors. In our previous study in adolescents at age 14, we observed a strong relationship between weekend sleep schedules and regional medial prefrontal cortex grey matter volumes. Here, we aimed to assess whether this relationship remained in this group of adolescents of the general population at the age of 16 (n=101; mean age 16.8 years; 55% girls). We further examined grey matter volumes in the hippocampi and the amygdalae, calculated with voxel-based morphometry. In addition, we investigated the relationship between regional grey matter volumes with psychological functioning. Sleep was assessed with self-reports and psychological functioning with the Strengths and Difficulties Questionnaire and tests on working memory and impulsivity. Later weekend wake-up times were associated with smaller grey matter volumes in the medial prefrontal cortex and the amygdalae, and greater weekend delays in wake-up time were associated with smaller grey matter volumes in the right hippocampus and amygdala. The medial prefrontal cortex region mediated the correlation between weekend wake up time and both externalising and internalising symptoms. Paying attention to regular sleep habits during adolescence could act as a protective factor against the emergence of psychopathology via enabling favourable brain development. * (AAL) : Anatomical Automatic Labeling; (AUDIT) : Alcohol Use Disorders Identification Test; (CANTAB) : Cambridge Automated Neuropsychological Test Battery; (FWE) : Family Wise Error; (MPRAGE) : Magnetisation Prepared Rapid Acquisition Gradient Echo; (mPFC) : Medial Prefrontal Cortex; (MNI) : Montreal Neurologic Institute; (fMRI) : functional Magnetic Resonance Imaging; (ROI) : Region Of Interest; (SPM) : Statistical Parametric Mapping; (SDQ) : Strengths and Difficulties Questionnaire; (VBM) : Voxel-Based Morphometry; (WD) : Weekday; (WE) : Weekend;

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