Association of emotional and behavioral problems with the development of the substantia nigra, subthalamic nucleus, and red nucleus volumes and asymmetries from childhood to adolescence: A longitudinal cohort study

Abstract The substantia nigra (SN), subthalamic nucleus (STN), and red nucleus (RN) have been widely studied as important biomarkers of degenerative diseases. However, how they develop in childhood and adolescence and are affected by emotional behavior has not been studied thus far. This population-based longitudinal cohort study used data from a representative sample followed two to five times. Emotional and behavioral problems were assessed with the Strengths and Difficulties Questionnaire (SDQ). Linear mixed models were used to map developmental trajectories and behavioral regulation. Using an innovative automated image segmentation technique, we quantified the volumes and asymmetries of the SN, STN and RN with 1226 MRI scans of a large longitudinal sample of 667 subjects aged 6–15 years and mapped their developmental trajectories. The results showed that the absolute and relative volumes of the bilateral SN and right STN showed linear increases, while the absolute volume of the right RN and relative volume of the bilateral RN decreased linearly, these effects were not affected by gender. Hyperactivity/inattention weakened the increase in SN volume and reduced the absolute volume of the STN, conduct problems impeded the RN volume from decreasing, and emotional symptoms changed the direction of SN lateralization. This longitudinal cohort study mapped the developmental trajectories of SN, STN, and RN volumes and asymmetries from childhood to adolescence, and found the association of emotional symptoms, conduct problems, and hyperactivity/inattention with these trajectories, providing guidance for preventing and intervening in cognitive and emotional behavioral problems.