Restricted and repetitive behaviours are associated with noradrenergic alterations in neurodevelopmental disorders

Identifying early biomarkers of restricted and repetitive behaviours among children with neurodevelopmental disorders may support the development of targeted therapeutic interventions in both clinical and educational settings, ultimately improving their learning experiences and long-term developmental trajectories. The objectives of the study were to examine midbrain dopamine and norepinephrine integrity in children with and without neurodevelopmental disorders using neuromelanin-sensitive magnetic resonance imaging, and the association with restricted and repetitive behaviours. Participants were enrolled in the Child and Adolescent Brain Imaging Network (CABIN) or the Fetal Imaging and Neurodevelopment (FIND) studies. All participants completed MRI and behavioural assessments, including parent-reported RRBs measured with the Repetitive Behavior Scale-Revised. A total of 88 infants, children and adolescents (mean [SD] age, 9.47 [5.41] years; 46 males) were included. Age positively predicted neuromelanin-MRI signal intensity in the substantia nigra ({beta}=.75, p<.001) and locus coeruleus ({beta}=.38, p=0.007). Further, locus-coeruleus neuromelanin-MRI signal intensity was significantly higher in children with ASD and ADHD compared to TD peers (both, p<.007). Among children with autism, lower signal predicted more severe self-injurious behaviours ({beta}=-.420, p=.006) and restricted interests ({beta}=-.629, p<.001). Findings indicate a role for neuromelanin concentration in the locus coeruleus as a candidate biomarker for restricted and repetitive behaviours, particularly in children with autism. These behaviours may reflect reduced noradrenergic signalling and impaired capacity for arousal regulation and behavioural control in children with lower LC neuromelanin signal. Findings highlight the importance of targeting the noradrenergic system when developing therapeutic strategies. Pharmacological interventions aimed at modulating the noradrenergic system and school-based strategies supporting arousal regulation, behavioural flexibility, and cognitive control may help reduce symptom severity and improve functioning.