Predicting depression risk in early adolescence via multimodal brain imaging

Depression is an incapacitating psychiatric disorder with high prevalence in adolescent populations that is influenced by many risk factors, including family history of depression. The ability to predict who may develop depression before adolescence, when rates of depression increase markedly, is important for early intervention and prevention. Using a large longitudinal sample from the Adolescent Brain Cognitive Development (ABCD) Study (2658 participants after imaging quality control, between 9-10 years at baseline), we applied machine learning methods on a set of comprehensive multimodal neuroimaging features to predict depression risk at the two-year follow-up from the baseline visit. Features include derivatives from structural MRI, diffusion tensor imaging, and task and rest functional MRI. A rigorous cross-validation method of leave-one-site-out was used. Additionally, we tested the prediction models in a high-risk group of participants with parental history of depression (N=625). The results showed all brain features had prediction scores significantly better than expected by chance. When predicting depression onset in the high-risk group, brain features from resting-state functional connectomes showed the best classification performance, outperforming other brain features based on structural MRI and task-based fMRI. Results demonstrate that the functional connectivity of the brain can predict the risk of depression in early adolescence better than other univariate neuroimaging derivatives, highlighting the key role of the interacting elements of the connectome capturing more individual variability in psychopathology compared to measures of single brain regions.