Brain Structural Associations with Depression in a Large Early Adolescent Sample (The ABCD Cohort)

Background: Depression is the leading cause of disability worldwide with >50% of cases emerging before the age of 25yrs. Large-scale neuroimaging studies in depression implicate robust structural brain differences in the disorder.  However most studies have been conducted in adults and therefore, the temporal origins of depression-related imaging features remain unknown. This has important implications for understanding aetiology and informing timings of potential intervention. Methods: Here, we examine associations between brain structure (cortical metrics and white matter microstructural integrity) and depression ratings (from caregiver and child), in a large sample of early adolescents from the Adolescent Brain and Cognitive Development (ABCD) Study (N=9981, 9-11-year olds). Findings: We report significantly decreased global cortical and white matter metrics, and regionally in frontal, limbic and temporal areas in adolescent depression (Cohen’s d = -0.018 to -0.041, β = -0.019 to -0.057). Further, we report consistently stronger imaging associations for caregiver-reported compared to child-reported depression ratings. Divergences between reports (caregiver vs child) were found to significantly relate to negative socio-environmental factors (e.g., family conflict, absolute β=0.048 to 0.169). Interpretation: Depression ratings in early adolescence were associated with similar imaging findings to those seen in adult depression samples, suggesting neuroanatomical abnormalities may be present early in the disease course, arguing for the importance of early intervention. Associations between socio-environmental factors and reporter discrepancy warrant further consideration, both in the wider context of the assessment of adolescent psychopathology, and in relation to their role in aetiology. Funding: The study is funded by Wellcome Trust Strategic Award “Stratifying Resilience and Depression Longitudinally” (STRADL) (Reference 104036/Z/14/Z) and MRC Mental Health Data Pathfinder Award (Reference MC_PC_17209). HCW is supported by a JMAS SIM fellowship from the Royal College of Physicians of Edinburgh and by an ESAT College Fellowship from the University of Edinburgh. AMM receives the Wellcome Trust Strategic Award (Reference 104036/Z/14/Z). Declaration of Interests: AMM has received research funding from The Sackler Trust, Eli Lilly and Janssen. No other conflicts of interest declared by other authors. Ethics Approval Statement: The study was approved by the National Institute of Mental Health Data Archive, United States (NIMH). Data was accessed through the NDA data base (http://nda.nih.gov/abcd, Federal-Wide Assurance: FWA00018101).