Abstract

BackgroundDepression is the leading cause of disability worldwide with > 50% of cases emerging before the age of 25 years. 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 largely unknown. This has important implications for understanding aetiology and informing timings of potential intervention.MethodsHere, we examine associations between brain structure (cortical metrics and white matter microstructural integrity) and depression ratings (from caregiver and child), in a large sample (N = 8634) of early adolescents (9 to 11 years old) from the US-based, Adolescent Brain and Cognitive Development (ABCD) Study®. Data was collected from 2016 to 2018.FindingsWe 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).InterpretationDepression 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.FundingWellcome Trust

Highlights

  • Major depressive disorder (MDD) is a chief cause of disability [1] with a heritability of approximately 37% [2]

  • MDD diagnosis for the child as reported by caregivers was associated with significantly lower total cortical volume (Cohen’s d = À0Á022, p = 0Á013) and global fractional anisotropy (FA) (Cohen’s d = À0Á027, p = 7Á96 £ 10À4)

  • We demonstrated that MDD and depressive symptoms (DS) were associated with similar imaging findings as seen in adult samples, including reduced global cortical volume and global fractional anisotropy (FA) (MDD: Cohen’s d range: À0Á022 to À0Á027, DS: b range: À0Á029 to À0Á057)

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Summary

Introduction

Major depressive disorder (MDD) is a chief cause of disability [1] with a heritability of approximately 37% [2]. Recent evidence from the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) consortium demonstrated widespread structural abnormalities in MDD from large adult samples, including reduced hippocampal volume, decreased frontal cortical thickness [8] (N = 10,105) and altered fronto-limbic and fronto-thalamic tract microstructure [9] (N = 2907). Since these highly powered studies have largely been conducted in adults, they preclude investigation of the neurobiology underlying the emergence and development of depression earlier in life.

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