Prospective associations between structural brain development and onset of depressive disorder during adolescence and emerging adulthood

Abstract Brain structural alterations are consistently reported in depressive disorders, yet it remains unclear whether these alterations reflect a pre-existing vulnerability or are the result of psychopathology. We aimed to investigate prospective adolescent neurodevelopmental risk markers for depressive disorder onset, using data from a fifteen-year longitudinal study. A risk-enriched community sample of 161 adolescents who had no history of depressive disorders participated in neuroimaging assessments conducted during early (age 12), mid (age 16) and late adolescence (age 19). Onsets of depressive disorders were assessed for the period spanning early adolescence through emerging adulthood (post-baseline, ages 12 to 27). Forty-six participants (28 female) experienced a first episode of a depressive disorder during the follow-up period; eighty-three participants (36 female) received no mental disorder diagnosis. Joint modelling was used to investigate whether brain structure (subcortical volume, cortical thickness and surface area) or age-related changes in brain structure were associated with the risk of depressive disorder onset. Analyses revealed that age-related increases in a) amygdala volume (hazard ratio [HR] 3.01, pFDR 0.036), and b) thickness of temporal (parahippocampal [HR 3.73, p 0.004] and fusiform gyri [HR 4.14, p 0.003]), insula (HR 4.49, p 0.024) and occipital (lingual gyrus, HR 4.19, p 0.013) regions were associated with the onset of depressive disorder. Findings suggest that relative increases in amygdala volume and temporal, insula, and occipital cortical thickness across adolescence may reflect disturbances of normative brain development, predisposing some individuals to depression. This raises the possibility that prior findings of grey matter decreases in clinically depressed individuals may instead reflect alterations that are caused by disorder-related factors.