Prospective Associations Between Structural Brain Development and Onset of Depressive Disorder During Adolescence and Emerging Adulthood

Brain structural alterations are consistently reported in depressive disorders, yet it remains unclear whether these alterations exist prior to disorder onset and thus may reflect a preexisting vulnerability. The authors investigated prospective adolescent neurodevelopmental risk markers for depressive disorder onset, using data from a 15-year longitudinal study. A community sample of 161 adolescents participated in neuroimaging assessments conducted during early (age 12), mid (age 16), and late (age 19) adolescence. Onsets of depressive disorders were assessed for the period spanning early adolescence through emerging adulthood (ages 12-27). Forty-six participants (28 female) experienced a first episode of a depressive disorder during the follow-up period; 83 participants (36 female) received no mental disorder diagnosis. Joint modeling 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. Age-related increases in amygdala volume (hazard ratio=3.01), and more positive age-related changes (i.e., greater thickening or attenuated thinning) of temporal (parahippocampal gyrus, hazard ratio=3.73; fusiform gyrus, hazard ratio=4.14), insula (hazard ratio=4.49), and occipital (lingual gyrus, hazard ratio=4.19) regions were statistically significantly associated with the onset of depressive disorder. Relative increases in amygdala volume and temporal, insula, and occipital cortical thickness across adolescence may reflect disturbances in brain development, contributing to depression onset. This raises the possibility that prior findings of reduced gray matter in clinically depressed individuals instead reflect alterations that are caused by disorder-related factors after onset.