Structural Brain Development and Depression Onset During Adolescence: A Prospective Longitudinal Study

Objective: The authors sought to investigate whether the structural development of limbic, striatal, and prefrontal regions that are critically implicated in the pathophysiology of depression is associated with adoleseent-onset depression. Method: In a longitudinal design, a risk-enriched community sample of 86 adolescents (41 of them female) who had no history of depressive disorders participated in neuroimaging assessments conducted during early (age 12) and mid-adolescence (age 16). Onset of depressive disorders was assessed for the period spanning early to late adolescence (ages 12 to 18). Thirty participants experienced a first episode of a depressive disorder during the follow-up period. The authors assessed whether onset of depressive disorder was associated with structural change in limbic, striatal, and prefrontal cortical regions from early to mid-adolescence. Results: Volumetric change in the hippocampus, amygdala, and putamen from early to mid-adolescence was associated with the onset of depression during adolescence. Attenuated growth of the hippocampus and attenuated reduction in putamen volume over time were associated with the onset of depression. Sex moderated the association between amygdala growth and depression such that exaggerated growth and attenuated growth of the amygdala were associated with depression in females and males, respectively. Across time, smaller nucleus accumbens volume was associated with depression in females only. Conclusions: These findings suggest that alterations in the developmental trajectories of limbic and striatal regions during adolescence may represent a neurobiological manifestation of a risk factor for the development of depression during this critical period and thus may provide clues as to etiological mechanisms of this disorder.