Brain Structural Signatures of Adolescent Depressive Symptom Trajectories: A Longitudinal Magnetic Resonance Imaging Study

Objective: Most evidence for structural brain abnormalities associated with adolescent depression is based on cross-sectional study designs that do not take into account the dynamic course of depressive symptoms and brain maturation across adolescence. In this study, a longitudinal design was used to investigate the association between different trajectories of depressive symptoms and longitudinal changes in brain structure throughout adolescence. Method: One hundred forty-nine adolescents were assessed on depressive symptoms and underwent structural magnetic resonance imaging at 12 years of age and were followed up multiple times until 19 years. Three depressive symptom trajectories (low-stable [n = 97], early-decreasing [n = 33], late-increasing [n = 19]) were identified, and effects of group and group by time on hippocampus and amygdala volume and prefrontal cortical thickness and surface area were evaluated. Results: The early-decreasing symptoms group exhibited differences in cortical surface area compared to the low stable and late-increasing symptoms groups, moderated by sex. Specifically, females in the early-decreasing symptoms group showed lower anterior cingulate and orbitofrontal cortex surface areas across adolescence compared to females in the other groups. Males in the early-decreasing symptoms group showed lower right orbitofrontal cortex surface area expansion over time compared to males in the low-stable and late-increasing symptoms groups. No effects were found for cortical thickness or for hippocampus and amygdala volume. Conclusion: Alterations in cortical surface area were specifically observed in young people experiencing depressive symptoms in early adolescence. These findings suggest that early adolescence is a particularly sensitive period for cortical surface area abnormalities associated with depressive symptoms and could provide a critical window for treatment of (subthreshold) depressive symptoms.