As a part of a longitudinal study of risk and protective factors for adolescent depression, Whittle et al. studied 86 adolescents screened from the community for key affective features that are thought to confer risk for or resilience to depression. Between ages 12 and 18, the study subjects participated in four assessment waves addressing mental health and medical and developmental status; waves 1 and 3 included structural neuroimaging. During the study period, 30 participants experienced a new onset of major depression, allowing the authors to investigate the predictors of adolescent depression. In this first neuroimaging study to use a longitudinal design to inform risk for adolescent depression, gender differences in brain development associated with later depression were found. For boys, attenuation of growth of the hippocampus, putamen, and amygdala between ages 12 and 16 were detected, and for girls, increased growth of the amygdala and decreased growth of the nucleus accumbens were found. The authors speculate that the development of these regions, known to be involved in the modulation of stress and emotion reactivity, may become altered in high-risk individuals by either a process of neuronal damage or a disruption of neurogenesis. In contrast, they speculate that attenuation of the decrease in putamen volume in depressed adolescents may be due to a deficit in synaptic pruning or myelination, processes that are active in gray matter development during adolescence. Based on their design, the authors conclude that this altered pattern of development represents a biomarker of vulnerability rather than a result of the disorder, since it was evident before the onset of depression.