Functional Brain Activation to Emotionally Valenced Faces in School-Aged Children with a History of Preschool-Onset Major Depression

Background: Recent research has demonstrated that clinical depression can emerge as early as the preschool period. Here, we examine brain function in children with a history of preschool-onset depression (PO-MDD) in comparison with healthy children. Methods: Participants were medication naive school-aged children (ages 7-11) with PO-MDD (n = 22) or no psychiatric history (n = 16) followed longitudinally as part of the Preschool Depression Study. We used functional magnetic resonance imaging measures of blood oxygen level-dependent signal to examine functional brain activity in response to emotionally valenced faces (sad, fearful, angry, happy, neutral) following a negative mood induction provided to all children. Results: In categorical group comparisons, children with PO-MDD demonstrated increased activity in parietal cortex in response to sad faces but no differences in brain activity in a priori regions of interest (e. g., amygdala). However, in dimensional analyses, the severity of depression symptoms at the baseline preschool assessment predicted increased responses to sad faces in amygdala, hippocampal, parietal, and orbital frontal regions. Conclusions: School-aged children with a history of PO-MDD showed patterns of functional brain responses to emotionally evocative stimuli similar to patterns found in adults and adolescents with major depression. These patterns were most strongly related to the severity of depression during the preschool period, suggesting that the magnitude of early symptoms may be particularly important for understanding altered brain function. These findings suggest that an early episode of depression before age 6 may be associated with enduring brain change or may represent a biomarker that was present even before the preschool episode.