Abstract
Adolescents with depression are at elevated risk for maladaptive risk behaviors, underscoring the importance of understanding neurobiological alterations in reward function in this population. However, reward function alterations associated with depression, particularly in the presence of co-occurring manic symptoms (i.e., mixed manic features), remain poorly understood. In this study, 154 12–18-year-olds (ndepression without mixed manic features = 65; ndepression with mixed manic features = 56; nhealthy controls = 33) and their primary caregiver completed questionnaires, clinical interviews, and fMRI during the monetary incentive delay task. Neural response during monetary reward anticipation, as well as tissue iron concentrations, important for dopamine neurophysiology, were derived from the striatum and used to predict group membership and severity of mixed manic features. Exploratory whole brain functional activation analyses were also conducted. Lower caudate activation (in the outlier-excluded analysis) was associated with membership in the depression with mixed manic features group. Across both depression groups, higher caudate and dorsolateral prefrontal cortex (dlPFC) activation was associated with greater mixed manic feature severity. In addition, lower tissue iron concentration in the putamen and higher tissue iron concentration in the caudate were each associated with membership in the depression without mixed features group. These findings suggest that reward-related neural activation differentiates mixed manic features, whereas alterations in tissue iron characterize adolescent depression more broadly.