Depression and anxiety disorders together account for the majority of mental health disorders in childhood and adolescence and are often comorbid. 1 Ghandour R.M. Sherman L.J. Vladutiu C.J. Ali M.M. Lynch S.E. Bitsko R.H. Blumberg S.J. Prevalence and treatment of depression, anxiety, and conduct problems in US children. The frequent co-occurrence of these disorders has motivated clinicians and researchers to consider dimensional taxonomy models that focus on neurobiological substrates which explain transdiagnostic constructs of functioning (eg, reward processing abnormalities). Such an approach would redefine not only depression and anxiety disorders but could also revolutionize clinical care, as such biobehavioral targets, rather than a traditional primary diagnosis, could serve as the basis for treatment planning. In this issue of the Journal, Auerbach and colleagues 2 Auerbach R.P. Pagliaccio D. Hubbard N.A. Reward-Related Neural Circuitry in Depressed and Anxious Adolescents: A Human Connectome Project. examined whether and how a key structure involved in reward processing, the nucleus accumbens (NAcc), is altered in adolescents, ages 14-17 years, with depression and/or anxiety (including generalized anxiety, separation anxiety, social anxiety, specific phobia, agoraphobia, and panic) disorders and whether NAcc morphometry and function would improve prediction of 6-month symptomatology. As part of the Boston Adolescent Neuroimaging of Depression and Anxiety (BANDA) initiative, 3 Hubbard N.A. Siless V. Frosch I.R. Goncalves M. Lo N. Wang J. Bauer C.C. Conroy K. Cosby E. Hay A. Jones R. Brain function and clinical characterization in the Boston adolescent neuroimaging of depression and anxiety study. the researchers compared 129 adolescents with primary diagnoses of depression and/or anxiety and 64 psychiatrically healthy controls on gray matter volumes of the NAcc and on functional activation of the NAcc during a monetary incentive delay task using MRI protocols harmonized with the Human Connectome project (http://www.humanconnectomeproject.com/). Compared to healthy adolescents, depressed/anxious adolescents exhibited significantly smaller volumes of the NAcc and blunted NAcc responses to reward receipt. Among the 88 depressed/anxious adolescents and 57 healthy controls who provided symptom data 6 months later, the researchers also found that inclusion of NAcc volumes, but not reward-related responses of the NAcc on the task, significantly improved statistical prediction of subsequent depression symptoms.