The prevalence of major depressive disorder (MDD) is relatively low in childhood (i.e., 1-3%), but increases substantially during adolescence. By the age of 18, approximately 15% of adolescents will have experienced at least one episode of MDD. A growing body of research implicates abnormalities in reward circuitry as playing a critical role in the development and maintenance of depressive symptoms in adolescents. Importantly, these reward-circuitry abnormalities have been linked to anhedonia (i.e., decreased pleasure or blunted reactivity to rewarding stimuli). Behavioral Activation (BA) represents a promising - and relatively simple to deliver - nonpharmacologic intervention for adolescent depression, which has been shown to be at least as effective as Cognitive Behavioral Therapy (CBT) with regards to symptom reduction and lowering the risk of relapse in adult samples. More recently, promising data have emerged from the application of BA to depressed adolescents. BA can be conceptualized as a treatment directly targeting anhedonia. More specifically, BA targets anhedonia through behavioral change strategies aimed at gradually increasing patients' exposure to and engagement with rewarding stimuli and positively reinforcing experiences. Given this treatment focus, BA may be particularly beneficial for adolescents struggling with relatively elevated levels of anhedonic symptoms. Accordingly, the present study will examine the role of anhedonia and reward functioning in predicting treatment response in BA. In addition, analyses will be conducted examining the reward-related neural and behavioral mechanisms underlying anhedonic symptom improvement in BA. To test hypotheses, this study integrates assessments of reward functioning from three units of analysis: 1) neural circuits (i.e., via a functional magnetic resonance imaging [fMRI] monetary reward task probing neural reward- circuitry functioning), 2) behavioral (i.e., with a probabilisti reward task [PRT] designed to objectively probe anhedonic behavior) and 3) self-report (i.e., Snaith-Hamilton Pleasure Scale [SHAPS] and Ecological Momentary Assessment [EMA]). In addition to the proposed research, the four-year K23 Award will allow the candidate to develop competency in three complementary areas. First, participants will undergo fMRI at pre- and post-treatment while completing a monetary reward task probing reward-circuitry functioning. Dr. Diego Pizzagalli (mentor), a leader in the use of fMRI to investigate the pathophysiology of depression and anhedonia, and Dr. Blaise Frederick (consultant), lead physicist at the McLean Imaging Center, will provide critical training in the acquisition, processing, and analysis of fMRI data. This training will allow the candidate to develop the skills necessary to integrate functiona neuroimaging into his depression treatment research program to more deeply probe the underlying neural mechanisms of symptom improvement. Individual mentorship and hands-on training will be supplemented by coursework in fMRI methodology, including 1) the Functional MRI Visiting Fellowship, an fMRI course offered through the Athinoula A. Martinos Center at the Harvard-Massachusetts Institute of Technology (MIT) Division of Health Sciences & Technology (HST); 2) MATLAB for Medicine offered through MIT/HST; 3) SPM8 for Basic and Clinical Investigators at MIT; and 4) Structural and Functional Brain Connectivity via MRI and fMRI offered through the Martinos Center. Second, to obtain a more fine- grained and naturalistic assessment of symptom change and the extent to which adolescents acquire and utilize the skills encouraged in BA, the applicant will receive training in Ecological Momentary Assessment (EMA) from Dr. Erika Forbes (co-mentor), a pioneer in the use of EMA with depressed and healthy adolescents. Dr. Garret Fitzmaurice (consultant) will provide statistical consultation in Growth Curve Modeling to test the longitudinal psychosocial (EMA) and neural (fMRI) hypothesis proposed in the project. Finally, the proposed training plan would allow the candidate to substantially deepen his understanding of the functional neuroanatomy of adolescent depression, with a particular focus on the neural circuitry subserving reward processing and anhedonia (Drs. Pizzagalli & Forbes). Clinical consultation and supervision will be obtained through meetings with Drs. Sona Dimidjian (consultant), a leading authority in BA, and Thrstur Bjrgvinsson (consultant), Director of the Behavioral Health Partial Program at McLean Hospital. Collectively, the proposed research and training will provide the applicant with a strong foundation in fMRI and EMA, and may yield important findings regarding the reward-related pretreatment predictors and mechanisms of symptom improvement in anhedonic and depressed youth. Upon completion of the project, the candidate will be optimally prepared to pursue an innovative research program integrating neural, behavioral and psychosocial research methods to answer these important questions. In sum, this award would allow the candidate to transition into a well-rounded and independent researcher armed with an array of complementary and cutting-edge assessment and neuro-investigative tools for the study of depression in youth.
The prevalence of depression increases dramatically during adolescence, and it is associated with a range of negative short- and long-term consequences. A growing body of research strongly implicates anhedonia and abnormal neural reward circuitry as playing a central role in the development and maintenance of depression in adolescents. The overarching goal of the project is to identify neural and behavioral reward-related mechanisms that underlie anhedonic and depressive symptom improvement in adolescents, with the ultimate goal of using this knowledge to improve treatment outcomes for depressed youth.
