Neuroimaging studies of depression have suggested aberrant brain network relationships in this disorder. Despite these compelling findings there have been very few investigations examining the developmental timing of these alterations in children experiencing the earliest known form of depression, Preschool Depression (PD). The purpose of this mentored Patient-Oriented Career Development Award (K23) is to provide the applicant with the skills and experience necessary to begin filling this knowledge gap. The unique mentorship and training opportunities available to the applicant complement his strong background in clinical psychology and research with clinical populations. The applicant's long-term goal is to develop an independent programmatic line of research investigating the developmental neurobiology of depression. To facilitate this goal, instruction and mentoring are proposed in 1) applying a systematic approach to the study of functional brain network development in PD using functional magnetic resonance imaging (fMRI) 2) methods for studying the relationships between brain networks and behavior in PD and 3) methods for studying the convergence between network organization and task based fMRI activity in PD. An expert interdisciplinary team of mentors and consultants will support the proposed research and training plan. The feasibility of the proposed award is enhanced by the availability of a large set of fMRI data from an ongoing longitudinal neuroimaging study of school age children with a history of PD and their same age healthy peers (NIMH MH090786) as well as a high level of success in obtaining pilot fMRI data from healthy and depressed preschoolers (4-6 years old). Using these samples, a systematic approach investigating functional brain networks at the level of individual brain regions or region pairs, targeted subnetworks, and whole brain networks (using graph theory methods) is planned for aim 1. As a second aim, the behavioral correlates associated with group differences identified in aim 1 will be examined. Patterns of overlap between group differences in brain network organization and fMRI task-based activity during an emotion face-viewing paradigm (collected in the same individuals) will be the focus of a planned exploratory aim. It is hypothesized that 1) PD will be associated with disrupted Default Mode Network connectivity 2) atypical network organization will be related to depression severity and emotion regulation difficulties in PD and 3) a high level of overlap between network and task based group differences will be present. The study of brain networks in PD may reveal unique and early occurring neurobiological markers of risk for continued mood difficulties and/or later depression; information potentially critical for developing novel preventative treatments aimed at minimizing depression's public health burden. The complimentary training and research plans proposed in this application will facilitate the applicant's transition into an independent researc career addressing NIMH research priorities that emphasize discoveries in the brain and behavioral sciences (Strategic Plan) and the study of brain networks in psychopathology (RDoC).
The training and research goals outlined in the current application will enable the candidate to become an independent researcher in the field of translational developmental neuroscience, with unique expertise that could significantly increase our developmental understanding of brain networks in depression and how they go awry in this impairing disorder. Despite growing recognition of depression as a 'network illness', there have been very few studies examining functional brain network organization in children with very early occurring depression. Such studies could lead to the earlier identification of children who will later develop MDD and inform new preventive treatment efforts aimed at minimizing the significant burden of this important public health issue. Thus, the proposed award addresses important federal research priorities aimed at reducing the impact of depression on public health.
