The primary aim of the this collaborative R01 application is to conduct a longitudinal neuroimaging study of developmental changes in the function and structure of ventral-prefrontal limbic cortical networks key to emotion processing in a unique cohort of children with preschool onset Major Depressive Disorder (PO-MDD) as they transition from school age to early adolescence. To achieve this goal, we propose to conduct structural and functional neuroimaging at 3 timepoints in healthy and PO-MDD children ascertained as part of an ongoing R01 to Joan Luby, M.D. The proposed study would capture children at the 5th and 6th (final) annual waves of data collection in this continuing R01 and would conduct an additional scan and diagnostic assessment at a subsequent planned wave. Detailed longitudinal diagnostic, psychosocial, biological and family history and parenting data are already available in the study sample. The proposed study provides an invaluable opportunity to examine the effects of depression severity and course, as well as key biological and psychosocial mediators/moderators assessed during early childhood, on the structure and function of prefrontal limbic emotion systems known to be altered in older children and adults with MDD. It will also provide the first available longitudinal data on alterations in brain maturation in childhood MDD. Preliminary neuroimaging data from the study population have been obtained as part of a small NIMH supplement and support several of the specific hypotheses. To characterize differences in regional volume and cortical integrity based on innovative high dimensional computational anatomy approaches, we will focus on the neuromorphometry of the following regions: the ventral medial prefrontal cortex, pregenual cingulate, amygdala and hippocampus. Diffusion tensor imaging (DTI) will also be employed in a complementary fashion to further characterize cortical, subcortical and white matter tract structural integrity. To characterize differences in the functional neuroanatomy of emotion processing in these same regions, we propose to use functional magnetic resonance imaging during an emotion recognition paradigm and to assess functional connectivity. Based on the design of the proposed study and the available well-studied sample with PO-MDD, we will have the unique opportunity to fill a critical gap in the literature and investigate developmental changes in brain maturation related to childhood onset MDD.

Public Health Relevance

The proposed study will address how preschool onset and childhood recurrent depression impact brain development in children. We will address the impact of chronicity and severity of early depressive episodes on the structure and function of brain regions known to be key in emotion processing. The study will conduct 3 scans during school age and early adolescence in children with preschool onset MDD compared to healthy controls. Based on the design of the study, we will also have the opportunity to address the role of risk and protective factors in this process including parent child relationship, stressful life events and social support.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Research Project (R01)
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Study Section
Special Emphasis Panel (ZRG1-BDCN-N (02))
Program Officer
Garriock, Holly A
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Washington University
Schools of Medicine
Saint Louis
United States
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Luby, Joan L; Agrawal, Arpana; Belden, Andy et al. (2018) Developmental Trajectories of the Orbitofrontal Cortex and Anhedonia in Middle Childhood and Risk for Substance Use in Adolescence in a Longitudinal Sample of Depressed and Healthy Preschoolers. Am J Psychiatry 175:1010-1021
Barch, Deanna M; Belden, Andy C; Tillman, Rebecca et al. (2018) Early Childhood Adverse Experiences, Inferior Frontal Gyrus Connectivity, and the Trajectory of Externalizing Psychopathology. J Am Acad Child Adolesc Psychiatry 57:183-190
Sylvester, Chad M; Whalen, Diana J; Belden, Andy C et al. (2018) Shyness and Trajectories of Functional Network Connectivity Over Early Adolescence. Child Dev 89:734-745
Pagliaccio, David; Pine, Daniel S; Barch, Deanna M et al. (2018) Irritability Trajectories, Cortical Thickness, and Clinical Outcomes in a Sample Enriched for Preschool Depression. J Am Acad Child Adolesc Psychiatry 57:336-342.e6
Whalen, Diana J; Sylvester, Chad M; Luby, Joan L (2017) Depression and Anxiety in Preschoolers: A Review of the Past 7 Years. Child Adolesc Psychiatr Clin N Am 26:503-522
Luby, Joan L; Barch, Deanna; Whalen, Diana et al. (2017) Association Between Early Life Adversity and Risk for Poor Emotional and Physical Health in Adolescence: A Putative Mechanistic Neurodevelopmental Pathway. JAMA Pediatr 171:1168-1175
Kertz, Sarah J; Sylvester, Chad; Tillman, Rebecca et al. (2017) Latent Class Profiles of Anxiety Symptom Trajectories From Preschool Through School Age. J Clin Child Adolesc Psychol :1-16
Luking, Katherine R; Neiman, Jamie S; Luby, Joan L et al. (2017) Reduced Hedonic Capacity/Approach Motivation Relates to Blunted Responsivity to Gain and Loss Feedback in Children. J Clin Child Adolesc Psychol 46:450-462
Sylvester, C M; Petersen, S E; Luby, J L et al. (2017) Face processing in adolescents with positive and negative threat bias. Psychol Med 47:800-809
Whalen, Diana J (2017) Using Hybrid Modeling to Determine the Latent Structure of Psychopathology. Biol Psychiatry 81:e41-e42

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