Impairments in the capacity for cognitive emotion regulation (ER) have been shown in Major Depressive Disorder (MDD). Investigations of cognitive ER tasks during fMRI have detected alterations in neural activity associated with cognitive ER in depressed compared to healthy adults. Despite these compelling findings, to date, there have been studies examining the neural correlates of cognitive ER in depressed versus healthy children. The proposed training and research plans are intended to provide the skill and experience necessary to become a developmental affective neuroscientist focused on addressing this critical gap in the literature. The specific hypothesis behind the proposed research is that neural circuits underlying cognitive ER may provide valid neurobehavioral markers of childhood MDD. Depressed children are expected to exhibit positive correlations between neural activity in ventral brain regions (e.g., the amygdala) thought to be responsible for appraising emotion stimuli, and neural activity in dorsal brain regions thought to underlie cognitive strategies for reappraising emotional experiences (e.g. prefrontal cortices [PFC]). Healthy children are expected to exhibit the inverse relationship. Using the same fMRI paradigm proposed in this application, initial preliminary findings appear to support this hypothesis. The feasibility of the research plan is enhanced by the availability of a large NIMH R01 study population of depressed and healthy children. Utilizing this sample, first a pilot study aimed at examining the construct validity of fMRI as a neurobiological assessment tool of children's cognitive ER is planned. The pilot study will provide opportunities to modify and optimize the fMRI task. Next, the cognitive ER task developed will be used to test the hypothesis about differences in neural circuitry in a larger sub-group of healthy and depressed children.
The second aim i s based on empirical evidence suggesting that dysfunctional neural activity in emotion processing and ER brain regions in adult samples are strongly correlated with impaired cognitive ER processes. Over 4 decades of cognitive-behavioral findings have implicated these same dysfunctional cognitive ER processes and subsequent maladaptive strategies (e.g., suppression and rumination) in the development and course of MDD. Thus, examining the neurodevelopmental substrates of cognitive ER during childhood may provide the opportunity to identify neurobehavioral markers of risk for and/or the diagnosis of MDD in childhood. Early identification of neurobehavioral markers may contribute to the advancement of novel preventive interventions aimed at minimizing the burden of MDD on the public health. To date, no study has used fMRI to examine the neural substrates of ER in healthy and depressed children. The unique mentorship and training opportunities available to the applicant would provide the necessary education and experience to launch a career as an independent scientist in the field of Translational Developmental Neuroscience. A future program of research examining the neurobehavioral underpinnings of abnormal ER development in mood-disordered children is planned.

Public Health Relevance

Training outlined in this proposal will enable the candidate to become a developmental affective neuroscientist, with unique expertise that could significantly increase our understanding of the neural circuitry involved in the development of mood disorders in depressed and healthy children. Despite highly suggestive findings using fMRI in depressed adults and behavioral data in depressed children, no studies to date have investigated cognitive emotion regulation during fMRI in depressed children. The proposed study has the potential to provide neural markers of childhood depression, which could lead to earlier identification of MDD and implementation of novel preventive interventions aimed at minimizing the burden of this mental health issue on the public.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01MH090515-03
Application #
8212479
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Garriock, Holly A
Project Start
2010-04-01
Project End
2014-01-31
Budget Start
2012-02-01
Budget End
2013-01-31
Support Year
3
Fiscal Year
2012
Total Cost
$142,063
Indirect Cost
$10,523
Name
Washington University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
Luby, Joan L; Belden, Andy C; Jackson, Joshua J et al. (2016) Early Childhood Depression and Alterations in the Trajectory of Gray Matter Maturation in Middle Childhood and Early Adolescence. JAMA Psychiatry 73:31-8
Murphy, Eric R; Barch, Deanna M; Pagliaccio, David et al. (2016) Functional connectivity of the amygdala and subgenual cingulate during cognitive reappraisal of emotions in children with MDD history is associated with rumination. Dev Cogn Neurosci 18:89-100
Belden, Andy C; Barch, Deanna M; Oakberg, Timothy J et al. (2015) Anterior insula volume and guilt: neurobehavioral markers of recurrence after early childhood major depressive disorder. JAMA Psychiatry 72:40-8
Belden, Andy C; Pagliaccio, David; Murphy, Eric R et al. (2015) Neural Activation During Cognitive Emotion Regulation in Previously Depressed Compared to Healthy Children: Evidence of Specific Alterations. J Am Acad Child Adolesc Psychiatry 54:771-81
Pagliaccio, David; Luby, Joan L; Bogdan, Ryan et al. (2015) HPA axis genetic variation, pubertal status, and sex interact to predict amygdala and hippocampus responses to negative emotional faces in school-age children. Neuroimage 109:1-11
Pagliaccio, David; Luby, Joan L; Bogdan, Ryan et al. (2015) Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation. J Abnorm Psychol 124:817-33
Luby, Joan L; Gaffrey, Michael S; Tillman, Rebecca et al. (2014) Trajectories of preschool disorders to full DSM depression at school age and early adolescence: continuity of preschool depression. Am J Psychiatry 171:768-76
Belden, Andy C; Luby, Joan L; Pagliaccio, David et al. (2014) Neural activation associated with the cognitive emotion regulation of sadness in healthy children. Dev Cogn Neurosci 9:136-47
Pagliaccio, David; Luby, Joan L; Luking, Katherine R et al. (2014) Brain-behavior relationships in the experience and regulation of negative emotion in healthy children: implications for risk for childhood depression. Dev Psychopathol 26:1289-303
Pagliaccio, David; Luby, Joan L; Bogdan, Ryan et al. (2014) Stress-system genes and life stress predict cortisol levels and amygdala and hippocampal volumes in children. Neuropsychopharmacology 39:1245-53

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