My long-term career goal is to develop an independent research program to elucidate the neurobiological mechanisms underlying emotion dysregulation (ED) in child psychopathology beginning with attention-deficit/hyperactivity disorder (ADHD). As a critical first step, the objectives of this research plan are to examine the clinical characteristics and neural correlates of low frustration tolerance, an impairing form of ED, in children with ADHD using behavioral tasks and multimodal neuroimaging techniques. The goal of this research is to inform prevention and intervention efforts for those children with ADHD at greatest risk for negative outcomes due to ED. Children with ADHD who have difficulty with emotion regulation, including poor frustration tolerance, are at greatest risk for increased psychiatric problems, greater social impairments, and poorer self-esteem. Therefore, it is critical to understand the clinical characteristics (e.g., symptoms and impairments) and neural correlates associated with low frustration tolerance in children with ADHD. As a clinical psychologist, my graduate training focused on the evidence-based assessment and treatment of children with ADHD which led to my interest in understanding ED in children with ADHD. Following my dissertation, which examined emotion regulation as a mediator between ADHD and depression, I realized the need to understand ED from a neurobiological perspective which required the use of affective neuroscience techniques including multi-modal neuroimaging. Therefore, I completed a brief postdoctoral fellowship which exposed me to the application/use of affective neuroscience techniques in child psychiatric research. However, this experience did not provide the comprehensive, formalized training in neuroimaging required to pursue my long-term career goal. As an Assistant Professor at Johns Hopkins University (JHU) School of Medicine, I have access to the mentorship and institutional resources necessary to obtain this comprehensive training. As such, the K23 mechanism would allow me to devote 85% of my time and effort to obtain this required training, conduct the proposed research plan, and ultimately become an independent clinical researcher. Together, JHU and Kennedy Krieger Institute (KKI) provide a world-class environment in which to pursue training in pediatric neuroimaging research. At KKI, the Center for Neurodevelopmental and Imaging Research (CNIR) focuses on understanding the brain-behavior interactions underlying neurodevelopmental disorders including ADHD, and is uniquely equipped to support my needs. Further, my mentorship team, led by Stewart Mostofsky, M.D. (CNIR Director, primary mentor), includes experts in neuroscience (Dr. Mori), child psychopathology (particularly frustration and irritability; Drs. Findling, Leibenluft), and bio-statistics (Dr. Lindquist) who will provide me with the intellectual resources required to achieve both my training objectives and implement the proposed research project. The cumulative experiences laid out in my training plan will provide the foundation for an independent research program with the goal of receiving an R01 prior to the end of the K23 award. My training objectives are intended to address critical gaps in my knowledge and training to prepare me for an independent research career. Specifically, I plan to: (1) gain formalized training in the use/application of neuroimaging technologies to pediatric psychiatric populations; (2) obtain training in the examination of the brain-behavior interactions underlying emotional processing and regulation; (3) obtain training in neuroimaging statistics and programming; (4) improve research collaboration, scientific writing (i.e., grant and manuscript), and presentation skills; and (5) obtain additional training in the responsible conduct of research. I will accomplis these training objectives through coursework, guidance from my mentors/consultants with expertise in particular components of my training plan, completion of my research project, and attendance at relevant seminars, workshops, and conferences. The research project proposed in this application is the first study to examine the clinical characteristics and neural correlate of low frustration tolerance in children with ADHD using a multi-method neuroimaging and behavioral approach. While children with ADHD are often observed to have a deceased threshold for frustration, there have been no studies of the neurobehavioral mechanisms underlying low frustration tolerance in children with ADHD making this project innovative. Using two frustrating behavioral tasks, including a task developed by the application in collaboration with Dr. Mostofsky, this study will first characterize low frustration tolerance in children with ADHD compared to typically developing (TD) by comparing groups on task performance and examining the association between task performance and symptoms (i.e., ADHD symptoms, irritability, etc.). Additionally, I will employ structural and functional brain neuroimaging to prbe the underlying brain circuits implicated in poor frustration tolerance in ADHD vs. TD children. The findings from this study will contribute to improved understanding of the behavior and emotional dysregulation which characterizes ADHD, with the ultimate goal of improving the identification of and outcomes for individuals with ADHD.

Public Health Relevance

Emotion dysregulation is a key impairment for children with Attention-Deficit/Hyperactivity Disorder (ADHD), one of the most common psychiatric disorders of childhood. This research will identify the clinical features and brain regions involved in low frustration tolerance, a form of emotion dysregulation, in children with ADHD. As low frustration tolerance at home, school and social settings is a significant problem for many children with ADHD, this line of research has the potential to inform early identification, prevention, and targeted intervention efforts for those children with ADHD at greatest risk of poor outcomes.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Mentored Patient-Oriented Research Career Development Award (K23)
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Child Psychopathology and Developmental Disabilities Study Section (CPDD)
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Sarampote, Christopher S
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Johns Hopkins University
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Seymour, Karen E; Tang, Xiaoying; Crocetti, Deana et al. (2017) Anomalous subcortical morphology in boys, but not girls, with ADHD compared to typically developing controls and correlates with emotion dysregulation. Psychiatry Res Neuroimaging 261:20-28
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