Research Topics
Mental illnesses impact public health significantly, and treatment advances have stalled, compounding this public health problem. Dr. Brotman’s long-term goal is to leverage neuroscience and therapeutics to develop and test novel interventions for serious psychiatric disorders. Given the impact of development on later psychopathology, she applies her expertise to studies of children. Specifically, the work of Neuroscience and Novel Therapeutics (NNT) aims to advance the field by: (1) using neuroscience to identify treatment targets; and (2) developing innovative, scalable, and cost-effective therapies based on their ability to engage these targets. While this research program currently targets pediatric and adolescent irritability, lessons learned in this area will inform complementary translational interventions and approaches for other pediatric conditions.
Severe irritability is one of the most common reasons that children present for mental health care; however, few effective treatments are available. Developing targeted, mechanism-based interventions is essential given the new DSM-5 diagnosis of Disruptive Mood Dysregulation Disorder (DMDD). NNT utilizes a translational neuroscience model of irritability that articulates core pathophysiological processes to guide novel interventions (Brotman et al., 2017). In particular, pathological irritability is conceptualized as aberrant emotional and behavioral responding to frustrative nonreward and threat. This model emerges directly from imaging studies by the Emotion and Development Branch and other groups, which have found that the circuitry underlying aberrant responding to frustration and threat involves perturbations in overlapping regions, including prefrontal cortex, striatum, and amygdala (e.g., Brotman et al., 2006; Brotman et al., 2007; Brotman et al., 2010; Kircanski et al., 2018).
Dr. Brotman is Principal Investigator on NIMH protocol 15-M-0182 examining two novel mechanism-based treatments for severe irritability in youth: (1) a computer-based treatment , interpretation bias training (IBT) that targets face emotion processing; (2) an exposure-based cognitive-behavioral research therapy.
Biography
Melissa A. Brotman, Ph.D., is the principal investigator of the Neuroscience and Novel Therapeutics Unit (NNT) in the Emotion and Development Branch at the National Institute of Mental Health (NIMH) Intramural Research Program (IRP). Dr. Brotman received her Ph.D. in clinical psychology from the University of Pennsylvania, where she specialized in cognitive behavioral therapy for mood and anxiety disorders. After completing her clinical internship at the Veterans Affairs Maryland Health Care System/University of Maryland-Baltimore, she completed post-doctoral training in neuroscience, focusing on functional magnetic resonance imaging (fMRI) and clinical phenotyping of severe irritability in youth. Currently, her neurodevelopmental, translational research integrates basic and clinical approaches to the study of mood disorders in children and adolescents. Specifically, she uses affective neuroscience techniques to understand the brain-based mechanisms underlying severe irritability in youth and leverages pathophysiological knowledge to guide the development of novel targeted interventions.
Dr. Brotman is a Member of the American College of Neuropsychopharmacology (ACNP) and Chair of the ACNP Membership Advisory Task Force. She has received multiple research awards, including the NIMH IRP Seymour S. Kety Memorial Training Award, Society of Biological Psychiatry Travel Award, ACNP Young Investigator Memorial Travel Award, and Career Development Institute Award. She has been awarded two NIH Bench-to-Bedside grants (2018-2020, 2020-2022), is a consultant on numerous extramural grants, and is on the Editorial Board of the Journal of Affective Disorders. Finally, mentoring is a focal aspect of her career, and her mentorship was recently recognized through the NIMH Outstanding Mentor Award.
Selected Publications
Duggan MR, Gomez GT, Joynes CM, Bilgel M, Chen J, Fattorelli N, Hohman TJ, Mancuso R, Cordon J, Castellano T, Koran MEI, Candia J, Lewis A, Moghekar A, Ashton NJ, Kac PR, Karikari TK, Blennow K, Zetterberg H, Martinez-Muriana A, De Strooper B, Thambisetty M, Ferrucci L, Gottesman RF, Coresh J, Resnick SM, Walker KA (2024). Proteome-wide analysis identifies plasma immune regulators of amyloid-beta progression. Brain Behav Immun 120, 604-619. https://doi.org/10.1016/j.bbi.2024.07.002. [Pubmed Link ]
Naim R, Dombek K, German RE, Haller SP, Kircanski K, Brotman MA (2024). An Exposure-Based Cognitive-Behavioral Therapy for Youth with Severe Irritability: Feasibility and Preliminary Efficacy. J Clin Child Adolesc Psychol 53, 260-276. https://doi.org/10.1080/15374416.2023.2264385. [Pubmed Link ]
Naim R, Haller SP, Linke JO, Jaffe A, Stoddard J, Jones M, Harrewijn A, Kircanski K, Bar-Haim Y, Brotman MA (2022). Context-dependent amygdala-prefrontal connectivity during the dot-probe task varies by irritability and attention bias to angry faces. Neuropsychopharmacology 47, 2283-2291. https://doi.org/10.1038/s41386-022-01307-3. [Pubmed Link ]
Brotman MA, Kircanski K, Stringaris A, Pine DS, Leibenluft E (2017). Irritability in Youths: A Translational Model. Am J Psychiatry 174, 520-532. https://doi.org/10.1176/appi.ajp.2016.16070839. [Pubmed Link ]
Kircanski K, White LK, Tseng WL, Wiggins JL, Frank HR, Sequeira S, Zhang S, Abend R, Towbin KE, Stringaris A, Pine DS, Leibenluft E, Brotman MA (2018). A Latent Variable Approach to Differentiating Neural Mechanisms of Irritability and Anxiety in Youth. JAMA Psychiatry 75, 631-639. https://doi.org/10.1001/jamapsychiatry.2018.0468. [Pubmed Link ]
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