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Neuroscience and Novel Therapeutics Unit

Neuroscience and Novel Therapeutics Unit (NNT)

Melissa A. Brotman, PhD, leads the Neuroscience and Novel Therapeutics Unit (NNT).  The goal of NNT is to leverage neuroscience and therapeutics to develop and test novel interventions for serious psychiatric disorders.

This is a model of how we integrate circuitry-based and theory-driven approaches to develop novel mechanism-based treatments.

Mental illness impacts public health significantly, and treatment advances have stalled, compounding this public health problem. In children, impairing clinical phenotypes characterized by irritability and anxiety are common, affecting up to 10% of all youth.  New treatments are needed, as developmentally applied interventions targeting aberrant mechanisms may lead to better long-term outcomes.

Given the impact of development on later psychopathology, we apply our expertise to studies of children. Specifically, NNT aims to: (1) use neuroscience to identify treatment targets; and (2) develop innovative and scalable therapies based on the ability to engage these targets.

This is a pathophysiological model of irritability in youth.

NNT utilizes a translational neuroscience model of irritability that articulates core pathophysiological processes (Brotman et al., 2017): (a) aberrant responses to frustration that are reinforced; and (b) ambiguous threat. This model of irritability emerges from imaging studies, demonstrating that the circuitry underlying aberrant frustration and threat responding involves perturbations in overlapping brain regions. 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.

This is a figure demonstrating the brain regions involved in aberrant reward and threat processing.