Unit on Neuroscience and Novel Therapeutics

National Institute Of Mental Health

Investigators

Linked publications, trials & patents

Abstract

First, in 2021, our program completed a multiple baseline novel frustration-exposure intervention for youth with severe irritability based on extinction principles. We published a protocol paper; N=41 youth were randomized; preliminary analyses demonstrated that irritability scores decreased significantly from the start of therapy to end of therapy. NNT acquires pre-treatment behavioral and task-based fMRI data to test the hypothesis that pre-treatment behavioral deficits in inhibition predict poorer treatment response. Second, in 2021, we published a randomized controlled trial (N=44, active vs. placebo) of a computer-based treatment engaging behavioral and neural targets of aberrant threat processing. In addition, we developed an analogous fMRI paradigm to probe neural correlates in a large (N>100) sample of youth with varying degrees of irritability. We found unique neural correlates associated with latent factor-derived phenotype of high irritability and anxiety. Third, we leverage technology to assess symptoms by utilizing digitally based event sampling (ecological momentary assessment). We collected data on over 100 youth and our manuscript is now in press. We developed a cognitive inhibition mobile application to probe children's inhibitory control. We published a protocol paper and have administered to over 50 youth remotely. These interventions provide the foundation for scalable, target-based interventions which are more easily disseminated, facilitating public health impact. Fourth, we published three additional behavioral phenotype papers probing threat attention, extinction recall, and, inhibitory control in youth with irritability and anxiety. Fifth, as threats engage evolutionarily conserved processes, our translational perspective has been supported by two Bench-to-Bedside Awards. Specifically, we reverse translated the Human Intruder Paradigm, (Kalin & Shelton 1989) into two clinical paradigms. Our fMRI (N=60) and eye-tracking (N=60) tasks parallel work in non-human primates. Ultimately, these mechanistic studies will allow for more targeted interventions for pathological irritability. Finally, the acute onset of the COVID-19 pandemic provides a rare opportunity to utilize existing pre-stress clinical and neural data to predict stress-related increases in psychopathology and associated neural dysfunction. In this study, we are examining associations among stress, genetic liability, brain function, and the development of psychopathology.