# Reward, impulsive sensation seeking and emotional dysregulation: neural mechanisms underlying risk for bipolar disorder in young adults

> **NIH NIH R37** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $745,928

## Abstract

PROJECT SUMMARY (See instructions): 
Bipolar Disorder (BD) is often misdiagnosed as Major Depressive Disorder (MDD) and poorly-treated. As 
risk for mental health problems increases in young adulthood, identifying objective neural marker predictors 
of future BD vs. MDD in young adults will provide neural markers for early risk identification and neural 
targets for new interventions to delay or prevent these debilitating disorders. The goal in the initial MERIT 
Award period was to adopt a transdiagnostic and dimensional approach to identify neural marker correlates 
and predictors of worsening manic/hypomanic vs. depressive symptoms in young adults, ultimately to 
distinguish BD from MDD risk. We showed that: elevated reward expectancy-related left ventrolateral 
prefrontal cortical (vlPFC) and prediction error-related left ventral striatal activity, lower PE-related right 
amygdala activity, and lower bilateral cingulum bundle fractional anisotropy (FA), a measure of white matter 
fiber collinearity, predicted current and/or future mania/hypomania; greater largescale (central executive 
[CEN], salience and default mode) network functional connectivity (FC) and greater CEN dorsolateral 
prefrontal cortical (dlPFC) activity during emotional regulation predicted current and future depression; 
while lower right uncinate fasciculus FA and greater left vlPFC and lower left inferior temporal cortical 
thickness were associated with greater mania/hypomania and depression. In the proposed MERIT 
extension, to yield robust neural markers of BD vs. MDD risk, we aim to examine: 1. an independent young 
adult sample (n=150 non mood disordered 18-30 year-olds) to test findings; 2. higher temporal resolution 
neural, and dopamine transmission, measures using fMRI-based source-localized electroencephalography 
(EEG) beta power/FC and midbrain neuromelanin contrast to noise ratio; 3. longitudinal neuroimaging to 
identify neural change predictors of worsening mania/hypomania and depression, and ultimately BD and 
MDD; 4. relationships among neural measures, response tendencies and symptom trajectories 
predisposing to BD and MDD, to better understand risk pathways for these disorders; and 5. young adults 
with 1st and/ or 2nd degree relatives with BD and MDD/ MDD, given their higher BD and MDD risk.

## Key facts

- **NIH application ID:** 10890223
- **Project number:** 4R37MH100041-11
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Mary Louise Phillips
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $745,928
- **Award type:** 4C
- **Project period:** 2024-01-01 → 2028-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10890223

## Citation

> US National Institutes of Health, RePORTER application 10890223, Reward, impulsive sensation seeking and emotional dysregulation: neural mechanisms underlying risk for bipolar disorder in young adults (4R37MH100041-11). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10890223. Licensed CC0.

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