# 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 · 2022 · $690,548

## Abstract

ABSTRACT. Bipolar Spectrum Disorders (BPSD) affect up to 4.5% of Americans, are the 4th leading cause of
disability worldwide, with onset peaking in early adulthood. Yet, it is very difficult to identify young adults at risk
for BPSD, as there are no objective biomarkers of BPSD risk. Identifying these biomarkers can be facilitated by
elucidating neural biomarkers of behaviors that predispose to key symptoms of BPSD: hypomania and mania.
While emotional dysregulation characterizes BPSD, it also characterizes, and predisposes to, anxiety,
depression, and anxiety, affective and personality disorders. Impulsive sensation seeking (ISS) comprises the
component traits impulsivity and sensation seeking. High trait ISS characterizes BPSD, and predisposes to
hypomania and mania in young adults. Thus, high trait ISS predisposes to hypo/mania, and emotional
dysregulation, to anxiety and depression. The combination of both may ultimately confer risk for BPSD. In the
first 4 years of R01MH100041, examining neural biomarkers of dimensions of psychopathology and 1-year
outcome neural predictors in transdiagnostically-recruited young adults, we show (in n=100) a positive
association between trait ISS and activity in reward circuitry: left ventrolateral prefrontal cortex (vlPFC) and
ventral striatum (VS) during uncertain reward expectancy (RE). Greater left vlPFC and VS activity to uncertain
RE is also shown by BPSD vs healthy adults. In MH100041, greater left vlPFC-parietal cortical functional
connectivity (FC) to uncertain RE is associated with greater mania severity 6 months post scan; and greater
left VS-left vlPFC resting state FC, with higher trait ISS. By contrast, greater amygdala activity, and lower
amygdala-dorsal/rostral anterior cingulate cortical (dACC/rACC) FC, during emotion processing and regulation
are associated with greater emotional dysregulation, anxiety and depression, and risk for anxiety, affective and
personality disorders. Elevated reward circuitry activity and FC to uncertain RE and rest are thus promising
neural biomarkers of hypo/mania risk, and, with the above amygdala-ACC abnormalities, may predispose to
BPSD. We propose a renewal of MH100041 to: 1. Replicate and extend our neural biomarker findings in a new
cohort of 180 young adults (18-30 years; recruited transdiagnostically; no BPSD); 2. Determine if these neural
biomarkers are present in a new group of 60 age- and gender-ratio-matched adults with BPSD (30 bipolar
disorder I, 30 bipolar disorder II, prototypical types of BPSD; remitted to avoid confounds of high severity
symptoms; unmedicated/ specific medications); 3. Identify across original and new non-BPSD cohorts neural
biomarkers of trait ISS and emotional dysregulation that predict worsening hypo/mania vs. worsening anxiety
and depression over extended (2 years’) follow up, and explore which neural biomarkers predispose to BPSD
vs. other disorders. Identifying neural biomarkers of BPSD risk will help to better identify BP...

## Key facts

- **NIH application ID:** 10318571
- **Project number:** 5R37MH100041-09
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Mary Louise Phillips
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $690,548
- **Award type:** 5
- **Project period:** 2014-03-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10318571

## Citation

> US National Institutes of Health, RePORTER application 10318571, Reward, impulsive sensation seeking and emotional dysregulation: neural mechanisms underlying risk for bipolar disorder in young adults (5R37MH100041-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10318571. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*