# Locomotor Activation and Mania Spectrum Risk: Circadian and Reward Mechanisms

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $678,960

## Abstract

ABSTRACT
Bipolar spectrum disorders [BSD] are impairing and costly psychiatric conditions that typically emerge in late
adolescence and early adulthood. Subthreshold mania symptoms, increasing in severity over the span of
months-to-years, remain the most important symptomatic precursor of future BSD onset. However, only a subset
of young people with subthreshold mania symptoms transition to a BSD and, regardless of later clinical diagnosis,
these symptoms severely impact real-world functioning and clinical outcome. While early treatment of
subthreshold mania symptoms appears increasingly imperative for a favorable prognosis, these symptoms are
difficult to distinguish from other psychiatric conditions. Too often, delayed symptom recognition results in
detrimental treatments and poor prognosis. Even if mania symptoms are correctly identified, it is unclear which
individuals will progress to a more severe course and thus require more intensive early treatment. As a result,
there remains a pressing clinical need to identify objective biobehavioral risk markers that will improve prevention
and intervention for the full mania spectrum. Psychomotor activation - increased activity or energy - is a cardinal
feature of the mania spectrum that can be quantified through objective measurement of locomotor activity. In a
comprehensive laboratory assessment and naturalistic follow-up study, we propose to uncover the biobehavioral
(circadian, reward) mechanisms driving locomotor activation and mania spectrum risk. We will recruit N=170
adolescents and young adults aged 16 to 24 years-old across a range of lifetime subthreshold mania symptoms
but with no prior history of a BSD. Participants will complete 2 weeks of field-based locomotor activity monitoring
with wrist actigraphy, followed by a comprehensive lab-based assessment of exploratory locomotor behavior,
circadian function, and reward sensitivity. Over follow-up, actigraphic locomotor activity and clinical status will be
indexed prospectively every 6-months for up to 3-years. Our primary aims will test the overarching hypothesis
that locomotor activation is a behavioral marker of mania symptom severity and progression [Aim 1], and that
neurobiological dysregulation of the circadian and reward systems drive locomotor activation [Aim 2] and mania
symptom progression over time [Aim 3]. We will use high-dimensional modeling approaches to identify
multivariate locomotor, circadian, reward profiles predictive of mania symptoms and their progression over time,
which will inform more comprehensive biobehavioral predictive models for the mania spectrum. Exploratory
analyses will 1) incorporate more nuanced locomotor metrics from a novel reverse-translational open field task
and 2) examine the specificity of our model to mania vs other clinical outcomes. Our results have the potential
to 1) improve early detection of mania symptoms through real-time, objective locomotor activity monitoring and
2) provide mania-rele...

## Key facts

- **NIH application ID:** 10462687
- **Project number:** 5R01MH124828-02
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Adriane M. Soehner
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $678,960
- **Award type:** 5
- **Project period:** 2021-08-06 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10462687

## Citation

> US National Institutes of Health, RePORTER application 10462687, Locomotor Activation and Mania Spectrum Risk: Circadian and Reward Mechanisms (5R01MH124828-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10462687. Licensed CC0.

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