# Oxidative Stress and Bipolar Disorder Trajectories

> **NIH NIH R01** · BRIGHAM AND WOMEN'S HOSPITAL · 2021 · $559,134

## Abstract

PROJECT SUMMARY
Individuals with bipolar disorder often experience functional and cognitive decline, especially in late-life. An
affected “mood network” in the brain has been proposed in bipolar disorder, which includes many of the brain
regions involved in affected processes. However, mechanisms underlying changes to this network are largely
unknown. Evidence from studies of animals and peripheral markers in humans suggests a role of oxidative
stress, an imbalance between the production of reactive oxygen species and availability of antioxidant
defenses. Our preliminary data suggest reduced availability of antioxidant defenses in the anterior cingulate
cortex in bipolar disorder, particularly in older adults. This project will take a lifespan and longitudinal approach
to study brain markers of oxidative stress as they relate to brain function and decline in bipolar disorder. The
central hypothesis is that reduced availability of antioxidant defenses in critical regions of the “mood network”
in later-life leads to alterations in brain activation and connectivity, and ultimately to cognitive and functional
decline in bipolar disorder. The long-term goal of understanding the role of oxidative stress in the pathophysiology
and trajectory of bipolar disorder may lead to the identification of critical periods for intervention or the development
of novel treatments. The specific aims are: 1) to examine the relationship between bipolar disorder and oxidative
stress in the brain in middle- and older-aged adults, 2) to assess oxidative stress in the brain as a mechanism
underlying known functional brain alterations in bipolar disorder, and 3) to conduct a pilot study to explore
changes in oxidative stress and its effect on the trajectory of bipolar disorder longitudinally. Having
accomplished the specific aims, this project will result in a rich dataset that will support future studies integrating
oxidative stress into a larger mechanistic framework for bipolar disorder across the lifespan.

## Key facts

- **NIH application ID:** 10198709
- **Project number:** 5R01MH110797-06
- **Recipient organization:** BRIGHAM AND WOMEN'S HOSPITAL
- **Principal Investigator:** Pamela Belmonte Mahon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $559,134
- **Award type:** 5
- **Project period:** 2016-09-13 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10198709

## Citation

> US National Institutes of Health, RePORTER application 10198709, Oxidative Stress and Bipolar Disorder Trajectories (5R01MH110797-06). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10198709. Licensed CC0.

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