# Brain network and cell-type elucidation of molecular dysregulations in bipolar disorder suicide

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 2024 · $636,834

## Abstract

ABSTRACT
Approximately 9.8 million United States adults experienced suicidal ideations in 2018, of which 1.3 million
attempted suicide. Of these affected individuals, ~48,000 died of suicide in 2018, making suicide the tenth
leading cause of death in the United States that year. The impacts of depressive symptoms in bipolar disorder
account for many suicides, especially in older men. Yet no specific anti-suicide treatments or biological
approaches to predicting suicide risk in bipolar disorder exist. In addition, several critical gaps exist in our current
knowledge of the molecular mechanisms underlying brain circuitry abnormalities implicated in suicidal behaviors.
The high prevalence of global suicide rates, in excess of over one million deaths every year globally, is a
significant problem. Our long-term goals are to elucidate the brain mechanisms for bipolar disorder-related
suicides and to better define the molecular abnormalities underlying suicide risk in bipolar disorder in general
and in older men who suffer a disproportional risk of dying by suicide. Our previous postmortem RNA-sequencing
studies have identified an anterior insula and subgenual anterior cingulate circuitry molecular abnormalities
associated with bipolar disorder diagnoses and suicide risk. These results led to our central hypothesis that the
anterior insula and subgenual anterior cingulate brain circuitry will harbor dysregulated brain circuitry and cellular
gene expression profiles in inflammatory signaling in bipolar disorder, and more so in older men brain donors
who died by suicide. Towards this hypothesis, we have discovered specific gene expression abnormalities of
this brain circuitry in postmortem bipolar disorder suicides. Based on our preliminary transcriptomics findings,
we propose two Specific Aims to 1) identify downregulated/reduced molecular profiles in the anterior insula and
subgenual anterior cingulate brain regions in bipolar disorder and bipolar suicide deaths using bulk tissue RNA-
sequencing, and 2) identify downregulation/reduction of molecular profiles in the anterior insula and subgenual
anterior cingulate brain regions in bipolar disorder suicide deaths at the cellular level using single-nucleus RNA-
sequencing. These results will potentially uncover novel molecular mechanisms underlying bipolar disorder
morbidity and suicide in a critical brain circuitry known to control emotion monitoring and mood states.
Furthermore, these findings may be extrapolated to other mood illnesses and advance our understanding of
brain circuitry biological changes underlying complex maladaptive behaviors like suicide.

## Key facts

- **NIH application ID:** 10767080
- **Project number:** 1R01MH134791-01
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **Principal Investigator:** Mbemba Jabbi
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $636,834
- **Award type:** 1
- **Project period:** 2024-05-15 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10767080

## Citation

> US National Institutes of Health, RePORTER application 10767080, Brain network and cell-type elucidation of molecular dysregulations in bipolar disorder suicide (1R01MH134791-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10767080. Licensed CC0.

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