# Diurnal Molecular Rhythms of the Human Hypothalamus and Involvement in Bipolar Disorder

> **NIH NIH R01** · UNIVERSITY OF MISSISSIPPI MED CTR · 2022 · $391,972

## Abstract

Project Summary
Accumulating evidence supports the involvement of circadian rhythm dysfunction in bipolar disorder (BD). There
is currently a critical need for identifying the neuropathological correlates of circadian dysfunction in human
subjects with BD, and linking these correlates to functional consequences. We focus on the suprachiasmatic
nucleus (SCN), the master clock of mammalian organisms, and its major output area the paraventricular nucleus
(PVN), a region critically involved in the regulation of stress and anxiety. Our preliminary data showing decreased
expression of somatostatin and the clock protein period 2 in the SCN indicate impaired SCN molecular clock
rhythms in BD. Furthermore, decreased period 2 along with increased expression of the stress signaling
molecule corticotropin releasing factor in the PVN during the morning in subjects with bipolar disorder suggests
that weaker SCN rhythms impact downstream stress signaling, coinciding with the established increase in
severity of anxiety and depression and increased cortisol at this time of day. Studies in nocturnal rodents have
provided insight into how the SCN and PVN are involved in regulating stress and mood, suggesting that disrupted
SCN molecular clock rhythms can alter expression rhythms of clock molecules and stress response molecules
in regions involved in mood regulation. Our preliminary evidence suggesting weakened molecular clock rhythms
in the SCN of subjects with BD supports this hypothesis. There is currently a lack of information regarding the
cell specific expression rhythms of neuropeptides and clock molecules, and their association with stress
response molecules in these regions in humans. The proposed studies will establish the foundation necessary
to test our overarching hypothesis that altered molecular clock rhythms in the SCN in BD are associated with
altered clock rhythms and increased expression of stress response molecules in downstream regions involved
in stress response and mood regulation. We will test the hypotheses that i) expression of clock molecules,
neuropeptides, and corticotropin releasing factor follow diurnal rhythms of expression in the human SCN and
PVN ii) SCN and PVN molecular rhythms are disrupted in subjects with BD, associated with altered expression
of molecules implicated in genome wide association studies.

## Key facts

- **NIH application ID:** 10491157
- **Project number:** 5R01MH125833-02
- **Recipient organization:** UNIVERSITY OF MISSISSIPPI MED CTR
- **Principal Investigator:** Harry Pantazopoulos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $391,972
- **Award type:** 5
- **Project period:** 2021-09-20 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10491157

## Citation

> US National Institutes of Health, RePORTER application 10491157, Diurnal Molecular Rhythms of the Human Hypothalamus and Involvement in Bipolar Disorder (5R01MH125833-02). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10491157. Licensed CC0.

---

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