# Identification of molecular rhythm changes in postmortem tissue from individuals with psychiatric illness.

> **NIH NIH R01** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $553,835

## Abstract

Abstract
Circadian rhythm and sleep disruptions are a defining feature of psychiatric disorders like Bipolar disorder
(BP), schizophrenia (SCZ) and major depressive disorder (MDD). These disruptions to normal rhythmicity
include altered sleep/wake cycles, diurnal patterns of hormone levels, and circadian gene expression in
peripheral samples. Moreover, disruptions to the normal sleep/wake cycle often precipitate mood and
psychotic episodes, and may contribute to deficits in cognitive function. A number of treatments for psychiatric
disorders may derive their efficacy through stabilization or amplification of molecular rhythms in the brain.
However, the molecular rhythm changes that occur in human brain in subjects with psychiatric diseases remain
largely unknown. Measurement of rhythmic gene expression in the human brain is now possible. Two recent
studies, including one from our group, demonstrated molecular rhythmicity on a genome-wide scale by
employing a “time of death” analysis to order postmortem human brain samples around a 24-hour cycle. The
first study by Li et al. found that MDD subjects had major disruptions in molecular rhythms across six different
brain regions, including prefrontal cortex (PFC) area 46 and subgenual cingulate (SGC) area 25, compared
with comparison subjects. Using the same approach in a cohort of 146 control subjects (ranging in age from 16
to 96 years), we found that two PFC regions exhibited highly significant patterns of rhythmic gene expression.
Moreover, we found that normal aging was associated with a significant loss of rhythmicity in a number of
transcripts and a surprising gain of rhythmicity in others. Here we plan to study psychiatric disease populations.
In preliminary studies of subjects with SCZ and BP we find that SCZ is associated with a marked loss of
molecular rhythms of core clock genes in PFC area 46, whereas BP is associated with a phase advance in
rhythms in this region. Moreover, we measured molecular rhythms in isolated cell types (pyramidal cells and
parvalbumin (PV) containing cells) from specific cortical layers (3 and 5) of control subjects and subjects with
SCZ. Our data suggests that there are striking differences in the identity and timing of rhythmic genes in these
individual cell types in control subjects. Moreover, subjects with SCZ do not simply have a loss of rhythmicity in
these cells, but have a totally different rhythmic profile, suggesting that there are differences in the
transcriptional complex that governs molecular rhythmicity in these cells. In this study we will determine
changes in molecular rhythms associated with psychiatric diagnoses or specific clinical features such as
psychosis, mood and suicide independent of diagnosis in areas 46 and 25 (Aim #1). We will then determine
the layer and cell type specificity of changes in the PFC in these same subjects (Aim #2). Then we will test the
functional relevance of these molecular rhythms disruptions in specific cell types ...

## Key facts

- **NIH application ID:** 10133732
- **Project number:** 5R01MH111601-04
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Colleen A McClung
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $553,835
- **Award type:** 5
- **Project period:** 2018-07-10 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10133732

## Citation

> US National Institutes of Health, RePORTER application 10133732, Identification of molecular rhythm changes in postmortem tissue from individuals with psychiatric illness. (5R01MH111601-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10133732. Licensed CC0.

---

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