# Epigenetic involvement in socio-emotional behavior studied by PET- MRI

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2022 · $669,050

## Abstract

ABSTRACT
Histone deacetylases (HDACs), a family of enzymes that repress gene transcription through deacetylation,
represent one of the mechanisms through which environment can affect gene expression. Preclinical studies
have repeatedly demonstrated that the epigenetic enzymes HDACs play a key role for normal brain function,
including socio-emotional skills. In vivo and postmortem work in animals and humans has implicated regional
abnormalities in HDAC expression levels in psychiatric disorders. However, to date, little is known in terms of
the association between in vivo HDAC epigenetic enzymes expression and human behavior. The study of this
association is possible given the recent development of [11C]Martinostat, a positron emission tomography (PET)
imaging probe allowing the in vivo assessment of HDAC brain expression.
Neuropsychological traits associated with emotion regulation, social skills, anxiety, the ability or inability
(anhedonia) to experience pleasure, and sensitivity to reward are common and continuously distributed in the
general population. Taking advantage of this normal variation, we will investigate the relationships between
HDAC expression and neuropsychological profile. We propose to study the association between HDACs
expression determined by PET imaging and neuropsychological traits in healthy male and female young adults
(Aim 1). We will also investigate whether there are regional sex differences in HDAC brain expression in young
adults (Aim 2). Furthermore, using simultaneous PET- functional magnetic resonance imaging (fMRI), we will
determine the relationship between HDAC expression and brain activation in response to socio-emotional and
reward fMRI tasks (Aim 3).
In summary, this study will provide insights into the in vivo epigenetic landscape of HDACs in healthy male and
female adults, and its association with neuropsychological traits and brain activation. If regional HDACs
expression is sex-specific, it may contribute to known differences in disease susceptibility and disease
prevalence in males and females. A better understanding of normal epigenetic variations and their association
with behavioral phenotype in humans is an essential first step for the field of neuroepigenetics, and will have
implications for future studies investigating epigenetic dysregulation in psychiatric diseases.

## Key facts

- **NIH application ID:** 10518641
- **Project number:** 1R01MH128425-01A1
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Nicole R Zurcher Wimmer
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $669,050
- **Award type:** 1
- **Project period:** 2022-08-05 → 2027-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10518641

## Citation

> US National Institutes of Health, RePORTER application 10518641, Epigenetic involvement in socio-emotional behavior studied by PET- MRI (1R01MH128425-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10518641. Licensed CC0.

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