# Role  of  epigenetics  on  long-lasting  behavioral  and  gene-expression  changes  following  neonate  exposure  to  antidepressants

> **NIH NIH P20** · UNIVERSITY OF NORTH DAKOTA · 2020 · $205,624

## Abstract

ABSTRACT
Depression and anxiety are prevalent during pregnancy and commonly treated with serotonin selective
reuptake inhibitor (SSRI) antidepressants. These drugs pass freely from mother to placenta and alter the
serotonergic homeostasis in the developing fetus. However, serotonin acts as a trophic factor during
embryogenesis and plays an important role in structural development of the central nervous system which has
led to a number of studies investigating the short and long-term consequences to the fetus. Multiple rodent
models have demonstrated that neonate exposure to SSRIs during a developmentally sensitive time frame
equivalent to the 3rd trimester of human pregnancy leads to long-lasting behavioral changes associated with
anxiety and depression. These behavioral outcomes in the absence of continued exposure to the SSRI
suggests a drug-mediated impact on development through an epigenetic mechanism. This study will
investigate this assumption through use a novel transgenic mouse that harbors a mutant serotonin transporter
that renders the mouse insensitive to many SSRIs while maintaining normal serotonin transporter and
homeostasis. Mice will be evaluated for changes in gene expression, epigenetic marks, and behavior just after
SSRI treatment and/or as adult animals. The SSRI-insensitive mouse will provide a critical control to eliminate
background effects and pinpoint relevant targets that underlie this phenomenon. Identified targets can then be
explored in human populations with the intent of providing a clear understanding of risks involved with SSRI-
treatment during pregnancy.

## Key facts

- **NIH application ID:** 9976550
- **Project number:** 5P20GM104360-07
- **Recipient organization:** UNIVERSITY OF NORTH DAKOTA
- **Principal Investigator:** Loren Keith Henry
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $205,624
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9976550

## Citation

> US National Institutes of Health, RePORTER application 9976550, Role  of  epigenetics  on  long-lasting  behavioral  and  gene-expression  changes  following  neonate  exposure  to  antidepressants (5P20GM104360-07). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9976550. Licensed CC0.

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