# Molecular and Neural Circuitry Mechanisms Underlying Antidepressant Treatment Resistance

> **NIH NIH R01** · RUTGERS, THE STATE UNIV OF N.J. · 2020 · $387,500

## Abstract

PROJECT SUMMARY/ABSTRACT
 Approximately 32-35 million adults in the US population (16%) experience an episode of major
depression in their lifetime, and commonly used treatments, such as selective serotonin reuptake inhibitors
(SSRIs), are not ideal since only a subset of patients (~33%) achieves remission with initial treatment. The
reasons why some individuals remit to antidepressant treatments while others do not are unknown. Given that
antidepressants such as SSRIs are also commonly used to treat other psychiatric disorders, such as
generalized anxiety disorder and obsessive-compulsive disorder, it is of critical importance to determine the
differences between remitters and non-remitters to antidepressant treatment. Our overall research program
addresses this question by assessing antidepressant treatment resistance in mice. Preliminary data indicate
that both molecular and neural-circuit based approaches to modifying the dentate gyrus may be able to convert
behavioral non-responders to fluoxetine (a SSRI) into responders. Further preliminary data indicate that these
approaches may also work as augmentation strategies for several other classes of antidepressants. The
Specific Aims are: 1) Test the hypothesis that Activin signaling based modifications of dentate gyrus can alter
the behavioral response to fluoxetine through modulation of young adult-born granule cells; 2) To test the
hypothesis that circuit-based approaches to silencing mature dentate gyrus granule cells can alter the
behavioral response to fluoxetine and to determine whether there are functional differences in DG inputs
between responders and non-responders; and 3) Test the hypothesis that alterations in DG granule cells are a
common feature of behavioral non-response to different antidepressant treatments.

## Key facts

- **NIH application ID:** 9848010
- **Project number:** 5R01MH112861-04
- **Recipient organization:** RUTGERS, THE STATE UNIV OF N.J.
- **Principal Investigator:** BENJAMIN A SAMUELS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $387,500
- **Award type:** 5
- **Project period:** 2017-02-16 → 2022-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9848010

## Citation

> US National Institutes of Health, RePORTER application 9848010, Molecular and Neural Circuitry Mechanisms Underlying Antidepressant Treatment Resistance (5R01MH112861-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9848010. Licensed CC0.

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