# Lipid raft localization of Gs: a biomarker for depression and therapeutic response

> **NIH VA I01** · JESSE BROWN VA MEDICAL CENTER · 2021 · —

## Abstract

Every day, 21 veterans complete suicide, primarily due to the ramifications of untreated depression. Due to
fear and stigma, many do not seek treatment. For those who do, about one third of the time, no drug offers
relief and even those antidepressants that do work often require 6-8 weeks before therapeutic onset.
Unfortunately, no unifying hypothesis for a molecular/cellular basis of action for antidepressant drugs (or
depressive disorders) has emerged. Over the last several years, we have suggested that, in addition to
presynaptic targets (uptake sites), a number of antidepressant drugs have a post-synaptic mechanism of
action. Toward this end, we have observed that chronic treatment (3-5 days) of cultured neural or glial cells
with a number of chemically diverse antidepressant compounds translocates the heterotrimeric G protein Gsα
out of lipid rafts and into a closer association with adenylyl cyclase, icreasing produciot of the intracelylar
messenger, cAMP. Post-mortem tissue from depressed suicides shows just the opposite, with an increased
proportion of Gsα ensconsed in lipid rafts and preliminary data suggest that this is also observed in blood cells,
where the extent of Gsα in lipid rafts correlates with both depression and clinical response to antidepressants.
Furthermore, several psychedelic or dissociative anesthetic compounds may have antidepressant effects as
well as shorter therapeutic onset, and the proposed studies will search for a cellular “biosignature” for
antidepressant action. Proposed studies will also attempt to establish a mechanistic understanding for the
translocation of Gsα from lipid rafts as a hallmark of depression and as a conduit for antidepressant action.
One intent of the proposed studies is to develop a platform that can provide a cell-based screen for putative
antidepressant compounds as well as a screening tool to indicate personalized antidepressant choice. Another
intent of these studies is to provide a peripheral tissue biological marker for depression and an early (< 1 week)
indicator of successful antidepressant treatment that can be developed into a clinically useful, inexpensive and
readily-available biomarker for clinical use. The identification of a pathway for antidepressant action might lead
to novel antidepressant drugs, while the assignation of a quantitative value for depression may help overcome
stigma and encourage thousands of depressed veterans to seek treatment.

## Key facts

- **NIH application ID:** 10125420
- **Project number:** 2I01BX001149-09
- **Recipient organization:** JESSE BROWN VA MEDICAL CENTER
- **Principal Investigator:** MARK M. RASENICK
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2021
- **Award amount:** —
- **Award type:** 2
- **Project period:** 2011-10-01 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10125420

## Citation

> US National Institutes of Health, RePORTER application 10125420, Lipid raft localization of Gs: a biomarker for depression and therapeutic response (2I01BX001149-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10125420. Licensed CC0.

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