ORIGINAL RESEARCH article
Front. Psychiatry
Sec. Mood Disorders
Volume 16 - 2025 | doi: 10.3389/fpsyt.2025.1619243
This article is part of the Research TopicBiomarkers of Response to Interventions in PsychiatryView all 4 articles
A heterotrimeric G protein (Gsa) biomarker may predict antidepressant response in subjects with major depressive disorder
Provisionally accepted
- 1Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States
- 2Huntsman Mental Health Institute, University of Utah Health Care, Salt Lake City, Utah, United States
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The disproportionate sequestration of the heterotrimeric G protein (Gsa) in lipid raft regions during acute depressive episodes can impair neurotransmitter signaling by restricting its interaction with and activation of adenylate cyclase and consequently reduce cyclic adenosine monophosphate (cAMP) production.In humans, Gsα is measured as a peripheral biomarker from platelet samples by using prostaglandin-1 (PGE-1) to stimulate adenylyl cyclase.In two previous studies, Gsa biomarker responses were significantly lower in acutely depressed subjects with major depressive disorder (MDD) than healthy controls and were correlated with the magnitude of symptom severity.The potential utility of Gsa biomarker responses to anticipate antidepressant treatment (ADT) response was assessed in 19 acutely depressed MDD subjects receiving ADT for 6 weeks.Following 6 weeks of ADT, Gsα biomarker responses increased significantly in 11 ADT responders compared to 8 non-responders (Mann-Whitney U test; p= 0.033), particularly in subjects with the lowest Gsa biomarker values at screen. All 5 MDD subjects with Gsa biomarker screen values <1.5 nM cAMP/well became ADT responders with mean Gsα biomarker responses increasing >100% at 6 weeks in contrast to 10% in subjects with higher screen values (p= 0.012).ADT facilitates translocation of Gsa from the lipid raft region, particularly in MDD subjects who respond to ADT. The findings from this small hypothesis-generating study suggest that the Gsa biomarker assay has potential clinical utility to predict ADT response in depressed subjects with low baseline biomarker values. However, these are exploratory findings that must be replicated in larger studies.
Keywords: Antidepressants, Major Depressive Disorder, biomarkers, heterotrimeric G protein, GPCR: lipid raft: prediction of treatment response
Received: 27 Apr 2025; Accepted: 27 Jun 2025.
Copyright: © 2025 Targum, Gunay, Leow, Ajilore, Rapaport and Rasenick. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Steven D. Targum, Department of Psychiatry, College of Medicine, University of Illinois at Chicago, Chicago, 60608-1264, Illinois, United States
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