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PSYCHOPHARMACOLOGY
Novel Biomarker May Predict Patient Response to Antidepressants
January 16, 2022   

A pilot study evaluated the utility of a putative peripheral biomarker for depression and antidepressant treatment response. In depression, the heterotrimeric G protein Gsalpha (Gsα) is sequestered in lipid rafts, which leads to a reduction in adenylyl cyclase. Antidepressant treatment may translocate Gsα from lipid rafts and facilitate the stimulation of adenylyl cyclase in the non-raft membrane fraction, as measured by prostaglandin E1 (PGE1)-stimulated adenylyl cyclase activity. Indeed, this study found that patients with major depressive disorder (MDD; N=41) had lower PGE1 activation of adenylyl cyclase activity than controls (N=44), determined by an assay of platelet samples at screening (t=-2.3, p=0.02). After 6 weeks of open-label antidepressant treatment (escitalopram, citalopram, fluoxetine, duloxetine, venlafaxine XR, or nortriptyline), MDD patients who were treatment responders (N=11) had a significant increase in PGE1 stimulated adenylyl cyclase activity (62.0% mean increase) compared to non-responders (N=8; 4.6% mean decrease; t=2.14, p=0.050). A PGE1 stimulation increase by ≥30% from screen assessment had a positive predictive value for response of 80.0%. These results suggest that a simple, high-throughput-capable assay for depression and antidepressant response can be developed; however, additional studies that are larger, placebo-controlled, and include more frequent clinical and biomarker assessments must first be completed to confirm the findings of this study.

Reference:

Targum SD et al. Mol Psychiatry 2022; Epub ahead of print. Abstract.

For more information:

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Encore Presentation
What’s New? Emerging Concepts in the Treatment of MDD
CME/CE Credit: 0.75 | Expires: September 25, 2024

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Stahl's Essential Video
Stahl’s Essential Psychopharmacology, Chapter 06a: Mood Disorders: Key Neurotransmitter Networks
CME/CE Credit: 0.75 | Expires: December 16, 2024

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Encore Presentation
Hot Topics! The Latest in Psychopharmacology for Major Depressive Disorder
CME/CE Credit: 0.75 | Expires: September 25, 2024

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NEI Resources
Topic: Depression