Developing biomarkers in mood disorders research through the use of rapid-acting antidepressants
Open accessAbstract
An impediment to progress in mood disorders research is the lack of analytically valid and qualified diagnostic and treatment biomarkers. Consistent with the National Institute of Mental Health (NIMH)'s Research Domain Criteria (RDoC) initiative, the lack of diagnostic biomarkers has precluded us from moving away from a purely subjective (symptom-based) toward a more objective diagnostic system. In addition, treatment response biomarkers in mood disorders would facilitate drug development and move beyond trial-and-error toward more personalized treatments. As such, biomarkers identified early in the pathophysiological process are proximal biomarkers (target engagement), while those occurring later in the disease process are distal (disease pathway components). One strategy to achieve this goal in biomarker development is to increase efforts at the initial phases of biomarker development (i.e. exploration and validation) at single sites with the capability of integrating multimodal approaches across a biological systems level. Subsequently, resultant putative biomarkers could then undergo characterization and surrogacy as these latter phases require multisite collaborative efforts. We have used multimodal approaches - genetics, proteomics/metabolomics, peripheral measures, multimodal neuroimaging, neuropsychopharmacological challenge paradigms and clinical predictors - to explore potential predictor and mediator/moderator biomarkers of the rapid-acting antidepressants ketamine and scopolamine. These exploratory biomarkers may then be used for a priori stratification in larger multisite controlled studies during the validation and characterization phases with the ultimate goal of surrogacy. In sum, the combination of target engagement and well-qualified disease-related measures are crucial to improve our pathophysiological understanding, personalize treatment selection, and expand our armamentarium of novel therapeutics.
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Such an approach has the potential to further our understanding of both mechanisms of action for suicide-focused treatments as well as elucidate the neural correlates of suicide risk.
“Such an approach, which has already been implemented in rapid-acting clinical trials for depression (18), has the potential to further our understanding of both mechanisms of action for suicide-focused treatments as well as elucidate the neural correlates of suicide risk (19).”
From New methods for assessing rapid changes in suicide risk (2021) · cites this paper as [18]
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- [51]Li N Lee B Liu RJ mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists Science 2010 329 5994 959 64 20724638 PMC3116441
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- Authors
- Niciu, M. J., Mathews, D. C., Nugent, A. C., Ionescu, D. F., Furey, M. L., Richards, E. M., Machado-Vieira, R., & Zarate, C. A.
- Affiliations
- National Institutes of Health (US)
- Lundbeck (United States) (US)
- Experimental Therapeutics & Pathophysiology Branch, Intramural Research Program, National Institute of Mental Health; National Institutes of Health, and Department of Health and Human Services; Bethesda Maryland
- Corresponding author
- Zarate, Carlos A.
- Venue
- Depression and Anxiety
- Publisher
- Hindawi Limited
- Published
- 2013-12-18
- Volume
- 31
- Issue
- 4
- Pages
- 297-307
- ISSN
- 1091-4269 (ISSN-L)
- PMC
- PMC3984598
- OpenAlex
- W1605478008
- Cited by
- 45
- References
- 58
- Citations by year
- 2026: 1 · 2025: 1 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 6 · 2017: 6 · 2016: 2 · 2015: 7 · 2014: 12
- FWCI
- 0.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Depression and Anxiety (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (Z99 MH999999)
- National Institute of Mental Health (ZIAMH002927)
- Topics
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Electroconvulsive Therapy Studies
- Keywords
- mood disorders, biomarkers, rapid-acting antidepressants, ketamine, scopolamine, treatment response biomarkers, diagnostic biomarkers, Research Domain Criteria, personalized treatment, proteomics, metabolomics, neuroimaging, genetic predictors, surrogate markers, depression
- MeSH terms
- Analgesics, Antidepressive Agents, Humans, Ketamine, Research Design, Scopolamine, Biomarkers, Cholinergic Antagonists, Mood Disorders, Genomics, Metabolomics, Neuroimaging, Multimodal Imaging
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