Evidence map›Paper›PMID 41561376›Full record

ArticleiScience2026

Combining DNA methylation features and clinical characteristics predicts ketamine treatment response for PTSD.

Amir Valizadeh, John D Roache, Xinyu Zhang, Ying Hu, Ralitza Gueorguieva, Lynnette A Averill, Mohini Ranganathan, Zuoheng Wang, Douglas E Williamson, Paulo R Shiroma and 10 more

Abstract read
In one paragraph

Article in iScience, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

20 authors.

Amir ValizadehDepartment of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
John D RoacheDepartment of Psychiatry and Behavioral Sciences, University of Texas at San Antonio, San Antonio, TX, USA.
Xinyu ZhangDepartment of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
Ying HuCenter for Biomedical Informatics and Information Technology, National Cancer Institute, Bethesda, MD, USA.
Ralitza GueorguievaDepartment of Biostatistics, Yale School of Public Health, New Haven, CT, USA.
Lynnette A AverillMichael E. DeBakey VA Medical Center, Houston, TX, USA.
Mohini RanganathanDepartment of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
Zuoheng WangDepartment of Biomedical Informatics and Data Science, Yale School of Medicine, New Haven, CT, USA.
Douglas E WilliamsonDepartment of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, NC, USA.
Paulo R ShiromaMental Health Service Line, Minneapolis VA Health Care System, Minneapolis, MN, USA.
Matthew J GirgentiDepartment of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
Ismene L PetrakisDepartment of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
Argelio L López-RocaDepartment of Behavioral Health, Brooke Army Medical Center, Joint Base San Antonio-Fort Sam Houston, Houston, TX, USA.
Stacey Young-McCaughanDepartment of Psychiatry and Behavioral Sciences, University of Texas at San Antonio, San Antonio, TX, USA.
Terence M KeaneBehavioral Sciences Division, National Center for PTSD at VA Boston Healthcare System, Boston, MA, USA.
Alan L PetersonDepartment of Psychiatry and Behavioral Sciences, University of Texas at San Antonio, San Antonio, TX, USA.
Chadi G AbdallahMichael E. DeBakey VA Medical Center, Houston, TX, USA.
John H KrystalDepartment of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
Ke XuDepartment of Psychiatry, Yale School of Medicine, New Haven, CT, USA.
Consortium to Alleviate PTSD

Funding

Stress-immune mechanisms for people living with HIV, CUD and DepressionR01DA061995 · NIDA · YALE UNIVERSITY · PI Rajita Sinha, KE XU · 2024 to 2026
$2.7M
In vivo study of THC-induced immunogenome changes at single cell resolution in HIV-infected humansR01DA052846 · NIDA · YALE UNIVERSITY · PI XU, KE · 2020 to 2025
$2.5M
NIDA NIH HHS R01 DA052846NIDA NIH HHS R01 DA061995
6 · The paper itself

Abstract

Post-traumatic stress disorder (PTSD) exhibits extensive clinical and biological variability, making treatment challenging. The Consortium to Alleviate PTSD (CAP)-ketamine trial, the largest randomized study of ketamine for PTSD, found no overall benefit of ketamine over placebo, underscoring the necessity to identify responsive subgroups. Using pre-treatment blood DNA methylation profiles and clinical measures from the CAP-ketamine trial, we applied machine learning to predict treatment response. A model based on 1,208 methylation sites achieved higher predictive accuracy than models using clinical variables alone, and combining both data types further improved performance. The methylation-derived score distinguished responders with 92.9% accuracy. The predictive CpGs were enriched near genes involved in glutamatergic signaling and immune regulation, as well as established PTSD risk loci. These findings suggest that peripheral DNA methylation patterns can identify individuals likely to benefit from ketamine, advancing precision approaches to PTSD pharmacotherapy.

Indexed as

Mental stateprecision medicinepsychiatry

Identifiers

PMID41561376
PMCPMC12814687

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.