Evidence map›Paper›PMID 42262642›Full record

ArticleJournal of behavioral medicine2026

A longitudinal study of CLDN5 DNA methylation and PTSD.

Alessandra R Grillo, Sara E Wallander, Beth M McCormick, Xiang Zhao, Mark W Logue, Mark W Miller, Erika J Wolf

Abstract read
In one paragraph

Article in Journal of behavioral medicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

7 authors.

Alessandra R GrilloThe Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, MD, USA.ORCID http://orcid.org/0000-0002-9800-5541
Sara E WallanderNational Center for PTSD at VA Boston Healthcare System, 150 S. Huntington Ave. (116B-2), Boston, MA, 02130, USA.
Beth M McCormickNational Center for PTSD at VA Boston Healthcare System, 150 S. Huntington Ave. (116B-2), Boston, MA, 02130, USA.ORCID http://orcid.org/0009-0005-2679-2450
Xiang ZhaoDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.ORCID http://orcid.org/0000-0003-1720-5996
Mark W LogueNational Center for PTSD at VA Boston Healthcare System, 150 S. Huntington Ave. (116B-2), Boston, MA, 02130, USA.ORCID http://orcid.org/0000-0001-9347-7892
Mark W MillerNational Center for PTSD at VA Boston Healthcare System, 150 S. Huntington Ave. (116B-2), Boston, MA, 02130, USA.ORCID http://orcid.org/0000-0001-6393-8563
Erika J WolfNational Center for PTSD at VA Boston Healthcare System, 150 S. Huntington Ave. (116B-2), Boston, MA, 02130, USA. Erika.Wolf@va.gov.ORCID http://orcid.org/0000-0003-2666-2435

Funding

Longitudinal Neurometabolic Outcomes of Traumatic Stress-Related Accelerated Cellular AgingRF1AG068121 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI WOLF, ERIKA J · 2020 to 2020
$1.7M
Longitudinal Neurometabolic Outcomes of Traumatic Stress-Related Accelerated Cellular AgingR01AG068121 · NIA · BOSTON UNIVERSITY MEDICAL CAMPUS · PI WOLF, ERIKA J · 2024 to 2024
$639k
CSRD VA I01 CX001276NIA NIH HHS R01 AG068121NIA NIH HHS RF1 AG068121NIA NIH HHS RF1AG068121/ 4R01AG068121-02U.S. Department of Veterans Affairs I01 CX-001276-01
6 · The paper itself

Abstract

Posttraumatic stress disorder (PTSD) is associated with elevated risk for cognitive decline and neurodegeneration in later life, yet the underlying biological mechanisms remain poorly understood. One hypothesized pathway involves dysfunction of the blood-brain barrier (BBB) via altered expression of claudin-5 (CLDN5), a tight junction protein key to BBB integrity. Our prior cross-sectional study found that DNA methylation (DNAm) in blood at three CLDN5 loci was associated with trauma exposure, PTSD symptom severity, and plasma neurofilament light (NFL). Building on these results, this study examined whether CLDN5 DNAm in blood predicted future PTSD symptom severity, NFL, neuropsychological performance, and CLDN5 RNA expression in blood, a possible proxy for CLDN5 in the brain. Trauma-exposed Veterans (N = 221; 174 returned for follow-up) were assessed twice over 5.6 years on average. Participants completed diagnostic interviews, provided blood samples at both timepoints, and completed a neuropsychological battery at follow-up (California Verbal Learning Test-II, Wechsler Adult Intelligence Scale and Delis-Kaplan Executive Function System subtests). Baseline CLDN5 DNAm at cg21872764 predicted increased PTSD symptom severity at follow-up, accounting for baseline PTSD symptoms (β = .128, p = .035). This probe was associated with future CLDN5 RNA expression (β= -.186, p-adj = .035) as was cg00804504 (β = .185, p-adj = .035). CLDN5 DNAm at cg16773741, linked to cognitive decline, predicted working memory performance at follow-up (β = .269, p-adj = .015). No loci were associated with NFL levels after corrections for multiple testing. Results suggest that CLDN5 DNAm is associated with increased PTSD severity over time among Veterans with substantial trauma histories and is associated with neuropsychological functioning. This raises the possibility that BBB disruption is part of PTSD pathology, which may help identify the biology underlying comorbidity between PTSD and neurodegenerative disorders.

Indexed as

Blood–brain barrierClaudin-5DNA methylationNeurocognitive functioningNeurofilament lightPosttraumatic stress disorderVeterans

Identifiers

PMID42262642
PMCPMC13390723

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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.