Convergent Lower Expression of Redox-Linked Stress-Adaptation and Synaptic-Plasticity Genes in Major Depressive Disorder Across Seven Postmortem dlPFC Cohorts.

Overview

1. Department of Psychiatry, Medical University of Bialystok, 15-272 Bialystok, Poland
2. Centre of Regenerative Medicine, Medical University of Bialystok, 15-044 Bialystok, Poland
3. Department of Integrated Medical Care, Medical University of Bialystok, 15-096 Bialystok, Poland
4. Department of Clinical Pharmacy, Medical University of Bialystok, 15-222 Bialystok, Poland

Abstract

Major depressive disorder (MDD) has been linked to oxidative stress, mitochondrial dysfunction, and impaired neuronal plasticity, but the reproducibility of related transcriptomic alterations across postmortem brain cohorts remains uncertain. We performed a targeted cross-platform analysis of a prespecified 14-gene panel spanning antioxidant defense, mitochondrial-redox regulation, cellular stress responses, neurotrophic signaling, synaptic plasticity, and polyamine metabolism across seven postmortem dorsolateral prefrontal cortex cohorts comprising 146 MDD cases and 179 controls. Primary support required Fisher-combined evidence, Benjamini–Hochberg correction across the panel, and concordant MDD-minus-control direction across all available cohorts. NPTX2, EGR1, VGF, BDNF, and SAT1 met these criteria, with lower expression in MDD. The same five-gene pattern was supported by weighted signed Stouffer analysis, one-stage generalized least-squares models, random-effects meta-analysis, and 200,000 disease-label permutations; none produced at least five genes meeting the complete primary-support criterion (empirical p = 5.0 × 10−6). The most robust cross-cohort finding was a convergent lower-expression pattern across genes supporting redox-linked stress adaptation, polyamine homeostasis, neurotrophic signaling, activity-dependent transcription, and synaptic plasticity. This pattern suggests impaired molecular capacity for neuronal stress resilience and adaptive plasticity in MDD.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

No file of the authors' code could be read here: it is described below, and read at its source.

The paper's code and data availability statement is in the Data section.

Tracing map

Proposed by the machine: these links were found in the paper and verified at the source, without human review. The map will receive a Zenodo DOI once one of the paper's authors has validated it with their ORCID.

What the map holds:

• 1 repository of the authors' code, each at its verified commit, with its license and how the link was found in the paper;
• 0 scripts, each with its path and the digest of its content;
• no match between paragraphs and code yet;
• neither the text of the paper nor the code itself.

Its JSON (tracing-map.json) is deposited on Zenodo with its DOI once the map is validated.

Data

Datasets cited

• geo:GSE54567, at NCBI GEO; found in “Data Availability Statement”

Data Availability Statement

All datasets analyzed in this study are publicly available from the Gene Expression Omnibus under accession numbers GSE54567 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54567), GSE54568 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE54568), GSE102556 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE102556), GSE101521 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101521), GSE53987 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE53987), GSE208338 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE208338), and GSE213982 (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE213982). The analyses used publicly deposited series matrices, processed expression tables, and count matrices, as described in the Materials and Methods. The prespecified 14-gene panel and its biological-domain structure were fixed and documented in a time-stamped OSF project created on 29 May 2026, before the primary cross-cohort statistical analyses were conducted. The documentation is available at https://osf.io/8bfrs/overview?view_only=6f7fbb64f2da46ada7fd619c72a7d86d (accessed on 30 May 2026) Analysis code and processed input files required to reproduce the cohort-level tests, Fisher and sample-size-weighted signed Stouffer analyses, Benjamini–Hochberg correction, one-stage generalized least-squares analysis, random-effects meta-analysis, Shapiro–Wilk diagnostics, probe-level sensitivity analyses, exploratory diagnosis-by-sex analysis, descriptive cell-type localization, permutation analysis, and figure and table generation are provided in Supplementary File S1. FASTQ- and CEL-level reprocessing was not performed.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 5 authors, 8 keywords, 73 references.

Cite

This paper

Klepacki, H., Ordak, M., Kowalczuk, K., Hermanowicz, J. M., & Waszkiewicz, N. (2026). Convergent Lower Expression of Redox-Linked Stress-Adaptation and Synaptic-Plasticity Genes in Major Depressive Disorder Across Seven Postmortem dlPFC Cohorts. Antioxidants (Basel, Switzerland), 15(7), 908. https://doi.org/10.3390/antiox15070908

The tracing map gets a citation of its own once an author has validated it and it has a DOI.

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.1016/j.isci.2026.116825 [code]

Social hierarchy shapes behavioral and transcriptional responses to chronic stress and ketamine in male mice.

Journal: iScience

In common: depression, genetics / omics, 4 references

[2] doi:10.1186/s43556-026-00514-4

Transcription-protein dissociation reveals disrupted cellular stress pathways in the prefrontal cortex of depression and schizophrenia subjects.

Journal: Molecular biomedicine

In common: depression, histology / microscopy, cellular / molecular, 3 references

[3] doi:10.1111/jnc.70502 [code]

The Converging Effects of Different Categories of Antidepressants on the Brain: A Systematic Meta-Analysis of Public Transcriptional Profiling Data From the Hippocampus and Cortex.

Journal: Journal of neurochemistry

In common: depression, genetics / omics, cellular / molecular, 3 references

[4] doi:10.1016/j.isci.2026.116843

A<sub>3</sub> adenosine receptor regulates depression-like behaviors through astrocyte-nourished excitatory synapse formation.

Journal: iScience

In common: depression, cellular / molecular, 3 references

[5] doi:10.1186/s13041-026-01304-3

Genome-wide mapping of stress-responsive lncRNA, uc.104, reveals the chromatin-mediated regulation of stress and plasticity-related genes in the hippocampus of chronic restraint rats.

Journal: Molecular brain

In common: depression, genetics / omics, cellular / molecular, 2 references

[6] doi:10.1002/hbm.70605 [code]

BrainEnrich: Revealing Biological Insights for Imaging-Derived Phenotypes Through Transcriptomic Enrichment.

Journal: Human brain mapping

In common: depression, genetics / omics, 2 references

[7] doi:10.3389/fncom.2026.1799705

Structural synaptogenesis superior to functional modulation in a pruning-based recurrent network model of OCD.

Journal: Frontiers in computational neuroscience

In common: 3 references

[8] doi:10.1016/j.nicl.2026.104019 [code]

Stress-related hypofrontality in depression and its relation to altered activation prior to the stress response.

Journal: NeuroImage. Clinical

In common: depression, 2 references

[9] doi:10.1038/s41398-026-04094-3

A depression-like phenotype is associated with discrete defects in the primary hippocampal circuit.

Journal: Translational psychiatry

In common: depression, 2 references

[10] doi:10.1007/s12035-026-06041-1 [code]

Glucocorticoid Signaling in PSC-Derived Neural Systems to Elucidate Mechanisms of Stress-Induced Psychiatric Vulnerability.

Journal: Molecular neurobiology

In common: genetics / omics, cellular / molecular, 2 references

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.