Evidence map›Paper›PMID 42210495›Full record

ArticlePsychiatry and clinical neurosciences2026

Integrative methylation and miRNA dysregulation in dlPFC reveal distinct molecular signatures of suicide and non-suicide subtypes in major depressive disorder.

Aleena Francis, Yogesh Dwivedi

Abstract read
In one paragraph

Article in Psychiatry and clinical neurosciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

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4 · The record

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5 · Who and what money

Authors and funding

2 authors.

Aleena FrancisDepartment of Psychiatry and Behavioral Neurobiology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Yogesh DwivediDepartment of Psychiatry and Behavioral Neurobiology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.ORCID https://orcid.org/0000-0002-5359-4717

Funding

Novel regulatory role of nuclear miRNAs in repatterning the transcriptional and post-transcriptional dynamics in MDD brainR01MH128994 · NIMH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI Yogesh Dwivedi · 2022 to 2026
$3.5M
Plasma Exosomal MicroRNAs as Promising Novel Biomarkers for Suicidality and Treatment OutcomeR01MH107183 · NIMH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI DWIVEDI, YOGESH, SHELTON, RICHARD CHARLES · 2015 to 2019
$3.5M
MicroRNA Correlates of Childhood Maltreatment and SuicidalityR01MH124248 · NIMH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI DWIVEDI, YOGESH, SHELTON, RICHARD CHARLES · 2021 to 2025
$3.4M
Epitranscriptomic Mapping of Novel N6-Adenosine-based RNA Methylation in MDD BrainR01MH118884 · NIMH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI DWIVEDI, YOGESH · 2019 to 2023
$3.0M
Neural-Derived Plasma Exosomal MicroRNAs As Promising Novel Biomarkers for Suicidality and Treatment Outcome in AdolescentsR01MH130539 · NIMH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI DWIVEDI, YOGESH, SHELTON, RICHARD CHARLES · 2022 to 2024
$2.2M
Novel cell type-specific epigenetic role of nuclear lncRNAs in 3D heterochromatization and transcriptional repatterning in the MDD brainR56MH138596 · NIMH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI DWIVEDI, YOGESH · 2025 to 2025
$730k
NIMH NIH HHS R01 MH107183NIMH NIH HHS R01MH107183NIMH NIH HHS R01 MH118884NIMH NIH HHS R01MH118884NIMH NIH HHS R01 MH124248NIMH NIH HHS R01MH124248NIMH NIH HHS R01 MH128994NIMH NIH HHS R01MH128994NIMH NIH HHS R01 MH130539NIMH NIH HHS R01MH130539NIMH NIH HHS R56 MH138596NIMH NIH HHS R56MH138596
6 · The paper itself

Abstract

aimMajor depressive disorder (MDD) is a leading cause of disability and carries a high risk of suicide. MicroRNAs (miRNAs) are epigenetic regulators implicated in MDD and can be regulated by DNA methylation, potentially reshaping downstream gene networks. We investigated methylation-linked miRNA dysregulation and explored whether these changes are specifically associated with suicide among MDD patients.

methodsGenome-wide DNA methylation profiling of the dorsolateral prefrontal cortex from 15 MDD patients who died by suicide (MDD+S), 17 MDD patients who died from causes other than suicide (MDD-S), and 16 controls (C) using the Illumina 850K MethylationEPIC array was integrated with small RNA sequencing-based miRNA quantification to identify miRNA-associated differentially methylated probes (DMPs), link methylation to miRNA expression, and infer downstream targets and pathways.

resultsDifferential methylation analysis (P ≤ 0.05) revealed 139 miRNA-linked DMPs in C vs. MDD+/-S, 135 in C vs. MDD-S, 179 in C vs. MDD+S, and the highest in MDD+S vs. MDD-S (235). CpG-miRNA pairing (within 1500kb promoter) followed by Spearman correlation identified inverse associations between CpG β values and miRNA expression, with the most consistent signals in suicide-status-stratified subsets, including cg06341821-hsa-miR-574-3p and cg25451306-hsa-miR-2110 in MDD+S-related contrasts, and cg06179179-hsa-miR-595 in MDD-S-related contrasts. High-confidence target prediction and ClueGO enrichment indicated distinct biology: miR-595 target genes in MDD-S were enriched for interferon/innate immune signaling, whereas miR-2110 target genes in MDD+S were enriched for ligand-gated ion channel activity and synaptic/receptor signaling.

conclusionThis integrated approach identifies methylation-regulated miRNA pathways that may play key roles in the molecular pathogenesis of MDD and suicide.

Indexed as

DNA MethylationDorsolateral Prefrontal CortexMajor Depressive DisorderMicroRNAsSuicideAdultEpigenesis, GeneticFemaleHumansMaleMiddle AgedMicroRNAsdepressiondlPFCmethylationmiRNAsuicide

Identifiers

PMID42210495
PMCPMC13537329

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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.