Evidence map›Paper›PMID 24662927›Full record

ArticleMolecular psychiatry2015

Astrocytic abnormalities and global DNA methylation patterns in depression and suicide.

C Nagy, M Suderman, J Yang, M Szyf, N Mechawar, C Ernst, G Turecki

Open access · bronzeAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular psychiatry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 175 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
175citing papers in PubMed, 8 pooled it
9.4field-weighted citation impact, top 1% of its field
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

175 citing papers in PubMed, 8 syntheses or guidelines pooled it, 306 citations in OpenAlex.

  1. Pooled it
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  4. Genetics and epigenetics of self-injurious thoughts and behaviors: Systematic review of the suicide literature and methodological considerations.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2022
    Pooled it
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  9. Trial
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  12. Synaptic effects of interleukin-6 on human iPSC-derived dopaminergic neurons.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Article
  13. Article
  14. Review
  15. Cerebellar astrocytic alterations in depression.Translational psychiatry · 2026
    Article
  16. Article
  17. Review
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  19. Article
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115 more citing papers are in PubMed but not listed here.

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 at 2 institutions in 1 country.

C Nagy1] McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada [2] Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada.
M Suderman1] McGill Centre for Bioinformatics, McGill University, Montreal, QC, Canada [2] Sackler Program for Epigenetics and Developmental Psychobiology, McGill University, Montreal, QC, Canada.
J YangMcGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
M Szyf1] Sackler Program for Epigenetics and Developmental Psychobiology, McGill University, Montreal, QC, Canada [2] Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada.
N Mechawar1] McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada [2] Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada [3] Department of Psychiatry, McGill University, Montreal, QC, Canada.
C Ernst1] McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada [2] Department of Psychiatry, McGill University, Montreal, QC, Canada.
G Turecki1] McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada [2] Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada [3] Department of Psychiatry, McGill University, Montreal, QC, Canada.
McGill University · CADouglas Mental Health University Institute · CA

Funding

Canadian Institutes of Health Research MOP 119429
6 · The paper itself

Abstract

Astrocytes are glial cells specific to the central nervous system and involved in numerous brain functions, including regulation of synaptic transmission and of immune reactions. There is mounting evidence suggesting astrocytic dysfunction in psychopathologies such as major depression, however, little is known about the underlying etiological mechanisms. Here we report a two-stage study investigating genome-wide DNA methylation associated with astrocytic markers in depressive psychopathology. We first characterized prefrontal cortex samples from 121 individuals (76 who died during a depressive episode and 45 healthy controls) for the astrocytic markers GFAP, ALDH1L1, SOX9, GLUL, SCL1A3, GJA1 and GJB6. A subset of 22 cases with consistently downregulated astrocytic markers was then compared with 17 matched controls using methylation binding domain-2 (MBD2) sequencing followed by validation with high-resolution melting and bisulfite Sanger sequencing. With these data, we generated a genome-wide methylation map unique to altered astrocyte-associated depressive psychopathology. The map revealed differentially methylated regions (DMRs) between cases and controls, the majority of which displayed reduced methylation levels in cases. Among intragenic DMRs, those found in GRIK2 (glutamate receptor, ionotropic kainate 2) and BEGAIN (brain-enriched guanylate kinase-associated protein) were most significant and also showed significant correlations with gene expression. Cell-sorted fractions were investigated and demonstrated an important non-neuronal contribution of methylation status in BEGAIN. Functional cell assays revealed promoter and enhancer-like properties in this region that were markedly decreased by methylation. Furthermore, a large number of our DMRs overlapped known Encyclopedia of DNA elements (ENCODE)-identified regulatory elements. Taken together, our data indicate significant differences in the methylation patterns specific to astrocytic dysfunction associated with depressive psychopathology, providing a potential framework for better understanding this disease phenotype.

Indexed as

DepressionDNA MethylationDown-RegulationSuicideAdultAldehyde DehydrogenaseAstrocytesCase-Control StudiesConnexin 43Epigenesis, GeneticFemaleFormyltetrahydrofolate DehydrogenaseGenome-Wide Association StudyGlial Fibrillary Acidic ProteinGlutamate-Ammonia LigaseHumansAldehyde DehydrogenaseConnexin 43Formyltetrahydrofolate DehydrogenaseGJA1 protein, humanGlial Fibrillary Acidic ProteinGlutamate-Ammonia LigaseLGSN protein, humanOxidoreductases Acting on CH-NH Group DonorsSOX9 protein, humanSOX9 Transcription Factor

Identifiers

PMID24662927
PMCPMC5293540
OpenAlexW1987836975

What OpenQuestion holds

Textmetadata
Read underepoch 390

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.