Evidence map›Paper›PMID 41072639›Full record

ArticleBiological psychiatry2026

Sex Differences in Brain Cell Type-Specific Chromatin Accessibility in Schizophrenia.

Yixuan Ma, Kiran Girdhar, Gabriel E Hoffman, John F Fullard, Jaroslav Bendl, Panos Roussos

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biological psychiatry, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Yixuan MaCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, New York; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; Graduate School of Biomedical Science, Icahn School of Medicine at Mount Sinai, New York, New York.
Kiran GirdharCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, New York; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Gabriel E HoffmanCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, New York; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; Mental Illness Research Education and Clinical Center, James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York; Center for Precision Medicine and Translational Therapeutics, James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York.
John F FullardCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, New York; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Jaroslav BendlCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, New York; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York.
Panos RoussosCenter for Disease Neurogenomics, Icahn School of Medicine at Mount Sinai, New York, New York; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, New York; Mental Illness Research Education and Clinical Center, James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York; Center for Precision Medicine and Translational Therapeutics, James J. Peters Department of Veterans Affairs Medical Center, Bronx, New York. Electronic address: panagiotis.roussos@mssm.edu.

Funding

Understanding the molecular mechanisms that contribute to neuropsychiatric symptoms in Alzheimer DiseaseR01AG067025 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FINKBEINER, STEVEN M, HAROUTUNIAN, VAHRAM · 2019 to 2023
$11.8M
Higher Order Chromatin and Genetic Risk for Alzheimer's DiseaseR01AG050986 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ROUSSOS, PANAGIOTIS · 2015 to 2025
$11.2M
Understanding the protective and neuroinflammatory role of human brain immune cells in Alzheimer DiseaseR01AG065582 · NIA · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAROUTUNIAN, VAHRAM, ROUSSOS, PANAGIOTIS · 2020 to 2024
$9.9M
Molecular Profiling of SchizophreniaR01MH110921 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CHESS, ANDREW J, ROUSSOS, PANAGIOTIS · 2016 to 2020
$6.9M
The 3D genome in transcriptional regulation across the postnatal life span, with implications for schizophrenia and bipolar disorderU01MH116442 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKBARIAN, SCHAHRAM, DRACHEVA, STELLA · 2018 to 2022
$5.9M
A regulome and transcriptome atlas of fetal and adult human neurogenesisRF1MH128970 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI CAI, LONG, HOF, PATRICK R · 2021 to 2021
$5.5M
Multiethnic genomic epigenomic and transcriptomic fine-mapping and functional validation analysis of schizophrenia and bipolar disorder risk lociR01MH125246 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ROUSSOS, PANAGIOTIS · 2021 to 2025
$5.0M
Integrated Multiscale Networks in SchizophreniaR01MH109897 · NIMH · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BRENNAND, KRISTEN JENNIFER, ROUSSOS, PANAGIOTIS · 2016 to 2020
$3.0M
BLRD VA I01 BX002395BLRD VA I01 BX004189NIA NIH HHS R01 AG050986NIA NIH HHS R01 AG065582NIA NIH HHS R01 AG067025NIMH NIH HHS R01 MH109897NIMH NIH HHS R01 MH110921NIMH NIH HHS R01 MH125246NIMH NIH HHS RF1 MH128970NIMH NIH HHS U01 MH116442
6 · The paper itself

Abstract

backgroundUnderstanding of the sex-specific role of the noncoding genome in serious mental illnesses, particularly schizophrenia (SCZ), remains largely incomplete.

methodsTo address this gap, we explored sex differences in 1393 chromatin accessibility profiles, derived from neuronal and non-neuronal nuclei of 2 distinct cortical regions from 234 cases with serious mental illness and 235 controls.

resultsWe identified sex-specific enhancer-promoter interactions and showed that they regulate genes involved in X-chromosome inactivation (XCI). Additionally, examining chromosomal conformation allowed us to identify sex-specific cis- and trans-regulatory domains (CRDs and TRDs). Colocalization of sex-specific TRDs with SCZ common risk variants pinpointed male-specific regulatory regions controlling a number of metabolic pathways. Moreover, enhancers from female-specific TRDs were associated with 2 genes known to escape XCI-XIST, which encodes a long noncoding RNA (lncRNA) that coats the X chromosome and initiates XCI, and JPX, a regulatory lncRNA that activates XIST transcription-underlying the importance of TRDs in deciphering sex differences in SCZ.

conclusionsOverall, these findings provide extensive characterization of sex differences in the brain epigenome and disease-associated regulomes.

Indexed as

BrainChromatinSchizophreniaSex CharacteristicsAdultEnhancer Elements, GeneticFemaleHumansMaleNeuronsRNA, Long NoncodingX Chromosome InactivationChromatinRNA, Long NoncodingXIST non-coding RNAChromatin accessibilityGene regulationGeneticsSchizophreniaSex differencesXCI

Identifiers

PMID41072639
PMCPMC12575074

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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.