Evidence map›Paper›PMID 41542610›Full record

ArticlebioRxiv : the preprint server for biology2026

Gonadal and sex chromosomal contributions to sex differences in mammalian brain organization.

Jason P Lerch, Juliana Shin, Jacob Ellegood, Haley Hrncir, Brian J Nieman, Allan Mackenzie-Graham, Xia Yang, Arthur P Arnold, Armin Raznahan

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 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

9 authors.

Jason P LerchOxford Centre for Integrative Neuroimaging, University of Oxford, United Kingdom.
Juliana ShinDepartment of Integrative Biology & Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
Jacob EllegoodMedical Biophysics, University of Toronto, ON, Canada.ORCID 0000-0003-1504-3321
Haley HrncirDepartment of Integrative Biology & Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
Brian J NiemanMedical Biophysics, University of Toronto, ON, Canada.
Allan Mackenzie-GrahamAhmanson-Lovelace Brain Mapping Center, Department of Neurology, University of California, Los Angeles, Los Angeles, CA, USA.
Xia YangDepartment of Integrative Biology & Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
Arthur P ArnoldDepartment of Integrative Biology & Physiology, University of California, Los Angeles, Los Angeles, CA, USA.ORCID 0000-0002-9908-9767
Armin RaznahanSection on Developmental Neurogenomics, Human Genetics Branch, NIMH Intramural Research Program, NIH, Bethesda, MD, USA.

Funding

Section on Developmental NeurogenomicsZIAMH002949 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI RAZNAHAN, ARMIN · 2016 to 2025
$30.0M
Training Grant in Genomic Analysis and InterpretationT32HG002536 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Valerie A Arboleda, Harold Pimentel · 2002 to 2026
$8.6M
Coupling neuroimaging with CLARITY and single cell genomics to dissect sex differences in the developing brainR01HD100298 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARNOLD, ARTHUR P, LERCH, JASON P. · 2020 to 2024
$2.2M
Discriminating hormonal and sex chromosomal origins of sex differences in the septohippocampal circuitR21MH129020 · NIMH · TEMPLE UNIV OF THE COMMONWEALTH · PI BANGASSER, DEBRA A, YANG, XIA · 2022 to 2023
$430k
Intramural NIH HHS ZIA MH002949NHGRI NIH HHS T32 HG002536NICHD NIH HHS R01 HD100298NIMH NIH HHS R21 MH129020
6 · The paper itself

Abstract

Sex differences in brain development may contribute to well-known sex differences in behavior and neuropsychiatric risk - making it important to comprehensively map and mechanistically annotate normative sex differences in brain organization. Most sex differences in mammalian brain organization have previously been attributed to differential effects of gonadal hormones based on outcomes from rodent endocrine manipulations at canonical subcortical foci of male-biased brain volume. However, a systematic quantification of both gonadal and sex chromosome dosage (SCD) contributions across all regions of sex-biased brain volume has been lacking. Here, using structural neuroimaging scans from wild-type (n=670) and transgenic mice that dissociate gonadal, X-, and Y-chromosome effects (n=181), we show that: many more brain regions are volumetrically sex-biased than previously recognized; gonadal effects dominate throughout this expanded map of sex differences; several regions also show prominent SCD contributions to anatomical sex differences, which can both reinforce or counteract gonadal effects in a regionally specific manner. Targeted single nucleus RNA sequencing at a region of female-biased cerebellar volume reveals that combined gonadal and SCD effects also drive sex-biased cellular gene expression. These findings revise our understanding of the spatial distribution and causal basis of sex-differences in the mammalian brain, illuminating a key axis of biological variation in health and disease.

Identifiers

PMID41542610
PMCPMC12803231

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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 Socratic graph.