Evidence map›Paper›PMID 32127526›Full record

ArticleTranslational psychiatry2020

Imaging-genetics of sex differences in ASD: distinct effects of OXTR variants on brain connectivity.

Leanna M Hernandez, Katherine E Lawrence, N Tanya Padgaonkar, Marisa Inada, Jackson N Hoekstra, Jennifer K Lowe, Jeffrey Eilbott, Allison Jack, Elizabeth Aylward, Nadine Gaab and 10 more

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

Article in Translational psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 2 pooled it
3.3field-weighted citation impact, top 7% 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

30 citing papers in PubMed, 2 syntheses or guidelines pooled it, 52 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Trial
  4. Article
  5. Subcortical dopamine DEuropean journal of nuclear medicine and molecular imaging · 2026
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  9. Distinct early development trajectories in Nf1Journal of neurodevelopmental disorders · 2025
    Article
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  15. Review
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  18. Article
  19. Why do we need sex-balanced studies of autism?Autism research : official journal of the International Society for Autism Research · 2023
    Article
  20. Article
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

20 authors at 7 institutions in 1 country.

Leanna M HernandezAhmanson-Lovelace Brain Mapping Center, University of California, Los Angeles, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0002-5816-7810
Katherine E LawrenceAhmanson-Lovelace Brain Mapping Center, University of California, Los Angeles, Los Angeles, CA, 90095, USA.ORCID http://orcid.org/0000-0002-0156-353X
N Tanya PadgaonkarAhmanson-Lovelace Brain Mapping Center, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Marisa InadaAhmanson-Lovelace Brain Mapping Center, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Jackson N HoekstraDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Jennifer K LoweDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Jeffrey EilbottAutism & Neurodevelopmental Disorders Institute, The George Washington University, Washington, DC, USA.
Allison JackAutism & Neurodevelopmental Disorders Institute, The George Washington University, Washington, DC, USA.
Elizabeth AylwardCenter for Integrative Brain Research, Seattle Children's Research Institute, Seattle, WA, USA.
Nadine GaabDepartment of Pediatrics, Harvard Medical School, Boston, MA, USA.
John D Van HornUSC Mark and Mary Stevens Neuroimaging and Informatics Institute, Laboratory of Neuro Imaging, Keck School of Medicine of USC, University of Southern California, Los Angeles, CA, USA.
Raphael A BernierDepartment of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
James C McPartlandDepartment of Pediatrics, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-2570-0746
Sara J WebbDepartment of Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA.
Kevin A PelphreyUniversity of Virginia School of Medicine, Charlottesville, VA, USA.
Shulamite A GreenAhmanson-Lovelace Brain Mapping Center, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Daniel H GeschwindDepartment of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Susan Y BookheimerDepartment of Psychiatry and Biobehavioral Sciences, University of California, Los Angeles, Los Angeles, CA, 90095, USA.
Mirella DaprettoAhmanson-Lovelace Brain Mapping Center, University of California, Los Angeles, Los Angeles, CA, 90095, USA. mirella@g.ucla.edu.
GENDAAR Consortium
University of California, Los Angeles · USGeorge Washington University · USUniversity of Washington · USHarvard University · USUniversity of Southern California · USUniversity of Virginia · USYale University · US

Funding

Yale Clinical and Translational Science Award (U Component)UL1TR001863 · NCATS · YALE UNIVERSITY · PI John H. Krystal, LUCILA OHNO-MACHADO · 2016 to 2026
$102.9M
Multimodal Developmental Neurogenetics of Females with ASDR01MH100028 · NIMH · YALE UNIVERSITY · PI Allison Elizabeth Jack, LAUREN KENWORTHY · 2012 to 2026
$37.8M
Mechanisms of Brain Dysmorphology in MN1 C-Terminal Truncation Syndrome, a Novel Intellectual Developmental Disability Disorder P50HD103524 · NICHD · UNIVERSITY OF WASHINGTON · PI DANIEL DOHERTY · 2020 to 2026
$9.9M
AN INFORMATICS FACILITY FOR NEUROIMAGINGC06RR015431 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TOGA, ARTHUR W · 2000 to 2000
$2.0M
Doctoral Training in Brain and Behavioral Development During Adolescence (UCLA BBDA)T32HD091059 · NICHD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Mirella Dapretto, ANDREW J FULIGNI · 2018 to 2026
$1.7M
High Capacity Storage System for Computational BiologyS10OD011939 · OD · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WOODS, ROGER P · 2012 to 2012
$598k
Gene-brain-environment interactions: Predicting social skill heterogeneity in ASDF32MH105167 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GREEN, SHULAMITE ABRA · 2014 to 2017
$159k
Impact of Cumulative Genetic Risk on Brain Connectivity in ASDF31MH110140 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI LAWRENCE, KATHERINE E · 2016 to 2019
$110k
Gene-brain-environment interactions as determinants of typical and atypical developmental trajectoriesF99NS105206 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SHARMA, LEANNA MARIE HERNANDEZ · 2017 to 2017
$39k
EXTRAMURAL RESEARCH FACILITIES CONSTRUCTIONC06RR012169 · NCRR · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI MAZZIOTTA, JOHN C · 1996 to 1997
–
NCATS NIH HHS UL1 TR001863NCRR NIH HHS C06 RR012169NCRR NIH HHS C06 RR015431NICHD NIH HHS P50 HD103524NICHD NIH HHS T32 HD091059NIH HHS S10 OD011939NIMH NIH HHS F31 MH110140NIMH NIH HHS F32 MH105167NIMH NIH HHS R01 MH100028NINDS NIH HHS F99 NS105206
6 · The paper itself

Abstract

Autism spectrum disorder (ASD) is more prevalent in males than in females, but the neurobiological mechanisms that give rise to this sex-bias are poorly understood. The female protective hypothesis suggests that the manifestation of ASD in females requires higher cumulative genetic and environmental risk relative to males. Here, we test this hypothesis by assessing the additive impact of several ASD-associated OXTR variants on reward network resting-state functional connectivity in males and females with and without ASD, and explore how genotype, sex, and diagnosis relate to heterogeneity in neuroendophenotypes. Females with ASD who carried a greater number of ASD-associated risk alleles in the OXTR gene showed greater functional connectivity between the nucleus accumbens (NAcc; hub of the reward network) and subcortical brain areas important for motor learning. Relative to males with ASD, females with ASD and higher OXTR risk-allele-dosage showed increased connectivity between the NAcc, subcortical regions, and prefrontal brain areas involved in mentalizing. This increased connectivity between NAcc and prefrontal cortex mirrored the relationship between genetic risk and brain connectivity observed in neurotypical males showing that, under increased OXTR genetic risk load, females with ASD and neurotypical males displayed increased connectivity between reward-related brain regions and prefrontal cortex. These results indicate that females with ASD differentially modulate the effects of increased genetic risk on brain connectivity relative to males with ASD, providing new insights into the neurobiological mechanisms through which the female protective effect may manifest.

Indexed as

Autism Spectrum DisorderBrainBrain MappingFemaleHumansMagnetic Resonance ImagingMaleNeural PathwaysReceptors, OxytocinRewardSex CharacteristicsOXTR protein, humanReceptors, Oxytocin

Identifiers

PMID32127526
PMCPMC7054353
OpenAlexW3010132840

What OpenQuestion holds

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LicenceCC BY
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.