Evidence map›Paper›PMID 41904269›Full record

ArticleMolecular psychiatry2026

A key gene modulating oxytocin efficacy in autism: genome-wide discovery and verification in randomized controlled trials datasets.

Hitoshi Kuwabara, Masaki Kojima, Seico Benner, Takeshi Otowa, Takamitsu Watanabe, Miho Kuroda, Keiho Owada, Walid Yassin, Junko Hamada, Yukiko Kano and 41 more

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Article in Molecular psychiatry, 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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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

51 authors.

Hitoshi Kuwabara *Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu City, Japan.
Masaki Kojima *Research Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Seico BennerDepartment of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu City, Japan.
Takeshi OtowaDepartment of Psychiatry, Teikyo University School of Medicine, Tokyo, Japan.
Takamitsu WatanabeInternational Research Center for Neurointelligence, The University of Tokyo Institutes for Advanced Study, Tokyo, Japan.ORCID http://orcid.org/0000-0002-8104-6873
Miho KurodaDepartment of Child Psychiatry, The University of Tokyo Hospital, Tokyo, Japan.
Keiho OwadaDepartment of Child Psychiatry, The University of Tokyo Hospital, Tokyo, Japan.
Walid YassinDepartment of Child Psychiatry, The University of Tokyo Hospital, Tokyo, Japan.ORCID http://orcid.org/0000-0001-9612-0485
Junko HamadaDepartment of Child Psychiatry, The University of Tokyo Hospital, Tokyo, Japan.
Yukiko KanoDepartment of Child Psychiatry, The University of Tokyo Hospital, Tokyo, Japan.
Yota UnoDepartment of Psychiatry, Nagoya University Graduate School of Medicine, Aichi, Japan.
Itaru KushimaDepartment of Psychiatry, Nagoya University Graduate School of Medicine, Aichi, Japan.ORCID http://orcid.org/0000-0002-0018-5178
Daisuke MoriDepartment of Psychiatry, Nagoya University Graduate School of Medicine, Aichi, Japan.ORCID http://orcid.org/0000-0002-9072-2546
Yuko AriokaDepartment of Psychiatry, Nagoya University Graduate School of Medicine, Aichi, Japan.ORCID http://orcid.org/0000-0002-1792-8812
Toshio MunesueResearch Center for Child Mental Development, Kanazawa University, Kanazawa, Japan.
Kiyoto KasaiDepartment of Neuropsychiatry, School of Medicine, The University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0002-4443-4535
Haruhiro HigashidaResearch Center for Child Mental Development, Kanazawa University, Kanazawa, Japan.
Osamu AbeDepartment of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.ORCID http://orcid.org/0000-0002-1180-2629
Hidemasa TakaoDepartment of Radiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
Tomoyasu WakudaDepartment of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu City, Japan.ORCID http://orcid.org/0000-0002-1924-8167
Yosuke KamenoDepartment of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu City, Japan.
Jun InoueDepartment of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu City, Japan.
Taeko HaradaResearch Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Aya YamauchiDepartment of Psychiatry, Nagoya University Graduate School of Medicine, Aichi, Japan.
Nanayo OgawaDepartment of Psychiatry, Nagoya University Graduate School of Medicine, Aichi, Japan.
Nami HondaDepartment of Psychiatry, Graduate School of Medicine, Tohoku University, Sendai, Japan.
Saya KikuchiDepartment of Psychiatry, Graduate School of Medicine, Tohoku University, Sendai, Japan.
Moe SetoDepartment of Psychiatry, Graduate School of Medicine, Tohoku University, Sendai, Japan.
Hiroaki TomitaDepartment of Psychiatry, Graduate School of Medicine, Tohoku University, Sendai, Japan.ORCID http://orcid.org/0000-0003-2628-880X
Noriko MiyoshiDepartment of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan.
Megumi MatsumotoDepartment of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan.
Yuko KawaguchiDepartment of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan.
Koji KanaiDepartment of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan.
Manabu IkedaDepartment of Psychiatry, Osaka University Graduate School of Medicine, Osaka, Japan.
Itta NakamuraDepartment of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Shuichi IsomuraDepartment of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Yoji HiranoDepartment of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Toshiaki OnitsukaDepartment of Neuropsychiatry, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Nagahide TakahashiResearch Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Mitsuko NakashimaDepartment of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan.ORCID http://orcid.org/0000-0001-7941-1774
Hirotomo SaitsuDepartment of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan.ORCID http://orcid.org/0000-0003-0723-0960
Kenji KondoDepartment of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan.
Masashi IkedaDepartment of Psychiatry, Nagoya University Graduate School of Medicine, Aichi, Japan.
Nakao IwataDepartment of Psychiatry, Fujita Health University School of Medicine, Aichi, Japan.ORCID http://orcid.org/0000-0003-3189-6076
Mihoko ShimadaDepartment of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
Tsukasa SasakiDepartment of Physical and Health Education, Graduate School of Education, The University of Tokyo, Tokyo, Japan.
Nori TakeiResearch Center for Child Mental Development, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Norio OzakiDepartment of Psychiatry, Nagoya University Graduate School of Medicine, Aichi, Japan.ORCID http://orcid.org/0000-0002-7360-4898
Hirotaka KosakaDepartment of Neuropsychiatry, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.ORCID http://orcid.org/0000-0003-2210-5025
Takashi OkadaDepartment of Psychiatry, Nagoya University Graduate School of Medicine, Aichi, Japan.ORCID http://orcid.org/0000-0001-5580-9913
Hidenori YamasueDepartment of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu City, Japan. yamasue@hama-med.ac.jp.ORCID http://orcid.org/0000-0002-2748-6317

Funding

Japan Agency for Medical Research and Development (AMED) JP19lk0201071; JP20lk0201116; JP18dm0107134MEXT | Japan Society for the Promotion of Science (JSPS) JP22H02997
6 · The paper itself

Abstract

Previous studies suggest that oxytocin has therapeutic potential for modulating core symptoms of autism spectrum disorder (ASD), although findings have been inconsistent. The unknown mechanisms underlying oxytocin's effects and the substantial individual variability in treatment response impede the development of effective oxytocin-based therapies. In this study, we conducted a genome-wide association study (GWAS) using data from a randomized controlled trial (RCT) that examined the effects of a single dose oxytocin on behavioral and neural correlates of ASD. We further tested the association between the SNP identified in the GWAS and clinical efficacy in an independent, larger dataset comprising participants from three additional RCTs. In these trials, males with high-functioning ASD received repeated doses of oxytocin, and treatment response was assessed using the social reciprocity domain of the Autism Diagnostic Observation Schedule (ADOS), the common primary outcome across all three studies. The GWAS identified a significant association between oxytocin-induced improvements in medial prefrontal cortex activity during a social judgment task and the single nucleotide polymorphism (SNP) rs1871303 in the ryanodine receptor 2 (RYR2) gene (β = 2.37, t = 7.82, df = 72, P = 3.47 × 10⁻⁹). The validation analysis supported the association between this RYR2 SNP and individual variability in ADOS reciprocity improvement (β = 0.194, t = 2.30, df = 135, P = 0.023), with no significant association observed for placebo response (P > 0.1). To our knowledge, this is the first GWAS to investigate the pharmacogenomics of oxytocin efficacy in ASD. These findings highlight RYR2 as a key gene influencing oxytocin response, possibly through its role in calcium channel signaling and regulation of endogenous oxytocin release.

Indexed as

Autism Spectrum DisorderAutistic DisorderOxytocinRyanodine Receptor Calcium Release ChannelAdolescentChildDatasets as TopicGenome-Wide Association StudyHumansMalePolymorphism, Single NucleotidePrefrontal CortexRandomized Controlled Trials as TopicSocial BehaviorTreatment OutcomeOxytocinRyanodine Receptor Calcium Release Channel

Identifiers

What Socratic holds

Textmetadata
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.