Evidence map›Paper›PMID 32066666›Full record

Trial reportTranslational psychiatry2020

Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios.

Lingli Zhang, Chu-Chung Huang, Yuan Dai, Qiang Luo, Yiting Ji, Kai Wang, Shining Deng, Juehua Yu, Mingyu Xu, Xiujuan Du and 6 more

Erratum issuedOpen access · goldAbstract readRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Translational psychiatry, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 69 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
69citing papers in PubMed, 3 pooled it
10.6field-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

69 citing papers in PubMed, 3 syntheses or guidelines pooled it, 129 citations in OpenAlex.

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  17. Novel therapeutics in autism spectrum disorder.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026
    Review
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9 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

16 authors at 4 institutions in 5 countries.

Lingli Zhang *Developmental and Behavioral Pediatric Department & Child Primary Care Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and MOE- Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chu-Chung Huang *Institute of Science and Technology for Brain-Inspired Intelligence, MOE-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, China.
Yuan Dai *Developmental and Behavioral Pediatric Department & Child Primary Care Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and MOE- Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Qiang Luo *Institute of Science and Technology for Brain-Inspired Intelligence, MOE-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, China. qluo@fudan.edu.cn.
Yiting JiDevelopmental and Behavioral Pediatric Department & Child Primary Care Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and MOE- Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Kai WangDevelopmental and Behavioral Pediatric Department & Child Primary Care Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and MOE- Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shining DengDevelopmental and Behavioral Pediatric Department & Child Primary Care Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and MOE- Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Juehua YuDevelopmental and Behavioral Pediatric Department & Child Primary Care Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and MOE- Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Mingyu XuDevelopmental and Behavioral Pediatric Department & Child Primary Care Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and MOE- Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Xiujuan DuDevelopmental and Behavioral Pediatric Department & Child Primary Care Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and MOE- Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Yun TangDevelopmental and Behavioral Pediatric Department & Child Primary Care Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and MOE- Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Chun ShenDevelopmental and Behavioral Pediatric Department & Child Primary Care Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and MOE- Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Jianfeng FengInstitute of Science and Technology for Brain-Inspired Intelligence, MOE-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, China.
Barbara J SahakianDevelopmental and Behavioral Pediatric Department & Child Primary Care Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and MOE- Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ching-Po LinInstitute of Science and Technology for Brain-Inspired Intelligence, MOE-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, China. chingpolin@gmail.com.ORCID http://orcid.org/0000-0001-6848-8776
Fei LiDevelopmental and Behavioral Pediatric Department & Child Primary Care Department, Brain and Behavioral Research Unit of Shanghai Institute for Pediatric Research and MOE- Shanghai Key Laboratory for Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. feili@shsmu.edu.cn.
Shanghai Jiao Tong University · CNFudan University · CNAllen Institute for Brain Science · USNational Yang Ming Chiao Tung University · TW

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Bumetanide has been reported to alter synaptic excitation-inhibition (E-I) balance by potentiating the action of γ-aminobutyric acid (GABA), thereby attenuating the severity of autism spectrum disorder (ASD) in animal models. However, clinical evidence of its efficacy in young patients with ASD is limited. This was investigated in the present clinical trial of 83 patients, randomised to the bumetanide group (bumetanide treatment, 0.5 mg twice daily) or the control group (no bumetanide treatment). Primary [Children Autism Rating Scale (CARS)], secondary [Clinical Global Impressions (CGI)], and exploratory [inhibitory (γ-aminobutyric acid, GABA) and excitatory (glutamate, Glx) neurotransmitter concentrations measured in the insular cortex (IC) and visual cortex (VC) by magnetic resonance spectroscopy (MRS)] outcome measures were evaluated at baseline and at the 3-month follow-up. Side effects were monitored throughout the treatment course. Compared with the control group, the bumetanide group showed significant reduction in symptom severity, as indicated by both total CARS score and number of items assigned a score ≥ 3. The improvement in clinical symptoms was confirmed by CGI. GABA/Glx ratio in both the IC and VC decreased more rapidly over the 3-month period in the bumetanide group than that in the control group. This decrease in the IC was associated with the symptom improvement in the bumetanide group. Our study confirmed the clinical efficacy of bumetanide on alleviating the core symptoms of ASD in young children and it is the first demonstration that the improvement is associated with reduction in GABA/Glx ratios. This study suggests that the GABA/Glx ratio measured by MRS may provide a neuroimaging biomarker for assessing treatment efficacy for bumetanide.

Indexed as

Autism Spectrum DisorderAutistic DisorderBumetanideChildChild, Preschoolgamma-Aminobutyric AcidGlutamic AcidHumansBumetanidegamma-Aminobutyric AcidGlutamic Acid

Identifiers

PMID32066666
PMCPMC7026137
OpenAlexW4239498725

What OpenQuestion holds

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LicenceCC BY
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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.