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Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios.
Zhang, Lingli; Huang, Chu-Chung; Dai, Yuan; Luo, Qiang; Ji, Yiting; Wang, Kai; Deng, Shining; Yu, Juehua; Xu, Mingyu; Du, Xiujuan; Tang, Yun; Shen, Chun; Feng, Jianfeng; Sahakian, Barbara J; Lin, Ching-Po; Li, Fei.
Affiliation
  • Zhang L; 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 Medici
  • Huang CC; Shanghai Institute of Pediatric Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Dai Y; Institute of Science and Technology for Brain-Inspired Intelligence, MOE-Key Laboratory of Computational Neuroscience and Brain-Inspired Intelligence, Fudan University, Shanghai, China.
  • Luo Q; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Brain Science and Human Phenom Institute, Fudan University, Shanghai, China.
  • Ji Y; 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 Medici
  • Wang K; Shanghai Institute of Pediatric Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Deng S; 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.
  • Yu J; State Key Laboratory of Medical Neurobiology and MOE Frontiers Center for Brain Science, Institute of Brain Science and Human Phenom Institute, Fudan University, Shanghai, China. qluo@fudan.edu.cn.
  • Xu M; Departments of Psychology and Psychiatry and the Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK. qluo@fudan.edu.cn.
  • Du X; 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 Medici
  • Tang Y; Shanghai Institute of Pediatric Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
  • Shen C; 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 Medici
  • Feng J; 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 Medici
  • Sahakian BJ; 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 Medici
  • Lin CP; 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 Medici
  • Li F; 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 Medici
Transl Psychiatry ; 10(1): 9, 2020 01 27.
Article in En | MEDLINE | ID: mdl-32066666
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Autistic Disorder / Autism Spectrum Disorder Type of study: Clinical_trials / Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limits: Child / Child, preschool / Humans Language: En Journal: Transl Psychiatry Year: 2020 Type: Article
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Autistic Disorder / Autism Spectrum Disorder Type of study: Clinical_trials / Diagnostic_studies / Prognostic_studies / Risk_factors_studies Limits: Child / Child, preschool / Humans Language: En Journal: Transl Psychiatry Year: 2020 Type: Article