ReviewFrontiers in pediatrics2014
GABAergic signaling as therapeutic target for autism spectrum disorders.
Review in Frontiers in pediatrics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 168 papers, 5 of them syntheses that pooled 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.
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.
Who cites it
168 citing papers in PubMed, 5 syntheses or guidelines pooled it, 301 citations in OpenAlex.
- Pooled it
- Effect of L-Carnosine in children with autism spectrum disorders: a systematic review and meta-analysis of randomised controlled trials.Amino acids · 2021Pooled it
- Treatment Effect of Bumetanide in Children With Autism Spectrum Disorder: A Systematic Review and Meta-Analysis.Frontiers in psychiatry · 2021Pooled it
- Is functional brain connectivity atypical in autism? A systematic review of EEG and MEG studies.PloS one · 2017Pooled it
- Pharmacological Modulation of GABA Function in Autism Spectrum Disorders: A Systematic Review of Human Studies.Journal of autism and developmental disorders · 2016Pooled it
- Bumetanide Treatment in 15 Children With Autism: A Randomised Waitlist-Control Study.Acta paediatrica (Oslo, Norway : 1992) · 2025Trial
- A Phase III Study of Bumetanide Oral Liquid Formulation for the Treatment of Children and Adolescents Aged Between 7 and 17 Years with Autism Spectrum Disorder (SIGN 1 Trial): Participant Baseline Characteristics.Child psychiatry and human development · 2023Trial
- Bumetanide for autism: more eye contact, less amygdala activation.Scientific reports · 2018Trial
- Drug Repurposing for Treating NCOR-Related Intellectual Disability.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Disruption of FOXG1 Impairs the Development of Striatal dSPNs, Thereby Contributing to ASD-Like Phenotypes.Neuroscience bulletin · 2026Article
- Social regression stems from a latent phase of GABAergic dysfunction and sensory breakdown in a model of synaptopathy.Molecular psychiatry · 2026Article
- A Developmental Neuroimmune Cascade Model of Autism Spectrum Disorder.International journal of molecular sciences · 2026Review
- Asymmetric neural dynamics of visuospatial attention in autism spectrum disorder.bioRxiv : the preprint server for biology · 2026Article
- Role of GABAMolecular biology reports · 2026Article
- Understanding the Complexity of Sleep Disturbances in ASD: From Mechanisms to Management.Diagnostics (Basel, Switzerland) · 2026Review
- Febrile Seizures and Subsequent Autism Spectrum Disorder: A Nationwide Population-Based Cohort Study.Children (Basel, Switzerland) · 2026Article
- Gami-Guibitang Attenuates Anxiety-like Behaviors and Modulates Hippocampal Synaptic Signaling in a Valproic Acid-Induced Mouse Model of Autism.Brain sciences · 2026Article
- GABAFrontiers in pharmacology · 2026Review
- Inapparent maternal ZIKV infection impacts fetal brain development and postnatal behavior.PLoS pathogens · 2026Article
- The Neuroimmunology of Autism.Molecular neurobiology · 2025Review
108 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
γ-Aminobutyric acid (GABA), the main inhibitory neurotransmitter in the adult brain, early in postnatal life exerts a depolarizing and excitatory action. This depends on accumulation of chloride inside the cell via the cation-chloride importer NKCC1, being the expression of the chloride exporter KCC2 very low at birth. The developmentally regulated expression of KCC2 results in extrusion of chloride with age and a shift of GABA from the depolarizing to the hyperpolarizing direction. The depolarizing action of GABA leads to intracellular calcium rise through voltage-dependent calcium channels and/or N-methyl-d-aspartate receptors. GABA-mediated calcium signals regulate a variety of developmental processes from cell proliferation migration, differentiation, synapse maturation, and neuronal wiring. Therefore, it is not surprising that some forms of neuro-developmental disorders such as autism spectrum disorders (ASDs) are associated with alterations of GABAergic signaling and impairment of the excitatory/inhibitory balance in selective neuronal circuits. In this review, we will discuss how changes of GABAA-mediated neurotransmission affect several forms of ASDs including the Fragile X, the Angelman, and Rett syndromes. Then, we will describe various animal models of ASDs with GABAergic dysfunctions, highlighting their behavioral deficits and the possibility to rescue them by targeting selective components of the GABAergic synapse. In particular, we will discuss how in some cases, reverting the polarity of GABA responses from the depolarizing to the hyperpolarizing direction with the diuretic bumetanide, a selective blocker of NKCC1, may have beneficial effects on ASDs, thus opening new therapeutic perspectives for the treatment of these devastating disorders.
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What OpenQuestion holds
Registered trials
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.