Bumetanide for autism: more eye contact, less amygdala activation

We recently showed that constraining eye contact leads to exaggerated increase of amygdala activation in autism. Here, in a proof of concept pilot study, we demonstrate that administration of bumetanide (a NKCC1 chloride importer antagonist that restores GABAergic inhibition) normalizes the level of amygdala activation during constrained eye contact with dynamic emotional face stimuli in autism. In addition, eye-tracking data reveal that bumetanide administration increases the time spent in spontaneous eye gaze during in a free-viewing mode of the same face stimuli. In keeping with clinical trials, our data support the Excitatory/Inhibitory dysfunction hypothesis in autism, and indicate that bumetanide may improve specific aspects of social processing in autism. Future double-blind placebo controlled studies with larger cohorts of participants will help clarify the mechanisms of bumetanide action in autism.

• Publication year

  2018

• Venue

  Scientific Reports

• Publication date

  2018-02-26

• Fields of study

  Medicine, Psychology

• Identifiers
  DOI 10.1038/s41598-018-21958-xPMID 29483603PMCID 5827728
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Oxytocin and Autism Spectrum Disorders.

  2018cited by this paper
• Improving

  2018cited by this paper
• The effect of constraining eye-contact during dynamic emotional face perception—an fMRI study

  2017cited by this paper
• How do adults and teens with self-declared Autism Spectrum Disorder experience eye contact? A qualitative analysis of first-hand accounts

  2017cited by this paper
• Look me in the eyes: constraining gaze in the eye-region provokes abnormally high subcortical activation in autism

  2017cited by this paper
• Hypersensitivity to low intensity fearful faces in autism when fixation is constrained to the eyes

  2017cited by this paper
• The Human Fetus Preferentially Engages with Face-like Visual Stimuli.

  2017cited by this paper
• NKCC1 Chloride Importer Antagonists Attenuate Many Neurological and Psychiatric Disorders.

  2017cited by this paper
• Effects of bumetanide on neurobehavioral function in children and adolescents with autism spectrum disorders

  2017cited by this paper
• Reduced GABAergic Action in the Autistic Brain.

  2016cited by this paper
• Epilepsy and Autism.

  2016cited by this paper
• A fast pathway for fear in human amygdala

  2016cited by this paper
• Is birth a critical period in the pathogenesis of autism spectrum disorders?

  2015cited by this paper
• Common mechanisms of excitatory and inhibitory imbalance in schizophrenia and autism spectrum disorders.

  2015cited by this paper
• Neurophysiological effects of acute oxytocin administration: systematic review and meta-analysis of placebo-controlled imaging studies.

  2015cited by this paper
• Improving emotional face perception in autism with diuretic bumetanide: A proof-of-concept behavioral and functional brain imaging pilot study

  2015cited by this paper
• Excitatory/Inhibitory Balance and Circuit Homeostasis in Autism Spectrum Disorders.

  2015cited by this paper
• Early Social Experience Affects the Development of Eye Gaze Processing

  2015cited by this paper
• Increased power of resting-state gamma oscillations in autism spectrum disorder detected by routine electroencephalography

  2015cited by this paper
• Wechsler Nonverbal Scale of Ability

  2014cited by this paper
• Wechsler Abbreviated Scale of Intelligence

  2014cited by this paper
• TARGET ARTICLE WITH COMMENTARIES AND RESPONSE Staring us in the face? An embodied theory of innate face preference

  2014cited by this paper
• Neurons in the monkey amygdala detect eye contact during naturalistic social interactions.

  2014cited by this paper
• GABAergic Signaling as Therapeutic Target for Autism Spectrum Disorders

  2014cited by this paper
• Oxytocin-Mediated GABA Inhibition During Delivery Attenuates Autism Pathogenesis in Rodent Offspring

  2014cited by this paper
• Atypical excitation–inhibition balance in autism captured by the gamma response to contextual modulation☆

  2013cited by this paper
• Amygdala Activation for Eye Contact Despite Complete Cortical Blindness

  2013cited by this paper
• Diagnostic and Statistical Manual of Mental Disorders

  2013cited by this paper
• A randomised controlled trial of bumetanide in the treatment of autism in children

  2012cited by this paper
• Impaired Gamma-Band Activity during Perceptual Organization in Adults with Autism Spectrum Disorders: Evidence for Dysfunctional Network Activity in Frontal-Posterior Cortices

  2012cited by this paper
• Interneuron dysfunction in psychiatric disorders

  2012cited by this paper
• Alterations of GABAergic Signaling in Autism Spectrum Disorders

  2011cited by this paper
• Neural bases of the non-conscious perception of emotional signals

  2010cited by this paper
• Compensatory Enhancement of Intrinsic Spiking upon NKCC1 Disruption in Neonatal Hippocampus

  2009cited by this paper
• The eye contact effect: mechanisms and development.

  2009cited by this paper
• Common circuit defect of excitatory-inhibitory balance in mouse models of autism

  2009cited by this paper
• The Role of Epilepsy and Epileptiform EEGs in Autism Spectrum Disorders

  2009cited by this paper
• New-onset psychiatric disorders in individuals with autism

  2008cited by this paper
• The autism‐epilepsy connection

  2007cited by this paper
• Excess of high frequency electroencephalogram oscillations in boys with autism.

  2007cited by this paper
• Response to Comment on "Maternal Oxytocin Triggers a Transient Inhibitory Switch in GABA Signaling in the Fetal Brain During Delivery"

  2007cited by this paper
• Distributed and interactive brain mechanisms during emotion face perception: evidence from functional neuroimaging.

  2007cited by this paper
• Epilepsy in autism spectrum disorders

  2007cited by this paper
• The Autism-Spectrum Quotient (AQ)—Adolescent Version

  2006cited by this paper
• Maternal oxytocin triggers a transient inhibitory switch in GABA signaling in the fetal brain during delivery.

  2006cited by this paper
• Epilepsy in Young Adults with Autism: A Prospective Population‐based Follow‐up Study of 120 Individuals Diagnosed in Childhood

  2005cited by this paper
• The Empathy Quotient: An Investigation of Adults with Asperger Syndrome or High Functioning Autism, and Normal Sex Differences

  2004cited by this paper
• Model of autism: increased ratio of excitation/inhibition in key neural systems

  2003cited by this paper
• The Friendship Questionnaire: An Investigation of Adults with Asperger Syndrome or High-Functioning Autism, and Normal Sex Differences

  2003cited by this paper
• Membrane potential of CA3 hippocampal pyramidal cells during postnatal development.

  2003cited by this paper
• The Autism Diagnostic Observation Schedule—Generic: A Standard Measure of Social and Communication Deficits Associated with the Spectrum of Autism

  2000cited by this paper
• Catatonia in autistic spectrum disorders

  2000cited by this paper
• The K+/Cl− co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation

  1999cited by this paper
• Image registration using a symmetric prior—in three dimensions

  1999cited by this paper
• Preferential orienting to faces in newborns: a temporal-nasal asymmetry.

  1998cited by this paper
• The twenty-item Toronto Alexithymia Scale--I. Item selection and cross-validation of the factor structure.

  1994cited by this paper
• Autism Diagnostic Interview-Revised: A revised version of a diagnostic interview for caregivers of individuals with possible pervasive developmental disorders

  1994cited by this paper
• Biology and Cognitive Development: the Case of Face Recognition, Mark H. Johnson, John Morton. Blackwell, Oxford (1991), x, +180. Price £35.00 hardback, £10.95 paperback

  1992cited by this paper
• Giant synaptic potentials in immature rat CA3 hippocampal neurones.

  1989cited by this paper
• Paradoxical reactions elicited by diazepam in children with classic autism.

  1987cited by this paper
• The emotional brain.

  1980cited by this paper
• Manual for the State-Trait Anxiety Inventory

  1970cited by this paper
• Cellular Neuroscience

  year unknowncited by this paper

• Treating autism with Bumetanide: Identification of responders using Q-Finder machine learning algorithm

  2026cites this paper
• Available Treatments for Autism Spectrum Disorder: From Old Strategies to New Options

  2025cites this paper
• Embryonic exposure to valproic acid and neonicotinoid deteriorates the hyperpolarizing GABA shift and impairs long-term potentiation of excitatory transmission in the local circuit of intermediate medial mesopallium of chick telencephalon.

  2025cites this paper
• Emotion Reactivity and Regulation in Autistic Adults: A Systematic Review Across RDoC Units of Analysis

  2025cites this paper
• Pattern of fixation explains atypical eye processing during observation of faces with direct or averted gaze in autism (results of the INFoR Cohort)

  2025cites this paper
• Bumetanide Treatment in 15 Children With Autism: A Randomised Waitlist‐Control Study

  2025cites this paper
• Limitations of genomics to predict and treat autism: a disorder born in the womb

  2025cites this paper
• Effect of Bumetanide on Neural Correlates of Emotion Recognition in Youth With Autism Spectrum Disorder: An Event-related Potential Study

  2025cites this paper
• A Hierarchical Graph Convolutional Network With Infomax-Guided Graph Embedding for Population-Based ASD Detection

  2025cites this paper
• Dynamic Functional Network Connectivity Analysis in Autism Spectrum Disorder: An EEG Study

  2024cites this paper
• Bumetanide to treat autism spectrum disorders: are complex administrative regulations fit to treat heterogeneous disorders?

  2024cites this paper
• The domestic chick as an animal model of autism spectrum disorder: building adaptive social perceptions through prenatally formed predispositions

  2024cites this paper
• An Update on Psychopharmacological Treatment of Autism Spectrum Disorder.

  2024cites this paper
• The pediatric psychopharmacology of autism spectrum disorder: A systematic review part II: The future.

  2024cites this paper
• Coherence and divergence in autonomic‐subjective affective space

  2023cites this paper
• Bumetanide oral solution for the treatment of children and adolescents with autism spectrum disorder: Results from two randomized phase III studies

  2023influential citation
• Self-reported eye contact sensitivity and face processing in chromosome 22q11.2 deletion syndrome

  2023cites this paper
• Pharmacology of Compounds Targeting Cation-Chloride Cotransporter Physiology.

  2023cites this paper
• Evaluation of bumetanide as a potential therapeutic agent for Alzheimer’s disease

  2023cites this paper
• EEG-based brain connectivity analysis in autism spectrum disorder: Unraveling the effects of bumetanide treatment

  2023cites this paper
• Overwhelmed by the man in the moon? Pareidolic objects provoke increased amygdala activation in autism.

  2023cites this paper
• Reading the room: Autistic traits, gaze behaviour, and the ability to infer social relationships

  2023cites this paper
• No transfer of arousal from other’s eyes in Williams syndrome

  2023cites this paper
• Effects of Bumetanide on Neurocognitive Functioning in Children with Autism Spectrum Disorder: Secondary Analysis of a Randomized Placebo-Controlled Trial

  2023cites this paper
• Dysregulation of GABAergic Signaling in Neurodevelomental Disorders: Targeting Cation-Chloride Co-transporters to Re-establish a Proper E/I Balance

  2022cites this paper
• Long-term administration of bumetanide improve functional recovery after spinal cord injury in rats

  2022cites this paper
• BUMETANIDE IN AUTISM SPECTRUM DISORDER

  2022cites this paper
• Discrepancy between high non-verbal intelligence and low accuracy at reading emotional expressions in the eyes reflects the magnitude of social–emotional difficulties in autism

  2022cites this paper
• A Wholistic View of How Bumetanide Attenuates Autism Spectrum Disorders

  2022cites this paper
• Pupil dilation predicts modulation of direct gaze on action value calculations.

  2022cites this paper
• Antihypertensive drugs and brain function: mechanisms underlying therapeutically beneficial and harmful neuropsychiatric effects

  2022cites this paper
• Repetitive Restricted Behaviors in Autism Spectrum Disorder: From Mechanism to Development of Therapeutics

  2022cites this paper
• NKCC1 and KCC2: Structural insights into phospho-regulation

  2022cites this paper
• GABAergic System Dysfunction in Autism Spectrum Disorders

  2022cites this paper
• The GABA Polarity Shift and Bumetanide Treatment: Making Sense Requires Unbiased and Undogmatic Analysis

  2022cites this paper
• How Staying Negative Is Good for the (Adult) Brain: Maintaining Chloride Homeostasis and the GABA-Shift in Neurological Disorders

  2022cites this paper
• [Early prognostic of ASD: A challenge].

  2022cites this paper
• An Update on Psychopharmacological Treatment of Autism Spectrum Disorder

  2022cites this paper
• The postnatal GABA shift: a developmental perspective.

  2021cites this paper
• Using bumetanide to treat autism appears promising but further clinical trials are needed to confirm this approach

  2021cites this paper
• Microglial NKCC1 shapes microglial phenotype, cerebral inflammatory responses and brain injury

  2021cites this paper
• Phenobarbital, midazolam, bumetanide, and neonatal seizures: The devil is in the details

  2021cites this paper
• Machine learning analysis of pregnancy data enables early identification of a subpopulation of newborns with ASD

  2021cites this paper
• Alexithymia explains atypical spatiotemporal dynamics of eye gaze in autism.

  2021cites this paper
• Eye contact effect: The role of vagal regulation and reactivity, and self-regulation of attention

  2021cites this paper
• Design, Synthesis, In Vitro and In Vivo Characterization of Selective NKCC1 Inhibitors for the Treatment of Core Symptoms in Down Syndrome

  2021cites this paper
• Novel treatments for autism spectrum disorder based on genomics and systems biology.

  2021cites this paper
• Novel Concepts for the Role of Chloride Cotransporters in Refractory Seizures

  2021cites this paper
• Decades of Progress in the Psychopharmacology of Autism Spectrum Disorder

  2021cites this paper
• Prediction of behavioral improvement through resting-state EEG and clinical severity in a randomized controlled trial testing bumetanide in autism spectrum disorder.

  2021cites this paper
• Pharmacological tools to target NKCC1 in brain disorders.

  2021cites this paper
• Treatment Effect of Bumetanide in Children With Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

  2021cites this paper
• Long-term bumetanide administration altered behavioral pattern in mosaic Down’s Syndrome: A case report

  2021influential citation
• CNS pharmacology of NKCC1 inhibitors.

  2021cites this paper
• Bumetanide-related effect on attention to face parts in children and adolescents with autism spectrum disorder using the eye tracking algorithm

  2020cites this paper
• Bumetanide for Autism Spectrum Disorder: Current Evidence

  2020cites this paper
• Pharmacotherapy and Bumetanide in Autism Treatment

  2020cites this paper
• Bumetanide for autism: Open‐label trial in six children

  2020cites this paper
• WNK-SPAK/OSR1-CCC signaling in ischemic brain damage

  2020cites this paper
• Bumetanide to treat autism spectrum disorders: Clinical observations

  2020cites this paper
• Alterations in chloride transporter activity in stress and depression

  2020cites this paper
• The GABA developmental shift in health and disease

  2020cites this paper
• Gaze behaviour of individuals with autistic traits while assessing peer status

  2020cites this paper
• Disruptions in chloride transporter activity in autism spectrum disorders

  2020cites this paper
• A causal study of bumetanide on a marker of excitatory-inhibitory balance in the human brain

  2020cites this paper
• Discovery of a Small Molecule Drug Candidate for Selective NKCC1 Inhibition in Brain Disorders

  2020cites this paper
• Bumetanide for Core Symptoms of Autism Spectrum Disorder (BAMBI): A Single Center, Double-Blinded, Participant-Randomized, Placebo-Controlled, Phase Two, Superiority Trial.

  2020cites this paper
• Neuroendocrine, epigenetic, and intergenerational effects of general anesthetics

  2020cites this paper
• Get With the (Developmental) Program

  2020cites this paper
• Symptom improvement in children with autism spectrum disorder following bumetanide administration is associated with decreased GABA/glutamate ratios

  2020cites this paper
• Investigational drugs in early-stage clinical trials for autism spectrum disorder

  2019cites this paper
• Discovery and Characterization of Novel Selective NKCC1 Inhibitors for Down Syndrome and Brain Disorders withDepolarizing GABAergic Transmission

  2019cites this paper
• Do animal models hold value in Autism spectrum disorder (ASD) drug discovery?

  2019cites this paper
• Sex-Dependent Signaling Pathways Underlying Seizure Susceptibility and the Role of Chloride Cotransporters

  2019cites this paper
• Eye-Tracking Research in Autism Spectrum Disorder: What Are We Measuring and for What Purposes?

  2019cites this paper
• Sammenhengen mellom sosial fungering og sosial angst hos barn, ungdom og voksne med autisme

  2019cites this paper
• Off-Label Use of Bumetanide for Brain Disorders: An Overview

  2019cites this paper
• Targeting Peripheral Somatosensory Neurons to Improve Tactile-Related Phenotypes in ASD Models.

  2019cites this paper
• Social scene perception in autism spectrum disorder: An eye-tracking and pupillometric study

  2019cites this paper
• Longitudinal Effects of Bumetanide on Neuro-Cognitive Functioning in Drug-Resistant Epilepsy

  2019cites this paper
• Further studies of GABA and Glutamate imbalances in autism are important challenges for future research

  2018cites this paper
• Social Skills Deficits in Autism Spectrum Disorder: Potential Biological Origins and Progress in Developing Therapeutic Agents

  2018cites this paper
• Sleep deprivation versus melatonin to induce sleep during paediatric electroencephalography

  2018cites this paper
• Face reading difficulties in children with neurofibromatosis type 1: towards more personalized treatments

  2018influential citation
• Bumétanide et TSA

  2018cites this paper
• Bumetanide for Autism Spectrum Disorder in Children: A Review of Randomized Controlled Trials

  2018cites this paper
• Excitatory and inhibitory imbalance and atypical sensory sensitivity in autism

  year unknowncites this paper
• as a potential therapeutic agent for Alzheimers disease.

  year unknowninfluential citation