title: Improving emotional face perception in autism with diuretic bumetanide: a proof-of-concept behavioral and functional brain imaging pilot study.
abstract: Clinical observations have shown that GABA-acting benzodiazepines exert paradoxical excitatory effects in autism, suggesting elevated intracellular chloride (Cl-)i and excitatory action of GABA. In a previous double-blind randomized study, we have shown that the diuretic NKCC1 chloride importer antagonist bumetanide, that decreases (Cl-)i and reinforces GABAergic inhibition, reduces the severity of autism symptoms. Here, we report results from an open-label trial pilot study in which we used functional magnetic resonance imaging and neuropsychological testing to determine the effects of 10 months bumetanide treatment in adolescents and young adults with autism. We show that bumetanide treatment improves emotion recognition and enhances the activation of brain regions involved in social and emotional perception during the perception of emotional faces. The improvement of emotion processing by bumetanide reinforces the usefulness of bumetanide as a promising treatment to improve social interactions in autism.
authors.affiliation: MGH/HST Athinoula A. Martinos Center for Biomedical Imaging, USA; EPFL, Switzerland Gillberg Neuropsychiatric Center, Gothenburg, Sweden nouchine@nmr.mgh.harvard.edu.
authors.forename: Nouchine
authors.initials: N
authors.lastname: Hadjikhani
authors.affiliation: MGH/HST Athinoula A. Martinos Center for Biomedical Imaging, USA; EPFL, Switzerland.
authors.forename: Nicole R
authors.initials: NR
authors.lastname: Zürcher
authors.affiliation: EPFL, Switzerland.
authors.forename: Ophelie
authors.initials: O
authors.lastname: Rogier
authors.affiliation: EPFL, Switzerland.
authors.forename: Torsten
authors.initials: T
authors.lastname: Ruest
authors.affiliation: EPFL, Switzerland.
authors.forename: Loyse
authors.initials: L
authors.lastname: Hippolyte
authors.affiliation: INMED, France.
authors.forename: Yehezkel
authors.initials: Y
authors.lastname: Ben-Ari
authors.affiliation: Université de Brest, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Lemonnier
mesh_terms: D000293:Adolescent; D000328:Adult; D001321:Autistic Disorder / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D002034:Bumetanide / Q000627:therapeutic use*; D004644:Emotions; D005149:Facial Expression; D006801:Humans; D008279:Magnetic Resonance Imaging; D009483:Neuropsychological Tests; D010865:Pilot Projects; D049994:Sodium Potassium Chloride Symporter Inhibitors / Q000627:therapeutic use; D014796:Visual Perception; D055815:Young Adult
chemical_list: D049994:Sodium Potassium Chloride Symporter Inhibitors; D002034:Bumetanide
keywords: Autism spectrum disorders; GABA; bumetanide; emotion; fMRI; face perception; treatment