In animal models of autism spectrum disorder (ASD), the NKCC1 chloride-importer inhibitor bumetanide restores physiological (Cl−)i levels, enhances GABAergic inhibition and attenuates electrical and behavioral symptoms of ASD. In an earlier phase 2 trial; bumetanide reduced the severity of ASD in children and adolescents (3–11 years old). Here we report the results of a multicenter phase 2B study primarily to assess dose/response and safety effects of bumetanide. Efficacy outcome measures included the Childhood Autism Rating Scale (CARS), the Social Responsive Scale (SRS) and the Clinical Global Impressions (CGI) Improvement scale (CGI-I). Eighty-eight patients with ASD spanning across the entire pediatric population (2–18 years old) were subdivided in four age groups and randomized to receive bumetanide (0.5, 1.0 or 2.0 mg twice daily) or placebo for 3 months. The mean CARS value was significantly improved in the completers group (P: 0.015). Also, 23 treated children had more than a six-point improvement in the CARS compared with only one placebo-treated individual. Bumetanide significantly improved CGI (P: 0.0043) and the SRS score by more than 10 points (P: 0.02). The most frequent adverse events were hypokalemia, increased urine elimination, loss of appetite, dehydration and asthenia. Hypokalemia occurred mainly at the beginning of the treatment at 1.0 and 2.0 mg twice-daily doses and improved gradually with oral potassium supplements. The frequency and incidence of adverse event were directly correlated with the dose of bumetanide. Therefore, bumetanide improves the core symptoms of ASD and presents a favorable benefit/risk ratio particularly at 1.0 mg twice daily.

, et al.. Serious games to teach social interactions and emotions to individuals with autism spectrum disorders (ASD). Computers and Education, Elsevier, 2017, 113, pp.195-211. 10.1016/j.compedu.2017 M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT Serious games to teach social interactions and emotions to individuals with autism spectrum disorders (ASD)Charline M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT Abstract:The use of information communication technologies (ICTs) in therapy offers new perspectives for treating many domains in individuals with autism spectrum disorders (ASD) because they can be used in many different ways and settings and they are attractive to the patients. We reviewed the available literature on serious games that are used to teach social interactions to individuals with ASD. After screening the Medline, Science Direct and ACM Digital Library databases, we found a total of 31 serious games: 16 that targeted emotion recognition or production and 15 that targeted social skills. There was a significant correlation between the number of reports per year and the year of publication. Serious games appeared promising because they can support training on many different skills and they favour interactions in diverse contexts and situations, some of which may resemble real life.However, the currently available serious games exhibit some limitations: (i) most of them are developed for High-Functioning individuals; (ii) their clinical validation has rarely met the evidence-based medicine standards; (iii) the game design is not usually described; and, (iv) in many cases, the clinical validation and playability/game design are not compatible.Future research agendas should encompass (i) more robust studies in terms of methodology (large samples, control groups, longer treatment periods, follow-up to assess whether changes remain stable, etc.) to assess serious game efficacy; (ii) more collaboration between clinical and computer/game design experts; and (iii) more serious games that are adapted to Low-Functioning ASD individuals.

BackgroundIt is widely accepted that emotion processing difficulties are involved in Autism Spectrum Conditions (ASC). An increasing number of studies have focused on the development of training programs and have shown promising results. However, most of these programs are appropriate for individuals with high-functioning ASC (HFA) but exclude individuals with low-functioning ASC (LFA). We have developed a computer-based game called JeStiMulE based on logical skills to teach emotions to individuals with ASC, independently of their age, intellectual, verbal and academic level.The aim of the present study was to verify the usability of JeStiMulE (which is its adaptability, effectiveness and efficiency) on a heterogeneous ASC group. We hypothesized that after JeStiMulE training, a performance improvement would be found in emotion recognition tasks.MethodsA heterogeneous group of thirty-three children and adolescents with ASC received two one-hour JeStiMulE sessions per week over four weeks. In order to verify the usability of JeStiMulE, game data were collected for each participant. Furthermore, all participants were presented before and after training with five emotion recognition tasks, two including pictures of game avatars (faces and gestures) and three including pictures of real-life characters (faces, gestures and social scenes).ResultsDescriptive data showed suitable adaptability, effectiveness and efficiency of JeStiMulE. Results revealed a significant main effect of Session on avatars (ANOVA: F (1,32) = 98.48, P < .001) and on pictures of real-life characters (ANOVA: F (1,32) = 49.09, P < .001). A significant Session × Task × Emotion interaction was also found for avatars (ANOVA: F (6,192) = 2.84, P = .01). This triple interaction was close to significance for pictures of real-life characters (ANOVA: F (12,384) = 1.73, P = .057). Post-hoc analyses revealed that 30 out of 35 conditions found a significant increase after training.ConclusionsJeStiMulE appears to be a promising tool to teach emotion recognition not only to individuals with HFA but also those with LFA. JeStiMulE is thus based on ASC-specific skills, offering a model of logical processing of social information to compensate for difficulties with intuitive social processing.Trial registrationComité de Protection des Personnes Sud Méditerranée V (CPP): reference number 11.046 (https://cpp-sud-mediterranee-v.fr/).

BackgroundPhelan-Mc Dermid syndrome is a contiguous disorder resulting from 22q13.3 deletion implicating the SHANK3 gene. The typical phenotype includes neonatal hypotonia, moderate to severe intellectual disability, absent or delayed speech, minor dysmorphic features and autism or autistic-like behaviour. Recently, point mutations or micro-deletions of the SHANK3 gene have been identified, accompanied by a phenotype different from the initial clinically description in Phelan McDermid syndrome.Case presentationHere we present two case studies with similar psychiatric and genetic diagnosis as well as similar clinical history and evolution. The two patients were diagnosed with autism spectrum disorders in childhood and presented regression with catatonia features and behavioural disorders after a stressful event during adolescence. Interestingly, both patients presented mutation/microdeletion of the SHANK3 gene, inducing a premature stop codon in exon 21. Different pharmacological treatments (antipsychotics, benzodiazepines, mood stabilizer drugs, antidepressants, and methylphenidate) failed to improve clinical symptoms and lead to multiple adverse events. In contrast, lithium therapy reversed clinical regression, stabilized behavioural symptoms and allowed patients to recover their pre-catatonia level of functioning, without significant side effects.ConclusionThese cases support the hypothesis of a specific SHANK3 phenotype. This phenotype might be linked to catatonia-like deterioration for which lithium use could be an efficient treatment. Therefore, these cases provide an important contribution to the field of autism research, clinical genetics and possible pharmacological answers.Electronic supplementary materialThe online version of this article (doi:10.1186/s12888-015-0490-1) contains supplementary material, which is available to authorized users.

The use of Serious Games (SG) in the health domain is expanding. In the field of neurodegenerative disorders (ND) such as Alzheimer’s disease, SG are currently employed both to support and improve the assessment of different functional and cognitive abilities, and to provide alternative solutions for patients’ treatment, stimulation, and rehabilitation. As the field is quite young, recommendations on the use of SG in people with ND are still rare. In 2014 we proposed some initial recommendations (Robert et al., 2014). The aim of the present work was to update them, thanks to opinions gathered by experts in the field during an expert Delphi panel. Results confirmed that SG are adapted to elderly people with mild cognitive impairment (MCI) and dementia, and can be employed for several purposes, including assessment, stimulation, and improving wellbeing, with some differences depending on the population (e.g., physical stimulation may be better suited for people with MCI). SG are more adapted for use with trained caregivers (both at home and in clinical settings), with a frequency ranging from 2 to 4 times a week. Importantly, the target of SG, their frequency of use and the context in which they are played depend on the SG typology (e.g., Exergame, cognitive game), and should be personalized with the help of a clinician.