1. Althaus M, Groen Y, A AW, Noltes H, Tucha O, Sweep FC, Calcagnoli F, Hoekstra PJ. {{Do blood plasma levels of oxytocin moderate the effect of nasally administered oxytocin on social orienting in high-functioning male adults with autism spectrum disorder?}}. {Psychopharmacology (Berl)};2016 (Jun 2)
OBJECTIVE: The study investigated whether baseline plasma oxytocin (OXT) concentrations might moderate the effects of nasally administered OXT on social orienting. METHODS: Thirty-one males with Autism spectrum disorder (ASD) and thirty healthy males participated in a double-blind placebo-controlled crossover trial. After administration of the compound, participants were viewing pictures from the International Affective Picture System that represented a systematic variation of pleasant, unpleasant and neutral scenes with and without humans. The outcome measures were a cardiac evoked response (ECR) and a cortical evoked long latency parietal positivity (LPP). RESULTS: Males with ASD had significantly higher plasma baseline levels than the controls. In the absence of general treatment effects, higher baseline concentrations were found to be associated with larger treatment effects, particularly in the group of males with ASD. Higher post-treatment plasma OXT concentrations were found to be associated with smaller treatment effects and larger orienting responses in the placebo situation in the group of controls. CONCLUSIONS: We interpret our findings as suggesting that it is the central availability of OXT determining how much of the nasally administered OXT will become centrally absorbed and how much of it will become released into the bloodstream.
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2. Boban S, Wong K, Epstein A, Anderson B, Murphy N, Downs J, Leonard H. {{Determinants of sleep disturbances in Rett syndrome: Novel findings in relation to genotype}}. {Am J Med Genet A};2016 (Jun 3)
Rett syndrome is a rare but severe neurological disorder associated with a mutation in the methyl CpG binding protein 2 (MECP2) gene. Sleep problems and epilepsy are two of many comorbidities associated with this disorder. This study investigated the prevalence and determinants of sleep problems in Rett syndrome using an international sample. Families with a child with a confirmed Rett syndrome diagnosis and a MECP2 mutation registered in the International Rett Syndrome Phenotype Database (InterRett) were invited to participate. Questionnaires were returned by 364/461 (78.9%) either in web-based or paper format. Families completed the Sleep Disturbance Scale for Children and provided information on the presence, nature, and frequency of their child’s sleep problems. Multivariate multinomial regression was used to investigate the relationships between selected sleep problems, age group, and genotype and linear regression for the relationships between sleep disturbance scales and a range of covariates. Night waking was the most prevalent sleep problem affecting over 80% with nearly half (48.3%) currently waking often at night. Initiating and maintaining sleep was most disturbed for younger children and those with a p.Arg294* mutation. Severe seizure activity was associated with poor sleep after adjusting for age group, mutation type, and mobility. We were surprised to find associations between the p.Arg294* mutation and some sleep disturbances given that other aspects of its phenotype are milder. These findings highlight the complexities of aberrant MECP2 function in Rett syndrome and explain some of the variation in manifestation of sleep disturbances. (c) 2016 Wiley Periodicals, Inc.
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3. Braddock BA, Gabany C, Shah M, Armbrecht ES, Twyman KA. {{Patterns of Gesture Use in Adolescents With Autism Spectrum Disorder}}. {Am J Speech Lang Pathol};2016 (Jun 3):1-8.
Purpose: The purpose of this study was to examine patterns of spontaneous gesture use in a sample of adolescents with autism spectrum disorder (ASD). Method: Thirty-five adolescents with ASD ages 11 to 16 years participated (mean age = 13.51 years; 29 boys, 6 girls). Participants’ spontaneous speech and gestures produced during a narrative task were later coded from videotape. Parents were also asked to complete questionnaires to quantify adolescents’ general communication ability and autism severity. Results: No significant subgroup differences were apparent between adolescents who did not gesture versus those who produced at least 1 gesture in general communication ability and autism severity. Subanalyses including only adolescents who produced gesture indicated a statistically significant negative association between gesture rate and general communication ability, specifically speech and syntax subscale scores. Adolescents who gestured produced higher proportions of iconic gestures and used gesture mostly to add information to speech. Conclusions: The findings relate spontaneous gesture use to underlying strengths and weaknesses in adolescents’ speech and syntactical language development. More research examining cospeech gesture in fluent speakers with ASD is needed.
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4. Foote M, Arque G, Berman RF, Santos M. {{Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Motor Dysfunction Modeled in Mice}}. {Cerebellum};2016 (Jun 2)
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder that affects some carriers of the fragile X premutation (PM). In PM carriers, there is a moderate expansion of a CGG trinucleotide sequence (55-200 repeats) in the fragile X gene (FMR1) leading to increased FMR1 mRNA and small to moderate decreases in the fragile X mental retardation protein (FMRP) expression. The key symptoms of FXTAS include cerebellar gait ataxia, kinetic tremor, sensorimotor deficits, neuropsychiatric changes, and dementia. While the specific trigger(s) that causes PM carriers to progress to FXTAS pathogenesis remains elusive, the use of animal models has shed light on the underlying neurobiology of the altered pathways involved in disease development. In this review, we examine the current use of mouse models to study PM and FXTAS, focusing on recent advances in the field. Specifically, we will discuss the construct, face, and predictive validities of these PM mouse models, the insights into the underlying disease mechanisms, and potential treatments.
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5. Hacohen Y, Wright S, Gadian J, Vincent A, Lim M, Wassmer E, Lin JP. {{N-methyl-d-aspartate (NMDA) receptor antibodies encephalitis mimicking an autistic regression}}. {Dev Med Child Neurol};2016 (Jun 3)
Expressive dysphasia and mutism are common clinical features in children and adults with N-methyl-d-aspartate receptor antibodies (NMDAR-Ab) encephalitis, and are likely to result from NMDAR hypofunction. A prodromal loss of social and communication skills can typify that of an autistic regression, particularly when presenting under the age of 3 years. Here we describe two toddlers who presented with developmental regression, particularly of their social communication skills, mimicking an autistic regression, who were found to have NMDAR-Ab in the serum and cerebrospinal fluid. Although both patients had some other neurological features, they were subtle, which resulted in delayed diagnosis of NMDAR-Ab encephalitis. Importantly, immunotherapy was beneficial in both patients, with significant improvement of their language skills and behaviour.
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6. Heunis TM, Aldrich C, de Vries PJ. {{Recent Advances in Resting-State Electroencephalography Biomarkers for Autism Spectrum Disorder-A Review of Methodological and Clinical Challenges}}. {Pediatr Neurol};2016 (Apr 1)
BACKGROUND: Electroencephalography (EEG) has been used for almost a century to identify seizure-related disorders in humans, typically through expert interpretation of multichannel recordings. Attempts have been made to quantify EEG through frequency analyses and graphic representations. These « traditional » quantitative EEG analysis methods were limited in their ability to analyze complex and multivariate data and have not been generally accepted in clinical settings. There has been growing interest in identification of novel EEG biomarkers to detect early risk of autism spectrum disorder, to identify clinically meaningful subgroups, and to monitor targeted intervention strategies. Most studies to date have, however, used quantitative EEG approaches, and little is known about the emerging multivariate analytical methods or the robustness of candidate biomarkers in the context of the variability of autism spectrum disorder. METHODS: Here, we present a targeted review of methodological and clinical challenges in the search for novel resting-state EEG biomarkers for autism spectrum disorder. RESULTS: Three primary novel methodologies are discussed: (1) modified multiscale entropy, (2) coherence analysis, and (3) recurrence quantification analysis. Results suggest that these methods may be able to classify resting-state EEG as « autism spectrum disorder » or « typically developing », but many signal processing questions remain unanswered. CONCLUSIONS: We suggest that the move to novel EEG analysis methods is akin to the progress in neuroimaging from visual inspection, through region-of-interest analysis, to whole-brain computational analysis. Novel resting-state EEG biomarkers will have to evaluate a range of potential demographic, clinical, and technical confounders including age, gender, intellectual ability, comorbidity, and medication, before these approaches can be translated into the clinical setting.
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7. Leung C, Chan S, Lam T, Yau S, Tsang S. {{The effect of parent education program for preschool children with developmental disabilities: A randomized controlled trial}}. {Res Dev Disabil};2016 (May 31);56:18-28.
AIM: This study aimed to evaluate the efficacy of a parent education program, the Happy Parenting program, for Chinese preschool children with developmental disabilities. METHODS: This study adopted randomized controlled trial design without blinding. Participants were randomized into intervention group (n=62) who were offered the Happy Parenting program delivered by educational psychologists and trainee educational psychologists, and a control group (n=57) who were offered a parent talk after the intervention group had completed treatment. Parent participants were requested to complete questionnaires on their children’s behavior, their parenting stress, and discipline strategies. RESULTS: Analysis was by intention-to-treat. The results indicated significant decrease in child problem behaviors, parenting stress and dysfunctional discipline strategies in the intervention group at post-intervention. CONCLUSION: This study provided promising evidence on the effectiveness of a parent education program, the Happy Parenting program, for Chinese preschool children with developmental disabilities.
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8. Limpitikul WB, Dick IE, Ben-Johny M, Yue DT. {{An autism-associated mutation in CaV1.3 channels has opposing effects on voltage- and Ca(2+)-dependent regulation}}. {Sci Rep};2016;6:27235.
CaV1.3 channels are a major class of L-type Ca(2+) channels which contribute to the rhythmicity of the heart and brain. In the brain, these channels are vital for excitation-transcription coupling, synaptic plasticity, and neuronal firing. Moreover, disruption of CaV1.3 function has been associated with several neurological disorders. Here, we focus on the de novo missense mutation A760G which has been linked to autism spectrum disorder (ASD). To explore the role of this mutation in ASD pathogenesis, we examined the effects of A760G on CaV1.3 channel gating and regulation. Introduction of the mutation severely diminished the Ca(2+)-dependent inactivation (CDI) of CaV1.3 channels, an important feedback system required for Ca(2+) homeostasis. This reduction in CDI was observed in two major channel splice variants, though to different extents. Using an allosteric model of channel gating, we found that the underlying mechanism of CDI reduction is likely due to enhanced channel opening within the Ca(2+)-inactivated mode. Remarkably, the A760G mutation also caused an opposite increase in voltage-dependent inactivation (VDI), resulting in a multifaceted mechanism underlying ASD. When combined, these regulatory deficits appear to increase the intracellular Ca(2+) concentration, thus potentially disrupting neuronal development and synapse formation, ultimately leading to ASD.
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9. Markkanen E, Meyer U, Dianov GL. {{DNA Damage and Repair in Schizophrenia and Autism: Implications for Cancer Comorbidity and Beyond}}. {Int J Mol Sci};2016;17(6)
Schizophrenia and autism spectrum disorder (ASD) are multi-factorial and multi-symptomatic psychiatric disorders, each affecting 0.5%-1% of the population worldwide. Both are characterized by impairments in cognitive functions, emotions and behaviour, and they undermine basic human processes of perception and judgment. Despite decades of extensive research, the aetiologies of schizophrenia and ASD are still poorly understood and remain a significant challenge to clinicians and scientists alike. Adding to this unsatisfactory situation, patients with schizophrenia or ASD often develop a variety of peripheral and systemic disturbances, one prominent example of which is cancer, which shows a direct (but sometimes inverse) comorbidity in people affected with schizophrenia and ASD. Cancer is a disease characterized by uncontrolled proliferation of cells, the molecular origin of which derives from mutations of a cell’s DNA sequence. To counteract such mutations and repair damaged DNA, cells are equipped with intricate DNA repair pathways. Oxidative stress, oxidative DNA damage, and deficient repair of oxidative DNA lesions repair have been proposed to contribute to the development of schizophrenia and ASD. In this article, we summarize the current evidence of cancer comorbidity in these brain disorders and discuss the putative roles of oxidative stress, DNA damage and DNA repair in the aetiopathology of schizophrenia and ASD.
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10. May T, Cornish K, Rinehart NJ. {{Exploring factors related to the anger superiority effect in children with Autism Spectrum Disorder}}. {Brain Cogn};2016 (May 31);106:65-71.
Despite face and emotion recognition deficits, individuals with Autism Spectrum Disorder (ASD) appear to experience the anger superiority effect, where an angry face in a crowd is detected faster than a neutral face. This study extended past research to examine the impacts of ecologically valid photographic stimuli, gender and anxiety symptoms on the anger superiority effect in children with and without ASD. Participants were 81, 7-12year old children, 42 with ASD matched on age, gender and perceptual IQ to 39 typically developing (TYP) children. The photographic stimuli did not impact on task performance in ASD with both groups exhibiting the anger superiority effect. There were no gender differences and no associations with anxiety. Age was associated with the effect in the TYP but not ASD group. These findings confirm a robust effect of speeded detection of threat in ASD which does not appear to be confounded by gender or anxiety, but may have different underlying age-associated mechanisms.
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11. Puig-Alcaraz C, Fuentes-Albero M, Cauli O. {{Relationship between adipic acid concentration and the core symptoms of autism spectrum disorders}}. {Psychiatry Res};2016 (May 25);242:39-45.
Dicarboxylic acids are an important source of information about metabolism and potential physiopathological alterations in children with autism spectrum disorders (ASDs). We measured the concentration between dicarboxylic adipic and suberic acids in children with an ASD and typically-developing (TD) children and analyzed any relationships between the severity of the core symptoms of ASDs and other clinical features (drugs, supplements, drugs, or diet). The core symptoms of autism were evaluated using the DSM-IV criteria, and adipic acid and suberic acid were measured in urine samples. Overall, no increase in the concentration of adipic acid in children with ASDs compared to TD children, however when considering vitamin B supplementation in ASD there were significantly increased level of urinary adipic acid in children with an ASD not taking vitamin B supplementation compared to supplemented children or to TD children. No significant difference were observed in suberic acid. Interestingly, the increase in adipic acid concentration was significantly and indirectly correlated with the severity of the deficit in socialization and communication skills in children with an ASD. Therefore, therapeutic treatments aimed at decreasing adipic acid concentration might not be beneficial for treating the core symptoms of ASDs.
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12. Santocchi E, Guiducci L, Fulceri F, Billeci L, Buzzigoli E, Apicella F, Calderoni S, Grossi E, Morales MA, Muratori F. {{Gut to brain interaction in Autism Spectrum Disorders: a randomized controlled trial on the role of probiotics on clinical, biochemical and neurophysiological parameters}}. {BMC Psychiatry};2016;16:183.
BACKGROUND: A high prevalence of a variety of gastrointestinal (GI) symptoms is frequently reported in patients with Autism Spectrum Disorders (ASD). The GI disturbances in ASD might be linked to gut dysbiosis representing the observable phenotype of a « gut-brain axis » disruption. The exploitation of strategies which can restore normal gut microbiota and reduce the gut production and absorption of toxins, such as probiotics addition/supplementation in a diet, may represent a non-pharmacological option in the treatment of GI disturbances in ASD. The aim of this randomized controlled trial is to determine the effects of supplementation with a probiotic mixture (Vivomixx(R)) in ASD children not only on specific GI symptoms, but also on the core deficits of the disorder, on cognitive and language development, and on brain function and connectivity. An ancillary aim is to evaluate possible effects of probiotic supplementation on urinary concentrations of phthalates (chemical pollutants) which have been previously linked to ASD. METHODS: A group of 100 preschoolers with ASD will be classified as belonging to a GI group or to a Non-GI (NGI) group on the basis of a symptom severity index specific to GI disorders. In order to obtain four arms, subjects belonging to the two groups (GI and NGI) will be blind randomized 1:1 to regular diet with probiotics or with placebo for 6 months. All participants will be assessed at baseline, after three months and after six months from baseline in order to evaluate the possible changes in: (1) GI symptoms; (2) autism symptoms severity; (3) affective and behavioral comorbid symptoms; (4) plasmatic, urinary and fecal biomarkers related to abnormal intestinal function; (5) neurophysiological patterns. DISCUSSION: The effects of treatments with probiotics on children with ASD need to be evaluated through rigorous controlled trials. Examining the impact of probiotics not only on clinical but also on neurophysiological patterns, the current trial sets out to provide new insights into the gut-brain connection in ASD patients. Moreover, results could add information to the relationship between phthalates levels, clinical features and neurophysiological patterns in ASD. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02708901 . Retrospectively registered: March 4, 2016.
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13. Schneider M, de Vries PJ, Schonig K, Rossner V, Waltereit R. {{mTOR inhibitor reverses autistic-like social deficit behaviours in adult rats with both Tsc2 haploinsufficiency and developmental status epilepticus}}. {Eur Arch Psychiatry Clin Neurosci};2016 (Jun 4)
Epilepsy is a major risk factor for autism spectrum disorder (ASD) and complicates clinical manifestations and management of ASD significantly. Tuberous sclerosis complex (TSC), caused by TSC1 or TSC2 mutations, is one of the medical conditions most commonly associated with ASD and has become an important model to examine molecular pathways associated with ASD. Previous research showed reversal of autism-like social deficits in Tsc1 +/- and Tsc2 +/- mouse models by mammalian target of rapamycin (mTOR) inhibitors. However, at least 70 % of individuals with TSC also have epilepsy, known to complicate the severity and treatment responsiveness of the behavioural phenotype. No previous study has examined the impact of seizures on neurocognitive reversal by mTOR inhibitors. Adult Tsc2 +/- (Eker)-rats express social deficits similar to Tsc2 +/- mice, with additive social deficits from developmental status epilepticus (DSE). DSE was induced by intraperitoneal injection with kainic acid at post-natal days P7 and P14 (n = 12). The experimental group that modelled TSC pathology carried the Tsc2 +/- (Eker)-mutation and was challenged with DSE. The wild-type controls had not received DSE (n = 10). Four-month-old animals were analysed for social behaviour (T1), then treated three times during 1 week with 1 mg/kg everolimus and finally retested in the post-treatment behavioural analysis (T2). In the experimental group, both social interaction and social cognition were impaired at T1. After treatment at T2, behaviour in the experimental group was indistinguishable from controls. The mTOR inhibitor, everolimus, reversed social deficit behaviours in the Tsc2 haploinsufficiency plus DSE animal model to control levels.
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14. Ward B, Tanner BS, Mandleco B, Dyches TT, Freeborn D. {{Sibling Experiences: Living with Young Persons with Autism Spectrum Disorders}}. {Pediatr Nurs};2016 (Mar-Apr);42(2):69-76.
Like other young people, those with autism spectrum disorder (ASD) have an impact on siblings in both positive and negative ways. Research indicates positive attributes include maturity and responsibility; positive self-concept; less quarrelling and competition; admiration for the person with ASD; and satisfactory sibling relationships. Negative attributes include fear of frightening or violent behavior, decreased sibling intimacy, and social and emotional difficulties. However, most research relies on information from parents/teachers, rather than from siblings. Therefore, this qualitative descriptive study explored experiences of 11 brothers and 11 sisters living with a young person with ASD through audiorecorded semi-structured interviews. Analysis revealed the overall theme was contradiction. Participants recognized difficulties (decreased parental attention, extra responsibility, bothersome behaviors, communication difficulties) and positive aspects (became empathetic, loved and appreciated the child, realized the experience was life-changing) of living with a young person with ASD. Younger siblings frequently reflected on childhood experiences, wished they could play together, and mentioned what the young person could do. Adolescent siblings learned life lessons from the experience, talked about life changes when ASD was diagnosed, and seemed introspective and protective toward the young person with ASD. Male siblings often wished they played more often while growing up with the young person, and frequently mentioned the child/adolescent’s aggressive behaviors; female siblings focused on relationship and communication difficulties of the young person ASD. Interventions to help siblings provide positive behavioral support, engage in developmentally appropriate play, and communicate reciprocally are warranted. Nurses can help parents understand siblings’ perceptions and can encourage parents to support siblings.
15. Yang EJ, Ahn S, Lee K, Mahmood U, Kim HS. {{Correction: Early Behavioral Abnormalities and Perinatal Alterations of PTEN/AKT Pathway in Valproic Acid Autism Model Mice}}. {PLoS One};2016;11(6):e0157202.
[This corrects the article DOI: 10.1371/journal.pone.0153298.].
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16. Zheng Z, Zhang L, Zhu T, Huang J, Qu Y, Mu D. {{Association between Asthma and Autism Spectrum Disorder: A Meta-Analysis}}. {PLoS One};2016;11(6):e0156662.
OBJECTIVE: We conducted a meta-analysis to summarize the evidence from epidemiological studies of the association between asthma and autism spectrum disorder (ASD). METHODS: A literature search was conducted using PubMed, Embase, and Cochrane library for studies published before February 2nd, 2016. Observational studies investigating the association between asthma and ASD were included. A random effects model was used to calculate the pooled risk estimates for the outcome. Subgroup analysis was used to explore potential sources of heterogeneity and publication bias was estimated using Begg’s and Egger’s tests. RESULTS: Ten studies encompassing 175,406 participants and 8,809 cases of ASD were included in this meta-analysis. In the cross-sectional studies, the prevalence of asthma in ASD was 20.4%, while the prevalence of asthma in controls was 15.4% (P < 0.001). The pooled odds ratio (OR) for the prevalence of asthma in ASD in the cross-sectional studies was 1.26 (95% confidence interval (CI): 0.98-1.61) (P = 0.07), with moderate heterogeneity (I2 = 65.0%, P = 0.02) across studies. In the case-control studies, the pooled OR for the prevalence of asthma in ASD was 0.98 (95% CI: 0.68-1.43) (P = 0.94), and there was no evidence of an association between asthma and ASD. No evidence of significant publication bias on the association between asthma and ASD was found. CONCLUSIONS: In conclusion, the results of this meta-analysis do not suggest an association between asthma and ASD. Further prospective studies ascertaining the association between asthma and ASD are warranted. Lien vers le texte intégral (Open Access ou abonnement)
