1. An KM, Ikeda T, Yoshimura Y, Hasegawa C, Saito DN, Kumazaki H, Hirosawa T, Minabe Y, Kikuchi M. {{Altered Gamma Oscillations during Motor Control in Children with Autism Spectrum Disorder}}. {J Neurosci};2018 (Sep 5);38(36):7878-7886.
Autism is hypothesized to result in a cortical excitatory and inhibitory imbalance driven by inhibitory interneuron dysfunction, which is associated with the generation of gamma oscillations. On the other hand, impaired motor control has been widely reported in autism. However, no study has focused on the gamma oscillations during motor control in autism. In the present study, we investigated the motor-related gamma oscillations in autism using magnetoencephalography. Magnetoencephalographic signals were recorded from 14 right-handed human children with autism (5 female), aged 5-7 years, and age- and IQ-matched 15 typically developing children during a motor task using their right index finger. Consistent with previous studies, the autism group showed a significantly longer button response time and reduced amplitude of motor-evoked magnetic fields. We observed that the autism group exhibited a low peak frequency of motor-related gamma oscillations from the contralateral primary motor cortex, and these were associated with the severity of autism symptoms. The autism group showed a reduced power of motor-related gamma oscillations in the bilateral primary motor cortex. A linear discriminant analysis using the button response time and gamma oscillations showed a high classification performance (86.2% accuracy). The alterations of the gamma oscillations in autism might reflect the cortical excitatory and inhibitory imbalance. Our findings provide an important clue into the behavioral and neurophysiological alterations in autism and a potential biomarker for autism.SIGNIFICANCE STATEMENT Currently, the diagnosis of autism has been based on behavioral assessments, and a crucial issue in the diagnosis of autism is to identify objective and quantifiable clinical biomarkers. A key hypothesis of the neurophysiology of autism is an excitatory and inhibitory imbalance in the brain, which is associated with the generation of gamma oscillations. On the other hand, motor deficits have also been widely reported in autism. This is the first study to demonstrate low motor performance and altered motor-related gamma oscillations in autism, reflecting a brain excitatory and inhibitory imbalance. Using these behavioral and neurophysiological parameters, we classified autism and control group with good accuracy. This work provides important information on behavioral and neurophysiological alterations in patients with autism.
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2. Bosco P, Giuliano A, Delafield-Butt J, Muratori F, Calderoni S, Retico A. {{Brainstem enlargement in preschool children with autism: Results from an intermethod agreement study of segmentation algorithms}}. {Hum Brain Mapp};2018 (Sep 5)
The intermethod agreement between automated algorithms for brainstem segmentation is investigated, focusing on the potential involvement of this structure in Autism Spectrum Disorders (ASD). Inconsistencies highlighted in previous studies on brainstem in the population with ASD may in part be a result of poor agreement in the extraction of structural features between different methods. A sample of 76 children with ASD and 76 age-, gender-, and intelligence-matched controls was considered. Volumetric analyses were performed using common tools for brain structures segmentation, namely FSL-FIRST, FreeSurfer (FS), and Advanced Normalization Tools (ANTs). For shape analysis SPHARM-MAT was employed. Intermethod agreement was quantified in terms of Pearson correlations between pairs of volumes obtained by the different methods. The degree of overlap between segmented masks was quantified in terms of the Dice index. Both Pearson correlations and Dice indices, showed poor agreement between FSL-FIRST and the other methods (ANTs and FS), which by contrast, yielded Pearson correlations greater than 0.93 and average Dice indices greater than 0.76 when compared with each other. As with volume, shape analyses exhibited discrepancies between segmentation methods, with particular differences noted between FSL-FIRST and the others (ANT and FS), with under- and over-segmentation in specific brainstem regions. These data suggest that research on brain structure alterations should cross-validate findings across multiple methods. We consistently detected an enlargement of brainstem volume in the whole sample and in the male cohort across multiple segmentation methods, a feature particularly driven by the subgroup of children with idiopathic intellectual disability associated with ASD.
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3. Hergersberg M. {{A fascinating overview of the biology of fragile X syndrome}}. {Eur J Hum Genet};2018 (Sep 3)
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4. Hollocks MJ, Lerh JW, Magiati I, Meiser-Stedman R, Brugha TS. {{Anxiety and depression in adults with autism spectrum disorder: a systematic review and meta-analysis}}. {Psychol Med};2018 (Sep 4):1-14.
Adults with autism spectrum disorder (ASD) are thought to be at disproportionate risk of developing mental health comorbidities, with anxiety and depression being considered most prominent amongst these. Yet, no systematic review has been carried out to date to examine rates of both anxiety and depression focusing specifically on adults with ASD. This systematic review and meta-analysis examined the rates of anxiety and depression in adults with ASD and the impact of factors such as assessment methods and presence of comorbid intellectual disability (ID) diagnosis on estimated prevalence rates. Electronic database searches for studies published between January 2000 and September 2017 identified a total of 35 studies, including 30 studies measuring anxiety (n = 26 070; mean age = 30.9, s.d. = 6.2 years) and 29 studies measuring depression (n = 26 117; mean age = 31.1, s.d. = 6.8 years). The pooled estimation of current and lifetime prevalence for adults with ASD were 27% and 42% for any anxiety disorder, and 23% and 37% for depressive disorder. Further analyses revealed that the use of questionnaire measures and the presence of ID may significantly influence estimates of prevalence. The current literature suffers from a high degree of heterogeneity in study method and an overreliance on clinical samples. These results highlight the importance of community-based studies and the identification and inclusion of well-characterized samples to reduce heterogeneity and bias in estimates of prevalence for comorbidity in adults with ASD and other populations with complex psychiatric presentations.
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5. Lee S, Chun HS, Lee J, Park HJ, Kim KT, Kim CH, Yoon S, Kim WK. {{Plausibility of the zebrafish embryos/larvae as an alternative animal model for autism: A comparison study of transcriptome changes}}. {PLoS One};2018;13(9):e0203543.
Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder characterized by impaired or abnormal social interaction and communication and by restricted and repetitive behaviour. ASD is highly prevalent in Asia, Europe, and the United States, and the frequency of ASD is growing each year. Recent epidemiological studies have indicated that ASD may be caused or triggered by exposure to chemicals in the environment, such as those in the air or water. Thus, toxicological studies are needed to examine chemicals that might be implicated. However, the experimental efficiency of existing experimental models is limited, and many models represent challenges in terms of animal welfare. Thus, alternative ASD animal models are necessary. To address this, we examined the efficacy of the zebrafish embryo/larva as an alternative model of ASD. Specifically, we exposed zebrafish to valproic acid (0, 12.5, 25, 50, or 100 muM), which is a chemical known to induce autism-like effects. We then analysed subsequent developmental, behavioural, and transcriptomic changes. We found that 100 muM and 50 muM valproic acid decreased the hatching rate and locomotor activity of zebrafish embryos/larvae. Transcriptomic analysis revealed significant alterations in a number of genes associated with autism, such as adsl, mbd5, shank3, and tsc1b. Additionally, we found changes in gene ontology that were also reported in previous studies. Our findings indicate that zebrafish embryos/larvae and humans with ASD might have common physiological pathways, indicating that this animal model may represent an alternative tool for examining the causes of and potential treatments for this illness.
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6. Marchezan J, Winkler Dos Santos EGA, Deckmann I, Riesgo RDS. {{Immunological Dysfunction in Autism Spectrum Disorder: A Potential Target for Therapy}}. {Neuroimmunomodulation};2018 (Sep 5):1-20.
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with an unknown etiology and currently few effective therapies. Immune system alterations have being demonstrated in ASD, both in humans and via animal models; immune imbalance thus arises as a possible pathway for drug intervention. In this review, the studies were classified into 2 major groups: (1) clinical research whose authors classify therapies with primary anti-inflammatory and immunomodulatory actions, making use of: sulforaphane, celecoxib, lenalidomide, pentoxifylline, spironolactone, flavonoid luteolin, corticosteroids, oral immunoglobulin, intravenous immunoglobulin, cell therapy, dialyzable lymphocyte extracts, minocycline, and pioglitazone; and (2) other ASD therapies already used or currently under study whose initial characteristics were neither anti-inflammatory nor immunomodulatory initially, but displayed a capacity for immunomodulation throughout the treatment: risperidone, vitamin D, omega-3, Ginkgo biloba, L-carnosine, N-acetylcysteine, and microbiome restoration. These studies used various data acquisition methodologies. Questions arose such the need for randomized and placebo-controlled studies with greater numbers of participants as well as the use of biomarkers to refine the treatment of autistic subjects.
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7. Masiran R. {{Autism and trichotillomania in an adolescent boy}}. {BMJ Case Rep};2018 (Sep 5);2018
An adolescent with autism spectrum disorder and improperly treated attention deficit hyperactivity disorder presented with recurrent hair pulling. Treatment with selective serotonin reuptake inhibitor and stimulant improved these conditions.
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8. Napoli E, Schneider A, Wang JY, Trivedi A, Carrillo NR, Tassone F, Rogawski M, Hagerman RJ, Giulivi C. {{Allopregnanolone Treatment Improves Plasma Metabolomic Profile Associated with GABA Metabolism in Fragile X-Associated Tremor/Ataxia Syndrome: a Pilot Study}}. {Mol Neurobiol};2018 (Sep 5)
Currently, there is no effective treatment for the fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset neurodegenerative disorder. In this pilot study, we evaluated whether allopregnanolone, a natural neurosteroid that exerts beneficial effects in neurodegenerative diseases, nervous system injury, and peripheral neuropathies, could improve lymphocytic bioenergetics and plasma pharmacometabolomics in six males with FXTAS (68 +/- 3 years old; FMR1 CGG repeats 94 +/- 4; FXTAS stages ranging from 3 to 5) enrolled in a 12-week open-label intervention study conducted at the University of California Davis from December 2015 through July 2016. Plasma pharmacometabolomics and lymphocytic mitochondria function were assessed at baseline (on the day of the first infusion) and at follow-up (within 48 h from the last infusion). In parallel, quantitative measurements of tremor and ataxia and neuropsychological evaluations of mental state, executive function, learning, memory, and psychological symptoms were assessed at the same time points. Allopregnanolone treatment impacted significantly GABA metabolism, oxidative stress, and some of the mitochondria-related outcomes. Notably, the magnitude of the individual metabolic response, as well as the correlation with some of the behavioral tests, was overwhelmingly carrier-specific. Based on this pilot study, allopregnanolone treatment has the potential for improving cognitive and GABA metabolism in FXTAS aligned with the concept of precision medicine.
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9. Rubenstein E, Bishop-Fitzpatrick L. {{A Matter of Time: The Necessity of Temporal Language in Research on Health Conditions that Present with Autism Spectrum Disorder}}. {Autism Res};2018 (Sep 5)
Relatively consistent findings from recent studies using population-level data identify heightened physical and psychiatric morbidity in autistic people compared to the general population. Health problems that commonly present with autism spectrum disorder (ASD) are generally discussed in the literature as « co-occurring » or « comorbid » regardless of their known or hypothesized causal mechanisms. In this commentary, we introduce a new temporally focused terminology to describe health conditions that present with ASD. Emphasizing the temporal development of health conditions in research will help the field understand whether conditions are (1) « truly co-occurring » (share an etiologic origin with ASD in utero and are a defining characteristic of a subphenotype), (2) « resulting » (caused by ASD related disparity or the health effect of behaviors developed to cope with ASD symptoms), or (3) « associated » (conditions more common in individuals with ASD with etiology not yet known or hypothesized, or an artifact of diagnostic process or trends). Whether a health condition is « truly co-occurring », « resulting », or « associated » has implications for how we design interventions to prevent and treat health conditions in people on the autism spectrum. Ultimately, we think that using clear and temporally focused language can set us on a path to better deduce etiology and develop effective prevention and intervention efforts for health conditions that impact the lives of autistic individuals. We hope that this approach to temporal language to describe health conditions that present with ASD promotes thought and discussion in research, advocate, and autistic communities. Autism Res 2018. (c) 2018 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Research finds autistic people have more health problems than the general population but we do not understand why. In this commentary, we argue researchers need to use language describing the timing of health problems in autistic people, specifying whether problems truly co-occur (share a cause), result from autism-related disparities, or are more common in autistic people for an unknown reason. Clarifying language can provide more specificity in research and improve efforts to prevent and treat health problems in autistic people.
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10. Shivers CM, Jackson JB, McGregor CM. {{Functioning Among Typically Developing Siblings of Individuals with Autism Spectrum Disorder: A Meta-Analysis}}. {Clin Child Fam Psychol Rev};2018 (Sep 3)
The literature on typically developing siblings of individuals with autism spectrum disorder (ASD-Sibs) provides inconsistent results, with some studies reporting ASD-Sibs are more likely to have negative outcomes than comparison groups, and others reporting no significant differences. Therefore, the purpose of this study was to meta-analytically aggregate study effect sizes to more accurately calculate the degree to which ASD-Sibs function similarly or differently compared to siblings of people who do not have ASD. Studies were eligible for inclusion if they had a sample of ASD-Sibs older than 5; reported on emotional, psychological, behavioral, or social functioning; and provided information necessary for calculating relevant effect sizes. Results from 69 independent samples indicated that ASD-Sibs have significantly more negative outcomes than comparison groups overall (g = – 0.26); specific areas of functioning in which ASD-Sibs fared worse include internalizing behavior problems, psychological functioning, beliefs, social functioning, and the sibling relationship, but no significant differences in adjustment, attention/hyperactivity, externalizing behavior problems, coping, or family functioning. Noteworthy sub-areas of functioning in which ASD-Sibs also fared worse included beliefs about disability (g = – 0.56), anxiety symptoms (g = – 0.25), and depression symptoms (g = – 0.36). In terms of comparison group, ASD-Sibs had significantly lower functioning than siblings of individuals with other intellectual and developmental disabilities (g = – 0.31), including Down syndrome (g = – 0.40) and siblings of individuals without any disabilities (g = – 0.31). Clinicians and service providers should work to ensure that ASD-Sibs are included in family interventions and support strategies, and researchers should further explore individual differences that may relate to enhanced or impaired functioning in ASD-Sibs.
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11. Siegel M. {{The Severe End of the Spectrum: Insights and Opportunities from the Autism Inpatient Collection (AIC)}}. {J Autism Dev Disord};2018 (Sep 3)
Research on individuals severely affected by autism, including those who are minimally verbal, have intellectual disability or challenging behaviors, has become less common. The Autism Inpatient Collection (AIC) was initiated so data on this group is available to the research community. Ten studies utilizing phenotypic data from the first 350 AIC participants are presented. Greater autism severity, sleep disturbance, and psychiatric disorders are risks for hospitalization; fluently verbal youth experience more depression and oppositional symptoms; lower adaptive/coping skills are associated with increased problem behaviors; lower IQ is a risk for SIB; post-traumatic and suicidal symptoms are common; and challenging behaviors improve with specialized inpatient treatment. A new measure of emotion regulation and prescribing practices are described and future research discussed.
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12. Vargason T, McGuinness DL, Hahn J. {{Gastrointestinal Symptoms and Oral Antibiotic Use in Children with Autism Spectrum Disorder: Retrospective Analysis of a Privately Insured U.S. Population}}. {J Autism Dev Disord};2018 (Sep 3)
A retrospective analysis of administrative claims data from a large U.S. health insurer was performed to study a potential association between oral antibiotic use during early childhood and occurrence of later gastrointestinal (GI) symptoms in children with autism spectrum disorder (ASD). Among 3253 children with ASD, 37.0% had a GI-related diagnosis during the last 2 years of their 5-year health coverage enrollment period, compared to 20.0% of 278,370 children from the general population without an ASD diagnosis. Greater numbers of oral antibiotic fills during the first 3 years of enrollment were found to significantly increase the hazard rate of having a later GI-related diagnosis (adjusted hazard ratio 1.48; 95% confidence interval 1.34, 1.63) in children both with and without ASD.
