1. Anshu K, Nair AK, Kumaresan UD, Kutty BM, Srinath S, Laxmi TR. {{Altered attentional processing in male and female rats in a prenatal valproic acid exposure model of autism spectrum disorder}}. {Autism Res}. 2017.
Attention is foundational to efficient perception and optimal goal driven behavior. Intact attentional processing is crucial for the development of social and communication skills. Deficits in attention are therefore likely contributors to the core pathophysiology of autism spectrum disorder (ASD). Clinical evidence in ASD is suggestive of impairments in attention and its control, but the underlying mechanisms remain elusive. We examined sustained, spatially divided attention in a prenatal valproic acid (VPA) model of ASD using the 5-choice serial reaction time task (5-CSRTT). As compared to controls, male and female VPA rats had progressively lower accuracy and higher omissions with increasing attentional demands during 5-CSRTT training, and showed further performance decrements when subjected to parametric task manipulations. It is noteworthy that although VPA exposure induced attentional deficits in both sexes, there were task parameter specific sex differences. Importantly, we did not find evidence of impulsivity or motivational deficits in VPA rats but we did find reduced social preference, as well as sensorimotor deficits that suggest pre-attentional information processing impairments. Importantly, with fixed rules, graded difficulty levels, and more time, VPA rats could be successfully trained on the attentional task. To the best of our knowledge, this is the first study examining attentional functions in a VPA model. Our work underscores the need for studying both sexes in ASD animal models and validates the use of the VPA model in the quest for mechanistic understanding of aberrant attentional functions and for evaluating suitable therapeutic targets. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We studied rats prenatally exposed to valproic acid (VPA), an established rodent model of autism. Both male and female VPA rats had a range of attentional impairments with sex-specific characteristics. Importantly, with fixed rules, graded difficulty levels, and more time, VPA rats could be successfully trained on the attentional task. Our work validates the use of the VPA model in the quest for evaluating suitable therapeutic targets for improving attentional performance.
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2. de la Batie CD, Barbier V, Roda C, Brassier A, Arnoux JB, Valayannopoulos V, Guemann AS, Pontoizeau C, Gobin S, Habarou F, Lacaille F, Bonnefont JP, Canoui P, Ottolenghi C, De Lonlay P, Ouss L. {{Autism spectrum disorders in propionic acidemia patients}}. {J Inherit Metab Dis}. 2017.
Propionic acidemia is the result of a deficiency in propionyl-CoA carboxylase activity. Chronic neurologic and cognitive complications frequently occur, but the psychiatric evolution of the disorder is not well documented. We conducted a pedopsychiatric evaluation of 19 children, adolescents and young adults, aged between 2 and 25 years, using ADI-R, CARS-T, as well as ADOS when autism spectrum disorder was suspected. Previous psychometric examinations were also taken into consideration. Thirteen patients had an IQ < 80. Two patients presented with autism and two additional patients with other autism spectrum disorders. Five patients did not fulfill diagnostic criteria for autism spectrum disorder but showed difficulties indicative of a broader autism phenotype (BAP). Four other patients had severe anxiety manifestations related to their disease. Two patients presented with acute psychotic episodes. The number of decompensations in the first 3 years of life was lower in patients with autism spectrum disorder or related symptoms. These patients were also older when they were assessed (median age of 15 years old versus 11 years old). There was no significant correlation between 3-hydroxypropionate levels during the first 6 years of life and autism spectrum disorder diagnosis. In conclusion, autism spectrum disorder is frequent in patients with propionic acidemia. These patients should undergo in-depth psychiatric evaluation and be screened for autism spectrum disorder. Further studies are needed to understand the underlying mechanisms. Lien vers le texte intégral (Open Access ou abonnement)
3. Goin-Kochel RP, Trinh S, Barber S, Bernier R. {{Gene Disrupting Mutations Associated with Regression in Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2017.
Approximately one-third of children with autism spectrum disorder (ASD) reportedly lose skills within the first 3 years, yet a causal mechanism remains elusive. Considering evidence of strong genetic effects for ASD and findings that distinct phenotypes in ASD associate with specific genetic events, we examined rates of parent-reported regression in the Simons Simplex Collection with likely gene disrupting mutations from five distinct classes: FMRP target genes, genes encoding chromatin modifiers, genes expressed preferentially in embryos, genes encoding postsynaptic density proteins, and essential genes. Children with ASD and mutations in postsynaptic density genes were more likely to experience regression, while a trend suggested that children with ASD and mutations in embryonic genes were less likely to have skill losses.
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4. Holingue C, Newill C, Lee LC, Pasricha PJ, Daniele Fallin M. {{Gastrointestinal symptoms in autism spectrum disorder: A review of the literature on ascertainment and prevalence}}. {Autism Res}. 2017.
There is no standard approach to measuring GI symptoms in individuals with ASD, despite postulated interactions. The objectives of this study were to (a) describe the range of GI symptom ascertainment approaches in studies of ASD, (b) describe the range of prevalence estimates across studies, and (c) assess associations between ascertainment approach and prevalence estimates. Studies published from 1/1/1980 to 1/31/2017 were collected via PubMed. Eligibility included studies with at least ten individuals with ASD that measured GI symptoms or conditions. We excluded review and hypothesis papers. We extracted information on study design, GI symptom ascertainment method, demographics, and ASD diagnostic criteria. From a subset of studies, we extracted GI symptom estimates. Out of a possible 386 titles, 144 were included. The prevalence range for constipation was 4.3-45.5% (median 22%), for diarrhea was 2.3-75.6% (median 13.0%), and for any or more than one symptom was 4.2-96.8% (median 46.8%). GI symptoms differed significantly by age of individuals, primary goal of study, study design, study sample, and who reported symptoms (P < .05). Due to small sample size, we were not able to test for associations between every GI symptom and study characteristic of interest, or examine associations between GI symptoms and intellectual or verbal disability. Studies used a broad range of methods to ascertain GI symptoms in ASD. GI symptoms varied widely across these studies, with significant differences by study characteristics. Our findings highlight the need for a reliable, valid GI assessment tool to be used consistently across studies of ASD. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: We reviewed studies having to do with autism spectrum disorder and the gastrointestinal system, dating back to 1980. We found that the median prevalence of constipation was 22.2%, diarrhea 13.0%, and any symptom 46.8%. All symptoms had a wide range of estimates across studies. GI symptoms were associated with characteristics of the study, including who measured the GI symptoms. We call for the development of a reliable and valid GI questionnaire for studies of ASD. Lien vers le texte intégral (Open Access ou abonnement)
5. Kalikiri MK, Mamidala MP, Rao AN, Rajesh V. {{Analysis and functional characterization of sequence variations in ligand binding domain of thyroid hormone receptors in autism spectrum disorder (ASD) patients}}. {Autism Res}. 2017.
Autism spectrum disorder (ASD) is a neuro developmental disorder, reported to be on a rise in the past two decades. Thyroid hormone-T3 plays an important role in early embryonic and central nervous system development. T3 mediates its function by binding to thyroid hormone receptors, TRalpha and TRbeta. Alterations in T3 levels and thyroid receptor mutations have been earlier implicated in neuropsychiatric disorders and have been linked to environmental toxins. Limited reports from earlier studies have shown the effectiveness of T3 treatment with promising results in children with ASD and that the thyroid hormone levels in these children was also normal. This necessitates the need to explore the genetic variations in the components of the thyroid hormone pathway in ASD children. To achieve this objective, we performed genetic analysis of ligand binding domain of THRA and THRB receptor genes in 30 ASD subjects and in age matched controls from India. Our study for the first time reports novel single nucleotide polymorphisms in the THRA and THRB receptor genes of ASD individuals. Autism Res 2017. (c)2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Thyroid hormone (T3) and thyroid receptors (TRalpha and TRbeta) are the major components of the thyroid hormone pathway. The link between thyroid pathway and neuronal development is proven in clinical medicine. Since the thyroid hormone levels in Autistic children are normal, variations in their receptors needs to be explored. To achieve this objective, changes in THRA and THRB receptor genes was studied in 30 ASD and normal children from India. The impact of some of these mutations on receptor function was also studied.
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6. Matthews NL, Malligo A, Smith CJ. {{Toward the identification of adaptive functioning intervention targets for intellectually-able, transition-aged youth with autism: An examination of caregiver responses on the Vineland-II}}. {Autism Res}. 2017.
Little is known about specific adaptive functioning impairments in intellectually-able individuals with autism spectrum disorder. In adolescents (n = 22) and young adults (n = 22) matched on composite IQ scores, this study examined profiles of cognitive and adaptive functioning, and caregiver responses on individual Vineland-II items. Adaptive functioning standard scores were significantly lower than IQ scores, and the adult group had significantly lower adaptive functioning standard scores than the adolescent group. Examination of caregiver responses to individual Vineland-II items identified more than 100 potential intervention targets. Differences favoring the adult group were observed on only 16 items across all three adaptive functioning domains, suggesting that little skill development is occurring during the transition to adulthood. Future research will examine the relevance of identified intervention targets to optimal outcomes. Autism Res 2017,. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: Adolescents and young adults with autism spectrum disorder (ASD) without intellectual disability demonstrated impaired adaptive functioning skills (i.e., age appropriate skills necessary for independent living). Development of adaptive functioning skills appears to slow with age among individuals without intellectual disability. Findings clarify the specific adaptive functioning skills that transition-aged youth with ASD have difficulty completing independently and will inform the development of interventions to increase the likelihood of independent living in adulthood.
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7. May T, Pang KC, O’Connell MA, Williams K. {{Typical Pubertal Timing in an Australian Population of Girls and Boys with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2017.
Secondary data analyses from the Longitudinal Study of Australian Children Kindergarten cohort were performed to understand any alterations in pubertal timing in Autism Spectrum Disorder (ASD) in a population sample. Timing of parent-reported pubertal events (ages 8-9, 10-11, 12-13 years), and self-report (14-15 years; N = 3454 no ASD, N = 94 with ASD) included breast development, menses, skin changes, growth spurt, body hair, deepening voice and facial hair. Survival analyses and Cox regression controlling for covariates showed no evidence of altered pubertal onset amongst males with ASD. In contrast to some past studies, there was also no difference in pubertal timing in females with ASD. These exploratory findings suggest typical puberty timing in a population representative group of young people with ASD.
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8. Moody EJ, Reyes N, Ledbetter C, Wiggins L, DiGuiseppi C, Alexander A, Jackson S, Lee LC, Levy SE, Rosenberg SA. {{Screening for Autism with the SRS and SCQ: Variations across Demographic, Developmental and Behavioral Factors in Preschool Children}}. {J Autism Dev Disord}. 2017.
The Social Communication Questionnaire (SCQ) and the Social Responsiveness Scales (SRS) are commonly used screeners for autism spectrum disorder (ASD). Data from the Study to Explore Early Development were used to examine variations in the performance of these instruments by child characteristics and family demographics. For both instruments, specificity decreased as maternal education and family income decreased. Specificity was decreased with lower developmental functioning and higher behavior problems. This suggests that the false positive rates of the SRS and the SCQ are associated with child characteristics and family demographic factors. There is a need for ASD screeners that perform well across socioeconomic and child characteristics. Clinicians should be mindful of differential performance of these instruments in various groups of children.
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9. Muratori F, Tonacci A, Billeci L, Catalucci T, Igliozzi R, Calderoni S, Narzisi A. {{Erratum to: Olfactory Processing in Male Children with Autism: Atypical Odor Threshold and Identification}}. {J Autism Dev Disord}. 2017.
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10. Tonnsen B, Scherr J, Reisinger D, Roberts J. {{Behavioral Markers of Emergent Stranger Anxiety in Infants and Toddlers with Fragile X Syndrome}}. {J Autism Dev Disord}. 2017.
Studying anxiety in neurogenetic syndromes may inform the intersection of biological and developmental risks, facilitating effective and targeted interventions. We longitudinally examined stranger fear in infants and toddlers with fragile X syndrome (FXS; n = 46) and typical controls (n = 33), as well as associations between observed stranger fear and rating scales of anxiety, withdrawal and autism features within FXS. Results indicated atypical facial fear in FXS, although facial fear did not index anxiety, autistic symptoms or social withdrawal. Instead, lower withdrawal was associated with decreased distress vocalizations across age, and higher autistic symptoms were associated with lower intensity escape behaviors. Early stranger fear in FXS reflects both typical and atypical dimensions and may help index emergence of social anxiety in this population.
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11. Wolfenden C, Wittkowski A, Hare DJ. {{Symptoms of Autism Spectrum Disorder (ASD) in Individuals with Mucopolysaccharide Disease Type III (Sanfilippo Syndrome): A Systematic Review}}. {J Autism Dev Disord}. 2017.
The prevalence of autism spectrum disorder (ASD) in many genetic disorders is well documented but not as yet in Mucopolysaccharidosis type III (MPS III). MPS III is a recessively inherited metabolic disorder and evidence suggests that symptoms of ASD present in MPS III. This systematic review examined the extant literature on the symptoms of ASD in MPS III and quality assessed a total of 16 studies. Results indicated that difficulties within speech, language and communication consistent with ASD were present in MPS III, whilst repetitive and restricted behaviours and interests were less widely reported. The presence of ASD-like symptoms can result in late diagnosis or misdiagnosis of MPS III and prevent opportunities for genetic counselling and the provision of treatments.
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12. Thiemann-Bourque KS, McGuff S, Goldstein H. {{Training Peer Partners to Use a Speech-Generating Device With Classmates With Autism Spectrum Disorder: Exploring Communication Outcomes Across Preschool Contexts}}. {J Speech Lang Hear Res}. 2017: 1-15.
Purpose: This study examined effects of a peer-mediated intervention that provided training on the use of a speech-generating device for preschoolers with severe autism spectrum disorder (ASD) and peer partners. Method: Effects were examined using a multiple probe design across 3 children with ASD and limited to no verbal skills. Three peers without disabilities were taught to Stay, Play, and Talk using a GoTalk 4+ (Attainment Company) and were then paired up with a classmate with ASD in classroom social activities. Measures included rates of communication acts, communication mode and function, reciprocity, and engagement with peers. Results: Following peer training, intervention effects were replicated across 3 peers, who all demonstrated an increased level and upward trend in communication acts to their classmates with ASD. Outcomes also revealed moderate intervention effects and increased levels of peer-directed communication for 3 children with ASD in classroom centers. Additional analyses revealed higher rates of communication in the added context of preferred toys and snack. The children with ASD also demonstrated improved communication reciprocity and peer engagement. Conclusions: Results provide preliminary evidence on the benefits of combining peer-mediated and speech-generating device interventions to improve children’s communication. Furthermore, it appears that preferred contexts are likely to facilitate greater communication and social engagement with peers.
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13. Park E, Cohen I, Gonzalez M, Castellano MR, Flory M, Jenkins EC, Brown WT, Schuller-Levis G. {{Is Taurine a Biomarker in Autistic Spectrum Disorder?}}. {Adv Exp Med Biol}. 2017; 975: 3-16.
Taurine is a sulfur-containing amino acid which is not incorporated into protein. However, taurine has various critical physiological functions including development of the eye and brain, reproduction, osmoregulation, and immune functions including anti-inflammatory as well as anti-oxidant activity. The causes of autistic spectrum disorder (ASD) are not clear but a high heritability implicates an important role for genetic factors. Reports also implicate oxidative stress and inflammation in the etiology of ASD. Thus, taurine, a well-known antioxidant and regulator of inflammation, was investigated here using the sera from both girls and boys with ASD as well as their siblings and parents. Previous reports regarding taurine serum concentrations in ASD from various laboratories have been controversial. To address the potential role of taurine in ASD, we collected sera from 66 children with ASD (males: 45; females: 21, age 1.5-11.5 years, average age 5.2 +/- 1.6) as well as their unaffected siblings (brothers: 24; sisters: 32, age 1.5-17 years, average age 7.0 +/- 2.0) as controls of the children with ASD along with parents (fathers: 49; mothers: 54, age 28-45 years). The sera from normal adult controls (males: 47; females: 51, age 28-48 years) were used as controls for the parents. Taurine concentrations in all sera samples were measured using high performance liquid chromatography (HPLC) using a phenylisothiocyanate labeling technique. Taurine concentrations from female and male children with ASD were 123.8 +/- 15.2 and 145.8 +/- 8.1 muM, respectively, and those from their unaffected brothers and sisters were 142.6 +/- 10.4 and 150.8 +/- 8.4 muM, respectively. There was no significant difference in taurine concentration between autistic children and their unaffected siblings. Taurine concentrations in children with ASD were also not significantly different from their parents (mothers: 139.6 +/- 7.7 muM, fathers: 147.4 +/- 7.5 muM). No significant difference was observed between adult controls and parents of ASD children (control females: 164.8 +/- 4.8 muM, control males: 163.0 +/- 7.0 muM). However, 21 out of 66 children with ASD had low taurine concentrations (<106 muM). Since taurine has anti-oxidant activity, children with ASD with low taurine concentrations will be examined for abnormal mitochondrial function. Our data imply that taurine may be a valid biomarker in a subgroup of ASD. Lien vers le texte intégral (Open Access ou abonnement)
14. Yamaguchi H, Hara Y, Ago Y, Takano E, Hasebe S, Nakazawa T, Hashimoto H, Matsuda T, Takuma K. {{Environmental enrichment attenuates behavioral abnormalities in valproic acid-exposed autism model mice}}. {Behav Brain Res}. 2017; 333: 67-73.
We recently demonstrated that prenatal exposure to valproic acid (VPA) at embryonic day 12.5 causes autism spectrum disorder (ASD)-like phenotypes such as hypolocomotion, anxiety-like behavior, social deficits and cognitive impairment in mice and that it decreases dendritic spine density in the hippocampal CA1 region. Previous studies show that some abnormal behaviors are improved by environmental enrichment in ASD rodent models, but it is not known whether environmental enrichment improves cognitive impairment. In the present study, we examined the effects of early environmental enrichment on behavioral abnormalities and neuromorphological changes in prenatal VPA-treated mice. We also examined the role of dendritic spine formation and synaptic protein expression in the hippocampus. Mice were housed for 4 weeks from 4 weeks of age under either a standard or enriched environment. Enriched housing was found to increase hippocampal brain-derived neurotrophic factor mRNA levels in both control and VPA-exposed mice. Furthermore, in VPA-treated mice, the environmental enrichment improved anxiety-like behavior, social deficits and cognitive impairment, but not hypolocomotion. Prenatal VPA treatment caused loss of dendritic spines in the hippocampal CA1 region and decreases in mRNA levels of postsynaptic density protein-95 and SH3 and multiple ankyrin repeat domains 2 in the hippocampus. These hippocampal changes were improved by the enriched housing. These findings suggest that the environmental enrichment improved most ASD-like behaviors including cognitive impairment in the VPA-treated mice by enhancing dendritic spine function.
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15. Cirnigliaro M, Barbagallo C, Gulisano M, Domini CN, Barone R, Barbagallo D, Ragusa M, Di Pietro C, Rizzo R, Purrello M. {{Expression and Regulatory Network Analysis of miR-140-3p, a New Potential Serum Biomarker for Autism Spectrum Disorder}}. {Front Mol Neurosci}. 2017; 10: 250.
Given its prevalence and social impact, Autism Spectrum Disorder (ASD) is drawing much interest. Molecular basis of ASD is heterogeneous and only partially known. Many factors, including disorders comorbid with ASD, like TS (Tourette Syndrome), complicate ASD behavior-based diagnosis and make it vulnerable to bias. To further investigate ASD etiology and to identify potential biomarkers to support its precise diagnosis, we used TaqMan Low Density Array technology to profile serum miRNAs from ASD, TS, and TS+ASD patients, and unaffected controls (NCs). Through validation assays in 30 ASD, 24 TS, and 25 TS+ASD patients and 25 NCs, we demonstrated that miR-140-3p is upregulated in ASD vs.: NC, TS, and TS+ASD (Tukey’s test, p-values = 0.03, = 0.01, < 0.0001, respectively). DeltaCt values for miR-140-3p and YGTSS (Yale Global Tic Severity Scale) scores are positively correlated (Spearman r = 0.33; Benjamini-Hochberg p = 0.008) and show a linear relationship (p = 0.002). Network functional analysis showed that nodes controlled by miR-140-3p, especially CD38 and NRIP1 which are its validated targets, are involved in processes convergingly dysregulated in ASD, such as synaptic plasticity, immune response, and chromatin binding. Biomarker analysis proved that serum miR-140-3p can discriminate among: (1) ASD and NC (Area under the ROC curve, AUC: 0.70; sensitivity: 63.33%; specificity: 68%); (2) ASD and TS (AUC: 0.72; sensitivity: 66.66%; specificity: 70.83%); (3) ASD and TS+ASD (AUC: 0.78; sensitivity: 73.33%; specificity: 76%). Characterization of miR-140-3p network would contribute to further clarify ASD etiology. Serum miR-140-3p could represent a potential non-invasive biomarker for ASD, easy to test through liquid biopsy. Lien vers le texte intégral (Open Access ou abonnement)
16. Grandgeorge M, Gautier Y, Brugailleres P, Tiercelin I, Jacq C, Lebret MC, Hausberger M. {{Social rivalry triggers visual attention in children with autism spectrum disorders}}. {Sci Rep}. 2017; 7(1): 10029.
Visual social attention is central to social functioning and learning and may act as a reinforcer. Social rivalry, which occurs when an individual is excluded from dyadic interactions, can promote interspecific learning by triggering attention. We applied it to an animal-assisted intervention, where the behaviour of ASD children was compared between an experimental (attention shift of the animal trainer from the dog-child to the dog only) and a control (attention maintained on the dyad) groups (study 1). The results show that ASD children are sensitive to the direction of (visual) social attention and may act, physically and visually, in order to regain it. When the animal trainer concentrated on the dog, the overall visual attention of the ASD children increased, suggesting a heightened awareness towards their environment. They oriented more towards the animal trainer and the dog, contrarily to the control group. The repetition of the procedure was even associated with increased joint attention with the animal trainer (study 2). Thus, ASD children do care about and seek human visual attention. They show an ability to adapt their social behaviour, which questions whether their known deficits in social competencies are hard wired or whether the deficits are in their expression.
