1. Booker SA, Simões de Oliveira L, Anstey NJ, Kozic Z, Dando OR, Jackson AD, Baxter PS, Isom LL, Sherman DL, Hardingham GE, Brophy PJ, Wyllie DJA, Kind PC. {{Input-Output Relationship of CA1 Pyramidal Neurons Reveals Intact Homeostatic Mechanisms in a Mouse Model of Fragile X Syndrome}}. {Cell Rep};2020 (Aug 11);32(6):107988.
Cellular hyperexcitability is a salient feature of fragile X syndrome animal models. The cellular basis of hyperexcitability and how it responds to changing activity states is not fully understood. Here, we show increased axon initial segment length in CA1 of the Fmr1(-/y) mouse hippocampus, with increased cellular excitability. This change in length does not result from reduced AIS plasticity, as prolonged depolarization induces changes in AIS length independent of genotype. However, depolarization does reduce cellular excitability, the magnitude of which is greater in Fmr1(-/y) neurons. Finally, we observe reduced functional inputs from the entorhinal cortex, with no genotypic difference in the firing rates of CA1 pyramidal neurons. This suggests that AIS-dependent hyperexcitability in Fmr1(-/y) mice may result from adaptive or homeostatic regulation induced by reduced functional synaptic connectivity. Thus, while AIS length and intrinsic excitability contribute to cellular hyperexcitability, they may reflect a homeostatic mechanism for reduced synaptic input onto CA1 neurons.
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2. Brusov OS, Klyushnik TP, Simashkova NV, Karpova NS, Faktor MI, Zozulya SA, Nikitina SG. {{[A combined marker of catatonia severity including autoimmune and thrombodynamic parameters in patients with autism spectrum disorder]}}. {Zh Nevrol Psikhiatr Im S S Korsakova};2020;120(7):86-93.
OBJECTIVE: To verify a working hypothesis that thrombodynamic parameters of hypercoagulation and neuro-immune test correlate with the severity of catatonia in patients with autism spectrum disorder (ASD), and the combination of these indicators can predict the severity of catatonia with high accuracy and precision. MATERIAL AND METHODS: Twenty-four patients with ASD (22 boys and 2 girls) with infantile psychosis in childhood autism (ICD-10 F84.02) were studied. The median age of the patients was 5,5 years. Neuro-immune and thrombodynamics tests were performed. RESULTS AND CONCLUSION: Thrombodynamic parameters of clot growth rates from the activator (V, Vi and Vst) are significantly higher than their normal values. The values of the time of spontaneous clots occurrence (Tsp) are significantly less than the lower limit values for the norm (30 min). It was also shown that the activity of leukocyte elastase (LE) and the functional activity of the α1 protein inhibitor (α1-PI) are significantly higher than their normal values. The values of the levels of autoantibodies to S100 protein (aabS100B) and the basic myelin protein (aabOBM) are within the normal range. The initial clot growth rate (Vi) and the time of spontaneous clots occurrence (Tsp) significantly correlate with the severity of catatonia: Spearman’s R is 0,55 for Vi (p=0,009) and -0,61for Tsp (p=0,002). Among the parameters of the neuro-immuno-test, only aabS100B indicator significantly correlates with the severity of catatonia. To increase the informative significance and accuracy of the contribution of the studied correlates of thrombodynamics and the neuro-immuno-test to the assessment of the severity of catatonia in children with ASD, a multivariate linear regression analysis was performed to construct a linear equation for the relationship between the severity of catatonia and correlates of thrombodynamics and a neuro-immuno-test. The determination coefficient R2, which determines the informational significance of the regression model, is 0,63. The remaining 37% is explained by unaccounted and not yet known factors.
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3. Clark M, Adams D. {{Listening to parents to understand their priorities for autism research}}. {PLoS One};2020;15(8):e0237376.
Involving the autism community in research increases the real-world translation and impact of findings. The current study explored the research priorities of parents of school-aged children on the autism spectrum across the home, school, and community settings. A combination of content analysis of an online questionnaire (n = 134) and Q-sort methodology (n = 9) was used. The most commonly identified research priorities in the online questionnaire were child health and well-being (home setting), socialisation and social support (school), and community awareness and understanding of autism (community). The Q-sort method highlighted different top priorities, with understanding the parent, sibling, child and family impact and stress the highest ranked priority for home, teacher/staff education and support for the school, and recognizing and supporting anxiety for the community. The implications of the findings are discussed in relation to shifting the framework of autism research to align research agendas with parental priorities.
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4. Freitas L, Henry JE, Kelley ME, Tonneau F. {{The effects of stimulus pairings on autistic children’s vocalizations: Comparing forward and backward pairings}}. {Behav Processes};2020 (Aug 9);179:104213.
In a procedure known as stimulus-stimulus pairing (Yoon and Bennett, 2000), the experimenter pairs a target sound (e.g., « bah ») with a child’s preferred item (e.g., a toy). Even though the stimulus pairings proceed independently of the child’s behavior, this procedure has proved capable of increasing imitation of the target sound in developmentally delayed children (Shillingsburg et al., 2015). The underlying behavioral processes remain poorly known, however, and few systematic variations of the basic procedure have been published. In the present experiment, with autistic children as participants, (a) we compared the effects of forward versus backward pairings on the imitation of target sounds, and (b) we evaluated formally the relation between the children’s preexisting verbal repertoires and the efficacy of the pairing procedure. As is often reported in the Pavlovian literature, backward pairings promoted lower levels of conditional responding than forward pairings. Also, we found a negative relation between a child’s verbal level and pairing efficacy: children with the lower scores on the Behavioral Language Assessment Form (Sundberg and Partington, 1998) exhibited more conditioning. These findings confirm in a single study what has been so far only suspected informally.
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5. Golden CEM, Yee Y, Wang VX, Harony-Nicolas H, Hof PR, Lerch JP, Buxbaum JD. {{Reduced axonal caliber and structural changes in a rat model of Fragile X syndrome with a deletion of a K-Homology domain of Fmr1}}. {Transl Psychiatry};2020 (Aug 12);10(1):280.
Fragile X syndrome (FXS) is a neurodevelopmental disorder that is caused by mutations in the FMR1 gene. Neuroanatomical alterations have been reported in both male and female individuals with FXS, yet the morphological underpinnings of these alterations have not been elucidated. In the current study, we found structural changes in both male and female rats that model FXS, some of which are similarly impaired in both sexes, including the superior colliculus and periaqueductal gray, and others that show sex-specific changes. The splenium of the corpus callosum, for example, was only impaired in males. We also found reduced axonal caliber in the splenium, offering a mechanism for its structural changes. Furthermore, we found that overall, male rats have higher brain-wide diffusion than female rats. Our results provide insight into which brain regions are vulnerable to a loss of Fmr1 expression and reveal an impairment at the level of the axon that could cause structural changes in white matter regions.
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6. Ji-Xu A, Vincent A. {{Maternal Immunity in Autism Spectrum Disorders: Questions of Causality, Validity, and Specificity}}. {J Clin Med};2020 (Aug 10);9(8)
Autism spectrum disorders (ASD) are complex neurodevelopmental disorders with unknown heterogeneous aetiologies. Epidemiological studies have found an association between maternal infection and development of ASD in the offspring, and clinical findings reveal a state of immune dysregulation in the pre- and postnatal period of affected subjects. Maternal immune activation (MIA) has been proposed to mediate this association by altering fetal neurodevelopment and leading to autism. Although animal models have supported a causal link between MIA and development of ASD, their validity needs to be explored. Moreover, considering that only a small proportion of affected offspring develop autism, and that MIA has been implicated in related diseases such as schizophrenia, a key unsolved question is how disease specificity and phenotypic outcome are determined. Here, we have integrated preclinical and clinical evidence, including the use of animal models for establishing causality, to explore the role of maternal infections in ASD. A proposed priming/multi-hit model may offer insights into the clinical heterogeneity of ASD, its convergence with related disorders, and therapeutic strategies.
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7. Johnson NL, Bekhet AK, Karenke T, Garnier Villareal M. {{Swim Program Pilot for Children with Autism: Impact on Behaviors and Health}}. {West J Nurs Res};2020 (Aug 14):193945920948867.
The purpose of this mixed methods pre-/post-pilot intervention study was to assess parental psychological health and child challenging behaviors before and after a swimming program for children with autism. Participants were 10 parent-child dyads. Child’s challenging behaviors were lower in the post testing (Cohen’s d = 0.07-0.45). Mean scores were improved for parent perception of general health (Cohen’s d = 0.22). Three themes emerged from the post swim program focus group: (a) Parent satisfaction with instructors with sub themes (i) firmness (ii) creativity, and (iii) promotion of social interaction and sharing, (b) improved child sleeping, and (c) family dynamics with sub themes (i) siblings wanted to swim and (ii) parents’ fear of drowning. Preliminary results point to improved child behaviors and parent perception of general health. Future studies can focus on expanding the swim program to include all family members.
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8. Kozhuhov A, Tfilin M, Turgeman G, Ornoy A, Yanai J, Abookasis D. {{Implementation of a six-around-one optical probe based on diffuse light spectroscopy for study of cerebral properties in a murine mouse model of autism spectrum disorder}}. {Appl Opt};2020 (Aug 10);59(23):6809-6816.
Light reflectance spectroscopy (LRS) is a multispectral technique, sensitive to the absorption and scattering properties of biological molecules in tissues. It is used as a noninvasive tool to extract quantitative physiological information from human tissues and organs. A near-infrared LRS based on a single optical probe was used to monitor changes in optical and hemodynamic parameters in a mouse model of autism. A murine model of autism induced by developmental exposure to valproic acid (VPA) was used. Since autism could be attributed to neuroanatomical changes, we hypothesize that these changes can be detected using the LRS because spectral properties depend on both molecular composition and structural changes. The fiber-optic probe in the setup consisted of seven small optical fibers: six fibers for illumination placed in a circular manner around a central single collection fiber. Overall, measurements demonstrate changes in diffused reflectance spectra, cerebral optical tissue properties (absorption and scattering), and chromophore levels. Furthermore, we were able to identify differences between male and female groups. Finally, the effectiveness of S-Adenosylmethionine as a drug therapy was studied and found to improve the hemodynamic outcome. For the first time, to the best of our knowledge, the LRS is utilized to study variations in brain parameters in the VPA autism model mice through an intact scalp.
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9. Marks K, Vincent A, Coutinho E. {{Maternal-Autoantibody-Related (MAR) Autism: Identifying Neuronal Antigens and Approaching Prospects for Intervention}}. {J Clin Med};2020 (Aug 7);9(8)
Recent studies indicate the existence of a maternal-autoantibody-related subtype of autism spectrum disorder (ASD). To date, a large number of studies have focused on describing patterns of brain-reactive serum antibodies in maternal-autoantibody-related (MAR) autism and some have described attempts to define the antigenic targets. This article describes evidence on MAR autism and the various autoantibodies that have been implicated. Among other possibilities, antibodies to neuronal surface protein Contactin Associated Protein 2 (CASPR2) have been found more frequently in mothers of children with neurodevelopmental disorders or autism, and two independent experimental studies have shown pathogenicity in mice. The N-methyl-D-aspartate receptor (NMDAR) is another possible target for maternal antibodies as demonstrated in mice. Here, we discuss the growing evidence, discuss issues regarding biomarker definition, and summarise the therapeutic approaches that might be used to reduce or prevent the transfer of pathogenic maternal antibodies.
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10. Nagano M, Zane E, Grossman RB. {{Structural and Contextual Cues in Third-Person Pronoun Interpretation by Children with Autism Spectrum Disorder and Their Neurotypical Peers}}. {J Autism Dev Disord};2020 (Aug 12)
This study investigates the use of structural and discourse contextual cues in the interpretation of third-person pronouns by children and adolescents with autism and their neurotypical peers. Results show that referent-biasing contextual information influences pronominal interpretation and modulates looking patterns in both groups compared to a context-neutral condition. These results go against the predictions of Weak Central Coherence and the notion that pragmatics in general is impaired in ASD, since the ASD group was able to use details in discourse context to influence the pronominal interpretation process. However, although discourse context influenced looking patterns in both groups, the groups nevertheless diverged in the nature of these patterns, suggesting that behavioral differences may emerge in more complicated discourse tasks.
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11. Ng ASL, Xu Z, Chen Z, Tan YJ, Lim WK, Ting SKS, Yu WY, Cheng QH, Foo JN, Tan EK, Lim TCC. {{NOTCH2NLC-linked neuronal intranuclear inclusion body disease and fragile X-associated tremor/ataxia syndrome}}. {Brain};2020 (Aug 13)
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12. Ni HC, Lin HY, Tseng WI, Gau SS. {{Association of self-regulation with white matter correlates in boys with and without autism spectrum disorder}}. {Sci Rep};2020 (Aug 14);10(1):13811.
Previous studies demonstrated distinct neural correlates underpinning impaired self-regulation (dysregulation) between individuals with autism spectrum disorder (ASD) and typically developing controls (TDC). However, the impacts of dysregulation on white matter (WM) microstructural property in ASD and TDC remain unclear. Diffusion spectrum imaging was acquired in 59 ASD and 62 TDC boys. We investigated the relationship between participants’ dysregulation levels and microstructural property of 76 WM tracts in a multivariate analysis (canonical correlation analysis), across diagnostic groups. A single mode of brain-behavior co-variation was identified: participants were spread along a single axis linking diagnosis, dysregulation, diagnosis-by-dysregulation interaction, and intelligence to a specific WM property pattern. This mode corresponds to diagnosis-distinct correlates underpinning dysregulation, which showed higher generalized fractional anisotropy (GFA) associated with less dysregulation in ASD but greater dysregulation in TDC, in the tracts connecting limbic and emotion regulation systems. Moreover, higher GFA of the tracts implicated in memory, attention, sensorimotor processing, and perception associated with less dysregulation in TDC but worse dysregulation in ASD. No shared WM correlates of dysregulation between ASD and TDC were identified. Corresponding to previous studies, we demonstrated that ASD and TDC have broad distinct white matter microstructural property underpinning self-regulation.
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13. Patel S, Dale RC, Rose D, Heath B, Nordahl CW, Rogers S, Guastella AJ, Ashwood P. {{Maternal immune conditions are increased in males with autism spectrum disorders and are associated with behavioural and emotional but not cognitive co-morbidity}}. {Transl Psychiatry};2020 (Aug 14);10(1):286.
Epidemiological and animal research shows that maternal immune activation increases the risk of autism spectrum disorders (ASD) in offspring. Emerging evidence suggests that maternal immune conditions may play a role in the phenotypic expression of neurodevelopmental difficulties in children with ASD and this may be moderated by offspring sex. This study aimed to investigate whether maternal immune conditions were associated with increased severity of adverse neurodevelopmental outcomes in children with ASD. Maternal immune conditions were examined as predictors of ASD severity, behavioural and emotional well-being, and cognitive functioning in a cohort of 363 children with ASD (n = 363; 252 males, 111 females; median age 3.07 [interquartile range 2.64-3.36 years]). We also explored whether these outcomes varied between male and female children. Results showed that maternal asthma was the most common immune condition reported in mothers of children with ASD. A history of maternal immune conditions (p = 0.009) was more common in male children with ASD, compared to female children. Maternal immune conditions were associated with increased behavioural and emotional problems in male and female children. By contrast, maternal immune conditions were not associated with decreased cognitive function. The findings demonstrate that MIA may influence the expression of symptoms in children with ASD and outcomes may vary between males and females.
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14. Sorrell MR, Killian KA. {{Innate immune system function following systemic RNA-interference of the Fragile X Mental Retardation 1 gene in the cricket Acheta domesticus}}. {J Insect Physiol};2020 (Aug 10):104097.
Fragile X syndrome (FXS), caused by a mutation in the Fragile X Mental Retardation 1 (FMR1) gene, is a common form of inherited mental retardation. Mutation of the gene leads to a loss of the gene product Fragile X Mental Retardation Protein (FMRP). While a loss of FMRP has been primarily associated with neural and cognitive deficits, it has also been reported to lead to immune system dysfunction in both humans and flies. We used the Acheta domesticus transcriptome to identify a highly conserved cricket ortholog of FMR1 (adfmr1). We cloned a partial cDNA of adfmr1, used systemic RNA interference (RNAi) to knockdown adfmr1 expression, and examined the impact of this knockdown (KD) on the cellular and humoral responses of the insect innate immune system. Following RNAi, both male and female crickets exhibited an increase in the number of circulating hemocytes, a decrease in total hemolymph phenoloxidase (PO) activity, and an increase in fat body lysozyme expression. Despite similar changes in these immune parameters in both sexes, male and female crickets responded differently to an immune challenge. Most KD males failed to survive an intra-abdominal injection of bacterial lipopolysaccharide, while KD females were just as likely as control females to survive this challenge. Our results support that decreased fmr1 expression can alter the cellular and humoral defenses of the insect innate immune system, and may lead to a decrease in male, but not female, immunocompetence.
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15. Taneja N, Litt MD. {{Caregivers’ Barriers to Dental Care for Children with Autism Spectrum Disorder}}. {J Dent Child (Chic)};2020 (May 15);87(2):98-102.
Purpose: To investigate caregivers’ perspective on barriers to dental care for children with autism spectrum disorder (ASD).
Methods: A cross-sectional survey assessing perceived barriers to dental care was administered to 46 caregivers who had a child with ASD (study group) and 37 who had children without ASD (control group) but with chronic health issues.
Results: The barriers most frequently reported in the study group were difficulty finding a dentist who would treat their child (32 percent) and the child’s uncooperative behavior (39 percent). A significantly higher number of caregivers of children with ASD agreed that their child was uncooperative and that such behavior was a barrier to finding care (chi-square=15.22, P =0.0001). The number of barriers reported by caregivers of children with ASD was greater than that reported by the other caregivers. Caregivers of children with severe ASD perceived having the most barriers to care.
Conclusion: There are many barriers faced by caregivers in getting dental treatment for their children with ASD. Understanding the difficulty caregivers have in securing dental care for their children with ASD may help dentists and agencies work to improve access.
16. Ventura P, de Giambattista C, Spagnoletta L, Trerotoli P, Cavone M, Di Gioia A, Margari L. {{Methylphenidate in Autism Spectrum Disorder: A Long-Term Follow up Naturalistic Study}}. {J Clin Med};2020 (Aug 7);9(8)
Autism spectrum disorder (ASD) often co-occurs with attention deficit/hyperactivity disorder (ADHD). Although methylphenidate (MPH) efficacy and safety are well-demonstrated for ADHD, evidences are scant in the context of ASD. This naturalistic study aimed to analyze long-term MPH efficacy and safety in 40 ADHD children and adolescents with comorbid ASD, comparing them with 40 ones affected by ADHD without ASD. Treatment lasted from 6 to 156 months (longer than 24 months in more than three quarters of patients). Efficacy and safety were measured by clinical global impression and children global assessment scales; influence of intellectual functioning was examined. Comparisons between groups were made by Wilcoxon or Friedmann tests; relationships between functioning scores and other characteristics were analyzed by ordinal logistic and linear regression. Results demonstrated that MPH in patients with ASD was associated with significative reduction of illness severity, clinical improvement and amelioration of global functioning, without significant differences with patients having ADHD without ASD. The trend of reduction of illness severity and increase of global functioning were favorably related with intellectual functioning. No serious adverse events were reported. The findings showed that long-term MPH was effective and well-tolerated in ADHD children and adolescents with comorbid high functioning ASD.
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17. Walęcka M, Wojciechowska K, Wichniak A. {{Central coherence in adults with a high-functioning autism spectrum disorder. In a search for a non-self-reporting screening tool}}. {Appl Neuropsychol Adult};2020 (Aug 14):1-7.
BACKGROUND: Autism spectrum disorder in adults, especially high-functioning ones, is often difficult to differentiate from other mental disorders. Therefore, many adults with ASD are misdiagnosed, and their social difficulties are not adequately addressed. Moreover, frequent comorbid issues make diagnosis a challenging prospect. Most of the available screening and diagnostic tools rely on self-reporting, which can be a biased method. Weak Central Coherence is one of the main cognitive theories of ASD. According to research, individuals with ASD are slower in comparison to typically developed control on the uptake of context. The study goal was to see if the central coherence tasks could be used as a reliable screening marker that differentiates between high-functioning ASD and typically developed controls. METHOD: Thirty males with ASD (as in DSM-5) and 30 demographically matched controls were investigated with Central Coherence Inferences Tests. Tests’ scores and reaction times needed to complete the tasks in both groups were compared. RESULTS: High-functioning participants with ASD achieved a similar score in central coherence tests as the typically developed control group, but they needed significantly more time to solve them. The ROC analysis for both central coherence tests revealed AUC values of 0.73 in differentiating ASD from typically developed controls. CONCLUSIONS: The results are discussed in reference to the clinical application of central coherence as a possible screening marker. Further research directions are proposed in terms of differential diagnosis of adults with ASD.
