1. Bricout VA, Pace M, Dumortier L, Baillieul F, Favre-Juvin A, Guinot M. {{Reduced Cardiorespiratory Capacity in Children with Autism Spectrum Disorders}}. {Journal of clinical medicine}. 2018; 7(10).
Background-Children with autistic spectrum disorders (ASDs) are frequently hampered by motor impairment. It limits them from regularly practicing physical activities and results in a lower physical fitness even though low cardiorespiratory fitness is one of the most important predictors of all-cause mortality. This study aimed to investigate the cardiorespiratory fitness of boys with ASD compared to typically developed children. Methods-forty male children participated. Twenty were control children (CONT-10.0 +/- 1.6 years) and 20 were ASD children (ASD-10.7 +/- 1.2 years; intellectual quotient > 70). All participants completed an incremental exercise test on a treadmill. An evaluation of motor characteristics by three tests was conducted (muscular strength; explosive power; flexibility). Assessments of daily physical activity were obtained by questionnaires (PAQ-C) and by actigraphy. Results-in the ASD group, aerobic capacity values (VO2peak), effort duration and maximal speed were significantly lower compared to CONT (p < 0.05). Flexibility, explosive power and muscular strength were significantly lower in ASD compared to CONT (p < 0.05). Similarities between all children were observed for physical activity evaluation by actigraphy and with the PAQ-C. Conclusions-children with ASD had lower cardiorespiratory fitness than CONT despite similar physical activity levels. Our results suggested that the difference may be due to motor discrepancies. Lien vers le texte intégral (Open Access ou abonnement)
2. Capal JK, Carosella C, Corbin E, Horn PS, Caine R, Manning-Courtney P. {{EEG endophenotypes in autism spectrum disorder}}. {Epilepsy & behavior : E&B}. 2018.
OBJECTIVES: The association between autism spectrum disorder (ASD) and epilepsy is well-known. Abnormalities on electroencephalography (EEG) results have been reported in patients with ASD without a history of seizures. However, little is known about the relationship between abnormalities on EEG results and the core features of ASD. The purpose of the study was to determine the relationship between the presence of epilepsy and/or abnormalities on EEG results and disease-associated impairments in young children with ASD. METHODS: Data were collected from medical records at Cincinnati Children’s Hospital Medical Center (CCHMC) of patients with well-characterized ASD. Patients were subdivided into three groups: ASD without epilepsy but with abnormal EEG results, ASD without epilepsy and normal EEG results, and ASD with epilepsy. Developmental (Mullen Scales of Early Learning (MSEL)), adaptive (Vineland Adaptive Behavior Scales (VABS)), behavioral (Child Behavior Checklist), and language (Preschool Language Scales (PLS)) assessments, along with birth and developmental histories, medications, and medical comorbidities were collected. Electroencephalography data were abstracted from reports and included presence, characterization, and location of abnormalities. RESULTS: Analysis was performed on 443 patients with ASD. Seventy patients (15.8%) had epilepsy at the time of ASD diagnosis. Out of 372 patients with ASD and no epilepsy, 95 (25.5%) had an abnormal EEG result (67.4% epileptiform, 36.8% other abnormalities). Majority of epileptiform discharges were focal (83%) and most commonly seen in the left temporal region. The group with abnormal EEG results exhibited more impaired adaptive functioning when compared with the group with normal EEG results (p<0.05). The group with abnormal EEG results was more similar to the group with epilepsy, differing only in expressive language (p<0.01) and fine motor (p<0.05) skills on the Mullen Scales. The group with epilepsy exhibited lower scores in all areas of developmental and adaptive functioning compared with the group with normal EEG results (p<0.05). At the time of analysis, 13 patients (8 in the group with abnormal EEG results, 5 in the group with normal EEG results) developed epilepsy at a mean age of 10.5years+/-3.3years. CONCLUSIONS: The presence of an abnormal EEG result or epilepsy in the setting of ASD suggests worse developmental and adaptive functioning. Further analysis will help to clarify associations and offer insight into treatment for this subpopulation without epilepsy but with abnormal EEG results. Lien vers le texte intégral (Open Access ou abonnement)
3. Courchet V, Roberts AJ, Meyer-Dilhet G, Del Carmine P, Lewis TL, Jr., Polleux F, Courchet J. {{Haploinsufficiency of autism spectrum disorder candidate gene NUAK1 impairs cortical development and behavior in mice}}. {Nature communications}. 2018; 9(1): 4289.
Recently, numerous rare de novo mutations have been identified in patients diagnosed with autism spectrum disorders (ASD). However, despite the predicted loss-of-function nature of some of these de novo mutations, the affected individuals are heterozygous carriers, which would suggest that most of these candidate genes are haploinsufficient and/or lead to expression of dominant-negative forms of the protein. Here, we tested this hypothesis with the candidate ASD gene Nuak1 that we previously identified for its role in the development of cortical connectivity. We report that Nuak1 is haploinsufficient in mice with regard to its function in cortical development. Furthermore Nuak1(+/-) mice show a combination of abnormal behavioral traits ranging from defective spatial memory consolidation, defects in social novelty (but not social preference) and abnormal sensorimotor gating. Overall, our results demonstrate that Nuak1 haploinsufficiency leads to defects in the development of cortical connectivity and a complex array of behavorial deficits.
Lien vers le texte intégral (Open Access ou abonnement)
4. Eggleston JD, Landers MR, Bates BT, Nagelhout E, Dufek JS. {{Weighted Walking Influences Lower Extremity Coordination in Children on the Autism Spectrum}}. {Perceptual and motor skills}. 2018: 31512518803178.
There is sparse quantitative research regarding gait coordination patterns of children on the autism spectrum, though previous studies, relying only upon observational data, have alluded to characteristically poor movement coordination. This study compared walking with a weighted vest, a backpack carriage, and an unloaded walking condition on lower extremity coordination among 10 male children (aged 8-17 years) on the autism spectrum. All participants completed 15 gait trials in the following three conditions: (a) unloaded, (b) wearing a backpack weighted with 15% body mass, and (c) wearing a vest weighted with 15% body mass. We used continuous relative phase analysis to quantify lower extremity coordination and analyzed data through both group and single-subject comparisons. We used the Model Statistic to test for statistical significance at each of the normalized data points for each segment couple (thigh-leg, leg-foot, and thigh-foot). The first 10 and last 10 stride blocks were tested for possible accommodation strategies. Group comparisons revealed no coordination changes among the three conditions (likely due to insufficient statistical power), while single-subject comparisons exposed significant decreased variability in gait coordination patterns ( p < .05) in both loaded conditions, relative to the unloaded condition. These participants exhibited variable coordination patterns during the unloaded gait. When walking with loads, coordination pattern variability of the lower extremities was decreased. This finding suggests that walking while carrying or wearing heavy objects may reduce the number of potential motor pattern choices and thus decrease the overall variability of lower extremity movement patterns. Additional research with a larger and more diverse participant sample is required to confirm this conclusion. Lien vers le texte intégral (Open Access ou abonnement)
5. Gomez-Fernandez A, de la Torre-Aguilar MJ, Gil-Campos M, Flores-Rojas K, Cruz-Rico MD, Martin-Borreguero P, Perez-Navero JL. {{Children With Autism Spectrum Disorder With Regression Exhibit a Different Profile in Plasma Cytokines and Adhesion Molecules Compared to Children Without Such Regression}}. {Frontiers in pediatrics}. 2018; 6: 264.
Background: In the etiopathogenesis of autism spectrum disorder (ASD), it has been suggested that a proinflammatory condition, as well as an alteration in adhesion molecules in the early stages of neurodevelopment, may play a role in the pathophysiology of the disorder. This study set out to evaluate the plasma levels of certain inflammatory cytokines, adhesion molecules, and growth factors in a sample of pediatric patients with ASD and compare them to the levels in a control group of healthy children. Methods: Fifty-four children (45 males and nine females) aged 2-6, who were diagnosed with ASD, and a control group of 54 typically-developing children of similar ages were selected. The diagnosis of ASD was carried out in accordance with the DSM-5 criteria and the data obtained from a developmental semi-structured clinical interview and the ADOS evaluation test. Additional testing was carried out to identify the children’s developmental level and severity of ASD symptomatology. Patients with ASD were further divided into two subgroups based on developmental parameters: ASD children with neurodevelopmental regression (AMR) and ASD children without neurodevelopmental regression (ANMR). Analyses of plasma molecules, such as cathepsin, IL1beta, IL6, IL8, MPO, RANTES, MCP, BDNF, PAI NCAM, sICAM, sVCAM and NGF, were performed. Results: Higher levels of NGF were observed in the ASD group compared with the levels in the control group (p < 0.05). However, in the analysis of the ASD subgroups, lower plasma levels of NCAM and higher levels of NGF were found in the group of ASD children without developmental regression compared to the levels in the group of typically-developing children. Conclusions: These results suggest differences that could be related to different pathophysiological mechanisms in ASD. There is not a specific profile for the expression of relevant plasma cytokines, adhesion molecules or growth factors in children with ASD compared with that in typically-developing children. However, in the ANMR and AMR subgroups, some of the adhesion molecules and neuronal growth factors show differences that may be related to synaptogenesis. Lien vers le texte intégral (Open Access ou abonnement)
6. Kang J, Zhou T, Han J, Li X. {{EEG-based multi-feature fusion assessment for autism}}. {Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia}. 2018; 56: 101-7.
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder which affects the developmental trajectory in several behavioral domains, including impairments of social communication, cognitive and language abilities. In this paper, multi-feature fusion method based on EEG signal is used to extract as many as possible features including power spectrum analysis, bicoherence, entropy and coherence methods, then we use minimum redundancy maximum correlation (mRMR) algorithm to choose the features, which are applied to input to three classifiers to obtain accuracy classification results. We try to find some key biomarkers of ASD by examining the accuracy of classifier, using different models which use the combination of multiplex features. The results show when nine features are selected by SVM-linear classifier, the accuracy is up to 91.38%. This method might provide objective basis for clinical diagnosis of autism.
Lien vers le texte intégral (Open Access ou abonnement)
7. Karahmadi M, Tarrahi MJ, Vatankhah Ardestani SS, Omranifard V, Farzaneh B. {{Efficacy of Memantine as Adjunct Therapy for Autism Spectrum Disorder in Children Aged <14 Years}}. {Advanced biomedical research}. 2018; 7: 131. Background: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a recent increase in prevalence. A timely appropriate treatment for the disorder may play a crucial role in improvements in behaviors, interactions, and communications in an individual's life. It appears that evaluation of therapeutic approaches to the patients is essential and of importance. Thus, the aim of this study was to evaluate the efficacy of memantine as adjunct therapy in children with ASD. Materials and Methods: This randomized single-blind clinical trial included 60 children with ASD aged <14. The children undergoing applied behavior analysis (ABA) were divided into two groups of placebo and memantine (5 mg/day: a half of tablet in the morning and a half in the evening). After a 3-month course, improvements in symptoms of ASD were evaluated in both groups based on Gilliam autism rating scale. The collected data were analyzed with SPSS (version 20) using independent samples t-test, paired samples t-test, Chi-squared test and Fisher's exact test. Results: Both groups were similar in baseline characteristics including age, gender, and ASD symptoms (P > 0.05) but post intervention, total scores of ASD symptoms in both groups of memantine (mean score1 =95.20 +/- 14.49; mean score2=73.50 +/- 9.81) and control group (mean scorebefore = 91.50 +/- 14.35; mean scoreafter = 89.63 +/- 13.95) showed a decrease which was only significant in intervention group (P < 0.001). Conclusion: Accordingly, memantine administration as adjunct therapy can be more effective in improvement of ASD symptoms in children than ABA alone. Thus, it can be considered as a new selective adjunct therapy. Lien vers le texte intégral (Open Access ou abonnement)
8. Kidd VD. {{Cannabinoids in the Treatment of Autism Spectrum Disorder: Demanding Data Before Using Fad Therapies}}. {Pediatric neurology}. 2018.
Lien vers le texte intégral (Open Access ou abonnement)
9. Maddox BB, Kang-Yi CD, Brodkin ES, Mandell DS. {{Treatment Utilization by Adults with Autism and Co-Occurring Anxiety or Depression}}. {Research in autism spectrum disorders}. 2018; 51: 32-7.
Background: While a growing body of research suggests that talk therapies can reduce anxiety and depression in adults with autism spectrum disorder (ASD), we know little about what community treatment for these disorders looks like for them. The present study investigated whether treatment utilization differs between adults with and without ASD who have anxiety or depression. Method: Using Pennsylvania Medicaid claims data, adults aged 18-65 years diagnosed with ASD and depression or anxiety (n = 268) were matched 1:4 to adults with depression or anxiety disorder without ASD (n = 1,072). Chi-square tests and generalized linear models were used to estimate differences in diagnoses and psychiatric treatment between groups. Results: While the proportion of people prescribed benzodiazepine and antidepressants did not differ between groups, the ASD group had more days per month prescribed for all medications. Adults with ASD also were more likely to be prescribed multiple medications concurrently and to use case management. Adults without ASD were more likely to receive talk therapy for anxiety/depression. Among those receiving talk therapy, adults with ASD averaged more individual visits per month. Conclusions: Findings suggest that therapists may need more session time for adults with ASD, although it is unclear if this time is dedicated to anxiety or depression treatment. The greater use of psychotropic medications among adults with ASD may suggest unresponsiveness to the talk therapy they receive or greater clinical complexity.
Lien vers le texte intégral (Open Access ou abonnement)
10. Mohammadi F, Rakhshan M, Molazem Z, Zareh N, Gillespie M. {{Caregivers’ perception of dignity in teenagers with autism spectrum disorder}}. {Nursing ethics}. 2018: 969733018796679.
INTRODUCTION: Maintaining dignity is one of patients is one of the main ethical responsibilities of caregivers. However, in many cases, the dignity of patients, especially autistic teenagers is not maintained. The extent to which dignity needs are met for this group within the Iranian care system is difficult to determine as dignity is an abstract concept, and there are few related research studies reported. OBJECTIVES: The objective of this study is to find out caregivers perspectives on dignity in teenagers with autistic spectrum disorder. RESEARCH DESIGN: This study uses a qualitative research design. The data were collected through individual, semi-structured interviews and field notes developed during the interviews. In order to analyze the data, qualitative conventional content analysis was used. Participants and research context: In all, 16 professional caregivers for autistic teenagers working in public hospitals were recruited based on a targeted sampling method to reach data saturation from February 2016 to July 2017. FINDINGS: The findings of this study were presented in three main themes, « privacy, » « respecting individual identity, » and « comprehensive support, » and 11 categories. Ethical consideration: This study’s protocol was approved by the Research Ethics Committee of medical universities located in Southeast of Iran and the required ethical principles were followed throughout. DISCUSSION AND CONCLUSION: Based on the findings of this study from the perspective of caregivers, autistic teenagers need to be cared for and educated in a respectful environment where their privacy is maintained, their individual identities are respected, and they receive comprehensive familial, social, and financial support. These conditions would maintain the dignity of such teenagers and would result in appropriate behavioral outcomes. Therefore, it is suggested that a cultural, professional and institutional background in which all components of the autistic teenager’s dignity are protected and emphasized be provided.
Lien vers le texte intégral (Open Access ou abonnement)
11. Mousavi SM, Kamali E, Fatahi F, Babaie H, Salehi M. {{Autism and Probable Prerequisites: Severe and Scheduled Prenatal Stresses at Spotlight}}. {Iranian journal of public health}. 2018; 47(9): 1388-96.
Background: Due to the importance of prenatal maternal stress as environmental factor on autism, the influence of prenatal maternal psychological agitations was assessed in relation with the risk of autism. Methods: In this case-control study, some mothers of autistic children in Isfahan, central Iran, in 2014, were retrospectively compared with control mothers in terms of quantity, quality, and schedule of exposure to 45 stressful events in a 15-month period. In addition, dividing the stressors into two groups of genome-dependent/independent events, their prevalence was separately scrutinized and compared among patient and control families. Results: Although the child’s risk of autism increases significantly with the increase of maternal stress during months 4-7 of pregnancy, the increased stress during months 2-3 of pregnancy can lead to a significant increase in the severity of autism affliction as well as a slight but significant increase in the possibility of LFA in afflicted children (P<0.05). The overall prevalence of genome-dependent stressful events among two patient and control groups was significantly higher than that of genome-independent events (P=0.000), but genome-dependent events led to more stress inpatient families. Conclusion: Although the present study consistent with recent findings in the fields of epigenetics and gene-environment interactions can confirm the role of severe and scheduled prenatal stresses in causing autism, it does not deny the necessity of a perspective and wider study in Isfahan and Iran. Lien vers Pubmed
12. Nasr Esfahani F, Hakim Shooshtari M, Shirmohammadi Sosfadi R, Saeed F, Jalai F, Farsham A, Bidaki R. {{Internalizing and Externalizing Problems, Empathy Quotient, and Systemizing Quotient in 4 to 11 Years-Old Siblings of Children with Autistic Spectrum Disorder Compared to Control Group}}. {Iranian journal of psychiatry}. 2018; 13(3): 191-9.
Objective: This study was conducted to recognize the problems of living with a sibling with Autistic Spectrum Disorder (ASD) to improve their quality of life. Method : A total of 30 participants were selected among the 4-to11- year-old siblings of children who had referred to Tehran Psychiatric Institute due to autism spectrum disorder. For the control group, 30 children aged 4 to11years old who were the siblings of patients with chronic diseases referring to Pediatric Clinic of Rasoul-e Akram (PBUH) hospital were selected. Gilliam Autism Rating Scale-Second Edition (GARS-2) was filled out for patients and siblings participating in the study and Child Behavior Checklist was completed by their parents. Results: The mean age of the patients in this study was 4.46 +/- 9.66 years (range: 1.5-22 years), and the mean age in the healthy children was 2.54 +/- 8.18 years (range: 4-11 years). The mean scores of anxiety/depression, withdrawn/depressed, somatic complaints, social problems, thought problems, attention problems, and rule-breaking behavior subscale of CBCL (Child Behavior Checklist) were not significantly different between groups. Aggressive behavior was the only subscale that showed such difference (p = 0.008). Externalizing problems in children who had siblings with ASD was higher than children who had siblings with physical illness. In a group in which a sibling had ASD, sisters were more anxious/ depressed than brothers. Conclusion: Due to various psychological and social problems that siblings of children with ASD experience throughout their life, studying their psychological problems to improve their quality of life seems to be of paramount importance.
13. Nuber S, Jacob H, Kreifelts B, Martinelli A, Wildgruber D. {{Attenuated impression of irony created by the mismatch of verbal and nonverbal cues in patients with autism spectrum disorder}}. {PloS one}. 2018; 13(10): e0205750.
Perception of irony has been observed to be impaired in adults with autism spectrum disorder. In typically developed adults, the mismatch of verbal and nonverbal emotional cues can be perceived as an expression of irony even in the absence of any further contextual information. In this study, we evaluate to what extent high functioning autists perceive this incongruence as expressing irony. Our results show that incongruent verbal and nonverbal signals create an impression of irony significantly less often in participants with high-functioning autism than in typically developed control subjects. The extent of overall autistic symptomatology as measured with the autism-spectrum questionnaire (AQ), however, does not correlate with the reduced tendency to attribute incongruent stimuli as expressing irony. Therefore, the attenuation in irony attribution might rather be related to specific subdomains of autistic traits, such as a reduced tendency to interpret communicative signals in terms of complex intentional mental states. The observed differences in irony attribution support the assumption that a less pronounced tendency to engage in higher order mentalization processes might underlie the impairment of pragmatic language understanding in high functioning autism.
Lien vers le texte intégral (Open Access ou abonnement)
14. Srinivasan SM, Cavagnino DT, Bhat AN. {{Effects of Equine Therapy on Individuals with Autism Spectrum Disorder: A Systematic Review}}. {Review journal of autism and developmental disorders}. 2018; 5(2): 156-75.
Literature on effects of equine therapy in individuals with autism spectrum disorder (ASD) has grown in recent times. Equine therapy is an alternative multimodal intervention that involves utilizing a horse to enhance core impairments in ASD. Recent systematic reviews in this area have several limitations including inclusion of populations other than ASD, assessment of a variety of animal-assisted interventions other than equine therapy, and a failure to conduct quantitative analyses to provide accurate effect size estimates. We conducted a focused systematic review to address these limitations. Our review suggested that equine therapy has beneficial effects on behavioral skills and to some extent on social communication in ASD. The evidence for positive effects of equine therapy on perceptuo-motor, cognitive, and functional skills is currently limited.
Lien vers le texte intégral (Open Access ou abonnement)
15. Stafford LD. {{Food neophobia, autistic traits, and body mass index: a broader behavioral constellation?}}. {The American journal of clinical nutrition}. 2018; 108(4): 654-5.
Lien vers le texte intégral (Open Access ou abonnement)
16. Tu Z, Zhao H, Li B, Yan S, Wang L, Tang Y, Li Z, Bai D, Li C, Lin Y, Li Y, Liu J, Xu H, Guo X, Jiang YH, Zhang YQ, Li XJ. {{CRISPR/Cas9-mediated disruption of SHANK3 in monkey leads to drug-treatable autism-like symptoms}}. {Human molecular genetics}. 2018.
Monogenic mutations in the SHANK3 gene, which encodes a postsynaptic scaffold protein, play a causative role in autism spectrum disorder (ASD). Although a number of mouse models with Shank3 mutations have been valuable for investigating the pathogenesis of ASD, species-dependent differences in behaviors and brain structures post considerable challenges to use small animals to model ASD and to translate experimental therapeutics to the clinic. We have used CRISPR/Cas9 to generate a cynomolgus monkey model by disrupting SHANK3 at exon 6 and 12. Analysis of the live mutant monkey revealed the core behavioral abnormalities of ASD, including impaired social interaction and repetitive behaviors, and reduced brain network activities detected by positron-emission tomography (PET). Importantly, these abnormal behaviors and brain activities were alleviated by the antidepressant fluoxetine treatment. Our findings provide the first demonstration that the genetically modified non-human primate can be used for translational research of therapeutics for ASD.
Lien vers le texte intégral (Open Access ou abonnement)
17. Vivanti G, Dissanayake C, Fanning PAJ, Hocking DR. {{Reduced Motor Interference in Preschoolers with Autism Spectrum Disorder and Williams Syndrome}}. {Developmental neuropsychology}. 2018; 43(8): 751-63.
Motor interference occurs when action execution is hindered by the observation of an incongruent action. The present study used a novel eye-tracking paradigm to test the motor interference effect in 22 preschoolers with autism spectrum disorder (ASD), 14 preschoolers with Williams syndrome (WS), and 18 typically developing (TD) peers. In TD children, performance of a pre-determined action was slower after the observation of an incongruent motor action and faster following observation of a congruent motor action, indicating a motor interference effect. In both the ASD and WS groups, performance was unaffected by the congruent versus incongruent nature of the observed motor action.
Lien vers le texte intégral (Open Access ou abonnement)
18. Wallace GL, Llewellyn C, Fildes A, Ronald A. {{Autism spectrum disorder and food neophobia: clinical and subclinical links}}. {The American journal of clinical nutrition}. 2018; 108(4): 701-7.
Background: Autism spectrum disorder (ASD) has been linked with eating- and feeding-related atypicalities, including food neophobia (FN) (refusal to try unfamiliar foods), since its earliest description. Nevertheless, whether associations between ASD traits and FN extend subclinically into the broader population of children and their potential additive health impacts remains unexplored. Objective: We examined ASD-control group differences in FN and ASD trait-FN trait associations, as well as the ability of FN and autistic traits to predict one index of later health-related outcomes [body mass index (BMI)]. Design: Participants in the present study were a large community-based sample of 8- to 11-y-olds (n = 4564), including a relatively small group of children diagnosed with ASD (n = 37). Parents of these 8- to 11-y-old children completed assessments of FN and autistic traits and provided height and weight metrics at 12 y of age. Results: Children with ASD were rated as more food neophobic than their same-age non-ASD peers (2.67 +/- 0.83 compared with 2.22 +/- 0.73; P < 0.001), and there were subclinical associations between FN and ASD traits (social, communication, and restricted/repetitive behavior) in this community-based sample of children (P < 0.05). Moreover, whereas FN alone predicted lower BMI, the interaction of FN and ASD traits predicted higher BMI (P Lien vers le texte intégral (Open Access ou abonnement)
19. Wang H, Yin YX, Gong DM, Hong LJ, Wu G, Jiang Q, Wang CK, Blinder P, Long S, Han F, Lu YM. {{Cathepsin B inhibition ameliorates leukocyte-endothelial adhesion in the BTBR mouse model of autism}}. {CNS neuroscience & therapeutics}. 2018.
AIMS: Autism spectrum disorder (ASD) is a wide range of neurodevelopmental disorders involving deficits in social interaction and communication. Unfortunately, autism remains a scientific and clinical challenge owing to the lack of understanding the cellular and molecular mechanisms underlying it. This study aimed to investigate the pathophysiological mechanism underlying leukocyte-endothelial adhesion in autism-related neurovascular inflammation. METHODS: Male BTBR T+tf/J mice were used as an autism model. The dynamic pattern of leukocyte-endothelial adhesion in mouse cerebral vessels was detected by two-photon laser scanning microscopy (TPLSM). Using FACS, RT-PCR, and Western blotting, we explored the expression of cell adhesion molecules, the mRNA expression of endothelial chemokine, the protein levels of cathepsin B, and inflammatory mediators. RESULTS: We found a significant increase in leukocyte-endothelial adhesion in BTBR mice, accompanied by elevated expression of the adhesion molecule neutrophils CD11b and endothelial ICAM-1. Our data further indicate that elevated neutrophil cathepsin B levels contribute to elevated endothelial chemokine CXCL7 levels in BTBR mice. The pharmacological inhibition of cathepsin B reverses the enhanced leukocyte-endothelial adhesion in the cerebral vessels of autistic mice. CONCLUSION: Our results revealed the prominent role of cathepsin B in modulating leukocyte-endothelial adhesion during autism-related neurovascular inflammation and identified a promising novel approach for autism treatment.
Lien vers le texte intégral (Open Access ou abonnement)
20. Weiss EM, Rominger C, Hofer E, Fink A, Papousek I. {{Less differentiated facial responses to naturalistic films of another person’s emotional expressions in adolescents and adults with High-Functioning Autism Spectrum Disorder}}. {Progress in neuro-psychopharmacology & biological psychiatry}. 2018; 89: 341-6.
BACKGROUND: Reduced facial expressivity (flat affect) and deficits in nonverbal communicative behaviors are characteristic symptoms of autism spectrum disorder (ASD). Based on the important interpersonal functions of facial emotional responsiveness the present study aimed at a comprehensive and differentiated analysis of perceptible facial behavior in response to another person’s naturalistic, dynamic facial expressions of emotion. METHODS: In a group of 21 adolescent and adult individuals with High-Funtioning autism spectrum disorder (HF-ASD) and in 21 matched healthy controls we examined perceptible facial responses using the whole range of action units of the Facial Action Coding System (FACS) while participants were watching films displaying continuous, dynamic real-life facial expressions of four universal emotions (cheerfulness, anger, sadness, anxiety). The duration of the 80s films was in the typical range of casual face-to-face interactions. RESULTS: Overall, the number of congruent facial muscle movements while watching the emotion-laden stimulus films did not differ in the two groups. However, the comprehensive FACS analysis indicated that participants with HF-ASD displayed less differentiated facial responses to the watched emotional expressions. CONCLUSIONS: The unusual or awkward patterns of facial emotional responses in ASD may hamper the recognition of affect in other people as well as the interaction partner’s sense of interpersonal resonance, and thereby lead to social disadvantage in individuals with ASD.
