1. Blainey SH, Rumball F, Mercer L, Evans LJ, Beck A. {{An evaluation of the effectiveness of psychological therapy in reducing general psychological distress for adults with autism spectrum conditions and comorbid mental health problems}}. {Clin Psychol Psychother};2017 (Jul 26)
OBJECTIVE: To investigate the effectiveness of psychological therapy in reducing psychological distress for adults with autism spectrum conditions (ASC) and co-morbid mental health conditions in routine clinical practice. To explore the effect of individual characteristics and service factors on change in general distress. METHOD: In a specialist psychological therapies service for adults with ASC, the Clinical Outcomes in Routine Evaluation-Outcome Measure (CORE-OM) self-report questionnaire of psychological distress is completed by clients at start and end of therapy. Change over time and reliable and clinical change was assessed for 81 of a total of 122 clients (66.4%). Factors which may influence change over time were explored using available clinical information. RESULTS: Overall, there was a significant reduction in CORE-OM score during therapy with a small effect size. Most clients showed an improvement in psychological distress over therapy (75.4% improved, with 36.9% of these showing reliable changes). Significant and comparable reductions from pre-therapy to post-therapy were seen across the sample, showing that individual differences did not mediate therapy effectiveness. CORE-OM scores mediate the association between age of ASD diagnosis and hours of therapeutic input required, with greater age at diagnosis and higher distress associated with longer therapy duration. CONCLUSIONS: Our preliminary findings suggest that psychological therapy may be effective in reducing general distress for clients with ASC and co-morbid mental health conditions and should be routinely offered. Individuals who are diagnosed with ASD in adulthood are likely to require a longer course of therapy when their general distress scores are high. Key Practitioner Message Co-morbid mental health conditions are common in adults on the autism spectrum, but there is little evidence for what might be helpful in reducing rates of mental health conditions in this population. This study demonstrates that adapted psychological therapy offered in a specialist adult ASC service was somewhat effective in reducing distress for adults with autism. Individual characteristics and service factors did not influence the extent of change in general distress over the course of therapy; significant and comparable reductions in general distress from pre-therapy to post-therapy were seen across the sample. Individuals who are diagnosed with ASD in adulthood are likely to require a longer course of therapy when their pre-therapy general distress scores are high. Adaptations that may need to be made to services and to therapy delivery are discussed.
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2. Croen LA, Shankute N, Davignon M, Massolo ML, Yoshida C. {{Demographic and Clinical Characteristics Associated with Engagement in Behavioral Health Treatment Among Children with Autism Spectrum Disorders}}. {J Autism Dev Disord};2017 (Jul 26)
This study investigates demographic and clinical factors associated with initiation, continuation, and adherence to behavioral health treatment (BHT) among children with autism spectrum disorder. Among 293 insured children referred for applied behavior analysis (ABA) based BHT, 23% never initiated treatment. Among those initiating treatment, 31% discontinued treatment within 1 year of treatment initiation, and only 15% received 80% or more of recommended treatment hours. Younger age at referral to treatment, private health insurance, and receiving more than 10 h/week of BHT were associated with treatment engagement. Co-occurring psychiatric and medical conditions were related to treatment discontinuation among children 5 years or older. These findings suggest specific subgroups that may benefit from additional support with engaging in recommended behavioral health treatment.
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3. Davidson D, Vanegas SB, Hilvert E. {{Proneness to Self-Conscious Emotions in Adults With and Without Autism Traits}}. {J Autism Dev Disord};2017 (Jul 28)
Self-conscious emotions, such as shame, guilt and pride, facilitate our social interactions by motivating us to adhere to social norms and external standards. In this study, we examined proneness to shame, guilt, hubristic pride and authentic pride in adults with Autism Spectrum Disorder traits (ASD-T) and in neurotypical (NT) adults. Relations between proneness to self-conscious emotions and theory of mind (ToM), fear of negative evaluation, and social functioning were also assessed. Adults with ASD-T showed greater proneness to shame, and less proneness to guilt and pride than NT adults. Both ToM and fear of negative evaluation predicted proneness to self-conscious emotions in ASD-T. These findings are discussed in terms of understanding complex emotion processing in adults with ASD-T.
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4. Del Cole CG, Caetano SC, Ribeiro W, Kummer A, Jackowski AP. {{Adolescent adaptive behavior profiles in Williams-Beuren syndrome, Down syndrome, and autism spectrum disorder}}. {Child Adolesc Psychiatry Ment Health};2017;11:40.
BACKGROUND: Adaptive behavior can be impaired in different neurodevelopmental disorders and may be influenced by confounding factors, such as intelligence quotient (IQ) and socioeconomic classification. Our main objective was to verify whether adaptive behavior profiles differ in three conditions-Williams Beuren syndrome (WBS), Down syndrome (DS), and autism spectrum disorder (ASD), as compared with healthy controls (HC) and with each other. Although the literature points towards each disorder having a characteristic profile, no study has compared profiles to establish the specificity of each one. A secondary objective was to explore potential interactions between the conditions and socioeconomic status, and whether this had any effect on adaptive behavior profiles. METHODS: One hundred and five adolescents were included in the study. All adolescents underwent the following evaluations: the Vineland Adaptive Behavior Scale (VABS), the Wechsler Intelligence Scale for Children (WISC), and the Brazilian Economic Classification Criteria. RESULTS: Our results demonstrated that the WBS group performed better than the DS group in the communication domain, beta = -15.08, t(3.45), p = .005, and better than the ASD group in the socialization domain, beta = 8.92, t(-2.08), p = .013. The DS group also performed better than the ASD group in socialization, beta = 16.98, t(-2.32), p = .024. IQ was an important confounding factor, and socioeconomic status had an important effect on the adaptive behavior of all groups. CONCLUSIONS: There is a heterogeneity regarding adaptive behavior profiles in WBS, DS, and ASD. These data are important to better design specific strategies related to the health and social care of each particular group.
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5. Fusar-Poli L, Brondino N, Rocchetti M, Panisi C, Provenzani U, Damiani S, Politi P. {{Diagnosing ASD in Adults Without ID: Accuracy of the ADOS-2 and the ADI-R}}. {J Autism Dev Disord};2017 (Jul 28)
Diagnosing autism spectrum disorder (ASD) in adulthood often represents a challenge in clinical practice. The aim of the present study was to evaluate the sensitivity and specificity of the ADOS and ADI-R in diagnosing ASD in adults. 113 subjects with an IQ of 70 or above were assessed through an extensive clinical evaluation. The ADOS-2 Module 4 and the ADI-R were separately administered by staff members blind to clinical judgment. Our results cautiously confirm the accuracy of ADOS-2 Module 4, while suggest that ADI-R might not be reliable in adults without intellectual disability. Clinicians’ training and experience remains of primary importance while assessing adults who could potentially belong to the autism spectrum.
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6. Gong JB, Wang Y, Lui SSY, Cheung EFC, Chan RCK. {{Childhood trauma is not a confounder of the overlap between autistic and schizotypal traits: A study in a non-clinical adult sample}}. {Psychiatry Res};2017 (Jul 17);257:111-117.
Childhood trauma has been shown to be a robust risk factor for mental disorders, and may exacerbate schizotypal traits or contribute to autistic trait severity. However, little is known whether childhood trauma confounds the overlap between schizotypal traits and autistic traits. This study examined whether childhood trauma acts as a confounding variable in the overlap between autistic and schizotypal traits in a large non-clinical adult sample. A total of 2469 participants completed the Autism Spectrum Quotient (AQ), the Schizotypal Personality Questionnaire (SPQ), and the Childhood Trauma Questionnaire-Short Form. Correlation analysis showed that the majority of associations between AQ variables and SPQ variables were significant (p < 0.05). In the multiple regression models predicting scores on the AQ total, scores on the three SPQ subscales were significant predictors(Ps < 0.05). Scores on the Positive schizotypy and Negative schizotypy subscales were significant predictors in the multiple regression model predicting scores on the AQ Social Skill, AQ Attention Switching, AQ Attention to Detail, AQ Communication, and AQ Imagination subscales. The association between autistic and schizotypal traits could not be explained by shared variance in terms of exposure to childhood trauma. The findings point to important overlaps in the conceptualization of ASD and SSD, independent of childhood trauma. Lien vers le texte intégral (Open Access ou abonnement)
7. Gould J. {{Towards understanding the under-recognition of girls and women on the autism spectrum}}. {Autism};2017 (Aug);21(6):703-705.
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8. Gurau O, Bosl WJ, Newton CR. {{How Useful Is Electroencephalography in the Diagnosis of Autism Spectrum Disorders and the Delineation of Subtypes: A Systematic Review}}. {Front Psychiatry};2017;8:121.
Autism spectrum disorders (ASD) are thought to be associated with abnormal neural connectivity. Presently, neural connectivity is a theoretical construct that cannot be easily measured. Research in network science and time series analysis suggests that neural network structure, a marker of neural activity, can be measured with electroencephalography (EEG). EEG can be quantified by different methods of analysis to potentially detect brain abnormalities. The aim of this review is to examine evidence for the utility of three methods of EEG signal analysis in the ASD diagnosis and subtype delineation. We conducted a review of literature in which 40 studies were identified and classified according to the principal method of EEG analysis in three categories: functional connectivity analysis, spectral power analysis, and information dynamics. All studies identified significant differences between ASD patients and non-ASD subjects. However, due to high heterogeneity in the results, generalizations could not be inferred and none of the methods alone are currently useful as a new diagnostic tool. The lack of studies prevented the analysis of these methods as tools for ASD subtypes delineation. These results confirm EEG abnormalities in ASD, but as yet not sufficient to help in the diagnosis. Future research with larger samples and more robust study designs could allow for higher sensitivity and consistency in characterizing ASD, paving the way for developing new means of diagnosis.
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9. Herrema R, Garland D, Osborne M, Freeston M, Honey E, Rodgers J. {{Brief Report: What Happens When I Can No Longer Support My Autistic Relative? Worries About the Future for Family Members of Autistic Adults}}. {J Autism Dev Disord};2017 (Jul 28)
Very little is known about autism and adulthood. Family members are often the primary support for autistic adults and frequently express concerns about what the future will hold and what support will be available for their relative. 120 family members of autistic adults completed an online survey exploring concerns about the future for their relative. The most endorsed concerns were « their needs won’t be met » (77% worried weekly), « whether they will be happy » (72% worried weekly) and « who will care for them » (58% worried weekly). The results highlight the importance of implementing structured and timely support through collaboration with governmental policy, local commissioning and communication with charities to help prepare family members and their autistic relative for the future.
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10. Hull L, Mandy W, Petrides KV. {{Behavioural and cognitive sex/gender differences in autism spectrum condition and typically developing males and females}}. {Autism};2017 (Aug);21(6):706-727.
Studies assessing sex/gender differences in autism spectrum conditions often fail to include typically developing control groups. It is, therefore, unclear whether observed sex/gender differences reflect those found in the general population or are particular to autism spectrum conditions. A systematic search identified articles comparing behavioural and cognitive characteristics in males and females with and without an autism spectrum condition diagnosis. A total of 13 studies were included in meta-analyses of sex/gender differences in core autism spectrum condition symptoms (social/communication impairments and restricted/repetitive behaviours and interests) and intelligence quotient. A total of 20 studies were included in a qualitative review of sex/gender differences in additional autism spectrum condition symptoms. For core traits and intelligence quotient, sex/gender differences were comparable in autism spectrum conditions and typical samples. Some additional autism spectrum condition symptoms displayed different patterns of sex/gender differences in autism spectrum conditions and typically developing groups, including measures of executive function, empathising and systemising traits, internalising and externalising problems and play behaviours. Individuals with autism spectrum conditions display typical sex/gender differences in core autism spectrum condition traits, suggesting that diagnostic criteria based on these symptoms should take into account typical sex/gender differences. However, awareness of associated autism spectrum condition symptoms should include the possibility of different male and female phenotypes, to ensure those who do not fit the ‘typical’ autism spectrum condition presentation are not missed.
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11. Kabitzke P, Brunner D, He D, Fazio PA, Cox K, Sutphen J, Thiede L, Sabath E, Hanania T, Alexandrov V, Rasmusson R, Spooren W, Ghosh A, Feliciano P, Biemans B, Benedetti M, Luo Clayton A. {{Comprehensive Analysis of Two Shank3 and the Cacna1c Mouse Models of Autism Spectrum Disorder}}. {Genes Brain Behav};2017 (Jul 28)
To expand, analyze, and extend published behavioral phenotypes relevant to autism spectrum disorder (ASD), we present a study of three ASD genetic mouse models: Feng’s Shank3tm2Gfng model, hereafter Shank3/F, Jiang’s Shank3tm1Yhj model, hereafter Shank3/J, and the Cacna1c deletion model. The Shank3 models mimick gene mutations associated with Phelan-McDermid Syndrome and the Cacna1c model recapitulates the deletion underlying Timothy syndrome. The current study utilizes both standard and novel behavioral tests with the same methodology used in our previously published companion report on the Cntnap2 null and 16p11.2 deletion models. We found that some but not all behaviors replicated published findings and those that did replicate, such as social behavior and overgrooming in Shank3 models, tended to be milder than reported elsewhere. The Shank3/F model, and to a much lesser extent, the Shank3/J and Cacna1c models, showed hypoactivity and a general anxiety-like behavior triggered by external stimuli which pervaded social interactions. We did not detect deficits in a cognitive procedural learning test nor did we observe perseverative behavior in these models. We did, however, find differences in exploratory patterns of Cacna1c mutant mice suggestive of a behavioral effect in a social setting. In addition, only Shank3/F showed differences in sensory-gating. Both positive and negative results from this study will be useful in identifying the most robust and replicable behavioral signatures within and across mouse models of autism. Understanding these phenotypes may shed light of which features to study when screening compounds for potential therapeutic interventions.
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12. Kana RK, Sartin EB, Stevens C, Jr., Deshpande HD, Klein C, Klinger MR, Klinger LG. {{Neural networks underlying language and social cognition during self-other processing in Autism spectrum disorders}}. {Neuropsychologia};2017 (Jul 28);102:116-123.
The social communication impairments defining autism spectrum disorders (ASD) may be built upon core deficits in perspective-taking, language processing, and self-other representation. Self-referential processing entails the ability to incorporate self-awareness, self-judgment, and self-memory in information processing. Very few studies have examined the neural bases of integrating self-other representation and semantic processing in individuals with ASD. The main objective of this functional MRI study is to examine the role of language and social brain networks in self-other processing in young adults with ASD. Nineteen high-functioning male adults with ASD and 19 age-sex-and-IQ-matched typically developing (TD) control participants made « yes » or « no » judgments of whether an adjective, presented visually, described them (self) or their favorite teacher (other). Both ASD and TD participants showed significantly increased activity in the medial prefrontal cortex (MPFC) during self and other processing relative to letter search. Analyses of group differences revealed significantly reduced activity in left inferior frontal gyrus (LIFG), and left inferior parietal lobule (LIPL) in ASD participants, relative to TD controls. ASD participants also showed significantly weaker functional connectivity of the anterior cingulate cortex (ACC) with several brain areas while processing self-related words. The LIFG and IPL are important regions functionally at the intersection of language and social roles; reduced recruitment of these regions in ASD participants may suggest poor level of semantic and social processing. In addition, poor connectivity of the ACC may suggest the difficulty in meeting the linguistic and social demands of this task in ASD. Overall, this study provides new evidence of the altered recruitment of the neural networks underlying language and social cognition in ASD.
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13. Keenan EG, Gotham K, Lerner MD. {{Hooked on a feeling: Repetitive cognition and internalizing symptomatology in relation to autism spectrum symptomatology}}. {Autism};2017 (Jul 01):1362361317709603.
Repetitive cognition, including rumination such as that seen in depression, has been shown to correlate with depression symptoms in both typically developing individuals and individuals with autism spectrum disorder. Repetitive cognition is more common in autism spectrum disorder than in typically developing peers, as is depression; thus, this study evaluated the role of repetitive cognition in relation between autism spectrum symptomatology and depressive symptomatology. In all, 200 typically developing adults completed self-report questionnaires measuring autism spectrum symptomatology, different forms of repetitive cognition (general perseveration and depressive rumination), depression, and rejection sensitivity. Perseveration was found to mediate the relation between autism spectrum symptoms and depression, and to partially mediate the relation between autism spectrum symptoms and rejection sensitivity. We conclude that it is of vital importance to consider cognition when considering depression in autism spectrum disorder.
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14. Kerns CM, Wood JJ, Kendall PC, Renno P, Crawford EA, Mercado RJ, Fujii C, Collier A, Hoff A, Kagan ER, Small BJ, Lewin AB, Storch EA. {{The Treatment of Anxiety in Autism Spectrum Disorder (TAASD) Study: Rationale, Design and Methods}}. {J Child Fam Stud};2016 (Jun);25(6):1889-1902.
This paper describes the rationale, design, and methods of the Treatment for Anxiety in Autism Spectrum Disorders study, a three-site randomized controlled trial investigating the relative efficacy of a modular CBT protocol for anxiety in ASD (Behavioral Interventions for Anxiety in Children with Autism) versus standard CBT for pediatric anxiety (the Coping Cat program) and a treatment-as-usual control. The trial is distinct in its scope, its direct comparison of active treatments for anxiety in ASD, and its comprehensive approach to assessing anxiety difficulties in youth with ASD. The trial will evaluate the relative benefits of CBT for children with ASD and investigate potential moderators (ASD severity, anxiety presentation, comorbidity) and mediators of treatment response, essential steps for future dissemination and implementation.
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15. Kirsten TB, Bernardi MM. {{Prenatal lipopolysaccharide induces hypothalamic dopaminergic hypoactivity and autistic-like behaviors: Repetitive self-grooming and stereotypies}}. {Behav Brain Res};2017 (Jul 28);331:25-29.
Previous investigations by our group have shown that prenatal exposure to lipopolysaccharide (LPS), which mimics infection by gram-negative bacteria, induces social, cognitive, and communication deficits. For a complete screening of autistic-like behaviors, the objective of this study was to evaluate if our rat model also induces restricted and repetitive stereotyped behaviors. Thus, we studied the self-grooming microstructure. We also studied the neurochemistry of hypothalamus and frontal cortex, which are brain areas related to autism to better understand central mechanisms involved in our model. Prenatal LPS exposure on gestational day 9.5 increased the head washing episodes (frequency and time), as well as the total self-grooming. However, body grooming, paw/leg licking, tail/genital grooming, and circling behavior/tail chasing did not vary significantly among the groups. Moreover, prenatal LPS induced dopaminergic hypoactivity (HVA metabolite and turnover) in the hypothalamus. Therefore, our rat model induced restricted and repetitive stereotyped behaviors and the other main symptoms of autism experimentally studied in rodent models and also found in patients. The hypothalamic dopaminergic impairments seem to be associated with the autistic-like behaviors.
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16. Mandy W, Lai MC. {{Towards sex- and gender-informed autism research}}. {Autism};2017 (Aug);21(6):643-645.
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17. Mussey JL, Ginn NC, Klinger LG. {{Are males and females with autism spectrum disorder more similar than we thought?}}. {Autism};2017 (Aug);21(6):733-737.
Differences in behavioral and cognitive profiles have been suggested to potentially impact the presentation of social and communication symptoms in females with autism spectrum disorder. This study examined gender differences in age of diagnosis, cognitive profiles, social communication symptomatology, and autism spectrum disorder symptom severity in a community-based sample of 566 males and 113 females with autism spectrum disorder ranging in age from 1 year, 9 months to 56 years, 4 months. Results suggest either very small or no gender differences in age at diagnosis, intelligence quotient, cognitive profiles, or autism spectrum disorder symptom severity. This is a departure from clinical lore that females with autism spectrum disorder are more likely to have lower intelligence quotient and more severe impairments. There is a slight difference in symptom severity with females having higher average total Childhood Autism Rating Scale scores, but this difference is likely of minimal clinical significance. In contrast, on the Autism Diagnostic Observation Schedule-Generic, females were found to receive lower scores than males particularly on modules 2 and 3. Across males and females, individuals with stronger verbal problem-solving skills were found to receive lower Autism Diagnostic Observation Schedule-Generic module 3 scores. Given the language demands of this module, additional attention may be warranted when evaluating older children and adolescents for autism spectrum disorder.
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18. Padden C, James JE. {{Stress among Parents of Children with and without Autism Spectrum Disorder: A Comparison Involving Physiological Indicators and Parent Self-Reports}}. {J Dev Phys Disabil};2017;29(4):567-586.
Parents of children with Autism Spectrum Disorder (ASD) have been reported as experiencing higher levels of stress and poorer physical health than parents of typically developing children. However, most of the relevant literature has been based on parental self-reports of stress and health. While research on physiological outcomes has grown in recent years, gaps still exist in our understanding of the physiological effects, if any, of stress related to parenting a child with ASD. The present study compared parent-reported stress, anxiety, and depression, as well as selected physiological measures of stress (i.e., cortisol, alpha-amylase, and ambulatory blood pressure and heart rate) between matched groups of parents of children with (N = 38) and without (N = 38) ASD. Participants completed questionnaires, collected saliva samples for the purpose of measuring cortisol and alpha-amylase, and wore an ambulatory blood pressure monitor for 24 h. Parents of children with ASD reported significantly higher levels of parental distress, anxiety, and depression than parents of typically developing children. Parent-reported distress, anxiety, depression, and health were not correlated with physiological measures. With the exception that parents of children with ASD had significantly lower cortisol levels 30 min after waking, no other significant group differences were found for physiological measures. Parents of children with ASD reported significantly higher use of a number of adaptive coping strategies (e.g., emotional support) in comparison to parents of typically developing children. Results are discussed in the context of implications for future research directions, stress research, and practical implications for parental support.
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19. Paval D. {{A Dopamine Hypothesis of Autism Spectrum Disorder}}. {Dev Neurosci};2017 (Jul 28)
Autism spectrum disorder (ASD) comprises a group of neurodevelopmental disorders characterized by social deficits and stereotyped behaviors. While several theories have emerged, the pathogenesis of ASD remains unknown. Although studies report dopamine signaling abnormalities in autistic patients, a coherent dopamine hypothesis which could link neurobiology to behavior in ASD is currently lacking. In this paper, we present such a hypothesis by proposing that autistic behavior arises from dysfunctions in the midbrain dopaminergic system. We hypothesize that a dysfunction of the mesocorticolimbic circuit leads to social deficits, while a dysfunction of the nigrostriatal circuit leads to stereotyped behaviors. Furthermore, we discuss 2 key predictions of our hypothesis, with emphasis on clinical and therapeutic aspects. First, we argue that dopaminergic dysfunctions in the same circuits should associate with autistic-like behavior in nonautistic subjects. Concerning this, we discuss the case of PANDAS (pediatric autoimmune neuropsychiatric disorder associated with streptococcal infections) which displays behaviors similar to those of ASD, presumed to arise from dopaminergic dysfunctions. Second, we argue that providing dopamine modulators to autistic subjects should lead to a behavioral improvement. Regarding this, we present clinical studies of dopamine antagonists which seem to have improving effects on autistic behavior. Furthermore, we explore the means of testing our hypothesis by using neuroreceptor imaging, which could provide comprehensive evidence for dopamine signaling dysfunctions in autistic subjects. Lastly, we discuss the limitations of our hypothesis. Along these lines, we aim to provide a dopaminergic model of ASD which might lead to a better understanding of the ASD pathogenesis.
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20. Perets N, Segal-Gavish H, Gothelf Y, Barzilay R, Barhum Y, Abramov N, Hertz S, Morozov D, London M, Offen D. {{Long term beneficial effect of neurotrophic factors-secreting mesenchymal stem cells transplantation in the BTBR mouse model of autism}}. {Behav Brain Res};2017 (Jul 28);331:254-260.
Autism spectrum disorders (ASD) are neurodevelopmental disabilities characterized by severe impairment in social communication skills and restricted, repetitive behaviors. We have previously shown that a single transplantation of mesenchymal stem cells (MSC) into the cerebral lateral ventricles of BTBR autistic-like mice resulted in an improvement across all diagnostic criteria of ASD. We suggested that brain-derived neurotrophic factor (BDNF), a protein which supports the survival and regeneration of neurons secreted by MSC, largely contributed to the beneficial behavioral effect. In this study, we investigated the behavioral effects of transplanted MSC induced to secrete higher amounts of neurotrophic factors (NurOwn(R)), on various ASD-related behavioral domains using the BTBR mouse model of ASD. We demonstrate that NurOwn(R) transplantation had significant advantages over MSC transplantation in terms of improving communication skills, one and six months following treatment, as compared to sham-treated BTBR mice. Furthermore, NurOwn(R) transplantation resulted in reduced stereotypic behavior for as long as six months post treatment, compared to the one month improvement observed in the MSC treated mice. Notably, NurOwn(R) treatment resulted in improved cognitive flexibility, an improvement that was not observed by MSC treatment. Both MSC and NurOwn(R) transplantation induced an improvement in social behavior that lasted for six months. In conclusion, the present study demonstrates that a single transplantation of MSC or NurOwn(R) have long-lasting benefits, while NurOwn(R) may be superior to MSC treatment.
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21. Ramtekkar UP. {{DSM-5 Changes in Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder: Implications for Comorbid Sleep Issues}}. {Children (Basel)};2017 (Jul 27);4(8)
Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD) are the most common neurodevelopmental disorders. Despite significant comorbidity, the previous diagnostic criteria prohibited the simultaneous diagnosis of both disorders. Sleep problems are highly prevalent in both disorders; however, these have been studied independently for ADHD and ASD. In the context of revised criteria in the Diagnostic Statistical Manual of Mental Disorders 5th edition (DSM-5) that allows combined diagnosis of ADHD and ASD, this short review presents an overview of relationship between sleep problems, ADHD and ASD, as well as conceptualizing the shared pathophysiology. The practical considerations for clinical management of sleep problems in combination with ADHD and ASD are also discussed.
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22. Rubenstein E, Edmondson Pretzel R, Windham GC, Schieve LA, Wiggins LD, DiGuiseppi C, Olshan AF, Howard AG, Pence BW, Young L, Daniels J. {{The Broader Autism Phenotype in Mothers is Associated with Increased Discordance Between Maternal-Reported and Clinician-Observed Instruments that Measure Child Autism Spectrum Disorder}}. {J Autism Dev Disord};2017 (Jul 26)
Autism spectrum disorder (ASD) diagnosis relies on parent-reported and clinician-observed instruments. Sometimes, results between these instruments disagree. The broader autism phenotype (BAP) in parent-reporters may be associated with discordance. Study to Explore Early Development data (N = 712) were used to address whether mothers with BAP and children with ASD or non-ASD developmental disabilities were more likely than mothers without BAP to ‘over-‘ or ‘under-report’ child ASD on ASD screeners or interviews compared with clinician observation or overall impression. Maternal BAP was associated with a child meeting thresholds on a maternal-reported screener or maternal interview when clinician ASD instruments or impressions did not (risk ratios: 1.30 to 2.85). Evidence suggests acknowledging and accounting for reporting discordances may be important when diagnosing ASD.
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23. Sato W, Uono S, Kochiyama T, Yoshimura S, Sawada R, Kubota Y, Sakihama M, Toichi M. {{Structural Correlates of Reading the Mind in the Eyes in Autism Spectrum Disorder}}. {Front Hum Neurosci};2017;11:361.
Behavioral studies have shown that individuals with autism spectrum disorder (ASD) have impaired ability to read the mind in the eyes. Although this impairment is central to their social malfunctioning, its structural neural correlates remain unclear. To investigate this issue, we assessed Reading the Mind in the Eyes Test, revised version (Eyes Test) and acquired structural magnetic resonance images in adults with high-functioning ASD (n = 19) and age-, sex- and intelligence quotient-matched typically developing (TD) controls (n = 19). On the behavioral level, the Eyes Test scores were lower in the ASD group than in the control group. On the neural level, an interaction between group and Eyes Test score was found in the left temporoparietal junction (TPJ). A positive association between the Eyes Test score and gray matter volume of this region was evident in the control group, but not in the ASD group. This finding suggests that the failure to develop appropriate structural neural representations in the TPJ may underlie the impaired ability of individuals with ASD to read the mind in the eyes. These behavioral and neural findings provide support for the theories that impairments in processing eyes and the ability to infer others’ mental states are the core symptoms of ASD, and that atypical features in the social brain network underlie such impairments.
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24. Sheppard KW, Boone KM, Gracious B, Klebanoff MA, Rogers LK, Rausch J, Bartlett C, Coury DL, Keim SA. {{Effect of Omega-3 and -6 Supplementation on Language in Preterm Toddlers Exhibiting Autism Spectrum Disorder Symptoms}}. {J Autism Dev Disord};2017 (Jul 26)
Delayed language development may be an early indicator of autism spectrum disorder (ASD). Early intervention is critical for children with ASD, and the present study presents pilot data on a clinical trial of omega-3 and -6 fatty acid supplementation and language development, a secondary trial outcome, in children at risk for ASD. We randomized 31 children to receive an omega-3 and -6 supplement or a placebo for 3 months, and measured their language abilities at baseline and after supplementation. Gesture use, but not word production, increased for children in the treatment group more than children in the placebo group. These results suggest possible effectiveness of omega-3 and -6 supplementation for language development in children at risk for ASD.
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25. van Steenburgh JJ, Varvaris M, Schretlen DJ, Vannorsdall TD, Gordon B. {{Balanced bifrontal transcranial direct current stimulation enhances working memory in adults with high-functioning autism: a sham-controlled crossover study}}. {Mol Autism};2017;8:40.
BACKGROUND: Working memory (WM) often is impaired in autism spectrum disorder (ASD). Such impairment may underlie core deficits in cognition and social functioning. Transcranial direct current stimulation (tDCS) has been shown to enhance WM in both healthy adults and clinical populations, but its efficacy in ASD is unknown. We predicted that bifrontal tDCS would improve WM performances of adults with high-functioning autism during active stimulation compared to sham stimulation and that such enhancement would generalize to an untrained task. METHODS: Twelve adults with high-functioning ASD engaged in a battery of WM tasks that included backward spatial span, backward digit span, spatial n-back and letter n-back. While engaged, 40 min of 1.5 mA bifrontal stimulation was applied over the left and the right dorsolateral prefrontal cortices (DLPFC). Using a single-blind crossover design, each participant received left anodal/right cathodal stimulation, right anodal/left cathodal stimulation, or sham stimulation, in randomized counterbalanced order on three separate days. Following tDCS, participants again engaged in letter and spatial n-back tasks before taking the Brief Test of Attention (BTA). We used repeated-measures ANOVA to compare overall performance on the WM battery as measured by a composite of z-scores for all five measures. Post hoc ANOVAs, t tests, Friedman’s tests, and Wilcoxon signed-rank tests were used to measure the online and offline effects of tDCS and to assess performances on individual measures. RESULTS: Compared to sham stimulation, both left DLPFC anodal stimulation (t11 = 5.4, p = 0.0002) and right DLPFC anodal stimulation (t11 = 3.57, p = 0.004) improved overall WM performance. Left anodal stimulation (t11 = 3.9, p = 0.003) and right anodal stimulation (t11 = 2.7, p = 0.019) enhanced performances during stimulation. Enhancement transferred to an untrained task 50 min after right anodal stimulation (z11 = 2.263, p = 0.024). The tasks that showed the largest effects of active stimulation were spatial span backward (z11 = 2.39, p = 0.017) and BTA (z11 = 2.263, p = 0.024). CONCLUSIONS: In adults with high-functioning ASD, active bifrontal tDCS given during WM tasks appears to improve performance. TDCS benefits also transferred to an untrained task completed shortly after stimulation. These results suggest that tDCS can improve WM task performance and could reduce some core deficits of autism. TRIAL REGISTRATION: NCT01602263.
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26. Webster AA, Garvis S. {{The importance of critical life moments: An explorative study of successful women with autism spectrum disorder}}. {Autism};2017 (Aug);21(6):670-677.
Ten women with autism spectrum disorder participated in oral interviews in order to share their experiences since their diagnosis and to discuss the factors that had enabled them to achieve success in different aspects of their life. Participants were encouraged to share their perspectives on their success and to discuss the challenges they encountered in their daily lives and how they overcame these. Interviews were analysed using a narrative-themed approach. Participants indicated that both internal and external factors enabled them to achieve success in different aspects of their lives. These included being an agent of change, a changed identity after diagnosis, experiencing the belief of others in their capability and seeing themselves as a mentor to others. Their experiences with overcoming obstacles in their lives enabled them to develop self-efficacy and to shape their own success.
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27. Williams JHG, Cameron IM. {{The Actions and Feelings Questionnaire in Autism and Typically Developed Adults}}. {J Autism Dev Disord};2017 (Jul 28)
Impaired motor cognition may underpin empathy problems in autism. The actions and feelings questionnaire (AFQ), designed to examine individual differences in motor cognition, was completed fully by 1391 adults, of whom 326 reported a diagnosis of an autism spectrum condition (ASC). A confirmatory factor analysis supported a 3 factor model. The AFQ total and ‘feelings’ subscale scores correlated highly with the EQ and ROC curves were similar. Our findings suggest that individual differences in empathic traits are heavily accounted for by variance in mechanisms that serve sensorimotor learning (motor cognition) in relation to emotional states. The AFQ is a self-report tool that provides a valid indicator of autism status in adult populations.
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28. Yenkoyan K, Grigoryan A, Fereshetyan K, Yepremyan D. {{Advances in understanding the pathophysiology of autism spectrum disorders}}. {Behav Brain Res};2017 (Jul 28);331:92-101.
Autism spectrum disorders (ASD) are common heterogeneous neurodevelopmental disorders with typical triad of symptoms: impaired social interaction, language and communication abnormalities and stereotypical behavior. Despite extensive research, the etiology and pathogenesis of ASD remain largely unclear. The lack of solid knowledge on the mechanisms of these disorders decreases the opportunities for pathogenetic treatment of autism. Various theories where proposed in order to explain the pathophysiology underlying ASD. Despite the fact that none of them is able to completely explain the impairments in the nervous system of ASD patients, these hypotheses were instrumental in highlighting the most important mechanisms in the development of this complex disorder. Some new theories are based on neurovisualization studies, others on the data from genomic studies, which become increasingly available worldwide. As the research in this field is largely dependent on the animal models, there is an ongoing discussion and search for the most appropriate one adequately reproducing the pathology. Here we provide an overview of current theories of the origin and development of ASD discussed in the context of existing and proposed rodent models of ASD.
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29. Yi JJ, Paranjape SR, Walker MP, Choudhury R, Wolter JM, Fragola G, Emanuele MJ, Major MB, Zylka MJ. {{The autism-linked UBE3A T485A mutant E3 ubiquitin ligase activates the Wnt/beta-catenin pathway by inhibiting the proteasome}}. {J Biol Chem};2017 (Jul 28);292(30):12503-12515.
UBE3A is a HECT domain E3 ubiquitin ligase whose dysfunction is linked to autism, Angelman syndrome, and cancer. Recently, we characterized a de novo autism-linked UBE3A mutant (UBE3AT485A) that disrupts phosphorylation control of UBE3A activity. Through quantitative proteomics and reporter assays, we found that the UBE3AT485A protein ubiquitinates multiple proteasome subunits, reduces proteasome subunit abundance and activity, stabilizes nuclear beta-catenin, and stimulates canonical Wnt signaling more effectively than wild-type UBE3A. We also found that UBE3AT485A activates Wnt signaling to a greater extent in cells with low levels of ongoing Wnt signaling, suggesting that cells with low basal Wnt activity are particularly vulnerable to UBE3AT485A mutation. Ligase-dead UBE3A did not stimulate Wnt pathway activation. Overexpression of several proteasome subunits reversed the effect of UBE3AT485A on Wnt signaling. We also observed that subunits that interact with UBE3A and affect Wnt signaling are located along one side of the 19S regulatory particle, indicating a previously unrecognized spatial organization to the proteasome. Altogether, our findings indicate that UBE3A regulates Wnt signaling in a cell context-dependent manner and that an autism-linked mutation exacerbates these signaling effects. Our study has broad implications for human disorders associated with UBE3A gain or loss of function and suggests that dysfunctional UBE3A might affect additional proteins and pathways that are sensitive to proteasome activity.
