Autism Research and Treatment最新文献

{"title":"A Need for Consistency in Behavioral Phenotyping for ASD: Analysis of the Valproic Acid Model.","authors":"Olivia Larner,&nbsp;Jane Roberts,&nbsp;Jeffery Twiss,&nbsp;Linnea Freeman","doi":"10.1155/2021/8863256","DOIUrl":"https://doi.org/10.1155/2021/8863256","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a highly prevalent and impairing neurodevelopmental disorder that affects 1 : 54 persons. Over the last several decades, the reported incidence of ASD in the US has increased potentially due to increased awareness and improved diagnostic measurement. Although ASD prevalence is increasing, the etiology of ASD remains relatively unknown. To better understand the neurological basis of ASD, rodent models of ASD have been developed for research. Currently, there is not a standardized set of behavioral tests to quantify ASD-like behavior in rodents. The goal of this review is to present an overview of the methodologies used to analyze ASD-like behaviors in rodents, focusing on the valproic acid (VPA) model, and illustrate inconsistencies between different approaches. Despite that the <i>in utero</i> VPA rodent model for ASD is widely used and extensively characterized, behaviors vary substantially between different researchers. Moving forward, consistency in behavioral method analytics would benefit progress in evaluating interventions for all models of ASD and help to uncover unique qualities underlying mechanisms causing ASD signs and symptoms.</p>","PeriodicalId":8659,"journal":{"name":"Autism Research and Treatment","volume":"2021 ","pages":"8863256"},"PeriodicalIF":0.0,"publicationDate":"2021-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8004365/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25569589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autism Spectrum Disorder: Investigating Predictive Adaptive Behavior Skill Deficits in Young Children.","authors":"Emma Feige, Rhonda Mattingly, Teresa Pitts, Alan F Smith","doi":"10.1155/2021/8870461","DOIUrl":"10.1155/2021/8870461","url":null,"abstract":"<p><p>Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder that consists of difficulties with social communication and language, as well as the presence of restricted and repetitive behaviors. These deficits tend to present in early childhood and usually lead to impairments in functioning across various settings. Moreover, these deficits have been shown to negatively impact adaptive behavior and functioning. Thus, early diagnosis and intervention is vital for future success within this population. The purpose of this study was to further examine the subscales that comprise the adaptive behavior section of the Bayley®-III to determine which of the ten subscales are predictive of ASD in young children (i.e., ≤ three years of age). A retrospective file review of 273 children participating in Kentucky's early intervention program, First Steps, was completed. The children ranged in age from 18 to 35 months. A binary logistic regression was used to assess the subscales that comprise the adaptive behavior of the section of the Bayley®-III to determine which of the ten subscales are predictive of ASD in young children (i.e., ≤ three years of age). The results indicated that individual lower raw scores in communication, community use, functional preacademics, home living, health and safety, leisure, self-care, self-direction, and social subscales were predictive of an autism diagnosis.</p>","PeriodicalId":8659,"journal":{"name":"Autism Research and Treatment","volume":"2021 ","pages":"8870461"},"PeriodicalIF":0.0,"publicationDate":"2021-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25383281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxidative Stress, Folate Receptor Autoimmunity, and CSF Findings in Severe Infantile Autism.","authors":"Vincent T Ramaekers,&nbsp;Jeffrey M Sequeira,&nbsp;Beat Thöny,&nbsp;Edward V Quadros","doi":"10.1155/2020/9095284","DOIUrl":"https://doi.org/10.1155/2020/9095284","url":null,"abstract":"<p><strong>Background: </strong>Biomarkers such as oxidative stress, folate receptor alpha (FR<i>α</i>) autoimmunity, and abnormal brain serotonin turnover are common in autism.</p><p><strong>Methods: </strong>Oxidative stress biomarkers with pro- and antioxidants were measured in the severe form of infantile autism (<i>n</i> = 38) and controls (<i>n</i> = 24). Children and parents had repeated testing for serum FR autoantibodies, spinal fluid dopamine and serotonin metabolites, pterins, and N⁵-methyltetrahydrofolate (MTHF). Statistical analysis assessed correlations between variables. Genetic analysis included the SLC6A4 and SLC29A4 genes encoding synaptic serotonin reuptake proteins.</p><p><strong>Results: </strong>Compared to controls, the autism group showed a significant increase in oxidative DNA damage in lymphocytes, plasma ceruloplasmin and copper levels with a high copper/zinc ratio, thiol proteins, and superoxide dismutase (SOD) activity. Vitamin C levels were significantly diminished. In most autistic patients, the vitamin A (64%) and D (70%) levels were low. Serum FR autoantibodies fluctuating over 5-7 week periods presented in 68% of all autistic children, 41% of parents vs. 3.3% of control children and their parents. CSF showed lowered serotonin 5-hydroxyindole acetic acid (5HIAA) metabolites in 13 (34%), a low 5HIAA to HVA (dopamine metabolite) ratio in 5 (13%), low 5HIAA and MTHF in 2 (5%), and low MTHF in 8 patients (21%). A known SLC6A4 mutation was identified only in 1 autistic child with low CSF 5HIAA and a novel SLC29A4 mutation was identified in identical twins. Low CSF MTHF levels among only 26% of subjects can be explained by the fluctuating FR antibody titers. Two or more aberrant pro-oxidant and/or antioxidant factors predisposed to low CSF serotonin metabolites. Three autistic children having low CSF 5HIAA and elevated oxidative stress received antioxidative supplements followed by CSF 5HIAA normalisation.</p><p><strong>Conclusion: </strong>In autism, we found diverse combinations for FR autoimmunity and/or oxidative stress, both amenable to treatment. Parental and postnatal FR autoantibodies tend to block folate passage to the brain affecting folate-dependent pathways restored by folinic acid treatment, while an abnormal redox status tends to induce reduced serotonin turnover, corrected by antioxidant therapy. <i>Trial Registration</i>. The case-controlled study was approved in 2008 by the IRB at Liège University (Belgian Number: B70720083916). <i>Lay Summary</i>. Children with severe infantile autism frequently have serum folate receptor autoantibodies that block the transport of the essential vitamin folate across the blood-brain barrier to the brain. Parents are often asymptomatic carriers of these serum folate receptor autoantibodies, which in mothers can block folate passage across the placenta to their unborn child. This folate deficiency during the child's intrauterine development may predispose to ne","PeriodicalId":8659,"journal":{"name":"Autism Research and Treatment","volume":"2020 ","pages":"9095284"},"PeriodicalIF":0.0,"publicationDate":"2020-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/9095284","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38689340","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Is Earlier Better? The Relationship between Age When Starting Early Intervention and Outcomes for Children with Autism Spectrum Disorder: A Selective Review.","authors":"Patricia O Towle, Patricia A Patrick, Tamique Ridgard, Sofia Pham, Jaime Marrus","doi":"10.1155/2020/7605876","DOIUrl":"10.1155/2020/7605876","url":null,"abstract":"<p><p>Although the conventional wisdom is that \"earlier is better\" when it comes to intervention for children with ASD, it is not clear what evidence exists to support this notion. This review examined a group of studies that addressed outcomes for young children with ASD who started early intervention at a range of ages. The review was selective by including only papers that examined the age of initiation of treatment as well as baseline cognitive, language, or adaptive level and, in addition, employed a method to control for the covariance between early ability level and age of beginning intervention. Fourteen studies were identified and then compared on methods and outcomes. The support for \"earlier is better\" was mixed, but it was clear that complex relationships among predictor variables need to be explored in order to understand the role of age of starting early intervention for later outcomes.</p>","PeriodicalId":8659,"journal":{"name":"Autism Research and Treatment","volume":"2020 ","pages":"7605876"},"PeriodicalIF":0.0,"publicationDate":"2020-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7421097/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38300682","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural Mechanisms of Vicarious Reward Processing in Adults with Autism Spectrum Disorder.","authors":"Rachel K Greene,&nbsp;Cara R Damiano-Goodwin,&nbsp;Erin Walsh,&nbsp;Joshua Bizzell,&nbsp;Gabriel S Dichter","doi":"10.1155/2020/8014248","DOIUrl":"https://doi.org/10.1155/2020/8014248","url":null,"abstract":"<p><p>Previous studies examining the neural substrates of reward processing in ASD have explored responses to rewards for oneself but not rewards earned for others (i.e., vicarious reward). This omission is notable given that vicarious reward processing is a critical component of creating and maintaining social relationships. The current study examined the neural mechanisms of vicarious reward processing in 15 adults with ASD and 15 age- and gender-matched typically developing controls. Individuals with ASD demonstrated attenuated activation of reward-related regions during vicarious reward processing. Altered connectivity was also observed in individuals with ASD during reward receipt. These findings of altered neural sensitivity to vicarious reward processing may represent a mechanism that hinders the development of social abilities in ASD.</p>","PeriodicalId":8659,"journal":{"name":"Autism Research and Treatment","volume":"2020 ","pages":"8014248"},"PeriodicalIF":0.0,"publicationDate":"2020-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/8014248","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37810280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AMBRA1, Autophagy, and the Extreme Male Brain Theory of Autism","authors":"B. Crespi, Silven Read, A. Ly, P. Hurd","doi":"10.1155/2019/1968580","DOIUrl":"https://doi.org/10.1155/2019/1968580","url":null,"abstract":"The extreme male brain theory of autism posits that its male bias is mediated by exaggeration of male-biased sex differences in the expression of autism-associated traits found in typical populations. The theory is supported by extensive phenotypic evidence, but no genes have yet been described with properties that fit its predictions. The autophagy-associated gene AMBRA1 represents one of the top genome-wide “hits” in recent GWAS studies of schizophrenia, shows sex-differential expression, and has been linked with autism risk and traits in humans and mice, especially or exclusively among females. We genotyped the AMBRA1 autism-risk SNP in a population of typical humans who were scored for the dimensional expression of autistic and schizotypal traits. Females, but not males, homozygous for the GG genotype showed a significant increase in score for the single trait, the Autism Quotient-Imagination subscale, that exhibits a strong, significant male bias in typical populations. As such, females with this genotype resembled males for this highly sexually dimorphic, autism-associated phenotype. These findings support the extreme male brain hypothesis and indicate that sex-specific genetic effects can mediate aspects of risk for autism.","PeriodicalId":8659,"journal":{"name":"Autism Research and Treatment","volume":"217 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83624463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neural Mechanisms of Reward Prediction Error in Autism Spectrum Disorder","authors":"Maya G. Mosner, R. E. McLaurin, J. Kinard, S. Hakimi, Jacob M. Parelman, Jasmine S. Shah, Josh Bizzell, Josh Bizzell, R. Greene, P. Cernasov, E. Walsh, Merideth A. Addicott, T. Eisenlohr-Moul, R. M. Carter, G. Dichter","doi":"10.1155/2019/5469191","DOIUrl":"https://doi.org/10.1155/2019/5469191","url":null,"abstract":"Few studies have explored neural mechanisms of reward learning in ASD despite evidence of behavioral impairments of predictive abilities in ASD. To investigate the neural correlates of reward prediction errors in ASD, 16 adults with ASD and 14 typically developing controls performed a prediction error task during fMRI scanning. Results revealed greater activation in the ASD group in the left paracingulate gyrus during signed prediction errors and the left insula and right frontal pole during thresholded unsigned prediction errors. Findings support atypical neural processing of reward prediction errors in ASD in frontostriatal regions critical for prediction coding and reward learning. Results provide a neural basis for impairments in reward learning that may contribute to traits common in ASD (e.g., intolerance of unpredictability).","PeriodicalId":8659,"journal":{"name":"Autism Research and Treatment","volume":"11 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88085038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Improving Outcome in Infantile Autism with Folate Receptor Autoimmunity and Nutritional Derangements: A Self-Controlled Trial","authors":"V. Ramaekers, J. M. Sequeira, Marco DiDuca, G. Vrancken, A. Thomas, C. Philippe, Marie Peters, Annick Jadot, E. Quadros","doi":"10.1155/2019/7486431","DOIUrl":"https://doi.org/10.1155/2019/7486431","url":null,"abstract":"Background In contrast to multiple rare monogenetic abnormalities, a common biomarker among children with infantile autism and their parents is the discovery of serum autoantibodies directed to the folate receptor alpha (FRα) localized at blood-brain and placental barriers, impairing physiologic folate transfer to the brain and fetus. Since outcome after behavioral intervention remains poor, a trial was designed to treat folate receptor alpha (FRα) autoimmunity combined with correction of deficient nutrients due to abnormal feeding habits. Methods All participants with nonsyndromic infantile autism underwent a routine protocol measuring CBC, iron, vitamins, coenzyme Q10, metals, and trace elements. Serum FRα autoantibodies were assessed in patients, their parents, and healthy controls. A self-controlled therapeutic trial treated nutritional derangements with addition of high-dose folinic acid if FRα autoantibodies tested positive. The Childhood Autism Rating Scale (CARS) monitored at baseline and following 2 years of treatment was compared to the CARS of untreated autistic children serving as a reference. Results In this self-controlled trial (82 children; mean age ± SD: 4.4 ± 2.3 years; male:female ratio: 4.8:1), FRα autoantibodies were found in 75.6 % of the children, 34.1 % of mothers, and 29.4 % of fathers versus 3.3 % in healthy controls. Compared to untreated patients with autism (n=84) whose CARS score remained unchanged, a 2-year treatment decreased the initial CARS score from severe (mean ± SD: 41.34 ± 6.47) to moderate or mild autism (mean ± SD: 34.35 ± 6.25; paired t-test p<0.0001), achieving complete recovery in 17/82 children (20.7 %). Prognosis became less favorable with the finding of higher FRα autoantibody titers, positive maternal FRα autoantibodies, or FRα antibodies in both parents. Conclusions Correction of nutritional deficiencies combined with high-dose folinic acid improved outcome for autism, although the trend of a poor prognosis due to maternal FRα antibodies or FRα antibodies in both parents may warrant folinic acid intervention before conception and during pregnancy.","PeriodicalId":8659,"journal":{"name":"Autism Research and Treatment","volume":"35 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2019-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86556744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk for ASD in Preterm Infants: A Three-Year Follow-Up Study.","authors":"Ayelet Harel-Gadassi,&nbsp;Edwa Friedlander,&nbsp;Maya Yaari,&nbsp;Benjamin Bar-Oz,&nbsp;Smadar Eventov-Friedman,&nbsp;David Mankuta,&nbsp;Nurit Yirmiya","doi":"10.1155/2018/8316212","DOIUrl":"https://doi.org/10.1155/2018/8316212","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to examine the long-term risk for autism spectrum disorders (ASD) in individuals who are born preterm and full-term using both observational instruments and parental reports. Neonatal risk factors and developmental characteristics associated with ASD risk were also examined.</p><p><strong>Method: </strong>Participants included 110 preterm children (born at a gestational age of ≤ 34 weeks) and 39 full-term children assessed at ages 18, 24, and 36 months. The Autism Diagnostic Observation Schedule, the Modified Checklist for Autism in Toddlers, the Autism Diagnostic Interview-Revised, the Social Communication Questionnaire, and the Mullen Scales of Early Learning were administered.</p><p><strong>Results and conclusions: </strong>The long-term risk for ASD was higher when parental reports were employed compared to observational instruments. At 18 and 24 months, a higher long-term risk for ASD was found for preterm children compared to full-term children. At 36 months, only one preterm child and one full-term child met the cutoff for ASD based on the ADOS, yet clinical judgment and parental reports supported an ASD diagnosis for the preterm child only. Earlier gestational age and lower general developmental abilities were associated with elevated ASD risk among preterm children.</p>","PeriodicalId":8659,"journal":{"name":"Autism Research and Treatment","volume":"2018 ","pages":"8316212"},"PeriodicalIF":0.0,"publicationDate":"2018-11-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2018/8316212","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36766987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuromagnetic Beta-Band Oscillations during Motor Imitation in Youth with Autism.","authors":"I Buard, E Kronberg, S Steinmetz, S Hepburn, D C Rojas","doi":"10.1155/2018/9035793","DOIUrl":"10.1155/2018/9035793","url":null,"abstract":"<p><p>Children with ASD often exhibit early difficulties with action imitation, possibly due to low-level sensory or motor impairments. Impaired cortical rhythms have been demonstrated in adults with ASD during motor imitation. While those oscillations reflect an age-dependent process, they have not been fully investigated in youth with ASD. We collected magnetoencephalography data to examine patterns of oscillatory activity in the mu (8-13 Hz) and beta frequency (15-30 Hz) range in 14 adolescents with and 14 adolescents without ASD during a fine motor imitation task. Typically developing adolescents exhibited adult-like patterns of motor signals, e.g., event-related beta and mu desynchronization (ERD) before and during the movement and a postmovement beta rebound (PMBR) after the movement. In contrast, those with ASD exhibited stronger beta and mu-ERD and reduced PMBR. Behavioral performance was similar between groups despite differences in motor cortical oscillations. Finally, we observed age-related increases in PBMR and beta-ERD in the typically developing children, but this correlation was not present in the autism group. These results suggest reduced inhibitory drive in cortical rhythms in youth with autism during intact motor imitation. Furthermore, impairments in motor brain signals in autism may not be due to delayed brain development. In the context of the excitation-inhibition imbalance perspectives of autism, we offer new insights into altered organization of neurophysiological networks.</p>","PeriodicalId":8659,"journal":{"name":"Autism Research and Treatment","volume":"2018 ","pages":"9035793"},"PeriodicalIF":0.0,"publicationDate":"2018-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6083595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36431770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}