Autism Research and Treatment最新文献

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 in utero 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.

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.

Background: Biomarkers such as oxidative stress, folate receptor alpha (FRα) autoimmunity, and abnormal brain serotonin turnover are common in autism.

Methods: Oxidative stress biomarkers with pro- and antioxidants were measured in the severe form of infantile autism (n = 38) and controls (n = 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.

Results: 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.

Conclusion: 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. Trial Registration. The case-controlled study was approved in 2008 by the IRB at Liège University (Belgian Number: B70720083916). Lay Summary. 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

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.

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.

Background: 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.

Method: 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.

Results and conclusions: 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.

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.