1. Asato MR, Goldstein AC, Schiff M. {{Autism and inborn errors of metabolism: how much is enough?}}. {Dev Med Child Neurol}. 2015.
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2. Benitez-Burraco A, Boeckx C. {{Approaching motor and language deficits in autism from below: a biolinguistic perspective}}. {Front Integr Neurosci}. 2015; 9: 25.
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3. Cermak SA, Stein Duker LI, Williams ME, Lane CJ, Dawson ME, Borreson AE, Polido JC. {{Feasibility of a sensory-adapted dental environment for children with autism}}. {Am J Occup Ther}. 2015; 69(3): 6903220020p1-p10.
OBJECTIVE: To provide an example of an occupational therapy feasibility study and evaluate the implementation of a randomized controlled pilot and feasibility trial examining the impact of a sensory-adapted dental environment (SADE) to enhance oral care for children with autism spectrum disorder (ASD). METHOD: Twenty-two children with ASD and 22 typically developing children, ages 6-12 yr, attended a dental clinic in an urban hospital. Participants completed two dental cleanings, 3-4 mo apart, one in a regular environment and one in a SADE. Feasibility outcome measures were recruitment, retention, accrual, dropout, and protocol adherence. Intervention outcome measures were physiological stress, behavioral distress, pain, and cost. RESULTS: We successfully recruited and retained participants. Parents expressed satisfaction with research study participation. Dentists stated that the intervention could be incorporated in normal practice. Intervention outcome measures favored the SADE condition. CONCLUSION: Preliminary positive benefit of SADE in children with ASD warrants moving forward with a large-scale clinical trial.
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4. Chen L, Chen K, Lavery LA, Baker SA, Shaw CA, Li W, Zoghbi HY. {{MeCP2 binds to non-CG methylated DNA as neurons mature, influencing transcription and the timing of onset for Rett syndrome}}. {Proc Natl Acad Sci U S A}. 2015.
Epigenetic mechanisms, such as DNA methylation, regulate transcriptional programs to afford the genome flexibility in responding to developmental and environmental cues in health and disease. A prime example involving epigenetic dysfunction is the postnatal neurodevelopmental disorder Rett syndrome (RTT), which is caused by mutations in the gene encoding methyl-CpG binding protein 2 (MeCP2). Despite decades of research, it remains unclear how MeCP2 regulates transcription or why RTT features appear 6-18 months after birth. Here we report integrated analyses of genomic binding of MeCP2, gene-expression data, and patterns of DNA methylation. In addition to the expected high-affinity binding to methylated cytosine in the CG context (mCG), we find a distinct epigenetic pattern of substantial MeCP2 binding to methylated cytosine in the non-CG context (mCH, where H = A, C, or T) in the adult brain. Unexpectedly, we discovered that genes that acquire elevated mCH after birth become preferentially misregulated in mouse models of MeCP2 disorders, suggesting that MeCP2 binding at mCH loci is key for regulating neuronal gene expression in vivo. This pattern is unique to the maturing and adult nervous system, as it requires the increase in mCH after birth to guide differential MeCP2 binding among mCG, mCH, and nonmethylated DNA elements. Notably, MeCP2 binds mCH with higher affinity than nonmethylated identical DNA sequences to influence the level of Bdnf, a gene implicated in the pathophysiology of RTT. This study thus provides insight into the molecular mechanism governing MeCP2 targeting and sheds light on the delayed onset of RTT symptoms.
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5. Hellendoorn A, Wijnroks L, Leseman PP. {{Unraveling the nature of autism: finding order amid change}}. {Front Psychol}. 2015; 6: 359.
In this article, we hypothesize that individuals with autism spectrum disorder (ASD) are born with a deficit in invariance detection, which is a learning process whereby people and animals come to attend the relatively stable patterns or structural regularities in the changing stimulus array. This paper synthesizes a substantial body of research which suggests that a deficit in the domain-general perceptual learning process of invariant detection in ASD can lead to a cascade of consequences in different developmental domains. We will outline how this deficit in invariant detection can cause uncertainty, unpredictability, and a lack of control for individuals with ASD and how varying degrees of impairments in this learning process can account for the heterogeneity of the ASD phenotype. We also describe how differences in neural plasticity in ASD underlie the impairments in perceptual learning. The present account offers an alternative to prior theories and contributes to the challenge of understanding the developmental trajectories that result in the variety of autistic behaviors.
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6. Husk JS, Keim SA. {{Breastfeeding and Autism Spectrum Disorder in the National Survey of Children’s Health}}. {Epidemiology}. 2015.
BACKGROUND: Breastfeeding is thought to promote healthy cognitive development. A small number of studies have also reported a protective association between breastfeeding and autism spectrum disorder (ASD). The National Survey of Children’s Health (2007, 2011), a large nationally representative survey of US children, was examined to determine whether breastfeeding of infants is associated with later development of ASD. METHODS: Respondents with a child ages 2-5 years (n = 37,901) were queried about whether their child was currently diagnosed with ASD and about their child’s breastfeeding history. Additional information was available about child and family health history and family demographics. Survey-weighted logistic regressions were employed to examine ASD diagnosis as associated with several breastfeeding exposure metrics including a history of partial or exclusive breastfeeding for the first 3 or 6 months, and duration of partial or exclusive breastfeeding. RESULTS: Across models, a current diagnosis of ASD (n = 391) was unassociated with any measure of breastfeeding history. Adjusted odds ratios for categorical breastfeeding exposures ranged from 0.68 (confidence interval [CI] = 0.4, 1.3) for any partial breastfeeding to 0.74 (CI = 0.3, 1.7) for 6 months of exclusive breastfeeding. When exposure was measured continuously, adjusted odds ratios were 1.03 (CI = 0.97, 1.10) for each additional month of partial breastfeeding and 1.04 (CI = 0.96, 1.13) for each additional month of exclusive breastfeeding. CONCLUSION: These findings call into question the results from the small body of research that has examined this issue to date.
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7. Jantz PB, Bigler ED, Froehlich AL, Prigge MB, Cariello AN, Travers BG, Anderson J, Zielinski BA, Alexander AL, Lange N, Lainhart JE. {{WIDE RANGE ACHIEVEMENT TEST IN AUTISM SPECTRUM DISORDER: TEST-RETEST STABILITY}}. {Psychol Rep}. 2015.
-The principal goal of this descriptive study was to establish the test-retest stability of the Reading, Spelling, and Arithmetic subtest scores of the Wide Range Achievement Test (WRAT-3) across two administrations in individuals with autism spectrum disorder. Participants (N = 31) were males ages 6-22 years (M = 15.2, SD = 4.0) who were part of a larger ongoing longitudinal study of brain development in children and adults with autism spectrum disorder (N = 185). Test-retest stability for all three subtests remained consistent across administration periods (M = 31.8 mo., SD = 4.1). Age at time of administration, time between administrations, and test form did not significantly influence test-retest stability. Results indicated that for research involving individuals with autism spectrum disorder with a full scale intelligence quotient above 75, the WRAT-3 Spelling and Arithmetic subtests have acceptable test-retest stability over time and the Reading subtest has moderate test-retest stability over time.
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8. Jochaut D, Lehongre K, Saitovitch A, Devauchelle AD, Olasagasti I, Chabane N, Zilbovicius M, Giraud AL. {{Atypical coordination of cortical oscillations in response to speech in autism}}. {Front Hum Neurosci}. 2015; 9: 171.
Subjects with autism often show language difficulties, but it is unclear how they relate to neurophysiological anomalies of cortical speech processing. We used combined EEG and fMRI in 13 subjects with autism and 13 control participants and show that in autism, gamma and theta cortical activity do not engage synergistically in response to speech. Theta activity in left auditory cortex fails to track speech modulations, and to down-regulate gamma oscillations in the group with autism. This deficit predicts the severity of both verbal impairment and autism symptoms in the affected sample. Finally, we found that oscillation-based connectivity between auditory and other language cortices is altered in autism. These results suggest that the verbal disorder in autism could be associated with an altered balance of slow and fast auditory oscillations, and that this anomaly could compromise the mapping between sensory input and higher-level cognitive representations.
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9. Lerman DC, Hawkins L, Hillman C, Shireman M, Nissen MA. {{Adults with autism spectrum disorder as behavior technicians for young children with autism: Outcomes of a behavior skills training program}}. {J Appl Behav Anal}. 2015.
Adults with autism spectrum disorder (ASD), who were interested in working as behavior technicians for young children with autism, participated in 2 experiments. Participants included 5 adults with Asperger syndrome or pervasive developmental disorder not otherwise specified, 19 to 23 years old, and 11 children with autism, 3 to 7 years old. In Experiment 1, training of the adults focused on the implementation of mand training via incidental teaching. Experiment 2 focused on teaching participants to use discrete-trial training (DTT) with children who exhibited problem behavior. Both experiments showed that behavioral skills training was effective for teaching the adult participants the behavioral procedures needed to teach children with autism. In addition, the children acquired skills as a result of training. Results of Experiment 2 further demonstrated that the DTT skills generalized across untrained targets and children. Social validity ratings suggested that some participants’ teaching was indistinguishable from that of individuals without ASD.
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10. McIntosh CE, Thomas CM, Brattain CK. {{Nurses Identify Education and Communication Among Professionals as Essential in Serving ASD Children}}. {NASN Sch Nurse}. 2015.
Autism spectrum disorder (ASD) is a broad term encompassing a group of neurodevelopmental disabilities. Children with ASD present behavioral, communication, and social behaviors. One in 68 individuals is diagnosed with autism. With ASD prevalence continuing to rise, it makes sense for school nurses to identify areas that may be helpful in serving this population. This school nurse focus group study shared specific areas that would benefit school nurses when working with children with autism. Two glaring trends surfaced from the focus group-continuing education needs and communication among all school professionals (i.e., teachers, special education services).
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11. Mostafa G, Al-Ayadhi L. {{The possible link between elevated serum levels of epithelial cell-derived neutrophil- activating peptide-78 (ENA-78/CXCL5) and autoimmunity in autistic children}}. {Behav Brain Funct}. 2015; 11(1): 11.
BACKGROUND: In autoimmune disorders, the underlying pathogenic mechanism is the formation of antigen-antibody complexes which trigger an inflammatory response by inducing the infiltration of neutrophils. Epithelial cell-derived neutrophil-activating peptide-78 (ENA-78) is a chemokine that recruits and activates neutrophils, thus it could play a pathogenic role in inflammation and autoimmune disorders. Some autistic children have elevated levels of brain specific auto-antibodies. We are the first to evaluate serum expression of ENA-78 and its relation to antineuronal auto-antibodies in autistic children. METHODS: Serum ENA-78 and antineuronal auto-antibodies were measured by ELISA test in 62 autistic children aged between 4-11 years and 62 health-matched controls. RESULTS: Serum levels of ENA-78 were significantly higher in autistic children than healthy controls (P < 0.001). Increased serum levels of ENA-78 have been found in 69.35% of autistic patients. In addition, autistic children had significantly higher percent positivity of serum antineuronal auto-antibodies (64.5%) than healthy controls (6.45%), P < 0.001. There was a significant positive association between the positivity of serum antineuronal auto-antibodies and the elevated levels of serum ENA-78 (P < 0.001) in autistic children. CONCLUSIONS: Serum levels of ENA-78 were elevated in autistic children and they were significantly associated with the increased levels of serum antineuronal auto-antibodies. However, these data should be treated with caution until further research is conducted to determine the pathogenic role of ENA-78 in autism and its relation to brain specific auto-antibodies that have been found in some autistic children. The possible therapeutic role of ENA-78 antagonist in autistic children should be also studied.
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12. Normand CL, Sallafranque-St-Louis F. {{Cybervictimization of Young People With an Intellectual or Developmental Disability: Risks Specific to Sexual Solicitation}}. {J Appl Res Intellect Disabil}. 2015.
BACKGROUND: Studies demonstrate that youth are vulnerable to online sexual solicitation. However, no study has estimated this risk for youth diagnosed with an intellectual or developmental disability (IDD). METHODS: A literature review of the risk factors associated with online sexual solicitation in youths was done using electronic databases, such as PsychInFO, ERIC, MEDLINE and Scopus. RESULTS: Fifty-seven published papers were found relevant. However, only two pertained to the population with IDD. Sexual and physical abuse, social isolation, loneliness, depression, and chatting were found to increase the risk of being prey to sexual solicitation on the Internet. Many of these risk factors are even more prevalent in youth with IDD than in the general population. CONCLUSION: Recommendations are made for future research to help understand and prevent sexual cybersolicitation.
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13. Robinson S, Weiss JA, Lunsky Y, Ouellette-Kuntz H. {{Informal Support and Burden among Parents of Adults with Intellectual and/or Developmental Disabilities}}. {J Appl Res Intellect Disabil}. 2015.
BACKGROUND: Parents often play a lifelong role in supporting their sons and daughters with intellectual and/or developmental disabilities (IDD). There is a need to better understand parent resources, particularly when the individual with IDD has behaviour problems, as the latter has consistently been linked to parental burden. METHODS: The current study aimed to investigate the relationship between the behaviour support needs of 212 adults with IDD and parental burden, and whether perceived helpfulness of informal supports moderated this relationship. The helpfulness of individual sources of informal support was also explored. RESULTS: Informal support was negatively related to burden, although it did not act as a moderator. Individual sources varied in terms of how they were related to burden, but none acted as moderators. CONCLUSIONS: Although informal social support appears to be important to parents and may help alleviate burden, it does not appear to act as a moderator as anticipated.
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14. Saad K, Abdel-Rahman AA, Elserogy YM, Al-Atram AA, Cannell JJ, Bjorklund G, Abdel-Reheim MK, Othman HA, El-Houfey AA, Hashem EA, Abd El-Aziz NH, Abd El-Baseer KA, Ahmed AE, Ali AM. {{Vitamin D status in autism spectrum disorders and the efficacy of vitamin D supplementation in autistic children}}. {Nutr Neurosci}. 2015.
Objectives Autism spectrum disorder (ASD) is a developmental disorder characterized by pervasive deficits in social interaction, impairment in verbal and non-verbal communication, and stereotyped patterns of interests and activities. Vitamin-D deficiency was previously reported in autistic children. However, the data on the relationship between vitamin D deficiency and the severity of autism are limited. Methods We performed a case-controlled cross-sectional analysis conducted on 122 ASD children, to assess their vitamin D status compared to controls and the relationship between vitamin D deficiency and the severity of autism. We also conducted an open trial of vitamin D supplementation in ASD children. Results Fifty-seven percent of the patients in the present study had vitamin D deficiency, and 30% had vitamin D insufficiency. The mean 25-OHD levels in patients with severe autism were significantly lower than those in patients with mild/moderate autism. Serum 25-OHD levels had significant negative correlations with Childhood Autism Rating Scale (CARS) scores. Of the ASD group, 106 patients with low-serum 25-OHD levels (<30 ng/ml) participated in the open label trial. They received vitamin D3 (300 IU/kg/day not to exceed 5000 IU/day) for 3 months. Eighty-three subjects completed 3 months of daily vitamin D treatment. Collectively, 80.72% (67/83) of subjects who received vitamin D3 treatment had significantly improved outcome, which was mainly in the sections of the CARS and aberrant behavior checklist subscales that measure behavior, stereotypy, eye contact, and attention span. Conclusion Vitamin D is inexpensive, readily available and safe. It may have beneficial effects in ASD subjects, especially when the final serum level is more than 40 ng/ml. Trial registration number UMIN-CTR Study Design: trial Number: R000016846.
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15. Schuster S, Rivalan M, Strauss U, Stoenica L, Trimbuch T, Rademacher N, Parthasarathy S, Lajko D, Rosenmund C, Shoichet SA, Winter Y, Tarabykin V, Rosario M. {{NOMA-GAP/ARHGAP33 regulates synapse development and autistic-like behavior in the mouse}}. {Mol Psychiatry}. 2015.
Neuropsychiatric developmental disorders, such as autism spectrum disorders (ASDs) and schizophrenia, are typically characterized by alterations in social behavior and have been linked to aberrant dendritic spine and synapse development. Here we show, using genetically engineered mice, that the Cdc42 GTPase-activating multiadaptor protein, NOMA-GAP, regulates autism-like social behavior in the mouse, as well as dendritic spine and synapse development. Surprisingly, we were unable to restore spine morphology or autism-associated social behavior in NOMA-GAP-deficient animals by Cre-mediated deletion of Cdc42 alone. Spine morphology can be restored in vivo by re-expression of wild-type NOMA-GAP or a mutant of NOMA-GAP that lacks the RhoGAP domain, suggesting that other signaling functions are involved. Indeed, we show that NOMA-GAP directly interacts with several MAGUK (membrane-associated guanylate kinase) proteins, and that this modulates NOMA-GAP activity toward Cdc42. Moreover, we demonstrate that NOMA-GAP is a major regulator of PSD-95 in the neocortex. Loss of NOMA-GAP leads to strong upregulation of serine 295 phosphorylation of PSD-95 and moreover to its subcellular mislocalization. This is associated with marked loss of surface alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and defective synaptic transmission, thereby providing a molecular basis for autism-like social behavior in the absence of NOMA-GAP.Molecular Psychiatry advance online publication, 14 April 2015; doi:10.1038/mp.2015.42.
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16. Shimamoto C, Ohnishi T, Maekawa M, Watanabe A, Ohba H, Arai R, Iwayama Y, Hisano Y, Toyota T, Toyoshima M, Suzuki K, Shirayama Y, Nakamura K, Mori N, Owada Y, Kobayashi T, Yoshikawa T. {{Functional characterization of FABP3, 5 and 7 gene variants identified in schizophrenia and autism spectrum disorder and mouse behavioral studies}}. {Hum Mol Genet}. 2015; 24(8): 2409.
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17. van Belle J, van Hulst BM, Durston S. {{Developmental differences in intra-individual variability in children with ADHD and ASD}}. {J Child Psychol Psychiatry}. 2015.
BACKGROUND: Intra-individual variability reflects temporal variation within an individual’s performance on a cognitive task. Children with developmental disorders, such as ADHD and ASD show increased levels of intra-individual variability. In typical development, intra-individual variability decreases sharply between the ages 6 and 20. The tight link between intra-individual variability and age has led to the suggestion that it may be marker of neural development. As there is accumulating evidence that ADHD and ASD are characterised by atypical neurodevelopmental trajectories, we set out to explore developmental changes in intra-individual variability in subjects with ADHD and ASD. METHOD: We used propensity score matching to match a cross-sectional sample of children with ADHD, ASD and control subjects (N = 405, aged 6-19 years old) for age, IQ and gender. We used ex-Gaussian distribution parameters to characterise intra-individual variability on fast responses (sigma) and slow responses (tau). RESULT: Results showed that there was a similar decrease in mean response times with age across groups, and an interaction between age and group for measures of variability, where there was a much lower rate of change in the variability parameters (sigma and tau) for subjects with ASD compared with the other two groups. Subjects with ADHD had higher intra-individual variability, reflected by both sigma and tau, but the rate of decrease in variability with age was similar to that of the controls. CONCLUSION: These results suggest that subjects with ADHD, ASD and controls differ in the rate at which intra-individual variability decreases during development, and support the idea that intra-individual variability may be a marker of neural development, mimicking the neurodevelopmental changes in these disorders.
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18. Wall K. {{Autism and early years practice. A guide for early years professionals, teachers and parents}}. {J Child Adolesc Ment Health}. 2007; 19(2): 157-8.
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19. Xiang AH, Wang X, Martinez MP, Walthall JC, Curry ES, Page K, Buchanan TA, Coleman KJ, Getahun D. {{Association of maternal diabetes with autism in offspring}}. {JAMA}. 2015; 313(14): 1425-34.
IMPORTANCE: Information about the association of maternal diabetes and autism spectrum disorders (ASDs) in offspring is limited, with no report on the importance of timing of exposure during gestation. OBJECTIVE: To assess ASD risk associated with intrauterine exposure to preexisting type 2 diabetes and gestational diabetes mellitus (GDM) by gestational age at GDM diagnosis. DESIGN, SETTING, AND PATIENTS: Retrospective longitudinal cohort study including 322 323 singleton children born in 1995-2009 at Kaiser Permanente Southern California (KPSC) hospitals. Children were tracked from birth until the first of the following: date of clinical diagnosis of ASD, last date of continuous KPSC health plan membership, death due to any cause, or December 31, 2012. Relative risks of ASD were estimated by hazard ratios (HRs) using Cox regression models adjusted for birth year. EXPOSURES: Maternal preexisting type 2 diabetes (n = 6496), GDM diagnosed at 26 weeks’ gestation or earlier (n = 7456) or after 26 weeks’ gestation (n = 17 579), or no diabetes (n = 290 792) during the index pregnancy. MAIN OUTCOMES AND MEASURES: Clinical diagnosis of ASD in offspring. RESULTS: During follow-up, 3388 children were diagnosed as having ASD (115 exposed to preexisting type 2 diabetes, 130 exposed to GDM at </=26 weeks, 180 exposed to GDM at >26 weeks, and 2963 unexposed). Unadjusted annual ASD incidences were 3.26, 3.02, 1.77, and 1.77 per 1000 among children of mothers with preexisting type 2 diabetes, GDM diagnosed at 26 weeks or earlier, GDM diagnosed after 26 weeks, and no diabetes, respectively. The birth year-adjusted HRs were 1.59 (95% CI, 1.29-1.95) for preexisting type 2 diabetes, 1.63 (95% CI, 1.35-1.97) for GDM diagnosed at 26 weeks or earlier, and 0.98 (95% CI, 0.84-1.15) for GDM diagnosed after 26 weeks relative to no exposure. After adjustment for maternal age, parity, education, household income, race/ethnicity, history of comorbidity, and sex of the child, maternal preexisting type 2 diabetes was not significantly associated with risk of ASD in offspring (HR, 1.21; 95% CI, 0.97-1.52), but GDM diagnosed at 26 weeks or earlier remained so (HR, 1.42; 95% CI, 1.15-1.74). Antidiabetic medication exposure was not independently associated with ASD risk. Adjustment for a mother or older sibling with ASD in the full cohort and for maternal smoking, prepregnancy body mass index, and gestational weight gain in the subset with available data (n = 68 512) did not affect the results. CONCLUSIONS AND RELEVANCE: In this large, multiethnic clinical cohort of singleton children born at 28 to 44 weeks’ gestation, exposure to maternal GDM diagnosed by 26 weeks’ gestation was associated with risk of ASD in offspring.
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20. Yan CL, Zhang J, Hou Y. {{Decreased plasma levels of lipoxin A4 in children with autism spectrum disorders}}. {Neuroreport}. 2015; 26(6): 341-5.
The aim of this study was to evaluate the plasma levels of lipoxin A4 (LXA4), a mediator involved in the resolution of inflammation in Chinese children with autism spectrum disorders (ASD). From January 2013 to June 2014, a total of 150 children (75 confirmed ASD cases and 75 their age-matched and sex-matched control cases) participated in this study after consent was obtained from their parents. Clinical information was collected. Plasma levels of LXA4 were measured at baseline. The severity of ASD was assessed at admission using the Childhood Autism Rating Scale total score. The results indicated that the mean plasma levels of LXA4 were significantly lower in autistic children compared with the normal children (P<0.0001). There was a significant negative relationship between circulating LXA4 levels and severity of autism evaluated by Childhood Autism Rating Scale scores (P=0.006) after adjustment for the possible covariates. On the basis of the receiver operating characteristic curve, the optimal cutoff value of plasma LXA4 levels as an indicator for an auxiliary diagnosis of ASD was projected to be 81.5 pg/ml, which yielded a sensitivity of 90.7% and a specificity of 76.0%, with the area under the curve at 0.911 (95% confidence interval, 0.867-0.955). These results suggested that autistic children had lower plasma LXA4 levels, suggesting an increased susceptibility to recurring inflammation in these samples.
