1. Al-Mubarak B, Abouelhoda M, Omar A, AlDhalaan H, Aldosari M, Nester M, Alshamrani HA, El-Kalioby M, Goljan E, Albar R, Subhani S, Tahir A, Asfahani S, Eskandrani A, Almusaiab A, Magrashi A, Shinwari J, Monies D, Al Tassan N. {{Whole exome sequencing reveals inherited and de novo variants in autism spectrum disorder: a trio study from Saudi families}}. {Sci Rep};2017 (Jul 18);7(1):5679.
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with genetic and clinical heterogeneity. The interplay of de novo and inherited rare variants has been suspected in the development of ASD. Here, we applied whole exome sequencing (WES) on 19 trios from singleton Saudi families with ASD. We developed an analysis pipeline that allows capturing both de novo and inherited rare variants predicted to be deleterious. A total of 47 unique rare variants were detected in 17 trios including 38 which are newly discovered. The majority were either autosomal recessive or X-linked. Our pipeline uncovered variants in 15 ASD-candidate genes, including 5 (GLT8D1, HTATSF1, OR6C65, ITIH6 and DDX26B) that have not been reported in any human condition. The remaining variants occurred in genes formerly associated with ASD or other neurological disorders. Examples include SUMF1, KDM5B and MXRA5 (Known-ASD genes), PRODH2 and KCTD21 (implicated in schizophrenia), as well as USP9X and SMS (implicated in intellectual disability). Consistent with expectation and previous studies, most of the genes implicated herein are enriched for biological processes pertaining to neuronal function. Our findings underscore the private and heterogeneous nature of the genetic architecture of ASD even in a population with high consanguinity rates.
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2. Andersen CH, Thomsen PH, Nohr EA, Lemcke S. {{Maternal body mass index before pregnancy as a risk factor for ADHD and autism in children}}. {Eur Child Adolesc Psychiatry};2017 (Jul 15)
The risk of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorders (ASD) may be influenced by environmental factors such as maternal obesity before pregnancy. Previous studies investigating those associations have found divergent results. We aim to investigate in a large birth cohort this association further in children with ADHD, ASD and comorbid ADHD and ASD. Our study population consisted of 81,892 mother-child pairs participating in the Danish National Birth Cohort (DNBC). Information about pre-pregnancy weight and height was collected in week 16 of pregnancy; the analysis was divided into groups based on BMI. Children with a clinical diagnosis of ADHD and/or ASD were identified in the Danish health registries at an average age of 13.3 years. Hazard ratios (HRs) were estimated using time-to-event analysis. Compared to normal weight mothers, the risk of having a child with ADHD was significantly increased if the mother was overweight (HR = 1.28 [95% CI 1.15;1.48]), obese (HR = 1.47 [95% CI 1.26;1.71]) or severely obese (HR = 1.95 [95% CI 1.58;2.40]). The same pattern was seen for the combined ADHD and ASD group. Regarding ASD, an increased risk was observed in underweight (HR = 1.30 [95% CI 1.01;1.69]) and obese (HR = 1.39 [95% CI 1.11;1.75]) mothers. Subgroup analysis revealed that the association in the ADHD group could mostly be attributable to the hyperactive group. Maternal obesity before pregnancy is a risk factor for ADHD in children. Maternal obesity as well as underweight may also be associated with an increased risk for ASD.
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3. Belagodu AP, Fleming S, Galvez R. {{Neocortical developmental analysis of vasculature and their growth factors offer new insight into Fragile X Syndrome abnormalities}}. {Dev Neurobiol};2017 (Jul 18)
Fragile X Syndrome (FXS) is the most common single gene cause for Autism Spectrum Disorder and the most prevalent form of inherited mental retardation. Our prior studies have demonstrated that adult FXS mice have abnormal blood vessel density (BVD) and elevated Vascular Endothelial Growth Factor A expression (VEGF-A). VEGF-A is one of the most prominent regulators of BVD, and its abnormal expression is the most likely cause for FXS BVD abnormalities. We have demonstrated that attenuating elevated VEGF-A expression can ameliorate many non-vascular FXS abnormalities(Belagodu et al., 2017), suggesting that abnormal VEGF-A expression is an underlying cause for some FXS abnormalities. However, FXS is a developmental disorder and VEGF-A’s potential role in mediating FXS abnormalities during development have never been explored. Furthermore, VEGF-A is one protein in a family of proteins (VEGF-A, VEGF-B, VEGF-C, VEGF-D, & PLGF) that activate one of three primary receptors (VEGFR1, VEGFR2, & VEGFR3). Abnormal expression of any of these proteins could hinder proper development. The current study demonstrated that FXS mice do not exhibit normal BVD developmental patterns, resulting in elevated adult expression, most likely due to observed elevated VEGF-A adult expression. Interestingly, all five VEGF family of proteins exhibited altered developmental expression patterns that could cause abnormal development. However, none of the receptors exhibiting abnormal adult expression, but did exhibit altered developmental expression. Expanding upon our prior analyses, the current study provides additional interesting insight towards potential developmental mechanisms mediating FXS abnormalities, while offering further sites for age specific therapeutic interventions. This article is protected by copyright. All rights reserved.
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4. Chandradasa M, Champika L. {{Zoophilia in an adolescent with high-functioning autism from Sri Lanka}}. {Australas Psychiatry};2017 (Jul 01):1039856217715997.
OBJECTIVE: Zoophilia is a rare paraphilic disorder with intense sexual urges involving animals. Autism is characterised by impairments in social communication and repetitive, restricted behaviours (RRB). Reported cases of zoophilia are limited worldwide, and zoophilia in autism is rarer. METHOD: This is a case report describing this unique and relatively unrecognised association in a male adolescent from Sri Lanka. RESULTS: A 17-year-old boy diagnosed with autism has average intelligence and academic capabilities. He had spent increasing time at his grandparents’ cattle house. First, he was found masturbating near the cows and later having penetrative intercourse with a heifer. The shocked parents first sought traditional healing in the form of ‘thovil’, a demonic ritual of exorcist nature. Later, clinical evaluation found intense sexual urges towards cattle, which had led to marked distress and academic impairment. Sex hormone profile was normal. The adolescent was treated with a combination of cognitive-behaviour therapy and a selective serotonin reuptake inhibitor. CONCLUSION: We postulate that his persistent social difficulties contributed to the development of a paraphilic disorder. Unlike with his RRBs, he was markedly distressed about this sexual behaviour. Further research is required to explore this rarely reported, potential association.
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5. DeMayo MM, Song YJC, Hickie IB, Guastella AJ. {{A Review of the Safety, Efficacy and Mechanisms of Delivery of Nasal Oxytocin in Children: Therapeutic Potential for Autism and Prader-Willi Syndrome, and Recommendations for Future Research}}. {Paediatr Drugs};2017 (Jul 18)
In this article, we conduct a comprehensive review of existing evidence for the safety and therapeutic potential of intranasal oxytocin in pediatric populations. Unique considerations for dosing and delivery of oxytocin to the nasal passageway in pediatric populations and methods to promote adherence are reviewed. Intranasal oxytocin has been administered to 261 children in three open-label studies and eight randomized controlled trials. To date, the only published results in pediatric populations have focused on autism spectrum disorder (ASD) and Prader-Willi syndrome (PWS). Results regarding efficacy for improving social impairment in ASD are equivocal, partially due to mixed methodological designs, dosing regimens, and outcome measures. At present, there is no randomized controlled evidence that oxytocin provides benefit to individuals with PWS. There is no clear evidence of a link between oxytocin administration and any specific adverse event. Adverse events have been assessed using medical interviews, open reports, checklists, and physiological assessments. Adverse events reports have been largely classified as mild (n = 93), with few moderate (n = 9) or severe (n = 3) events reported. There were 35 additional adverse events reported, without severity ratings. Severe events, hyperactivity and irritability, occurred at first administration in both placebo and oxytocin groups, and subsided subsequent to discontinuation. We note that adverse event monitoring is inconsistent and often lacking, and reporting of its relationship to the study drug is poor. Only one study reported adherence data to suggest high adherence. Recommendations are then provided for the delivery of nasal sprays to the nasal passageway, monitoring, and reporting of efficacy, safety, and adherence for oxytocin nasal spray trials in pediatric populations.
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6. Esnafoglu E, Ayyildiz SN, Cirrik S, Erturk EY, Erdil A, Dagli A, Noyan T. {{Evaluation of serum Neuron-specific enolase, S100B, myelin basic protein and glial fibrilliary acidic protein as brain specific proteins in children with autism spectrum disorder}}. {Int J Dev Neurosci};2017 (Jul 13);61:86-91.
OBJECTIVE: Brain specific-proteins are not found in other tissues and measurement non-invasively in the blood may identify structurally and functionally damaged brain regions and identify the severity and prognosis of neuropsychiatric diseases. For this reason, we aimed to evaluate serum brain-specific protein values as brain damage markers in children with autism spectrum disorder (ASD). METHOD: 35 children with ASD and 31 healthy subjects were included in the study. Sociodemographic form and Childhood Autism Rating Scale (CARS) were applied to each subject. Serum neuron specific enolase (NSE), S100B, Myelin basic protein (MBP) and Glial fibrillary acidic protein (GFAP) values were measured with ELISA. RESULTS: There was no significant difference between the two groups for NSE, MBP and S100B values (p=0.242; p=0.768; p=0.672, respectively). However, GFAP values in the patient group were statistically significantly higher (mean+/-SD: 0.463+/-0.392ng/ml) than in the healthy control group (mean+/-SD: 0.256+/-0.111ng/ml) (p<0.001). In addition, there was a significant positive correlation between serum GFAP values and CARS score in all subjects and in the patient group (r=0.599; p<0.001 and r=0.380; p=0.024, respectively). CONCLUSIONS: While serum NSE, MBP, and S100B values cannot be considered as biomarkers for ASD, GFAP may be a biomarker and is suggested as a possible indicator of autism severity. Lien vers le texte intégral (Open Access ou abonnement)
7. Guivarch J, Murdymootoo V, Elissalde SN, Salle-Collemiche X, Tardieu S, Jouve E, Poinso F. {{Impact of an implicit social skills training group in children with autism spectrum disorder without intellectual disability: A before-and-after study}}. {PLoS One};2017;12(7):e0181159.
INTRODUCTION: Children with Autism Spectrum Disorders (ASDs) have problems with social skills. Social skills training groups are among the proposed therapeutic strategies, but their efficacy still needs to be evaluated. OBJECTIVE: To evaluate the efficacy of an implicit social skills training group in children with ASDs without intellectual disability. METHODS: A before-and-after study of children with ASD without intellectual disability was conducted in a child psychiatry day hospital, where they participated in an implicit group with cooperative games. Their social skills were assessed using the Social-Emotional Profile (SEP), the Childhood Autism Rating Scale (CARS), and the empathy quotient (EQ) before and after 22 weeks. RESULTS: Six patients aged 9 to 10 years old were evaluated. A significant increase in overall adaptation and social skills (median 8 and 7.7 points) in the SEP was demonstrated in addition to a significant reduction in the CARS score (median: 4 points), including in the field of social relationships. The EQ increased two-fold. DISCUSSION-CONCLUSION: This implicit group improved the children’s social skills. It would be interesting to evaluate the maintenance of these skills over time, examine more widespread results, and compare implicit and explicit groups.
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8. Joosten A. {{Professor Sylvia Rodger’s scholarship and contributions to the Autism Spectrum Disorder Body of Knowledge}}. {Aust Occup Ther J};2017 (Jul);64 Suppl 1:27-30.
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9. Kawada K, Mimori S, Okuma Y, Nomura Y. {{Involvement of endoplasmic reticulum stress and neurite outgrowth in the model mice of autism spectrum disorder}}. {Neurochem Int};2017 (Jul 12)
Neurodevelopmental disorders are congenital impairments, impeding the growth and development of the central nervous system. These disorders include autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder in Diagnostic and Statistical Manual of Mental Disorders-5. ASD is caused by a gene defect and chromosomal duplication. Despite numerous reports on ASD, the pathogenic mechanisms are not clear. The optimal methods to prevent ASD and to treat it are also not clear. Other studies have reported that endoplasmic reticulum (ER) stress contributes to the pathogenesis of neurodegenerative diseases. In this study, we have investigated ER stress condition and neuronal maturation in an ASD mice model employing male ICR mice. An ASD mice model was established by injecting with valproic acid (VPA) into pregnant mice. The offspring born from VPA-treated mothers were subjected to the experiments as the ASD model mice. The cerebral cortex and hippocampus of ASD model mice were found to be under high ER stress. The mRNA levels of Hes1 and Pax6 were decreased in the cerebral cortex of the ASD model mice, but not in the hippocampus. In addition, the mRNA level in Math1 was increased in the cerebral cortex. ER stress inhibited dendrite and axon extension in primary culture derived from the cerebral cortex of E14.5 mice. Furthermore, dendrite outgrowth was suppressed in primary culture derived from the cerebral cortex of ASD model mice by the same method. These results indicated the possibility that ER stress induces abnormal neuronal maturation in the embryonal cerebral cortex of ASD model mice employing male ICR mice. Therefore, ER stress may contribute to the pathogenesis of ASD.
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10. Lim ET, Uddin M, De Rubeis S, Chan Y, Kamumbu AS, Zhang X, D’Gama AM, Kim SN, Hill RS, Goldberg AP, Poultney C, Minshew NJ, Kushima I, Aleksic B, Ozaki N, Parellada M, Arango C, Penzol MJ, Carracedo A, Kolevzon A, Hultman CM, Weiss LA, Fromer M, Chiocchetti AG, Freitag CM, Church GM, Scherer SW, Buxbaum JD, Walsh CA. {{Rates, distribution and implications of postzygotic mosaic mutations in autism spectrum disorder}}. {Nat Neurosci};2017 (Jul 17)
We systematically analyzed postzygotic mutations (PZMs) in whole-exome sequences from the largest collection of trios (5,947) with autism spectrum disorder (ASD) available, including 282 unpublished trios, and performed resequencing using multiple independent technologies. We identified 7.5% of de novo mutations as PZMs, 83.3% of which were not described in previous studies. Damaging, nonsynonymous PZMs within critical exons of prenatally expressed genes were more common in ASD probands than controls (P < 1 x 10-6), and genes carrying these PZMs were enriched for expression in the amygdala (P = 5.4 x 10-3). Two genes (KLF16 and MSANTD2) were significantly enriched for PZMs genome-wide, and other PZMs involved genes (SCN2A, HNRNPU and SMARCA4) whose mutation is known to cause ASD or other neurodevelopmental disorders. PZMs constitute a significant proportion of de novo mutations and contribute importantly to ASD risk. Lien vers le texte intégral (Open Access ou abonnement)
11. Lunsky Y, Weiss JA, Paquette-Smith M, Durbin A, Tint A, Palucka AM, Bradley E. {{Predictors of emergency department use by adolescents and adults with autism spectrum disorder: a prospective cohort study}}. {BMJ Open};2017 (Jul 18);7(7):e017377.
OBJECTIVES: To determine predictors of emergency department (ED) visits in a cohort of adolescents and adults with autism spectrum disorder (ASD). DESIGN: Prospective cohort study. SETTING: Community-based study from Ontario, Canada. PARTICIPANTS: Parents reported on their adult sons and daughters with ASD living in the community (n=284). MAIN OUTCOME MEASURES: ED visits for any reason, ED visits for medical reasons and ED visits for psychiatric reasons over 1 year. RESULTS: Among individuals with ASD, those with ED visits for any reason were reported to have greater family distress at baseline (p<0.01), a history of visiting the ED during the year prior (p<0.01) and experienced two or more negative life events at baseline (p<0.05) as compared with those who did not visit the ED. Unique predictors of medical versus psychiatric ED visits emerged. Low neighbourhood income (p<0.01) and living in a rural neighbourhood (p<0.05) were associated with medical but not psychiatric ED visits, whereas a history of aggression (p<0.05) as well as being from an immigrant family (p<0.05) predicted psychiatric but not medical emergencies. CONCLUSIONS: A combination of individual and contextual variables may be important for targeting preventative community-based supports for individuals with ASD and their families. In particular, attention should be paid to how caregiver supports, integrative crisis planning and community-based services may assist in preventing or minimising ED use for this vulnerable population. Lien vers le texte intégral (Open Access ou abonnement)
12. Melogno S, Pinto MA, Di Filippo G. {{Sensory and Physico-Psychological Metaphor Comprehension in Children with ASD: A Preliminary Study on the Outcomes of a Treatment}}. {Brain Sci};2017 (Jul 17);7(7)
Recent research into difficulties in figurative language in children with ASD highlighted that it is possible to devise training interventions to overcome these difficulties by teaching specific strategies. This study describes how children with ASD can improve their capability to explain metaphors with a treatment. Two types of metaphors, in the « X is Y » form, were addressed: sensory and physico-psychological. To face the difficulties posed by these metaphors, the adult taught two strategies: inserting the connective « is like » between « X » and « Y », which transforms the metaphor into a simile; comparing « X » and « Y » by means of thinking maps. Two tests of metaphor comprehension were used, one based on sensory and the other on physico-psychological metaphors. Sixteen 10 year-old children participated into the study, including an experimental group formed by 8 children with ASD (n = 4) which had received the treatment, and a control group (n = 4) which had not, and 8 typically-developing (TD) children. At the post-test, the experimental group significantly outperformed the controls in explaining both types of metaphors, but only in the sensory metaphors did their performances reach TD children’s levels. These results illuminate how clinical treatment can positively influence the developmental trajectories of metaphor comprehension.
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13. Moazen-Zadeh E, Shirzad F, Karkhaneh-Yousefi MA, Khezri R, Mohammadi MR, Akhondzadeh S. {{Simvastatin as an Adjunctive Therapy to Risperidone in Treatment of Autism: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial}}. {J Child Adolesc Psychopharmacol};2017 (Jul 18)
OBJECTIVES: Providing novel treatments for autism has been a subject of long-standing research. Based on etiopathological findings, we aim at assessing potential therapeutic effects of statins, here simvastatin, on autism symptoms for the first time. METHODS: In this randomized, double-blind, placebo-controlled, parallel-group 10-week clinical trial, 70 drug-free children aged 4 to 12 years old with diagnosis of autistic disorder based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision, who had an Aberrant Behavior Checklist-Community (ABC-C) scale irritability subscale score of >/=12, were equally randomized to receive either simvastatin (20-40 mg/day) or placebo as an adjunct to risperidone (1-2 mg/day) whereas administration of both drugs was started simultaneously from baseline. Patients with comorbid psychiatric disorders, active medical conditions, severe intellectual disability, seizure disorders, history of any treatments for autism in the past 6 months, or history of current anti-inflammatory drug consumption were excluded. Primary outcome was defined as the difference in mean change of the ABC-C scale irritability subscale score from baseline to the endpoint ( www.irct.ir ; IRCT201602041556N86). RESULTS: Significant differences in change of the ABC-C scale irritability (mean difference [95% confidence interval (CI)] = -3.45 [-5.37 to -1.54], p = 0.001; Cohen’s d = 0.89) and hyperactivity/noncompliance (mean difference [95% CI] = -4.27 [-6.69 to -1.86], p = 0.001; Cohen’s d = 0.87) subscales scores were detected between the two arms. No significant difference was detected in case of the other three subscales. CONCLUSIONS: This study provides preliminary evidence for potential therapeutic effects of simvastatin in the treatment of autism that warrants further investigations.
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14. Muller RA. {{Abandoning ASD? A response to Waterhouse, London, and Gillberg}}. {Autism Res};2017 (Jul);10(7):1183.
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15. Patra S. {{Portraying the oddness of autism: My name is Khan; Indian Sesame street}}. {Asian J Psychiatr};2017 (Jul 08);30:28.
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16. Smith IC, Swain D, Murphy HG, Ollendick TH, White SW. {{The Under- and Over-Identification of Autism: Factors Associated With Diagnostic Referral}}. {J Clin Child Adolesc Psychol};2017 (Jul 17):1-7.
As reported prevalence and public awareness of Autism Spectrum Disorder (ASD) have grown in recent years, clinicians will likely see increased referrals for suspected ASD. The current study sought to elucidate factors associated with referral for possible ASD, as well as diagnostic outcome among youth referred for suspected ASD. Youth referred for psychological evaluations at an outpatient clinic (N = 69, 6-18 years, 48 male) were categorized into four groups: referred for suspected ASD and diagnosed as such, referred for ASD and not diagnosed as such, not referred for ASD but diagnosed as such, and neither referred for nor diagnosed with ASD. Approximately half of cases referred for suspected ASD did not meet diagnostic criteria. A significant effect of group was found for cognitive ability and anxiety. Youth receiving ASD diagnoses, regardless of whether they were referred for suspected ASD, demonstrated lower cognitive ability than children not receiving ASD diagnoses. Youth neither referred for nor diagnosed with ASD demonstrated lower anxiety than those who were referred and diagnosed. Maternal education significantly differed among the four groups. Although group differences are seen for youth cognitive ability, anxiety, and maternal education, we found no clear indicators differentiating referrals that were « accurate » (i.e., those diagnosed with ASD) and those that were not (i.e., those who did not receive ASD diagnosis). Comorbidity was high in all groups, including those referred primarily for ASD assessment, underscoring the importance of comprehensive assessment regardless of specificity of the referral.
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17. Strathearn L, Kim S, Bastian DA, Jung J, Iyengar U, Martinez S, Goin-Kochel RP, Fonagy P. {{Visual systemizing preference in children with autism: A randomized controlled trial of intranasal oxytocin}}. {Dev Psychopathol};2017 (Jul 17):1-11.
Several studies have suggested that the neuropeptide oxytocin may enhance aspects of social communication in autism. Little is known, however, about its effects on nonsocial manifestations, such as restricted interests and repetitive behaviors. In the empathizing-systemizing theory of autism, social deficits are described along the continuum of empathizing ability, whereas nonsocial aspects are characterized in terms of an increased preference for patterned or rule-based systems, called systemizing. We therefore developed an automated eye-tracking task to test whether children and adolescents with autism spectrum disorder (ASD) compared to matched controls display a visual preference for more highly organized and structured (systemized) real-life images. Then, as part of a randomized, double-blind, placebo-controlled crossover study, we examined the effect of intranasal oxytocin on systemizing preferences in 16 male children with ASD, compared with 16 matched controls. Participants viewed 14 slides, each containing four related pictures (e.g., of people, animals, scenes, or objects) that differed primarily on the degree of systemizing. Visual systemizing preference was defined in terms of the fixation time and count for each image. Unlike control subjects who showed no gaze preference, individuals with ASD preferred to fixate on more highly systemized pictures. Intranasal oxytocin eliminated this preference in ASD participants, who now showed a similar response to control subjects on placebo. In contrast, control participants increased their visual preference for more systemized images after receiving oxytocin versus placebo. These results suggest that, in addition to its effects on social communication, oxytocin may play a role in some of the nonsocial manifestations of autism.
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18. Waterhouse L, London E, Gillberg C. {{The ASD diagnosis has blocked the discovery of valid biological variation in neurodevelopmental social impairment}}. {Autism Res};2017 (Jul);10(7):1182.
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19. Zachi EC, Costa TL, Barboni MTS, Costa MF, Bonci DMO, Ventura DF. {{Color Vision Losses in Autism Spectrum Disorders}}. {Front Psychol};2017;8:1127.
Autism spectrum disorders (ASDs) are neurodevelopmental conditions characterized by impairments in social/communication abilities and restricted behaviors. The present study aims to examine color vision discrimination in ASD children and adolescents without intellectual disability. The participants were also subdivided in order to compare color vision thresholds of autistic participants and those who achieved diagnostic criteria for Asperger Syndrome (AS). Nine subjects with autism, 11 participants with AS and 36 typically developing children and adolescents participated in the study. Color vision was assessed by the Cambridge Color Test (CCT). The Trivector protocol was administered to determine color discrimination thresholds along the protan, deutan, and tritan color confusion lines. Data from ASD participants were compared to tolerance limits for 90% of the population with 90% probability obtained from controls thresholds. Of the 20 ASD individuals examined, 6 (30%) showed color vision losses. Elevated color discrimination thresholds were found in 3/9 participants with autism and in 3/11 AS participants. Diffuse and tritan deficits were found. Mechanisms for chromatic losses may be either at the retinal level and/or reflect reduced cortical integration.
