Melatonin in autism spectrum disorders: a systematic review and meta-analysis.

To review current studies on the effectiveness of neurofeedback as a method of treatment of the core symptoms of autism spectrum disorders (ASD). Studies were selected based on searches in PubMed, Ovid MEDLINE, EMBASE, ERIC, and CINAHL using combinations of the following keywords: 'Neurofeedback' OR 'EEG Biofeedback' OR 'Neurotherapy' OR 'Mu-Rhythm' OR 'SMR' AND 'Autism' OR 'Autism Spectrum Disorder' OR 'Pervasive Developmental Disorder'. The existing evidence does not support the use of neurofeedback in the treatment of ASD. Studies with outcomes in favour of neurofeedback might be showing an improvement in comorbid attention-deficit-hyperactivity disorder symptoms rather than a true improvement in core ASD symptoms. Limitations of this review are those inherent in the studies available, including small sample size, short duration, variable diagnostic criteria, and insufficient control interventions, all causing a lack of generalizability.

Autism Spectrum Disorders (ASD) are a group of neuro‐developmental disorders caused by brain abnormalities which results in impaired social skills. There are five variants of the spectrum: Asperger Syndrome, Pervasive Developmental Disorder - Not Otherwise Specified, Autistic Disorders, Rett’s Syndrome and Childhood Disintegrative Disorders. These broad variants produce a wide variety of symptoms among children with ASD, where each child with ASD will have his own pattern of autism; however, all children with ASD will share the same deficits in the areas of social skills which include social interaction, verbal and non-verbal communication and unusual behavior/interest. Research on treatment in helping children with ASD to improve social skills is growing as the cases of children diagnosed with ASD are on the rise. Social Story™ is one of the proven methods of treatment in helping children with ASD to learn social skills. However, the current presentation format of Social Story™ has not been attractive and it requires intensive teacher‐student interaction for the full benefit of social skills acquisition. Numerous studies have proved that children with ASD are motivated and have a better understanding from reading or visual illustration learning rather than learning through spoken instructions. Results from studies have also discovered that the computer is attractive and engaging for children with ASD, as it offers much benefit to them. It has been said that learning is most effectual when motivated, thus, the purpose of this study is to discover a learning tool that children with ASD will be motivated to use on their own, and it is achievable by combining elements that they are interested in. This research focuses on the combination of Social Story™, 2D animation, and the computer as a medium of presentation to present an interactive pedagogical tool for children with ASD to learn social skills. This combination is anticipated to be an effective tool in teaching social skills to children with ASD, as they are naturally drawn to computers and visual cues, combined with the fact that Social Story™ has been effective in changing the social behavior of children with ASD. The prototype titled ‘I-Learn Social Story’ has been developed and evaluated on thirty children with ASD in a special school located in Kuching, Sarawak. A preliminary study has been conducted on three children with ASD prior to this final evaluation to ensure that the final prototype functions are properly based on the children’s needs. The method used in the evaluation study is the quantitative method, specifically single subject design, which is one type of experimental design. Results of the experimental study reveal that the prototype is effective in changing the participants’ social behavior and in improving their social skills. There are significant improvements in the appropriate social behavior, decrease in the inappropriate social behavior, and increase in the number of social interactions made by the participants. Thus, this study has contributed to the emergent research of treatment for children with ASD in social skills learning. The result of this study is important as we have discovered a novel method of treatment that can be used effectively in assisting children with ASD to improve their main deficit, social skills.

10 Tips For Testing Hearing in Children With Autism

Autism Spectrum Disorders (ASDs) are characterized by pervasive impairments in communication, socialization, and repetitive behaviors or interests. While there is a growing interest in early ASDs, very few studies have looked at the nature of these impairments before age 3. In order to better strengthen early assessment and intervention for ASDs, more knowledge is needed in this area. The current studies aimed to determine if, and in what ways, communication impairments are present in infants and toddlers (17-37 months) diagnosed with autism and Pervasive Developmental Disorder – Not Otherwise Specified (PDD-NOS). In the first study, infants with autism and PDD-NOS (i.e., the ASD group) were compared to typically developing infants. In the second study, three groups were compared: autism, PDD-NOS, and non-ASD related developmentally delayed. Differences in communication impairments were assessed using the endorsement of communication items found on the Baby and Infant Screen for Children with aUtIsm Traits (BISCUIT), Part 1. Differences in overall communication impairments were assessed, as well as differences on specific communication items. Results found that infants with an ASD exhibit greater communication impairments than do typically developing infants, with all items displaying significant differences. Additionally, significant differences were found in overall communication impairments between all three groups in the second study, with the majority of items differentiating between the groups. The implications of these results, as well as directions for future research, are discussed.

Autism in DSM-5

1. Chris Plauche Johnson, MEd, MD* 1. *Editorial Board After completing this article, readers should be able to: 1. Characterize the deficits of a child who has autism. 2. Describe the role of observing linguistic and social development in children who have autism. 3. Implement a strategy for surveillance and screening of young children. 4. Discuss the management of autism, including the use of medication. Primary care physicians (PCPs) caring for 1,000 children in a general practice should expect approximately six of their patients to meet the diagnosis of an autism spectrum disorder (ASD). (1) The impact of this prevalence is illustrated by a 2004 survey of PCPs revealing that 44% cared for 10 or more patients who had an ASD. (2) The ASDs include: autistic disorder (AD), Asperger disorder, and pervasive developmental disorder—not otherwise specified (PDD-NOS), a threshold term used when a child meets some but not all criteria necessary for a diagnosis of either AD or Asperger disorder. Research has documented the positive benefit of developmental and behavioral intervention for children who have ASDs, particularly when it is initiated prior to 3 years of age. (3) Early recognition of ASDs also is important for timely genetic counseling because younger siblings of children diagnosed as having ASDs have a 10 times increased risk of also having an ASD. The purpose of this review is to help the clinician recognize signs of ASDs that occur before age 2 years. Because the signs of Asperger disorder usually appear later, they are not discussed. The term “autism” is used in this review to represent both AD and its milder form, PDD-NOS. Currently, autism is diagnosed infrequently in children younger than 3 years of age. The diagnostic process is prompted most often by parental concern about absent or delayed speech. However, signs of autism, especially deficits in social skills and in preverbal gestural language, are present …

Does IVF increase the risk of autism spectrum disorders (ASDs)? No association between IVF and ASDs or any of its subtypes was found in this sample. Certain prenatal factors may increase the risk of ASDs. Studies on the association between IVF and ASDs have shown inconsistent results. IVF is known to increase the risk of perinatal problems but many of them are related to multiple pregnancies. This case-control study included 4164 autistic cases and 16 582 matched controls born in Finland in 1991-2005. The cases were diagnosed with ASDs by the year 2007. The maximum age at diagnosis was 16 years. Four controls were matched to each case. For singletons the matching criteria were date of birth, place of birth, sex and residency in Finland. For twins the birth order within a twin pair was included as well. In the whole sample, there were 63 cases (1.51%) and 229 controls (1.38%) born after IVF. No significant association was found between IVF and ASDs (adjusted odds ratio (OR): 0.9, 95% confidence interval (CI): 0.7-1.3) or its subtypes childhood autism (OR: 0.8, 95% CI: 0.4-1.5), Asperger's syndrome (OR: 0.9, 95% CI: 0.5-1.6) or other pervasive developmental disorder (OR: 1.0,95% CI: 0.6-1.6). When only singletons were included, there was an association between IVF and Asperger's syndrome in an unadjusted analysis (OR: 2.0, 95% CI: 1.1-3.5) but this was not significant when adjusted for mother's socioeconomic status or parity. When the analyses were conducted separately for boys and girls, there was a significant association between IVF and Asperger's syndrome for boys in an unadjusted analysis (OR: 2.1, 95% CI: 1.2-3.7) but this was not significant in the final adjusted model. Information both on IVF and on ASDs was based on registers and it is possible that there is some misclassification. No information on different subtypes of IVF or other assisted reproduction techniques was available. Statistical power may have been insufficient. This study showed no increased risk of ASDs in children born after IVF but studies with larger sample sizes and information on different subtypes of IVF are needed to confirm the finding. The study was supported by Autism Speaks, NIMH 1K02-MH65422 and NIEHS 1R01ES019004. There are no competing interests.

Introduction: Children with Autism Spectrum Disorder (ASD) suffer from insomnia at much higher rates than typically developing (TD) peers. Research indicates that sleep problems in ASD may be due to hypersensitivities to stimuli and melatonin deficiencies. Behavioral treatments for insomnia in ASD often include sleep hygiene recommendations to avoid physical activity and light intensity within two hours of bedtime. However, despite these recommendations, research examining the relationship between physical activity and light intensity close to bedtime and sleep outcomes in TD and ASD is sparse. The current study examines associations between pre-bedtime light intensity exposure, physical activity, and sleep in children with ASD and in TD children. Methods: Children with ASD (n=28, Mage=8.4, SD=1.7) and 27 TD children (n=27, Mage=8.9, SD=1.8) who met DSM-5 criteria for insomnia disorder completed 14 concurrent days of sleep diaries with parental assistance and 14 days of wrist worn actigraphy. Sleep diaries and actigraphy obtained estimates of sleep onset latency (SOL), wake time after sleep onset (WASO), and total sleep time (TST) for each night, and actigraphy also obtained light intensity exposure and average physical activity in five timeframes prior to bedtime (0-30 minutes, 0-60 minutes, 0-120 minutes, 120-240 minutes, and 240-360 minutes). Multi-level models examined intra-individual and inter-individual associations between pre-bedtime physical activity, light intensity, and subjective/actigraphic sleep outcomes, as well as whether these associations differed between children with ASD and TD. Results: Greater light intensity was associated with longer subjective SOL (B=0.18, p=0.04, 120-240 mins, inter-individual), longer subjective WASO (B=0.05, p<0.001, 120-240 mins, intra-individual), and shorter subjective TST (B=-0.42, p=0.02, 120-240 mins, inter-individual) in TD but not ASD. Greater light intensity was associated with longer subjective SOL (B=0.08, p=0.05, 0-60 mins, intra-individual), and longer subjective TST (B=1.25, p=0.04, 0-120 mins, inter-individual) for ASD, but not TD. Greater light intensity was associated with longer actigraphic SOL (B=0.07, p=0.05, 0-60 mins, inter-individual) in ASD, but not TD, and longer actigraphic WASO (B=0.02, p<0.01, 120-240 mins, intra-individual) in TD, but not ASD. Greater physical activity was associated with longer subjective TST (B=0.30, p=0.01, 0-30 mins, inter-individual; B=0.36, p<0.01, 0-60 mins, inter-individual; B=0.26, p=0.02, 0-120 mins, inter-individual) and shorter actigraphic SOL (B=-0.05, p=0.01, 240-360 mins, intra-individual) in both ASD and TD. Conclusion: Results do not support sleep hygiene recommendations for avoidance of pre-bedtime physical activity, but they generally support avoidance of pre-bedtime light intensity. We speculate that pre-bedtime light intensity exposure may interfere with sleep outcomes through impeding melatonin secretion. Further, our results do not support the mechanism that hypersensitivities to light or physical activity are primarily responsible for insomnia in ASD relative to TD, since both ASD and TD showed similar associations between light, physical activity, and sleep outcomes (i.e., greater pre-bedtime light associated with worse sleep and greater pre-bedtime activity associated with better sleep). Future research should examine the relationship between pre-bedtime light exposure and melatonin production in ASD and explore whether sleep hygiene recommendations to avoid pre-bedtime physical activity are warranted in ASD and TD.

Objective: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interactions and behavioral problems. Various genetic and environmental factors, including oxidative stress, are claimed to play a role in the etiopathogenesis of ASD. In this study, we aimed to examine the status of oxidative metabolism in ASD and the association between oxidative parameters and ASD symptom severity and subtype of ASD. Method: Thirty-three children and adolescents diagnosed with ASD (16 children diagnosed with autistic disorder, 13 children with pervasive developmental disorder not otherwise specified, and 4 children with Asperger syndrome) according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) and 28 healthy controls, aged 2-17 years, were recruited in this study. Total oxidant status (TOS) and total antioxidant status (TAS) were evaluated using Rel Assay Kit in children and adolescents. The oxidative stress index (OSI) was calculated by dividing the TOS values by the TAS values. Autistic symptoms for these patients were scored on the Childhood Autism Rating Scale (CARS). Results: In patients with ASD, TAS was statistically significantly lower and OSI statistically significantly higher than in healthy controls. There were no statistically significant differences in TOS between the ASD and control groups. There were no statistically significant differences between the subtypes of ASD in terms of oxidative stress parameters. In addition, TAS, TOS, and OSI values did not differ statistically significantly between the patients’ CARS groups, and were not associated with the CARS scores of the patients. Conclusion: Our findings suggest that oxidative imbalance is present in ASD and that oxidative stress may play a role in the etiopathogenesis of ASD. Therefore, it is suggested that antioxidants may have beneficial effects on ASD and may be a new therapeutic target in treating ASD.

The causes of autism spectrum disorders (ASDs) are unknown, although genetic and environmental influences have been implicated. Previous studies have suggested an association with birth defects, but most investigators have not addressed associations with specific diagnostic categories of ASD. In this study, the authors investigated the associations between birth defects and autism, Asperger syndrome, and pervasive developmental disorder not otherwise specified. Using Western Australian population-based linked data, the authors compared all children with ASD born in Western Australia during 1980-1995 (n = 465) with their siblings (n = 481) and population controls (n = 1,313) in a nested case-control study. The prevalence of birth defects was significantly higher in ASD cases than in population controls; this difference remained significant after adjustment for confounding factors. Odds ratios for birth defects were similar for autism (odds ratio (OR) = 2.0, 95% confidence interval (CI): 1.3, 3.0) and pervasive developmental disorder not otherwise specified (OR = 2.2, 95% CI: 1.1, 4.3) but not for Asperger syndrome (OR = 0.5, 95% CI: 0.1, 1.9). Birth defects in case siblings were not significantly different from those in cases and population controls. The association between birth defects and ASD may be due to underlying genetic and/or environmental factors common to both ASD and birth defects, or birth defects may predispose a child to ASD.

Autism is a neurodevelopmental disorder of complex etiology and is amongst the most heritable of neuropsychiatric disorders while sharing genetic liability with other neurodevelopmental disorders such as intellectual disability (ID). Autism spectrum disorders (ASDs) are defined more broadly and include autism, Asperger syndrome, childhood disintegrative disorder and pervasive developmental disorder not otherwise specified. Under the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition Revised (DSM-IVTR), these disorders are grouped together with Rett syndrome (“Rett’s disorder”) as pervasive developmental disorders. However, Rett syndrome has a reportedly distinct pathophysiology, clinical course, and diagnostic strategy (Levy & Schultz, 2009) and will likely be removed in the impending publication of DSM-V (APA, 2010). The new diagnostic manual will formally adopt the single diagnostic category “ASDs”, which is used here. Reported prevalence rates for ASDs range from 20 (Newschaffer et al. 2007) to 116 (Baird et al., 2006) per 10,000 children, and vary in accordance with diagnostic, sampling, and screening criteria. The Centers for Disease Control and Prevention (CDC) suggest that in the United States, the prevalence of ASDs is 1 in 110 (1/70 in boys and 1/315 in girls) (ADDM, 2009). The three primary characteristics of ASDs are communication impairments, social impairments, and repetitive/stereotyped behaviors. The DSM-IVTR, ICD-10, and many other diagnostic instruments require impairment in each of these domains for a diagnosis of autistic disorder. Within the last decade, a number of major technological developments have transformed our understanding of the genetic causes of autism, and the field continues to evolve rapidly. In this chapter, we will review three approaches to identifying genetic factors that contribute to the pathogenesis of ASDs: 1) common variants and genome-wide association studies (GWAS); 2) rare variants and copy number variation (CNV) studies, and 3) familial forms of autism and the role of next-generation sequencing (NGS) methods. Data from all three approaches underscores the conclusion that autism is a highly complex and heterogeneous disorder, involving a multifactorial etiology. Moreover, it is becoming increasingly apparent that autism is not a unitary disorder, and that the spectrum may consist of any number of different autisms that share similar symptoms or phenotypes. This conclusion has important implications for evaluation and treatment, which are discussed in the conclusion.

The COVID-19 pandemic has raised numerous concerns regarding its effects on individuals' health and lifestyle. We aim to analyze potential changes in adolescent sleep patterns from before and during the pandemic and identify specific predictors of changes. A subgroup of adolescents from a population-based birth cohort from Pelotas, Brazil, was assessed pre-pandemic (T1, November-2019 to March-2020) and peri-pandemic (T2, August-2021 to December-2021) in in-person interviews (n = 1,949). Sleep parameters, including sleep duration and latency time on workdays and free days, as well as social jetlag (SJL), were assessed using the Munich ChronoType Questionnaire (MCTQ). Socio-demographic, pre-pandemic, and pandemic-related predictors were analyzed. Changes in sleep parameters from T1 to T2 were estimated by multivariate latent change score modeling. The latent change factor shows a significant mean increase in workday sleep duration (M = 0.334, p < 0.001), workday sleep latency (M = 0.029, p = 0.002), and free day sleep latency (M = 0.021, p = 0.034), and a decreased in SJL (M = -0.758, p < 0.001) during the pandemic. Female adolescents presented higher increases in workday sleep duration. Adolescents who adopted a stricter social distancing level during the pandemic presented greater increases in workday sleep duration and smaller reductions in SJL. Self-evaluated insomnia during the pandemic predicted lower increases in workday and free day sleep duration and higher increases in workday and free day sleep latency. The COVID-19 outbreak brought certain advantages regarding increased sleep duration and reduced SJL. However, the observed increase in sleep latency and the influence of self-reported insomnia could be related to psychological distress inherent to the pandemic.

The ability to coordinate attention to events or objects between interactive social partners, referred to as social attention, is of great significance for adaptive social behaviors and nonverbal communications in our daily life, helping us to infer other person’s inner state (e.g., intentions, goals) and learn about where important events (e.g., food, danger) occur in the environment. In recent years, many studies have demonstrated that social cues (e.g., eye gaze, head orientation and walking direction of biological motion) can trigger reflexive attentional orienting effects using adapted central cueing paradigm originally designed by Posner. However, not all of us are equally adept at directing attention to where others are focusing on, and this ability is strongly impaired in individuals with autism spectrum disorder (ASD), a highly genetic neurodevelopmental disorder marked by striking social deficits and repetitive behaviors. Here we systematically reviewed recent work on abnormal social attention behaviors and its underlying neural mechanisms in ASD. We first expatiated a typical social attention behaviors indexed by covert and overt attention in ASD. It has been documented that ASD individuals tend to show reduced reflexive orienting effect manifesting itself in both covert attention and overt eye movement compared to typically developing individuals (TD). Yet some controversies concerning the malfunction of social attention in ASD remain to be resolved, based on some evidence demonstrating comparable orienting effect between ASD and TD group. Then we summarized the development course of social attention in ASD. Crucially, atypical orienting to eye gaze is more likely to be observed in younger children but not older children or adults with ASD. It is reasonable to postulate that ASD individuals may acquire this ability through overlearning the association between social cues and targets in everyday life as they grow older. Furthermore, we discussed the neural basis of abnormal social attention behaviors in ASD. Using a combination of psychophysical paradigms and neuroimaging techniques, researchers have reported atypical neural activities in superior temporal gyrus and prefrontal cortex under the supraliminal condition as well as abnormal activation in amygdala under the subliminal condition in the brain of ASD. Moreover, the ASD group showed much less difference in activation of frontoparietal attention networks between social and nonsocial attention task than the TD group, implying disruptive social attention in ASD. Finally, several perspectives on further investigations were put forward given the controversies and insufficient evidence concerning the malfunction of social attention in ASD. Future studies should employ multiple types of social cues (e.g., eye gaze and walking direction of biological motion) in conjunction with more ecological paradigms to investigate conscious and non-conscious social attention behaviors from a developmental approach. More importantly, more neuroimaging studies are needed to explore the functional connections among several key cortical regions and subcortical regions underlying atypical social attention behaviors in ASD. Such efforts will help to facilitate the early diagnosis and intervention of ASD.

To examine the diagnostic stability of a childhood diagnosis of Asperger Syndrome (AS) into adulthood in a prospective longitudinal study, and identify the predictors of stability. One hundred males with AS diagnosed in childhood (T0) according to Gillberg's AS criteria, were followed up prospectively into adulthood over an average of 19years (range 13-26years). Fifty males (mean age 30years) participated in this second follow-up (T2) of the cohort. Seventy-six had participated in a previous follow-up (T1) at mean age 22years (47 participated in both follow-ups). Diagnosis at T2 was assessed using three sets of diagnostic criteria (Gillberg's AS criteria, DSM-IV Pervasive Developmental Disorder (PDD) and DSM-5 Autism Spectrum Disorder (ASD) criteria) and compared to previous assessments. Background predictors of diagnostic stability were analyzed. General functioning at T2 was assessed and compared to T1. There was a decline in the stability of AS diagnosis over time, the rate dropping from 82% at T1 to 44% at T2, when using the Gillberg criteria. There was also a significant decrease in the rate of cases fulfilling any PDD diagnosis according to the DSM-IV, from 91% at T1 to 76% at T2 in the 47 cases followed up twice. Severity of autism spectrum symptoms at T1 was the main predictor of diagnostic stability at T2. Twenty percent of those meeting criteria for a PDD diagnosis according to DSM-IV, did not meet DSM-5 ASD criteria although they had marked difficulties in everyday life. Asperger Syndrome, when considered as an ASD/PDD diagnosis, was fairly stable into adulthood, but there was a significant increase over time in cases no longer meeting criteria for an ASD diagnosis according to the DSM-IV, or AS according to the Gillberg criteria. Cases with a stable diagnosis showed significantly more core ASD symptoms in adolescence/young adulthood.

CONTEXT AND OBJECTIVE: Autism spectrum disorders (ASDs) include autistic disorder, Asperger’s disorder and pervasive developmental disorder. The manifestations of ASDs can have an important impact on learning and social functioning that may persist during adulthood. The aim here was to summarize the evidence from Cochrane systematic reviews on interventions for ASDs. DESIGN AND SETTING: Review of systematic reviews, conducted within the Discipline of Evidence-Based Medicine, Escola Paulista de Medicina, Universidade Federal de São Paulo. METHODS: We included and summarized the results from Cochrane systematic reviews on interventions for ASDs. RESULTS: Seventeen reviews were included. These found weak evidence of benefits from acupuncture, gluten and casein-free diets, early intensive behavioral interventions, music therapy, parent-mediated early interventions, social skill groups, Theory of Mind cognitive model, aripiprazole, risperidone, tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRI); this last only for adults. No benefits were found for sound therapies, chelating agents, hyperbaric oxygen therapy, omega-3, secretin, vitamin B6/magnesium and SSRI for children.CONCLUSION: Acupuncture, gluten and casein-free diets, early intensive behavioral interventions, music therapy, parent-mediated early interventions, social skill groups and the Theory of Mind cognitive model seem to have benefits for patients with autism spectrum disorders (very low to low-quality evidence). Aripiprazole, risperidone, tricyclic antidepressants and SSRI (this last only for adults) also showed some benefits, although associated with higher risk of adverse events. Experimental studies to confirm a link between probable therapies and the disease, and then high-quality long-term clinical trials, are needed.