Association Between Sleep Deficiencies with Behavioral Problems in Autism Spectrum Disorder: Subtle Sex Differences.

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.

The aims of this chapter are to present the state of the science of sleep in individuals with autism spectrum disorder (ASD), including hypotheses for the high prevalence of chronic insomnia, possible etiologies of insomnia, and ecological and behavioral interventions for promoting optimal sleep. About two thirds of children with ASD have chronic insomnia, and these sleep problems have been shown to persist. The strongest evidence on promoting sleep in individuals with ASD is for sleep education, ecological changes, behavioral interventions, and exogenous melatonin. In 2012, the Sleep Committee of the Autism Treatment Network developed a practice pathway, based on expert consensus, to capture best practices for screening, identification, and treatment of sleep problems in ASD. An exemplar case is presented to integrate key constructs of the practice pathway.

Sleep Problems—Autism Toolkit

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and repetitive behaviors. Children with ASD are statistically more likely to experience early adversity; however, little is known about the types of early adversity that place these children at risk, the role of parenting as a protective factor, and how this early life stress impacts cognitive outcomes. We assessed early adversity in 302 children (ASD=98) aged 6-16 years old, using parent-based report. To identify protective factors, we assessed parenting styles using parent surveys. Executive functions were assessed in the children using the WISC-V. Children with ASD had an increased incidence of familial stressors compared to the typically developing (TD) group. Positive parenting was associated with a significant decrease in the incidence of familial adverse events for both children with ASD and TD children. Examining the relationship between adversity and cognitive outcomes, in young children (6-11 years) with ASD, environmental stressors were associated with cognitive impairments. Findings suggest children with ASD may be at higher risk for familial adversity than their TD peers. However, all children benefit from positive parenting styles, which may mitigate the adverse effects of family-based early life stress. LAY SUMMARY: Some key features of Autism Spectrum Disorder (ASD) include difficulties with communication and social impairments. This means that children with ASD may be more likely to experience early adversity (stressful social interactions which take place during childhood) than children without ASD. Research in typically developing (TD) children has shown that experiencing more stressful events in childhood can cause changes in the brain, which can potentially impact the child's memory, reasoning, and decision-making skills later in life. However, there is evidence to suggest that having a nurturing relationship with a parent can offset some of the negative impacts of childhood adversity. In our study, we found that children with ASD are more likely to experience family-related stress compared to TD children. Having a positive relationship with a parent, however, was linked to experiencing this type of stress less often for all children, regardless of whether they were diagnosed with ASD. We also found that stressors related to environmental factors like financial instability were associated with lower cognitive abilities in children with ASD under 12 years of age. Understanding how these factors interact and differ in children with ASD can help to build stronger families and help children with ASD to thrive throughout their development.

The brain's ability to encode temporal patterns and predict upcoming events is critical for speech perception and other aspects of social communication. Deficits in predictive coding may contribute to difficulties with social communication and overreliance on repetitive predictable environments in individuals with autism spectrum disorder (ASD). Using a mismatch negativity (MMN) task involving rhythmic tone sequences of varying complexity, we tested the hypotheses that (1) individuals with ASD have reduced MMN response to auditory stimuli that deviate in presentation timing from expected patterns, particularly as pattern complexity increases and (2) amplitude of MMN signal is inversely correlated with level of impairment in social communication and repetitive behaviors. Electroencephalography was acquired as individuals (age 6-21 years) listened to repeated five-rhythm tones that varied in the Shannon entropy of the rhythm across three conditions (zero, medium-1 bit, and high-2 bit entropy). The majority of the tones conformed to the established rhythm (standard tones); occasionally the fourth tone was temporally shifted relative to its expected time of occurrence (deviant tones). Social communication and repetitive behaviors were measured using the Social Responsiveness Scale and Repetitive Behavior Scale-Revised. Both neurotypical controls (n = 19) and individuals with ASD (n = 21) show stepwise decreases in MMN as a function of increasing entropy. Contrary to the result forecasted by a predictive coding hypothesis, individuals with ASD do not differ from controls in these neural mechanisms of prediction error to auditory rhythms of varied temporal complexity, and there is no relationship between these signals and social communication or repetitive behavior measures. LAY SUMMARY: We tested the idea that the brain's ability to use previous experience to influence processing of sounds is weaker in individuals with autism spectrum disorder (ASD) than in neurotypical individuals. We found no difference between individuals with ASD and neurotypical controls in brain wave responses to sounds that occurred earlier than expected in either simple or complex rhythms. There was also no relationship between these brain waves and social communication or repetitive behavior scores.

Introduction Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions characterized by impairments in social interaction, communication (both verbal and non-verbal), and repetitive behaviors. The global prevalence of ASD has increased significantly, with an estimated 28.3 million cases worldwide. Although many individuals with ASD have normal cognitive and language skills, difficulties with social interactions and understanding nonverbal cues can interfere with their ability to form romantic and sexual relationships, potentially leading to inappropriate behaviors and a distorted experience of sexuality. Objectives This paper aims to review the literature on sexuality in individuals with ASD, focusing on typical sexual behaviors, sexual preferences, as well as hypersexuality and paraphilic fantasies and behaviors within this population. Methods A non-systematic literature review was conducted, with article selection from PubMed using the keywords: “autism spectrum disorders”, “sexuality”, “hypersexuality” and “paraphilia”. Results Studies have shown that adolescents with ASD experience higher rates of inappropriate sexual behaviors and gender dysphoria compared to neurotypical peers. Variants in sexual orientation, including homosexuality, asexuality, and bisexuality, are more prevalent in this population. Recent research indicates that sexual experiences, both alone and with others, are common among individuals with high-functioning ASD, with one study revealing that 47% expressed interest in having a romantic partner. Despite this, adults with ASD, especially men, are generally less likely to be in romantic relationships. They also exhibit more hypersexual and paraphilic fantasies and behaviors than neurotypical individuals. Hypersexual behaviors are predominantly observed among male ASD individuals, while paraphilias, such as voyeurism and fetishism, are frequently reported among both ASD men and women. Sadistic and masochistic fantasies and behaviors are also common in this group. Conclusions The results indicate that individuals with ASD have a higher prevalence of sexual orientation variants and inappropriate behaviors compared to their peers. Although they have sexual interests and desires for relationships, their ability to express sexuality in a healthy way is hindered by communication deficits, social interaction challenges, and an unsupportive environment, exacerbated by inadequate sexual education. These challenges prevent many from fully embracing their sexuality. Specialized, evidence-based sexual education addressing the unique needs of individuals with ASD is essential for promoting healthier sexual behaviors and improving psychosocial well-being. Disclosure of Interest None Declared

PurposeSex differences in circumscribed interests (CI) may delay diagnosis for females with autism spectrum disorder (ASD); therefore, it is important to characterize sex differences in CI to determine if differential approaches to diagnostic assessment are warranted for females with ASD. The purpose of this paper is to examine sex differences in parent-reported quantity, content and functional impairment of children’s interests.Design/methodology/approachParent responses to the Interests Scale were analyzed using descriptive statistics and ANOVAs to determine diagnostic (ASD vs typical development (TD)) and sex differences between four groups of children ages six to ten years: ASD males, ASD females, TD males and TD females.FindingsGroups were comparable on the quantity of interests reported on the Interests Scale. Children with ASD demonstrated significantly more nonsocial interests and had greater functional impairment associated with their interests than TD children. A significant diagnosis×sex effect was found for the number of interests in folk psychology. Descriptively, males with ASD were more likely to have a primary interest in the traditionally male category of physics than females with ASD whose primary interest mainly fell into the categories of TV or the more traditionally female category of psychology.Originality/valueThese findings strengthen the results of Turner-Brown et al. (2011) by replicating their findings that children with ASD have more nonsocial interests and greater functional impairments related to their interests compared to TD children in a sample that is balanced on biological sex. However, there are distinctions between males and females with ASD in their primary interests that have implications for diagnostic assessment.

Sleep problems are highly prevalent in ADHD and autism spectrum disorder (ASD). Better insight in the etiology is of clinical importance since intervention and prevention strategies of sleep problems are directed at underlying mechanisms. We evaluated the association of sleep problems and sleep patterns with sleep hygiene (behavioral/environmental practices that influence sleep quality, e.g. caffeine use), access to electronic media, chronotype, and anxiety/depression in children aged 6–12 years with ADHD, ASD, or typical development (TD) using parental questionnaires. ANOVA and linear regression analyses were adjusted for age and sex. Children with ADHD and ASD showed more sleep problems (63.6 and 64.7%, vs 25.1% in TD) and shorter sleep duration than controls, while differences between ADHD and ASD were not significant. Sleep hygiene was worse in ADHD and ASD compared to TD, however, the association of worse sleep hygiene with more sleep problems was only significant in ASD and TD. There was a significant association of access to electronic media with sleep problems only in typically developing controls. Chronotype did not differ significantly between groups, but evening types were associated with sleep problems in ADHD and TD. Associations of greater anxiety/depression with more sleep problems were shown in ADHD and TD; however, anxiety/depression did not moderate the effects of chronotype and sleep hygiene. We conclude that sleep problems are highly prevalent in ADHD and ASD, but are differentially related to chronotype and sleep hygiene. In ASD, sleep problems are related to inadequate sleep hygiene and in ADHD to evening chronotype, while in TD both factors are important. Clinical implications are discussed.

Autism spectrum disorder (ASD) involves social communication difficulties and repetitive behaviors, and it has a growing prevalence worldwide. Symptoms include cognitive impairments, gastrointestinal (GI) issues, feeding difficulties, and psychological problems. A significant concern in ASD is food selectivity, leading to nutrient deficiencies. Common GI issues in ASD, such as constipation and irritable bowel syndrome, stem from abnormal gut flora and immune system dysregulation. Sensory sensitivities and behavioral challenges exacerbate these problems, correlating with neurological symptom severity. Children with ASD also exhibit higher oxidative stress due to low antioxidant levels like glutathione. Therapeutic diets, including ketogenic, high-antioxidant, gluten-free and casein-free, and probiotic-rich diets, show potential in managing ASD symptoms like behavior, communication, GI issues, and oxidative stress, though the evidence is limited. Various studies have focused on different populations, but there is increasing concern about the impact among children. This review aims to highlight the food preferences of the ASD population, analyze the effect of the physicochemical and nutritional properties of foods on the selectivity in its consumption, GI problems, and antioxidant deficiencies in individuals with ASD, and evaluate the effectiveness of therapeutic diets, including diets rich in antioxidants, gluten-free and casein-free, ketogenic and essential fatty acids, and probiotic-rich diets in managing these challenges.

Autism spectrum disorders (ASD) are composed of a range of conditions affecting the development of the nervous ststem; these groups of disorders are unified by characteristic impairments in social interaction, communication, and repetitive behaviors. Due to the somewhat hetereogeneous nature of these conditions, several environmental and genetic causes have been associated with ASD. Among the genetic causes, the CNTNAP2 gene is implicated in syndromic forms of ASD. As such, this gene has been studied in the context of animal model systems, primarily mice and rats; these studies have indicated that knockout of the CNTNAP2 gene results in features that are similar to that observed in human ASD. To further assess this animal model of ASD, in this study, we assessed the behavioral phenotypes of CNTNAP2 knockout mice using a range of behavioral assays targeting core and comorbid traits of ASD. We confirmed that CNTNAP2 mutant mice exhibited social interaction deficits, reduced ultrasonic vocalizations, repetitive behaviors, and hyperactivity, aligning with core and comorbid ASD features. Notably, we also identified novel findings: CNTNAP2 knockout mice displayed increased rearing behavior and lacked anxiety-like behaviors, diverging from the assumption that anxiety is a common feature of this model. These results demonstrate that CNTNAP2 knockout mice recapitulate key ASD-related behaviors while highlighting novel behavioral aspects; these data reinforce their utility as an animal model for studying ASD.

Autism in DSM-5

Fragile X syndrome (FXS) is the leading known monogenetic cause of autism spectrum disorder (ASD) and inherited form of intellectual disability (ID). As the major and growing public health problem worldwide, ASD is purely behaviorally defined whereas FXS is a medical/genetic disorder characterized by ID and ASD in males and learning and behavioral/emotional problems (social anxiety, attention network) in both genders. FXS is caused by a mutation in the Fragile X Mental Retardation 1 gene (FMR1) that leads to the epigenetic silencing of the gene and absence of its encoded protein, the fragile X mental retardation protein (FMRP). FMRP selectively targets approximately 4% of the transcribed mRNAs in the brain. Namely, to date, 842 such target mRNAs in mammalian brains have been identified and many of them converge on the same pathway as nonsyndromic ASD. Thus, FXS is the most studied 'disorder of synapse' model for syndromic ASD in the field of neuroscience. There are currently no effective treatments for either FXS or ASD. In this review article, we discuss recent progress and future directions in translating breakthrough preclinical findings that reveal potential therapeutic targets into clinical trials for humans with FXS of potential relevance for ASD. To date, a total of 20 double-blinded, randomized, placebo-controlled clinical trials in FXS have been identified through the FDA ClinicalTrial.gov website. The majority of these trials were completed between 2008-2015. These mostly phase II trials in adults and adolescents tested 13 compounds and have primarily targeted excitatory/inhibitory imbalance theory of FXS and ASD, namely a reversal of social/behavioral symptoms that are part of the core FXS phenotype but not the core synaptic dysfunction in FXS. Despite much progress in the field propelled by the preclinical advances, these clinical studies illustrate the gaps and challenges of translating therapies from animal models to humans with FXS and ASD ('building a bridge and walking on it'). Specifically, recent challenges in the clinical trials demonstrate the need to study for longer period of time (6-12 months), prepubertal age group(s), develop more objective clinical outcome measures (i.e., clinician-based, relevant learning paradigms, and desired biomarkers), and longer placebo run-ins to minimize the placebo impact for both FXS and ASD. Ultimately, a truly satisfactory FXS, and ASD, therapy may likely involve a combination of drugs (and learning paradigms), each targeting a different aspect of the core synaptic, cognitive and behavioral impairments in FXS.

Autism spectrum disorder (ASD) is a chronic disorder beginning early in development and comprising lifelong impairments in social communication and restricted and repetitive behaviours and interests. The manifestations of these core symptoms frequently vary across individuals, especially with differences in intellectual ability, and may change with age. In addition, people with ASD have high rates of co-occurring psychiatric disorders, including attention-deficit/hyperactivity disorder, anxiety and depression, tics/Tourette’s syndrome, and sleep problems. They frequently exhibit behaviours that challenge others, including aggression, self-injury, and high levels of irritability. Hence, their treatment and management requires a comprehensive approach to core and co-occurring symptoms. Management should include evidence-based approaches from health and also ASD-specific support from education, employment, social care, and the wider community. There is insufficient evidence to guide best practice, and more research on interventions is urgently required.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder defined by impairment in social communication and repetitive behaviors. Twin and family studies strongly support a genetic contribution to ASD risk but also indicate an important role for environmental factors, particularly non-shared environmental factors, which can include gene-environment interactions. An accelerating array of research has identified rare genetic risk factors in ASD. Rare prenatal exposures, such as valproic acid or rubella, also suggest a role for uncommon environmental risk factors in ASD. Less robust data support specific common genetic or environmental risk factors. A handful of studies have begun to explore the potential interaction between individual risk factors. Thus far, the most informative approach has been to evaluate potential common factors contributing risk within the context of a rare disorder with a high risk of ASD, such as fragile X syndrome or tuberous sclerosis. Extending beyond this approach will require careful attention to the potential biological relationships between individual risk factors, which may require initial studies in animal models before extending into human populations. Here, we review the initial forays into gene-environment interaction research in ASD and lay out the challenges and opportunities for future research in this important domain.

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterised by impairments in social communication, repetitive behaviours, and restricted interests. Emerging evidence suggests that immune system dysregulation, particularly alterations in the complement system, may contribute to ASD pathophysiology. This study aimed to compare the serum levels of complement proteins (C1q, C2, C3, C4, MBL, L-ficolin, and hsCRP) between children with ASD and non-ASD controls. A total of 88 children (44 with ASD and 44 age- and sex-matched healthy controls) participated in this study. Complement protein levels were measured using enzyme-linked immunosorbent assay (from serum samples. The severity of ASD symptoms was assessed using standardised diagnostic tools, including the Childhood Autism Rating Scale, the Autism Behaviour Checklist, and the Repetitive Behaviour Scale-Revised. Serum C1q levels were significantly lower in the ASD group (p < 0.001). C3 levels were lower (p = 0.033), while C2 levels were slightly higher (p = 0.015) in the ASD group. There are no significant differences in C4, MBL, or L-ficolin levels. Logistic regression analysis identified reduced C1q levels as a significant predictor of ASD (p = 0.001). However, this study found no significant correlations between complement levels and ASD symptom severity scores. The findings suggest that alterations in complement system proteins, particularly reduced serum C1q levels, may be associated with ASD. Given C1q’s critical role in synaptic pruning and neuroimmune regulation, these results support the hypothesis that complement system dysfunction may contribute to the pathophysiology of ASD.