Disturbances In Autism Spectrum Disorder Research Articles

Neuronal knockdown of Cullin3 as a Drosophila model of autism spectrum disorder

Mutations in Cullin-3 (Cul3), a conserved gene encoding a ubiquitin ligase, are strongly associated with autism spectrum disorder (ASD). Here, we characterize ASD-related pathologies caused by neuron-specific Cul3 knockdown in Drosophila. We confirmed that neuronal Cul3 knockdown causes short sleep, paralleling sleep disturbances in ASD. Because sleep defects and ASD are linked to metabolic dysregulation, we tested the starvation response of neuronal Cul3 knockdown flies; they starved faster and had lower triacylglyceride levels than controls, suggesting defects in metabolic homeostasis. ASD is also characterized by increased biomarkers of oxidative stress; we found that neuronal Cul3 knockdown increased sensitivity to hyperoxia, an exogenous oxidative stress. Additional hallmarks of ASD are deficits in social interactions and learning. Using a courtship suppression assay that measures social interactions and memory of prior courtship, we found that neuronal Cul3 knockdown reduced courtship and learning compared to controls. Finally, we found that neuronal Cul3 depletion alters the anatomy of the mushroom body, a brain region required for memory and sleep. Taken together, the ASD-related phenotypes of neuronal Cul3 knockdown flies establish these flies as a genetic model to study molecular and cellular mechanisms underlying ASD pathology, including metabolic and oxidative stress dysregulation and neurodevelopment.

Common and Distinct Disruptions of Cortical Surface Morphology Between Autism Spectrum Disorder Children With and Without SHANK3 Deficiency.

SH3 and Multiple Ankyrin Repeat Domains 3 (SHANK3)-caused autism spectrum disorder (ASD) may present a unique opportunity to clarify the heterogeneous neuropathological mechanisms of ASD. However, the specificity and commonality of disrupted large-scale brain organization in SHANK3-deficient children remain largely unknown. The present study combined genetic tests, neurobehavioral evaluations, and magnetic resonance imaging, aiming to explore the disruptions of both local and networked cortical structural organization in ASD children with and without SHANK3 deficiency. Multiple surface morphological parameters such as cortical thickness (CT) and sulcus depth were estimated, and the graph theory was adopted to characterize the topological properties of structural covariance networks (SCNs). Finally, a correlation analysis between the alterations in brain morphological features and the neurobehavioral evaluations was performed. Compared with typically developed children, increased CT and reduced nodal degree were found in both ASD children with and without SHANK3 defects mainly in the lateral temporal cortex, prefrontal cortex (PFC), temporo-parietal junction (TPJ), superior temporal gyrus (STG), and limbic/paralimbic regions. Besides commonality, our findings showed some distinct abnormalities in ASD children with SHANK3 defects compared to those without. Locally, more changes in the STG and orbitofrontal cortex were exhibited in ASD children with SHANK3 defects, while more changes in the TPJ and inferior parietal lobe (IPL) in those without SHANK3 defects were observed. For the SCNs, a trend toward regular network topology was observed in ASD children with SHANK3 defects, but not in those without. In addition, ASD children with SHANK3 defects showed more alterations of nodal degrees in the anterior and posterior cingulate cortices and right insular, while there were more disruptions in the sensorimotor areas and the left insular and dorsomedial PFC in ASD without SHANK3 defects. Our findings indicate dissociable disruptions of local and networked brain morphological features in ASD children with and without SHANK3 deficiency. Moreover, this monogenic study may provide a valuable path for parsing the heterogeneity of brain disturbances in ASD.

An update on the cause and treatment of sleep disturbance in children and adolescents with autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by abnormalities in social communication/interaction and restrictive, repetitive patterns of behavior. ASD is a relatively common psychiatric disorder, with a prevalence of approximately 1.7% in children. Although many children and adolescents with ASD visit the hospital for medical help for emotional and behavioral problems such as mood instability and self-harming behavior, there are also many visits for sleep disturbances such as insomnia and sleep resistance. Sleep disturbances are likely to increase fatigue and daytime sleepiness, impaired concentration, negatively impact on daytime functioning, and pose challenges in controlling anger and aggressive behavior. Sleep disturbance in children and adolescents with ASD negatively affects the quality of life, nothing to say the quality of life of their families and school members. In this review, sleep disturbances that are common in children and adolescents with ASD and adolescents are presented. The developmental and behavioral impacts of sleep disturbances in ASD were also considered. Finally, non-pharmacological and pharmacological treatments for sleep disturbances in children and adolescents with ASD and adolescents are reviewed.

Abnormal sleep physiology in children with 15q11.2-13.1 duplication (Dup15q) syndrome

BackgroundSleep disturbances in autism spectrum disorder (ASD) represent a common and vexing comorbidity. Clinical heterogeneity amongst these warrants studies of the mechanisms associated with specific genetic etiologies. Duplications of 15q11.2-13.1 (Dup15q syndrome) are highly penetrant for neurodevelopmental disorders (NDDs) such as intellectual disability and ASD, as well as sleep disturbances. Genes in the 15q region, particularly UBE3A and a cluster of GABAA receptor genes, are critical for neural development, synaptic protein synthesis and degradation, and inhibitory neurotransmission. During awake electroencephalography (EEG), children with Dup15q syndrome demonstrate increased beta band oscillations (12–30 Hz) that likely reflect aberrant GABAergic neurotransmission. Healthy sleep rhythms, necessary for robust cognitive development, are also highly dependent on GABAergic neurotransmission. We therefore hypothesized that sleep physiology would be abnormal in children with Dup15q syndrome.MethodsTo test the hypothesis that elevated beta oscillations persist in sleep in Dup15q syndrome and that NREM sleep rhythms would be disrupted, we computed: (1) beta power, (2) spindle density, and (3) percentage of slow-wave sleep (SWS) in overnight sleep EEG recordings from a cohort of children with Dup15q syndrome (n = 15) and compared them to age-matched neurotypical children (n = 12).ResultsChildren with Dup15q syndrome showed abnormal sleep physiology with elevated beta power, reduced spindle density, and reduced or absent SWS compared to age-matched neurotypical controls.LimitationsThis study relied on clinical EEG where sleep staging was not available. However, considering that clinical polysomnograms are challenging to collect in this population, the ability to quantify these biomarkers on clinical EEG—routinely ordered for epilepsy monitoring—opens the door for larger-scale studies. While comparable to other human studies in rare genetic disorders, a larger sample would allow for examination of the role of seizure severity, medications, and developmental age that may impact sleep physiology.ConclusionsWe have identified three quantitative EEG biomarkers of sleep disruption in Dup15q syndrome, a genetic condition highly penetrant for ASD. Insights from this study not only promote a greater mechanistic understanding of the pathophysiology defining Dup15q syndrome, but also lay the foundation for studies that investigate the association between sleep and cognition. Abnormal sleep physiology may undermine healthy cognitive development and may serve as a quantifiable and modifiable target for behavioral and pharmacological interventions.

RETRACTED ARTICLE: Vitamin A deficiency and sleep disturbances related to autism symptoms in children with autism spectrum disorder: a cross-sectional study

BackgroundVitamin A deficiency (VAD) and sleep disturbances have been reported in children with autism spectrum disorder (ASD). The influence of vitamin A (VA) levels on sleep regulation and sleep disturbances in ASD has garnered concern. The present study aimed to characterize the association of VA levels with sleep disturbances in children with ASD.MethodsThis cross-sectional study compared children with ASD (n = 856) to typically developing children (TDC; n = 316). We used the Children’s Sleep Habits Questionnaire to assess sleep disturbances, Childhood Autism Rating Scale to evaluate the severity of autism symptoms, and Autism Behavior Checklist and Social Responsiveness Scale to assess autism behaviors. Serum VA levels were estimated using high-performance liquid chromatography. Multivariable linear regression and two-way analysis of variance were performed to investigate if VAD was related to sleep disturbances in children with ASD.ResultsChildren with ASD had lower serum VA levels and a higher prevalence of sleep disturbances than TDC did. The incidence of VAD in ASD children with sleep disturbances was higher, and the symptoms more severe than those without sleep disturbances and TDC. Interestingly, the interaction between VAD and sleep disturbances was associated with the severity of autism symptoms.ConclusionVAD and sleep disturbances are associated with the core symptoms of ASD in children. Regular monitoring of sleep and VA levels may be beneficial for children with ASD.Trial registrationChinese Clinical Trial Registry, registration number: ChiCTR-ROC-14005442, registration date: December 9th 2014.

Sleep and Cognition in People with Autism Spectrum Condition: A Systematic Literature Review

Sleep disturbances have been found to increase severity of core autism spectrum disorder (ASD) symptoms such as social and communication difficulties and repetitive behaviours. However, very little is known about the impact of sleep on cognitive functioning in ASD. A systematic literature search identified fifteen original studies meeting inclusion and quality assessment criteria. Inter-rater reliability was strong (kappa=0.73). Multiple cognitive functions were negatively affected by sleep disturbances in ASD. This had a significant impact on daily functioning, as well as impacting families/carers. Possible sleep interventions include behavioural/cognitive training, pharmacological treatment, and sensory interventions. Combining objective and subjective sleep measures would help in early diagnosis, which may contribute towards developing interventions to help those with ASD as well as carers and families.

692 Longitudinal Stability of Sleep and Health Correlates in Adults with Autism Spectrum Disorder

Abstract Introduction Individuals with Autism Spectrum Disorder (ASD) experience sleep disturbances to a greater degree than the general population. The majority of research investigating sleep disturbances in ASD has focused on children and adolescents. The aim of the current study was to determine the stability and health correlates of self-reported sleep disturbances in adults with ASD. Methods Participants included 55 adults with ASD recruited from state-funded Pennsylvania programs (31.2±7.6 years old, 80% male, 10.9% minority). Patient-Reported Outcomes Measurement Information System (PROMIS) measures assessing Sleep Disturbances, Sleep-Related Impairment, Fatigue, Anxiety, Depression, Anger, and Physical Health, were completed at baseline and every 90 ± 14 days over a 2-year period. Intraclass correlation coefficients (ICC) were calculated for each sleep outcome, and interpreted as 0.00–0.20=“poor stability,” 0.21–0.40=“slight stability,” 0.41–0.60=“moderate stability,” 0.61–0.80=“substantial stability,” and 0.81–1.00=“almost perfect stability” across the first three time-points. Linear mixed models examined the independent association of sleep disturbances, sleep-related impairment, and fatigue on anxiety, depression, anger, and physical health over the two-year period. Results Sleep-related impairment (ICC=0.73) and fatigue (ICC=0.64) were substantially stable, while sleep disturbances were moderately stable (ICC=0.58). All three sleep-related outcomes were independently associated with anxiety (sleep-related impairment p=0.012; sleep disturbance p<0.001; fatigue p=<0.001) and anger (sleep-related impairment p=<0.001; sleep disturbance p=0.001; fatigue p<0.001) across the two-year period. Sleep disturbance (p=<0.001) and fatigue (p<0.001), but not sleep-related impairment (p=0.267), were associated with depression across the two-year period. In contrast, none of the sleep-related outcomes (sleep-related impairment p=0.285; sleep disturbance p=0.250; fatigue p=0.709) were associated with physical health over time. Conclusion Measures of sleep-related impairment, fatigue, and sleep disturbance remained stable over time, suggesting that they can provide clinicians and researchers with a brief, accurate, and reliable way to assess patient-reported sleep outcomes in adults with ASD. Furthermore, given the stability of these sleep measures and their independent association with elevated mental health outcomes, there is a need for evidence-based treatments targeting sleep difficulties and associated symptomology in adults with ASD, a particularly underserved population. Support (if any) Pennsylvania State Bureau of Autism Services through the Autism Services, Education, Resources, and Training (ASERT) grant

Sleep disturbances in autism spectrum disorder without intellectual impairment: relationship with executive function and psychiatric symptoms

The autism spectrum disorder (ASD) is a neurodevelopmental condition, frequently accompanied by medical and psychiatric pathology. One of the most commonly found problems associated with ASD is sleep disturbances, which are estimated to affect approximately 80% of the people with ASD, not only during childhood but also in the adolescence and adult stages. Nevertheless, the relationship of these sleep difficulties with autism severity, as well as other associated impairments such as executive functioning and psychiatric disorders (eg, depression), has not yet been widely studied. The main objective of the present study was to explore the relationship between sleep disturbances, subjective measures of executive function, and psychiatric pathology in the ASD population. To reach that goal, a group of 89 participants with ASD (44 children/adolescents and 45 adults) was recruited and evaluated with self-reported measures of executive function performance and psychiatric pathology tests. Multivariate analysis showed a significant association between sleep disturbances and psychiatric symptoms in both ASD groups, with greater sleep disturbances predicting more severe psychiatric pathology. No significant association was found with executive function in any group. Limitations included a small sample size and lack of objective measures. Sleep problems seem to be associated with the severity of psychiatric pathology throughout the lifespan, increasing the chance of developing psychiatric symptoms when they were present. Improving sleep quality in ASD at all ages may result in preventing and/or decreasing psychiatric pathology in this population.

Brain Metabolic Disturbances in Autism Spectrum Disorder: A systematic Review

Autism spectrum disorder (ASD) is a common neurodevelopmental condition marked by a lack of social contact and a pattern of restricted and repetitive behaviours (RRBs). Neuroimaging studies have revealed a lot about the underlying neurobiological mechanisms of ASD in the last decade. ASD and epilepsy are two neurodevelopmental conditions with a high incidence of comorbidity, implying that they share a similar neurodevelopmental process. However, there is currently no definitive way to determine when a child will inherit either or both syndromes, or to what extent related phenotypes will be affected. The current review presents brain imaging research to classify the brains of people with ASD over the lifespan.

Hair trace element concentrations in autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD)

BackgroundThe existing data demonstrate that alteration of trace element and mineral status in children with neurodevelopmental disorders including ASD and ADHD. However, comparative analysis of the specific patterns of trace element and mineral metabolism in children with ASD and ADHD was not performed. Therefore, the primary objective of the present study was to assess hair trace element and mineral levels in boys with ADHD, ASD, as well as ADHD with ASD. MethodsBoys with ADHD (n = 52), ASD (n = 53), both ADHD and ASD (n = 52), as well as neurotypical controls (n = 52) were examined. Hair analysis was performed using inductively-coupled plasma mass-spectrometry. ResultsThe obtained data demonstrate that hair Co, Mg, Mn, and V levels were significantly reduced in children with ADHD and ASD, and especially in boys with ADHD + ASD. Hair Zn was found to be reduced by 20% (p = 0.009) only in children with ADHD + ASD as compared to healthy controls. Factor analysis demonstrated that ASD was associated with significant alteration of hair Co, Fe, Mg, Mn, and V levels, whereas impaired hair Mg, Mn, and Zn content was also significantly associated with ADHD. In regression models hair Zn and Mg were negatively associated with severity of neurodevelopmental disorders. The revealed similarity of trace element and mineral disturbances in ASD and ADHD may be indicative of certain similar pathogenetic features. ConclusionThe obtained data support the hypothesis that trace elements and minerals, namely Mg, Mn, and Zn, may play a significant role in development of both ADHD and ASD. Improvement of Mg, Mn, and Zn status in children with ASD and ADHD may be considered as a nutritional strategy for improvement of neurodevelopmental disturbances, although clinical trials and experimental studies are highly required to support this hypothesis.

Parsing the Heterogeneity of Brain Metabolic Disturbances in Autism Spectrum Disorder

BackgroundDespite rising prevalence of autism spectrum disorder (ASD), its brain bases remain uncertain. Abnormal levels of N-acetyl compounds, glutamate+glutamine, creatine+phosphocreatine, or choline compounds measured by proton magnetic resonance spectroscopy suggest that neuron or glial density, mitochondrial energetic metabolism, and/or inflammation contribute to ASD neuropathology. The neuroanatomic distribution of these metabolites could help evaluate leading theories of ASD. However, most prior magnetic resonance spectroscopy studies had small samples (all <60, most <20), interrogated only a small fraction of the brain, and avoided assessing effects of age, sex, and IQ. MethodsWe acquired near-whole-brain magnetic resonance spectroscopy of N-acetyl compounds, glutamate+glutamine, creatine+phosphocreatine, and choline compounds in 78 children and adults with ASD and 96 typically developing children and adults, rigorously evaluating effects of diagnosis and severity on metabolites, as moderated by age, sex, and IQ. ResultsEffects of ASD and its severity included reduced levels of multiple metabolites in white matter and the perisylvian cortex and elevated levels in the posterior cingulate, consistent with white matter and social-brain theories of ASD. Regionally, both slower and faster decreases of metabolites with age were observed in ASD versus TD. Male-female metabolite differences were widely smaller in ASD than typically developing children and adults. ASD-specific decreases in metabolites with decreasing IQ occurred in several brain areas. ConclusionsResults support multifocal abnormal neuron or glial density, mitochondrial energetics, or neuroinflammation in ASD, alongside widespread starkly atypical moderating effects of age, sex, and IQ. These findings help parse the neurometabolic signature for ASD by phenotypic heterogeneity.

The Relationship Among Gastrointestinal Symptoms, Problem Behaviors, and Internalizing Symptoms in Children and Adolescents With Autism Spectrum Disorder.

Background: Many individuals with autism spectrum disorder (ASD) have co-occurring gastrointestinal (GI) symptoms, but the etiology is poorly understood. These GI symptoms often coincide with problem behaviors and internalizing symptoms, which reduces the quality of life for these individuals.Methods: This study examined the relationships among GI problems, problem behaviors, and internalizing symptoms in a sample of 340 children and adolescents with ASD who are patients at the University of Missouri Thompson Center for Autism & Neurodevelopmental Disorders.Results: The majority of patients experienced constipation (65%), about half experienced stomachaches or stomach pain (47.9%), and others experienced nausea (23.2%) or diarrhea (29.7%). Young children with aggressive problem behaviors were 11.2% more likely to have co-occurring nausea; whereas, older children showed more complex relationships between internalizing symptoms and GI symptoms. Older children with greater anxiety symptoms were 11% more likely to experience constipation, but 9% less likely to experience stomachaches. Older children with greater withdrawn behavior were 10.9% more likely to experience stomachaches, but 8.7% less likely to experience constipation. Older children with greater somatic complaints were 11.4% more likely to experience nausea and 11.5% more likely to experience stomachaches.Conclusions: Results suggest that the presentation of externalizing problem behavior and internalizing symptoms associated with GI problems differs between young children and older children with ASD. Therefore, behavior may have different relationships with GI symptoms at different ages, which may have implications for the treatment of and clinical approach to GI disturbances in ASD.

Identification of metabolic pathway disturbances using multimodal metabolomics in autistic disorders in a Middle Eastern population

We analyzed for the first time the metabolic profile of Lebanese children affected by autistic disorders to compare this profile to other metabolomics studies and to identify the associated metabolic disturbances. Urine samples of 40 patients with Autism spectrum disorder (ASD) and 40 healthy matched controls were analyzed using nuclear magnetic resonance (NMR) and liquid chromatography coupled to high-resolution mass spectrometry (LC–MS). Multivariate analysis on analytical data fusion was conducted on the training set of 50 urine samples, and then validated with a test set of 30 samples, this repeated 10 times. The model was also evaluated using a receiver operating characteristic curve showing a specificity and a sensitivity of 86% and 80%, respectively. Among the most significant metabolites that contributed to the discrimination between ASD and controls, we confirmed the perturbations of tyrosine, 2-hydroxybutyrate, creatine and glutamate. We found new metabolites such as trigonelline, cysteic acid and guanine. We found metabolic perturbations including amino acids, carbohydrates and oxidative stress pathways which added value for the contribution of known metabolic disturbances in ASD observed in populations of other ethnic and geographic origins.

Exploring sleep quality of young children with autism spectrum disorder and disruptive behaviors

Background and purposeSleep disturbances in autism spectrum disorder (ASD) are common and may impair daytime functioning as well as add to parental burden. In this well characterized sample of young children with ASD and disruptive behaviors, we examine the association of age and IQ in sleep disturbances using the Child Sleep Habits Questionnaire modified for ASD (CSHQ-ASD). We also test whether children with poor sleep have greater daytime behavioral problems than those with better sleep. Finally, we examine whether parental stress is higher in children with greater disruptive behaviors and sleep disturbances. Participants and methodsOne hundred and seventy-seven children with complete data out of 180 (mean age 4.7) with ASD participated in a randomized clinical trial. Parents completed the CSHQ-ASD and several other measures at study enrollment. The sample was divided into “poor sleepers” (upper quartile on the total score of the CSHQ-ASD) and “good sleepers” (lower quartile) for comparisons. Analyses were conducted to evaluate group differences on age, IQ, daytime disruptive behavior, social disability and parental stress. ResultsThe two groups of young children with ASD, good sleepers versus poor sleepers, were not different on age or cognitive level. Children in the poor sleeping group had significantly higher daytime behavioral problems including irritability, hyperactivity, social withdrawal and stereotypical behaviors. Parents in this group reported significantly higher levels of stress. ConclusionsThe finding of no age difference between good and poor sleepers in young children with ASD and disruptive behaviors suggests that sleep problems are unlikely to resolve as might be expected in typically developing children. Likewise, the good and poor sleepers did not significantly differ in IQ. These findings add strong support for the need to screen for sleep disturbances in all children with ASD, regardless of age and cognitive level. Poor sleepers exhibited significantly greater daytime behavioral problems and parents of children in this group reported significantly higher levels of stress. Above and beyond the co-occurring disruptive behavior, poor sleep quality appears to pose substantial additive burden on child and parents.

Attitudes toward risk and ambiguity in patients with autism spectrum disorder

Although the ability to make optimal decisions under uncertainty is an integral part of everyday life, individuals with autism spectrum disorder (ASD) frequently report that they experience difficulties with this skill. In behavioral economics, researchers distinguish two types of uncertainty to understand decision-making in this setting: risk (known probabilities) and ambiguity (unknown probabilities). However, it remains unclear how individuals with ASD behave under risk and ambiguity, despite growing evidence of their altered decision-making under uncertainty. We therefore extended previous research by studying the attitudes of those with ASD toward risk and ambiguity in both positive and negative contexts (i.e., gain and loss). In gain contexts, no significant difference was observed between the groups in risk attitudes, but ambiguity aversion was attenuated in ASD. In loss contexts, ambiguity attitudes did not significantly differ between the groups, but the ASD participants were less risk-seeking compared with the controls. In addition, insensitivity to the context change under risk and ambiguity in ASD was both significantly associated with poor social skills. These results improve our understanding of altered decision-making under uncertainty by disentangling the attitudes toward risk and ambiguity in ASD individuals. Applying behavioral economic tools may provide insights into the mechanisms underlying behavioral disturbances in ASD.

Attenuated contact heat-evoked potentials associated with sensory and social-emotional symptoms in individuals with autism spectrum disorder

Sensory disturbance is associated with socio-emotional problems in individuals with autism spectrum disorder (ASD). Most studies assess sensory symptoms by self-reports, which are largely limited by the language ability and self-awareness of the individuals. This study aims to investigate sensory disturbance by contact heat-evoked potentials (CHEP) in ASD individuals, and to examine the clinical correlates of CHEP parameters. We compared the CHEP parameters and reported pain between 31 ASD individuals (aged 20.5 ± 5.2 years) and and 22 typically-developing controls (TD, aged 21.4 ± 2.6), and correlated the CHEP parameters with self-reported sensory symptoms and attention/socio-emotional symptoms. We found that ASD individuals showed smaller P2-wave amplitudes than TD, even though they reported a similar level of pain. In TD individuals, a smaller P2-wave amplitude was related to higher scores on ‘low registration,’ ‘attention to detail,’ and ‘attention switching difficulties.’ In ASD individuals, longer N2-wave latency was related to higher scores on ‘sensory sensitivity’ and socio-emotional problems; while higher reported pain was associated with higher scores on ‘low registration,’ overall autistic severity, and longer N2-wave latency. Our findings of attenuated CHEP response in ASD, which was associated with sensory symptoms and socio-emotional problems, suggest a potential role for CHEP in studying sensory disturbances in ASD.

Genetic control of social behavior: Lessons from mutant mice

Social behavior is evolutionary conserved, and is thought to be evolved since it increased reproductive and survival fitness of living species. In humans, disturbances of social behavior are a peculiar pathological trait of neurodevelopmental disorders, namely autism spectrum disorder (ASD). ASD is defined by deficits in two core domains (social interaction/communication and repetitive/restrictive behaviors), which emerge during early postnatal development. ASD has a strong genetic component: copy number variations, de novo and familial mutations, as well as epigenetic modifications have been reported in a huge number of genes. Recent studies in mice demonstrate that mutations in a wide variety of ASD-associated genes can cause neurodevelopmental defects, which subsequently result in social behavior disturbances during early postnatal age and adulthood. From these studies, it clearly emerges that functionally interrelated cellular mechanisms underlie social behavior and its disturbances in ASD. Indeed, most of ASD-associated genes control neuronal differentiation and migration, growth of neuronal connections and synaptic function. Here we will present the recent advances in understanding the genetic determinants of social behavior, as they emerge from the study of ASD mouse models, and discuss the importance of these studies for the development of novel therapeutic approaches to overcome social disturbances in ASD.

Psychometric properties of the children's sleep habits questionnaire in children with autism spectrum disorder

Background and purposeSleep disturbances in autism spectrum disorder (ASD) are very common. Psychometrically sound instruments are essential to assess these disturbances. Children's Sleep Habit Questionnaire (CSHQ) is a widely used measure in ASD. The purpose of this study was to explore the psychometric properties of the CSHQ in a sample of children with ASD. Participants and methodsParents/caregivers of 310 children (mean age: 4.7) with ASD completed the CSHQ at study enrollment. Correlations between intelligence quotient (IQ) scores and the original CSHQ scales were calculated. Item endorsement frequencies and percentages were also calculated. A principal component analysis (PCA) was performed, and internal consistency was assessed for the newly extracted components. ResultsCorrelations between IQ scores and CSHQ subscales and total scores ranged from .015 to .001 suggesting a weak, if any, association. Item endorsement frequencies were high for bedtime resistance items, but lower for parasomnia and sleep-disordered breathing items. A PCA suggested that a five-component solution best fits the data. Internal consistency of the newly extracted five components ranged α = .87–.50. ConclusionsItem endorsement frequencies were highest for bedtime resistance items. A PCA suggested a five-component solution. Three of the five components (Sleep Routine Problems, Insufficient Sleep, and Sleep-onset Association Problems) were types of sleep disturbances commonly reported in ASD, but the other two components (Parasomnia/Sleep-disordered Breathing and Sleep Anxiety) were less clear. Internal consistencies ranged from mediocre to good. Further development of this measure for use in children with ASD is encouraged.

Sleep Disturbances in Autism Spectrum Disorders

Sleep problems have been commonly reported in children with autism spectrum disorder (ASD). This review takes a lifespan perspective in discussing recent findings on sleep disturbances in ASD, including sparse but pivotal studies in toddlers and adults. Current evidence shows that more than a mere comorbidity, sleep disturbances can represent a key factor in ASD. Already present before the age of 2, sleep problems are one of the early warning signs of ASD, which persist through lifespan. Genetic, epigenetic, psychological, and social/environmental factors involved in sleep disturbances in ASD contribute to better understand the core symptoms of autism (restricted and repetitive behaviors, communication, and social deficits). Although often considered as secondary by the therapeutic community, behavioral and pharmacological sleep interventions are efficient to reduce symptoms severity in ASD individuals and improve parents’ mental health. This review should convince the scientific and medical community to address sleep complaints and autism symptoms together rather than separate entities.

Agomelatine Effectiveness In Sleep Disturbances In Autism Spectrum Disorder

Agomelatine Effectiveness In Sleep Disturbances In Autism Spectrum Disorder