Emotional stress,cortisol response,and cortisol rhythm in autism spectrum disorders: A systematic review

BackgroundThis systematic review evaluated whether there is evidence for (i) increased emotional stress levels, and (ii) a different biological stress response or rhythm [i.e., cortisol stress response, diurnal rhythm, or cortisol awakening response (CAR)] in individuals with autism spectrum disorder (ASD) relative to controls. Thirdly, the evidence for an association between emotional and biological stress in ASD was reviewed.MethodMEDLINE, Cochrane Library, and SAGE journals were searched until December 2020. In this review, there were no limitations regarding age, sex, or intelligence quotient. Studies were only reviewed if results were compared with controls without a developmental disorder. Only salivary cortisol was considered as biological stress measure.ResultsThirty-one studies were reviewed. Significantly higher self- and parent-reported emotional stress levels were found in individuals with ASD compared to controls. Regarding biological stress, the few studies in adults reported comparable cortisol stress responses and rhythms between both groups. In children/adolescents with ASD relative to controls, an increased, blunted, or similar cortisol stress response was reported, whereas the CAR did not differ in most studies, and diurnal rhythm was described as blunted or similar. Most studies found no significant association between parent-reported emotional stress and biological stress in ASD.ConclusionsCurrent findings suggest that heightened emotional stress is a clinically significant factor in ASD. To unravel the cortisol response and rhythm, research in specific subgroups within the ASD spectrum is warranted, aiming at a higher frequency of cortisol measurements, preferably combined with momentary emotional stress measurements.     

The roles of cortisol and pro-inflammatory cytokines in assisting the diagnosis of autism spectrum disorder

Autism spectrum disorders (ASD) is a severe neurodevelopmental disorder characterized by impairments in social interaction and repetitive behaviors. Diagnosis of ASD is currently phenotype based with no reliable laboratory test available to assist clinicians. The desire for clinically useful and reliable biomarkers is strong. Researches have shown that individuals with autism often exhibit dysfunction of hypothalamic–pituitary–adrenal (HPA) axis and cytokines. The purpose of this study was to evaluate diurnal variation of cortisol (cortisol VAR), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) as potential biomarkers for ASD. The present results demonstrated that in comparison to the healthy controls, the individuals with autism showed a lower level of cortisol VAR, higher level of IL-6 and TNF-α. The levels of cortisol VAR, IL-6 and TNF-α have significantly correlations with the severity of ASD measured by CARS scores. The results of ROC analysis indicated the cortisol VAR, IL-6 and TNF-α were potential biomarkers in diagnosis of ASD. The combination of three factors performed the best sensitivity and specificity for diagnosis of ASD. Therefore, the present study may reveal a simple clinical approach with great potential for assisting the diagnosis of ASD.     

Women's posttraumatic stress symptoms and autism spectrum disorder in their children

Maternal posttraumatic stress disorder (PTSD) may be associated with autism spectrum disorder (ASD) in offspring through multiple pathways: maternal stress may affect the fetus; ASD in children may increase risk of PTSD in mothers; and the two disorders may share genetic risk. Understanding whether maternal PTSD is associated with child's ASD is important for clinicians treating children with ASD, as PTSD in parents is associated with poorer family functioning. We examined the association of maternal PTSD with offspring ASD in a large US cohort (N ASD cases = 413, N controls = 42,868). Mother's PTSD symptoms were strongly associated with child's ASD (RR 4–5 PTSD symptoms = 1.98, 95% CI = 1.39, 2.81; RR 6–7 symptoms = 2.89, 95% CI = 2.00, 4.18). Clinicians treating persons with ASD should be aware of elevated risk of PTSD in the mother. Genetic studies should investigate PTSD risk alleles in relation to ASD.     

An analysis of the predictors of comorbid psychopathology,gastrointestinal symptoms and epilepsy in children and adolescents with autism spectrum disorder

Mannion, Leader, and Healy (2013) examined the frequency of comorbid disorders in children and adolescents with autism spectrum disorder and the predictors of sleep problems. This study will extend this research by investigating the predictors of comorbidity in 89 participants. Age, gender, level of intellectual disability, presence of epilepsy, attention deficit/hyperactivity disorder (AD/HD) and an anxiety disorder were determined using a self-constructed demographic questionnaire. The Autism Spectrum Disorder-Comorbid for Children (ASD-CC) was administered to informants to assess symptoms of comorbid psychopathology. The Children's Sleep Habits Questionnaire (CSHQ) and Gastrointestinal symptom inventory were administered to assess sleep problems and gastrointestinal symptoms respectively. Sleep problems predicted gastrointestinal symptoms. Level of intellectual disability predicted gastrointestinal symptoms. Specifically, those with no intellectual disability were more likely to present with gastrointestinal symptoms. Gastrointestinal symptoms in turn predicted total comorbid psychopathology score and the individual subscales of worry/depressed, avoidant behavior, conduct behavior and tantrum behavior on the ASD-CC. Gender and ASD-CC total score predicted an individual having an anxiety disorder. Specifically, being male predicted an anxiety disorder. The ASD-CC subscales of worry/depressed and avoidant behavior predicted an anxiety disorder. The implications of these findings are discussed in the study.     

The relationship between race and comorbid symptoms in infants and toddlers with autism spectrum disorder

Researchers have indicated that persons with autism spectrum disorder (ASD) population evince higher rates of comorbid symptoms. While the relationship between comorbid symptoms and factors such as autism symptom severity, IQ level, age, communication abilities, and degree of social impairment were previously examined, there has been limited research on the effect of race in this area. The current study examined the potential role of race in comorbid symptoms in toddlers with ASD and atypically developing toddlers without a diagnosis of ASD using The Baby and Infant Screen for Children with aUtIsm Traits – Part 2 (BISCUIT-Part 2). Based on the current findings, African-American toddlers evinced higher rates of comorbid symptoms than Caucasian toddlers and toddlers of other races. In addition, toddlers with ASD evinced higher rates of comorbid symptoms than atypically developing toddlers without a diagnosis of ASD. Implications regarding these findings are discussed.     

Contributors to well-being and stress in parents of children with autism spectrum disorder

BackgroundParents of children with autism spectrum disorder (ASD) present more well-being and stress problems than parents of typically developing (TD) children. However not all parents present these problems. These problems can be due to a dynamic interaction between environmental antecedents, person antecedents, and mediating processes. Understanding how these factors separately contribute to explain parents’ well-being and stress can have implications for intervention programs. The aim of this study was to explain parents’ subjective well-being and physiological stress by considering whether they had a child with ASD or not and their child’s negativity (environmental antecedents), their perception of their child’s problems (person antecedents), and their use of reappraisal (mediating processes).MethodThirty-seven parents of children with ASD and 41 parents of TD children reported their subjective well-being and their physiological stress was assessed. Additionally, children’s negativity was observed, parents rated their perception of their child’s problems (autistic traits, emotion regulation ability, and lability/negativity), and parents reported their use of reappraisal.ResultsCompared to parents of TD children, parents of children with ASD reported having lower subjective well-being and had increased physiological stress. Parents’ perceptions of children’s lability/negativity and parents’ use of reappraisal were better predictors of parents’ subjective well-being than ASD and parents’ perceptions of children’s lability/negativity contributed to parents’ physiological stress as much as ASD.ConclusionsPrevention and intervention programs targeting parental well-being and stress will benefit from working with parents at the level of perceptual constructs and reappraisal ability.     

Correlation between EEG abnormalities and symptoms of autism spectrum disorder (ASD)

Children with ASD often suffer from epilepsy and paroxysmal EEG abnormality. Purposes of this study are the confirmation of incidence of epileptic seizures and EEG abnormalities in children with autism using a high performance digital EEG, to examine the nature of EEG abnormalities such as locus or modality, and to determine if the development of children with ASD, who have experienced developmental delay, improves when their epilepsy has been treated and maintained under control. A total of 1014 autistic children that have been treated and followed-up for more than 3 years at Yasuhara Children’s Clinic in Osaka, Japan, were included in this study. Each participant’s EEG had been recorded approximately every 6 months under sleep conditions. Epilepsy was diagnosed in 37% (375/1014) of the study participants. Almost all patients diagnosed with epilepsy presented with symptomatic epilepsy. The data showed that the participants with lower IQ had a higher incidence of epileptic seizures. Epileptic EEG discharges occurred in 85.8% (870/1014) of the patients. There was also a very high incidence of spike discharges in participants whose intellectual quotient was very low or low. Epileptic seizure waves most frequently developed from the frontal lobe (65.6%), including the front pole (Fp1 and Fp2), frontal part (F3, F4, F7 and F8) and central part (C3, Cz and C4). The occurrence rate of spike discharges in other locations, including temporal lobe (T3, T4, T5, T6), parietal lobe (P3, Pz, P4), occipital lobe (O1, O2) and multifocal spikes was less than 10%. These results support the notion that there is a relationship between ASD and dysfunction of the mirror neuron system. The management of seizure waves in children diagnosed with ASD may result in improves function and reduction of autistic symptoms.     

The cortisol,serotonin and oxytocin are associated with repetitive behavior in autism spectrum disorder

Repetitive behaviors (RBs) are a core feature of autism spectrum disorders (ASD). They constitute a major barrier to learning and social adaptation. Research on potential causes of RBs is still at an early stage. However, promising new ideas and evidence are emerging from neurobiology. Instead of testing single neurotransmitter or hormone, the present study examined the associations of cortisol, serotonin, and oxytocin on subscales of repetitive behavior scales-revised (RBS-R). The results demonstrated that the individuals with ASD showed higher levels of cortisol areas under curve (cortisol AUC), higher levels of serotonin, and lower level of oxytocin compared with the typically developing (TD) individuals. For individuals with ASD, the levels of cortisol AUC, serotonin and oxytocin were all significantly associated with total scores measured by RBS-R. In addition, the cortisol AUC was positively associated with the stereotyped and restricted behavior subscales scores. The level of serotonin was positively associated with the stereotyped and self-injurious behavior subscales scores. The level of oxytocin was negatively associated with compulsive, sameness and restricted behavior subscales scores. Therefore, cortisol, serotonin and oxytocin may all be involved in the occurrence of RBs in ASD. The occurrence of RBs in ASD may due to a variety of pathological factors, not just one factor.     

Epilepsy in autism spectrum disorder

The purpose of this review is to provide an overview of the research on epilepsy in autism spectrum disorder (ASD). Topics explored are the prevalence of epilepsy in ASD, the importance of studying epilepsy, as well as the questionnaire measures used to assess epilepsy side-effects. Research on the relationships between epilepsy and parental stress and psychological distress, developmental regression, language and communication, adaptive behavior, social skills, autism severity, challenging behavior, comorbid psychopathology, gastrointestinal symptoms, sleep problems, sensory issues and quality of life are also discussed. Finally, recommendations for treatment are given as well as areas where future research is needed.     

Impact of ADHD symptoms on autism spectrum disorder symptom severity

Despite the official exclusion criteria for autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD) in the DSM-IV and ICD-10, patients with ASD often show ADHD symptoms. We aimed to examine the potential influence of ADHD symptoms on autistic psychopathology in a large sample of patients with ASD. We tested the hypothesis that patients with ASD and an additional ADHD (ASD+) would show a higher severity of autistic symptoms than those with ASD only (ASD?). We measured autistic symptoms using the autism diagnostic observation schedule (ADOS-G), the autism diagnostic interview (ADI-R), and the social responsiveness scale (SRS). To measure overall psychopathology and ADHD symptoms, we used the child behavior checklist (CBCL) and the ADHD rating scale (FBB-ADHS), respectively. Group differences between the ASD+ and the ASD? group (group division was conducted according to the results of the FBB-ADHS) were calculated using a univariate analysis of variance (ANOVA). The ASD+ group showed a greater severity of autistic symptoms than the ASD? group, measured by the SRS and the ADI-R. Especially in the social interaction subscale (ADI-R), a significantly higher symptom severity was found in the ASD+ group. No significant group differences were found regarding autistic symptoms measured by the ADOS-G. Patients with ASD and an additional ADHD expressed a stronger severity of autistic symptoms than patients with ASD only. According to our results, the possibility of a co-diagnosis of ADS and ADHD, as is being planned in the DSM-5, is in line with earlier studies, is highly reasonable, will simplify research, and have therapeutic implications.     

Shuffling babies and autism spectrum disorder

Background and purposeBottom shuffling is a locomotion strategy that precedes independent walking in some infants. Shuffling babies are generally considered to have favorable outcomes. The aim of the present study was to reveal clinical features and neurodevelopmental outcomes of shuffling babies who visited a child developmental center.MethodsWe studied 48 shuffling babies who visited Toyota Municipal Child Development Center from April 2007 to March 2015. We excluded patients with cerebral palsy, Down syndrome, or congenital disorders. In 2018, we retrospectively reviewed the clinical charts of the enrolled children. We investigated family history, neurological findings, and the developmental outcome during the follow-up period.ResultsDuring the follow-up period, 20 children (42%) were diagnosed with ASD. Gross motor development in infancy was not different between infants with and without ASD. The rate of poor eye contact at the first visit and a delay in the first word speech were significantly higher in infants with ASD than in infants without ASD. A family history of bottom shuffling was significantly less frequent in infants with ASD (10%) than in those without (39%).ConclusionSome of bottom shufflers may represent ASD during follow-up. Paying attention to social and cognitive functions in shuffling babies is important.     

上海市松江区幼儿孤独谱系障碍流行病学特征调查

目的 了解上海市松江区公立幼儿园孤独谱系障碍(ASD)的流行现况.方法 以上海市松江区教育主管部门登记在册的33所公立幼儿园的幼儿作为调查对象,采用克氏孤独症行为量表和社会交往问卷进行筛查,对于筛查阳性者由儿少精神科医生根据美国精神疾病诊断与统计手册第五版(DSM-5)进行诊断.结果 共5704名儿童接受筛查,平均年龄(5.3±0.7)岁,其中男性2920名(51.2%),女性2784名(48.8%).6名儿童被诊断为ASD,男女比为5:1,时点患病率为1.05‰,年龄4.1~6.1岁,平均5.0岁.3名患儿的孕期及出生时存在高危因素.结论 上海市松江区公立幼儿园ASD患病率低于国内外报道,孕期保健应重视相关高危因素.     

Exploration of the correlation between autism spectrum disorder symptomology and tantrum behaviors

The purpose of the current study was to investigate the relationship between the presence of Autism Spectrum Disorder (ASD) symptoms and tantrum behaviors in 598 children ranging in age from two to sixteen years old who meet cutoffs for ASD. Diagnostic categories created in the current study were provided by the Autism Spectrum Disorder – Diagnostic Child Version (ASD-DC). Initial analysis replicated previous research revealing significant differences in the expression of tantrum behavior between the ASD, Atypical, and Normal groups. Pearson Bivariate correlations were then computed for each individual's ASD symptom score and their total score on the Tantrum behavior subscale. Follow-up correlations found significant positive correlations between individual's in the Atypical, Normal, and ASD categories and their scores for the Tantrum behavior subscale of the Autism Spectrum Disorders – Comorbidity for Children (ASD-CC). Post hoc analyses revealed that the correlation between ASD symptomology and tantrum behaviors in the Normal group was significantly different when compared to children in the ASD group.     

Catechol-O-methyltransferase Val158Met polymorphism and hyperactivity symptoms in Egyptian children with autism spectrum disorder

Catechol-O-methyltransferase (COMT) plays an important role in the catabolism of brain dopamine and norepinephrine, which have been implicated in the pathogenesis of Autism spectrum disorder (ASD) as well as in other neuropsychatric disorders. We aimed to investigate the association of COMT Val158Met gene polymorphism with ASD and to examine the influence of such genotypes on hyperactivity symptoms in ASD patients. Eighty ASD patients (mean age 9 ± 1.9 years) and 100 control children (mean age 8.9 ± 1.9 years) were examined. COMT Val58Met polymorphism was genotyped using Tetra-primer ARMS-PCR method. The clinical diagnosis of ASD and ADHD were confirmed according to the DSM-IV criteria for research. We found no significant difference in genotypes or alleles’ frequencies of COMT Val158Met polymorphism between ASD patients and control group. There was a significant association between COMT (Val/Val) genotype and both increasing CARS (p = 0.001) and hyperactivity scores (p = 0.006). Regarding Conner's Score, the DSM-IV hyperactive impulsive were significantly higher in Val/Val genotype than both Met/Val and Met/Met genotypes (p = 0.03). Our data suggested an association between COMT Val58Met polymorphism and hyperactivity symptoms in Egyptian children with ASD.     

Hope,social relations,and depressive symptoms in mothers of children with autism spectrum disorder

BackgroundRaising a child with autism spectrum disorder (ASD) may negatively impact maternal mental health outcomes. Feelings of loneliness and a lack of social support may contribute to these outcomes. One factor that may help to promote better outcomes is hope. The current study examined the associations between maternal hope, loneliness, social support, and depressive symptoms.MethodNinety-four mothers of a child with ASD participated in this online study. Mothers were predominantly Caucasian, middle class, and educated. Children ranged in age from 2 to 13 years. Mothers completed questionnaires assessing hope, loneliness, perceived social support from friends and family, and depressive symptoms.ResultsThe results of a multiple mediator model indicated that hope agency was indirectly associated with depressive symptoms via loneliness. In a follow-up serial mediation model, hope agency was associated with depressive symptoms through family support and loneliness.ConclusionsThe present study contributes to the growing body of research focusing on positive personality characteristics and mental health outcomes in mothers of children with ASD. Given that increased hopeful thinking was associated with less loneliness, the construct of hope should be given more attention in interventions that are aimed at improving maternal outcomes. Increasing hopeful thinking may be particularly important in aiding with improvement during psychotherapy for mothers with clinical levels of depressive symptoms.     

Affective problems,gastrointestinal symptoms,sleep problems,and challenging behaviour in children and adolescents with autism spectrum disorder

BackgroundPeople with autism spectrum disorder (ASD) can experience affective problems, gastrointestinal (GI) symptoms, sleep problems, and challenging behaviour. This study identified the frequency of affective problems and explored how they related to co-occurring conditions in children and adolescents with ASD.MethodParticipants were children and adolescents diagnosed with ASD using DSM-IV-TR criteria (n = 95), 40 % (n = 38) of whom also had a diagnosis of intellectual disability (ID). The following scales were completed by the participants’ parents or guardians: Child Behaviour Checklist (CBCL), Gastrointestinal Symptoms Inventory, Children’s Sleep Habits Questionnaire (CSHQ), and the Behaviour Problems Inventory-Short Form (BPI-S). Pearson’s correlations and independent sample t-tests were used to examine the relationships between variables. Two hierarchal multiple regressions examined predictors for affective problems in preschool and school-aged children with ASD.ResultsParticipants scored in the clinical range (69.5 %) and borderline range (10.5 %) for affective problems. Significant positive relationships were found between affective problems and sleep problems, GI symptoms, and challenging behaviour. ID and gender predicted affective problems in preschool aged children. In school-aged children, affective problems were predicted by ID, sleep problems, and aggressive/destructive behaviour severity. However, only 25 % of the variance in affective problems was accounted for.ConclusionsFuture research is needed to understand how affective problems are impacted by co-occurring conditions in children and adolescents with ASD. Affective problems are prevalent in this population and the quality of life for individuals may be improved if practitioners consider co-occurring conditions during clinical practice.     

Impaired representational gaze following in children with autism spectrum disorder

Using eye-tracking methodology, we compared spontaneous gaze following in young children with Autism Spectrum Disorder (mean age 5.8 years) to that of typically developing children (mean age 5.7 years). Participants saw videos in which the position of a hidden object was either perceptually visible or was only represented in another person’s mind. The findings indicate that children with Autism Spectrum Disorder were significantly less accurate in gaze following and observed the attended object for less time than typically developing children only in the Representational Condition. These results show that children with Autism Spectrum Disorder are responsive to gaze as a perceptual cue although they ignore its representational meaning.     

Comorbidity in autism spectrum disorder: A literature review

Comorbidity is defined as the co-occurrence of two or more disorders in the same person (Matson & Nebel-Schwalm, 2007). The current study provides a review of the literature on comorbidity, in relation to comorbid psychiatric and medical disorders in babies and infants, children, adults and across the lifespan. We also examine comorbid conditions such as attention deficit/hyperactivity disorder (AD/HD), epilepsy, gastrointestinal symptoms, sleep problems, feeding problems and toileting problems in individuals with autism spectrum disorder.     

Attention-deficit/hyperactivity disorder (AD/HD) in autism spectrum disorder

The purpose of this review is to provide an overview of the research on attention-deficit/hyperactivity disorder (AD/HD) in individuals with autism spectrum disorder (ASD). Topics explored are the prevalence of AD/HD, the importance of studying AD/HD, as well as the questionnaire measures used to measure AD/HD in individuals with ASD. Research on the relationship between AD/HD in ASD and parental stress and psychological distress, developmental regression, language and communication, adaptive behavior, social skills, autism severity, challenging behavior, comorbid psychopathology, gastrointestinal symptoms, sleep problems, epilepsy, sensory issues, motor difficulties, and quality of life are also discussed. Research on cardiac reactivity and executive functioning are also explored. Finally, recommendations for treatment are given as well as areas where future research is needed.     

Genes associated with autism spectrum disorder

Autism spectrum disorder (ASD) is a heterogeneous grouping of neurodevelopmental disorders characterized by impairment in social interaction, verbal communication and repetitive/stereotypic behaviors. Much evidence suggests that ASD is multifactorial with a strong genetic basis, but the underlying mechanisms are far from clear. Recent advances in genetic technologies are beginning to shed light on possible etiologies of ASD. This review discusses current evidence for several widely studied candidate ASD genes, as well as various rare genes that supports their relationship to the etiology of ASD. The majority of the data are based on molecular, cytogenetic, linkage and association studies of autistic subjects, but newer methods, including whole-exome sequencing, are also beginning to make significant contributions to our understanding of autism.