The effectiveness of an outdoor adventure programme for young children with autism spectrum disorder: a controlled study.

AIM: Outdoor adventure programmes aim to improve interpersonal relationships using adventurous activities. The current study examined the effectiveness of an outdoor adventure programme in children with autism spectrum disorders (ASD). METHOD: The study included 51 participants (40 males, 11 females; age 3y 4mo-7y 4mo) enrolled in ASD special education kindergartens. Only the intervention group (n=30) participated in the outdoor adventure programme for 13 weeks, completing challenging physical activities that required cooperation and communication with peers and instructors. The control group (n=21) was not significantly different from the research group in age, sex, cognitive, and adaptive behaviour measures. RESULTS: Outcomes after the intervention revealed significant improvement in social-communication and different directions in the two groups in the social cognition, social motivation, and autistic mannerisms subdomains of the Social Responsiveness Scale. While the group that received an outdoor adventure programme showed a tendency toward a reduction in severity, the control group showed the opposite (p<0.010). INTERPRETATION: The outdoor adventure programme required problem-solving skills and forced the child to communicate in exciting situations. This study suggests that an outdoor adventure programme may be an effective intervention in addition to traditional treatments in young children with ASD. Future studies should examine the outcome of outdoor adventure programmes delivered for longer periods of time and maintenance of the achievements over time.

CYP2D6 genotyping in paediatric patients with autism treated with risperidone: a preliminary cohort study.

AIM: To evaluate the association between cytochrome P450 2D6 (CYP2D6) phenotypes in paediatric patients with autistic spectrum disorders (ASD) treated with risperidone, adverse drug reactions (ADRs), and drug efficacy. METHOD: An observational cohort study of 40 children (34 males, six females; median age 7y range 3-18y) with autistic disorder, pervasive developmental disorder not otherwise specified, or Asperger syndrome diagnosed using the Autism Diagnostic Interview-Revised and treated with risperidone for at least 3 months. Charts were reviewed for demographic and clinical information, response to treatment was assessed by parents and the treating neurologist on a three-point scale, and information about ADRs was collected. Trough plasma levels of risperidone and its metabolites were determined and CYP2D6 genotyping was performed. RESULTS: Twenty-six patients responded to therapy and 11 patients exhibited ADRs. CYP2D6 genotyping showed two patients to be poor metabolizers, two ultra-rapid metabolizers, seven intermediate metabolizers, and 29 extensive metabolizers. Both ultra-rapid metabolizer patients were non-responders and had no ADRs. In contrast, both poor metabolizer patients were responders but experienced ADRs. No correlation was found between risperidone dosage and either risperidone or drug metabolite plasma levels. There was no difference in risperidone or metabolite plasma levels when comparing responders to non-responders, or when comparing patients with or without ADRs. INTERPRETATION: In patients with ASD treated with risperidone, a CYP2D6 phenotype may be associated with response to treatment and development of ADRs.

Friendship in Autism Spectrum Disorder Is Related to Diverse Developmental Changes Between Toddlerhood and Adolescence.

PURPOSE: Follow-up studies of children diagnosed with autism spectrum disorder (ASD) in early childhood that focus on friendship formation during adolescence are scarce. The present study focused on exploring characteristics possibly related to the ability to establish friendships during adolescence among children diagnosed with ASD in toddlerhood. METHODS: The cohort included 43 participants who underwent comprehensive assessments during toddlerhood and adolescence. Participants were divided into two groups [Friendship(+)/Friendship(-)] based on (1) adolescent social insight as assessed by professionals and (2) parental and adolescent self-reports regarding having or not having friends. No differences in IQ, ASD symptoms, or adaptive behavior during early childhood were found between the two groups. RESULTS: Different and better changes in social communication, adaptive socialization, and daily living skills were observed for the Friendship(+) group. Adolescents with ASD in the Friendship(+) group exhibited greater social independence. Attention-deficit/hyperactivity disorder incidence, anxiety symptom severity, and placement in mainstream or special education classes did not differ between the two groups. CONCLUSION: This long-term study highlights that for children with ASD, longitudinal growth in social communication and adaptive functioning is possible, highly important for and related to the development of the complex ability to establish friendship.

Sibling Relationships in Families of Autistic and Typical Children: Similarities and Differences in the Perspectives of Siblings and Mothers.

This study investigates mothers' and siblings' perspectives regarding similarities and differences in siblingships with and without autism. Twenty-nine typical children (Mage = 8.78 years, SD = 2.05) whose younger siblings have a diagnosis of autism and their mothers constituted the 'autism group.' Forty-six typical children (Mage = 9.12 years, SD = 2.06) with younger typical siblings and their mothers constituted the 'typical group'. Children and mothers completed the Sibling Relationship Questionnaires and were interviewed. Children's reports illustrated similarities in sibling relationships across groups, with no between-group differences in overall warmth, conflict, rivalry, or relative power in the sibling relationship. Mothers of autistic children reported their children to have less warmth and closeness (F(1,72) = 5.63, p = .02, η2 = .073) and less conflict (F(1,72) = 6.66, p = .012, η2 = .085) with their siblings than mothers of typical children. More disagreement was found between mothers and children in the autism group than in the typical group. Mothers and children reported less intimacy and less quarreling between the siblings in the autism group than in the typical group. The qualitative analysis suggests that siblings focused on the present experience, while mothers also referred to processes in the sibling relationship. Interviewees in the autism group referred to various specificities in the siblingships without explicitly using the term "autism". The findings highlight a typical-like experience for siblings of autistic children. At the same time, mothers' perspectives emphasize differences and challenges in siblingships, reporting a pattern of decreased involvement. It is important to consider both perspectives in research and clinical work with families of autistic children.

Immunological and autoimmune considerations of Autism Spectrum Disorders.

Autism Spectrum Disorders (ASD) are a group of heterogeneous neurodevelopmental conditions presenting in early childhood with a prevalence ranging from 0.7% to 2.64%. Social interaction and communication skills are impaired and children often present with unusual repetitive behavior. The condition persists for life with major implications for the individual, the family and the entire health care system. While the etiology of ASD remains unknown, various clues suggest a possible association with altered immune responses and ASD. Inflammation in the brain and CNS has been reported by several groups with notable microglia activation and increased cytokine production in postmortem brain specimens of young and old individuals with ASD. Moreover several laboratories have isolated distinctive brain and CNS reactive antibodies from individuals with ASD. Large population based epidemiological studies have established a correlation between ASD and a family history of autoimmune diseases, associations with MHC complex haplotypes, and abnormal levels of various inflammatory cytokines and immunological markers in the blood. In addition, there is evidence that antibodies that are only present in some mothers of children with ASD bind to fetal brain proteins and may be a marker or risk factor for ASD. Studies involving the injection of these ASD specific maternal serum antibodies into pregnant mice during gestation, or gestational exposure of Rhesus monkeys to IgG subclass of these antibodies, have consistently elicited behavioral changes in offspring that have relevance to ASD. We will summarize the various types of studies associating ASD with the immune system, critically evaluate the quality of these studies, and attempt to integrate them in a way that clarifies the areas of immune and autoimmune phenomena in ASD research that will be important indicators for future research.

Relationship between Parental Concerns about Social-Emotional Reciprocity Deficits and Their Children's Final ASD Diagnosis.

Concerns raised by parents regarding their child's development are compatible with the child's final diagnosis of autism spectrum disorder. A better understanding of the relationship between parental concerns and a final diagnosis of autism spectrum disorder is therefore critical. In the current study, we compared the frequencies of parental concerns related to DSM-5 criteria for autism spectrum disorder between pair-matched groups with and without a final diagnosis of autism spectrum disorder and determined which parental concerns predicted a final diagnosis of autism spectrum disorder. The cohort included 80 participants (48-154 months of age, IQ > 70) assessed for a possible autism spectrum disorder diagnosis. Parental concerns were retrieved from the free-description portion of the introductory questions of the Autism Diagnostic Interview-Revised and analyzed to assess whether they corresponded to any of the seven DSM-5 criteria for ASD. The two groups only differed in the frequency of parental concerns relating to deficits in social-emotional reciprocity. Parents of children diagnosed with autism spectrum disorder were four times as likely to report deficits in social-emotional reciprocity. This finding highlights the significance of parental concerns regarding deficits in social-emotional reciprocity in predicting a final diagnosis of autism spectrum disorder.

Parents' and Teachers' Perspectives of Autism and Co-Morbidity Symptom Severity in Young Children with ASD Over One School Year.

PURPOSE: Only a few studies examined the longitudinal pattern of parent-teacher reports on autism severity and comorbidities in autism spectrum disorder (ASD) and yielded conflicting results. The study's aims were to compare parents and teachers' perception of autism, attention deficit hyperactivity disorder (ADHD) and anxiety symptoms severity in children with ASD, at the start (T1) and end (T2) of the school year, to assess changes in their perception over time and to examine correlations between their reports. METHODS: The study included 73 participants, (M = 61), aged 2:10 - 7:6 years (M = 4:10, SD = 1:0), who attended ASD special education classes and were receiving intensive interventions. Parents and teachers completed measures of autism severity and ADHD and anxiety symptoms at T1 and T2. RESULTS: Teachers, in comparison to parents, rated more severe social-communication impairments and inattention symptoms at T1, but not at T2. A significant improvement in teachers' ratings of autism and inattention symptoms severity was documented at T2. At both time points, parents reported more severe anxiety symptoms. Significant correlations between parents' and teachers' reports were noted for autism severity at T1 and T2, but not for inattention and anxiety symptoms severity. CONCLUSION: The study emphasizes the contribution of multiple perspectives for better collaboration between home and school environments. Obtaining accurate information from parents and teachers at the start of the school year may help to identify factors needed for better adjustment at school and to better address difficulties at home.

Children with autism exhibit similar longitudinal changes in core symptoms when placed in special or mainstream education settings.

LAY ABSTRACT: Today, children with autism spectrum disorder (ASD) are placed in mainstream or special education settings somewhat arbitrarily with no clear clinical recommendations. Here, we compared changes in core ASD symptoms, as measured by the Autism Diagnostic Observation Schedule, 2nd edition (ADOS-2) clinical assessment, across ASD preschool children placed in special or mainstream education. Longitudinal changes in ADOS-2 scores did not differ significantly across settings over a 1- to 2-year period. While some children improved in core ASD symptoms, others deteriorated in both settings. This highlights the need to identify specific criteria for establishing meaningful placement recommendations.

[Autism spectrum disorders--a syndrome on the rise: risk factors and advances in early detection and intervention].

Autism spectrum disorders [ASD] are complex neurobehavioraL disorders defined by social and communication deficits and repetitive and stereotyped behaviors. The current estimated prevalence of ASD is approximately 1:100, which reflects a 15-fold increase from studies published a half-century ago. ASD is a highly heritable disorder, however, the exact cause of ASD is still unknown. ASD is associated with altered functional and structural connectivity patterns in the frontal and temporo-limbic brain regions that occur early in life. It is now believed that environmental factors may modulate phenotypical expression of ASD that are associated with the genetic predisposition. Several possible risk factors for ASD were investigated and included advanced parental age, birth complications, prematurity, Low birth weight and assisted conception. Numerous epidemioLogical reports have failed to confirm any association between immunizations and MMR specifically or thimerosaL exposure and risk for ASD. The diagnosis of ASD can be reLiably made in the second year of Life and appears to be relatively stable over time. However, diagnosis of very young children can be quite complex due to their clinical heterogeneity and varying patterns of onset that can differ from the typical autism symptoms of an older child. It is further challenging to distinguish between developmental and/or speech delay and ASD at this early age. Standardized tests for ASD diagnosis, developmental level and adaptive skiLls have been successfully used for accurate diagnosis of ASD. Research has recently focused on possible basic measures and/or biological markers that can assist with early diagnosis of ASD. Recent studies suggest that substantial gains can be achieved by intensive behavioral intervention initiated prior to 24 months, as neural plasticity is increased and chaLLenging behaviors are less prominent. Effective early intervention should begin soon after the diagnosis is made, and be individualized, intensive, and comprehensive and should include parent education, and behavioral intervention. It is highly important for pediatricians and experts in child neurology, development and child psychiatry to recognize the early signs of ASD, diagnostic tools and effective intervention methods.

Relationship between cognitive ability and predictors for age at the time of autism spectrum disorder diagnosis.

The rising prevalence of autism spectrum disorder (ASD) has increased awareness of the need for early diagnosis and intervention; however, not all children are diagnosed at preschool age. In the literature, findings regarding factors that may play a role in later diagnosis are inconsistent. Presence or absence of intellectual disability is a possible factor. This study aimed to identify factors associated with later diagnosis of ASD among children grouped according to low and high cognitive levels. Data of children who were previously diagnosed with ASD between 2002 and 2016 at a national autism center were analyzed. Better cognitive ability, having more siblings, and previous diagnosis of attention-deficit/hyperactivity disorder were predictors of later diagnosis among the entire cohort. Children exhibiting lower cognitive levels (LC-ASD; DQ/IQ < 70; n = 209) were diagnosed much earlier. Among this group, later ASD diagnosis was predicted by poorer adaptive behavior, more severe restricted and repetitive behaviors, and previous diagnosis of epilepsy. In the higher cognitive level group (HC-ASD; DQ/IQ ≥ 70; n = 321), familial variables and more severe social impairments were predictors of later ASD diagnosis. Clinicians should be aware of variables that may affect ASD diagnostic age among children with varying cognitive abilities.

Early diagnosis of autism in the community is associated with marked improvement in social symptoms within 1-2 years.

LAY ABSTRACT: It is widely believed that early diagnosis and treatment of autism spectrum disorder is essential for better outcome. This is demonstrated by the American Academy of Pediatrics recommendation to screen all 1.5-2.5-year-old toddlers for autism spectrum disorder. However, multiple longitudinal studies of children diagnosed with autism spectrum disorder at 1.5-6 years of age and treated in community settings have not reported any associations between earlier diagnosis and improved outcome in core autism spectrum disorder symptoms. In this study, we measured changes in core autism spectrum disorder symptoms over a 1-2-year period in 131 children diagnosed with autism spectrum disorder at 1.2-5 years of age, and treated in the community. The results revealed that children who were diagnosed before 2.5 years of age were three times more likely to exhibit considerable improvements in social autism spectrum disorder symptoms in comparison to children diagnosed at later ages. These results highlight the importance of early diagnosis and treatment of autism spectrum disorder even in community settings with heterogeneous services. In addition, these results motivate further prioritization of universal screening for autism spectrum disorder before 2.5 years of age.

Home-quarantine during the initial Covid-19 outbreak in Israel: parent perceived impact on children with ASD.

Background: Studies have reported that Covid-19 home-quarantine periods have had mostly negative psychological impact on children with ASD and their families. Here we examined parent perceived impact of a 6-week quarantine period imposed in Israel at the beginning of the Covid-19 outbreak, in mid-March 2020. Methods: An anonymous online questionnaire was completed by parents of 268 children with ASD. Parents rated deterioration/improvement in their child's behaviors, abilities, mood, sleep, and anxiety along with changes in their own mood, sleep, parenting skills, and family relationships. We performed t-tests and ANOVA analyses to assess the significance of perceived impact on each domain and potential differences in the impact across families with children of different ages, genders, and levels of required support as well as families that experienced different magnitudes of economic hardships. Results: Parents reported significant deterioration in their mood and sleep along with significant improvements in relationships with their spouse and child with ASD, and in their parenting skills. Parents also reported significant increases in the severity of tantrums, anxiety, and restricted and repetitive behavior symptoms along with significant improvements in social and communication abilities of their child with ASD. Ratings were significantly lower in families of ASD children who regularly require more support and in families that experienced economic hardships. Conclusions: While periods of home-quarantine create numerous hardships for families of children with ASD, they may also offer an opportunity for improving parenting skills, family relationships, and children's social communication abilities with potential relevance for improving remote services.

Abnormal white matter integrity in young children with autism.

This study investigated white matter integrity in young children with autism using diffusion tensor imaging (DTI). Twenty-two children with autism, mean age 3:2 years, and 32 controls, mean age 3:4 years, participated in the study. Tract-based spatial statistics (TBSS) revealed white matter abnormalities in several distinct clusters within the genu and body of the corpus callosum (CC), left superior longitudinal fasciculus (SLF) and right and left cingulum (Cg). TBSS-VOIs analysis was performed in the clusters where differences in fractional anisotropy (FA) were detected to investigate the relationship between changes in FA and diffusivity indices. In all VOIs, increase in FA was caused by a decrease in radial diffusivity (Dr), while no changes in axial diffusivity (Da) or mean diffusivity (MD) were observed. Tractography analysis was applied to further study the CC, SLF, and Cg. Witelson parcellation scheme was used for the CC. Significant increase in FA was seen in children with autism in the mid-body of the CC as well as in the left Cg. It is suggested that such abnormal white matter integrity in young children with autism may adversely affect connectivity between different brain regions and may be linked to some of the behavioral impairments apparent in autism.

Iron deficiency in children with attention deficit hyperactivity disorder.

BACKGROUND: Several studies have suggested that iron deficiency may be related to the pathophysiology of attention deficit hyperactivity disorder (ADHD) due to the role of iron in the production of dopamine and noradrenaline. OBJECTIVES: To evaluate the status of iron deficiency in ADHD children, using ferritin levels, a reliable measure of iron storage in body tissue, as an iron status marker, and to investigate a possible correlation between ferritin levels and the diagnosis of ADHD. METHODS: The study group included 113 newly referred ADHD children aged 5-15 years (mean age 8.8 +/- 2.7). RESULTS: Ferritin levels were below 20 ng/ml in 67 children (59%) and above 20 ng/ml in 46 (41%). There was a very low inverse statistical correlation between scores on Conners' Rating Scale and ferritin levels, probably without clinical significance. CONCLUSIONS: Our findings suggest that low iron stores may be related to ADHD pathophysiology; therefore, ferritin should be included in the overall evaluation of children with ADHD.

Dog training intervention improves adaptive social communication skills in young children with autism spectrum disorder: A controlled crossover study.

LAY ABSTRACT: There is some evidence that using therapy dogs for children with autism spectrum disorder generally results in improved social communication skills and reduced behavioral problems. However, well-controlled studies that examine its effectiveness are scarce. This study examined the effectiveness of a "Dog Training Intervention." The study included 73 participants diagnosed with autism spectrum disorder (61 males, 12 females) with age range of 2:10-7:6 years (M = 4:10 ± 1:0) who attend autism spectrum disorder-specific special education schools. The study population was divided into two groups. Each group received the dog training intervention during one part of the school year (first half or second half) in addition to the standard interventions provided by the special education school settings. The dog training intervention was given twice weekly for 4 months within the school setting. The group that received the dog training intervention first showed a significant increase in adaptive social and communication skills in comparison to the second group that did not receive the intervention in this period. This improvement was maintained after the dog training intervention. The second group, which received intervention at the second half of the year, showed improvement in communication and socialization adaptive skills only during the period in which they received the dog training intervention. The positive impact on social communication adaptive skills of the dog training intervention among young children with autism spectrum disorder suggests that dogs may serve as an effective model for establishing social interaction. Dog training intervention appears to be an effective adjunct treatment to the interventions provided in special education schools for young children with autism spectrum disorder.

Increased influence of prior choices on perceptual decisions in autism.

Autism spectrum disorder (ASD) manifests sensory and perceptual atypicalities. Recent theories suggest that these may reflect a reduced influence of prior information in ASD. Some studies have found reduced adaptation to recent sensory stimuli in ASD. However, the effects of prior stimuli and prior perceptual choices can counteract one-another. Here, we investigated this using two different tasks (in two different cohorts): (i) visual location discrimination and (ii) multisensory (visual-vestibular) heading discrimination. We fit the data using a logistic regression model to dissociate the specific effects of prior stimuli and prior choices. In both tasks, perceptual decisions were biased toward recent choices. Notably, the 'attractive' effect of prior choices was significantly larger in ASD (in both tasks and cohorts), while there was no difference in the influence of prior stimuli. These results challenge theories of reduced priors in ASD, and rather suggest an increased consistency bias for perceptual decisions in ASD.

Intensive behavioural interventions based on applied behaviour analysis for young children with autism: An international collaborative individual participant data meta-analysis.

LAY ABSTRACT: Early intensive applied behaviour analysis-based interventions are designed to support young autistic children's learning and development. Unfortunately, the available evidence about the effectiveness of these interventions remains unclear. Several reviews have focused on the published findings rather than contacting the authors to collect and analyse data about the individual participants in the original studies. Also, most of the studies were carried out by groups involved in delivering the interventions leading to the potential bias in interpreting the results. Our research team (supported by an international advisory group) carried out an independent individual patient data review by collecting the original participant data from the authors of the studies, to examine the effectiveness of these interventions. The results suggested that early intensive applied behaviour analysis-based interventions might lead to some changes in children's cognitive ability (intelligence quotient) and everyday life skills after 2 years, compared with standard treatments. However, all the studies had problems with the way they were designed. Also, few of the studies looked at outcomes that have been described as most important to autistic people or followed children beyond 2 years. We think that further systematic reviews of the existing evidence are unlikely to add to the findings of our review. Furthermore, we recommend that future research should investigate which types of supports and interventions are most effective for children and families, prioritising outcomes measures that are meaningful for the autism community and include, wherever possible, longer-term follow-up.

From Toddlerhood to Adolescence, Trajectories and Predictors of Outcome: Long-Term Follow-Up Study in Autism Spectrum Disorder.

This study is one of a very few prospective long-term studies in autism spectrum disorder (ASD). The study compared outcome trajectories in three adolescent groups (T2): "best outcome" (BO, n = 11) did not meet cut-off points for ASD and IQ scores ≥85; high functioning (HF-ASD, n = 14); and lower functioning (LF-ASD, n = 43). Additionally, the study searched for characteristics at toddlerhood (T1) that may predict belonging to the above groups. The study included 68 adolescents (63 males) diagnosed with ASD at toddlerhood (mean age: 13:10 years), mean follow-up time was 11:7 years. Participants underwent comprehensive assessments at T1 and T2. Different trajectories were found for the three defined groups. The BO group improved significantly in cognitive ability, autism severity, and adaptive skills in comparison to no improvement for the LF-ASD group or partial progress for the HF-ASD group. At toddlerhood, better cognition and less severe autism social affect symptoms were generally associated with a better outcome. Early social behaviors including better "pointing," "facial expression directed to others," "showing," and "response to joint attention" were associated with membership in the BO group. In addition, the BO group had the lowest prevalence of significant T2 inattention and anxiety symptoms. No significant differences between the three outcome groups were noted in the birth and prevalence of medical problems. Higher cognitive ability and better T1 showing and pointing behaviors predicted better outcome. The study points to the change in autism severity over time and to the prognostic value of early developmental abilities, social engagement behaviors, and the existence of comorbidities. Autism Res 2020, 13: 1130-1143. © 2020 International Society for Autism Research and Wiley Periodicals LLC. LAY SUMMARY: This long-term study compared characteristics of toddlers diagnosed with autism spectrum disorder (ASD) in three outcome groups in adolescence: best outcome (BO-average IQ/not meeting criteria for ASD), high-functioning ASD, and low-functioning ASD (LF-ASD). At toddlerhood, the BO group displayed less severe autism symptoms, mostly in sharing interests, compared to the LF-ASD group. The BO group had fewer inattention and anxiety symptoms than the two ASD groups. Additionally, early cognitive level and social engagement behaviors predicted outcome in ASD.

Toddlers to teenagers: Long-term follow-up study of outcomes in autism spectrum disorder.

This prospective study examined the developmental changes over time of adolescents diagnosed in toddlerhood with autism spectrum disorder and searched for child characteristics at toddlerhood that predict outcome at adolescence. The study included 65 participants who were divided into low cognitive (developmental quotient < 85; N = 41) and high cognitive (developmental quotient ⩾ 85; N = 21) groups in adolescence. Participants underwent a comprehensive assessment of cognitive ability, adaptive skills, and autism severity. Significant differences in the current clinical phenotypes and in developmental changes over time were found between the two cognitive groups. At baseline, the high cognitive group had significantly less severe social communication deficits. Only the high cognitive group showed a decrease in social communication deficits over time. Although the two groups did not differ in their adaptive skills at the time of diagnosis, the high cognitive group had better adaptive skills at adolescence. Better adaptive communication skills in toddlerhood were associated with better outcome at adolescence in cognitive ability, adaptive skills, and fewer autism symptoms. Less impaired baseline social affect and better cognitive ability predicted higher cognitive level and adaptive skills at adolescence. Cognitive potential of individuals with autism spectrum disorder plays an important role in long-term outcome and comprehensive evaluations at toddlerhood have strong prognostic value in adolescence.