Current changes in the occurrence of Autism Spectrum Disorders in Stockholm

The overall objective of this thesis is to estimate recent changes in and current prevalence of autism spectrum disorders (ASD) among young people in Stockholm County. An additional objective is to explore potential risk factors for ASD in view of the increasing occurrence in the population. For this purpose, a register-based total population study was set up and ASD case ascertainment validated as a means and research model for achieving the overall objective. All studies were based on the Stockholm Youth Cohort (SYC), a longitudinal total population study of 0-17 year olds resident in Stockholm County at any time since 2001. Prospectively compiled data for this population were merged from regional and national registers. In study I, we found that 96.0% of clinical case notes from randomly sampled ASD cases in the SYC were consistent with a diagnosis of ASD. Furthermore, we confirmed ASD in 82.5% of affected twins in the SYC by means of cross-validation against a twin study. In study II, we reported that ASD prevalence at the end of 2011 was 1.5% among 0-27 year olds (N=735,096), of whom 25.9% had a registered diagnosis of ID. The ASD prevalence was highest among teenagers at 2.4%. The male: female prevalence ratio for ASD decreased with age (from 3.3:1 among 0-12 year olds, to 1.9:1 among 18-27 year olds), particularly for ASD without ID. Between 2001 and 2011, the prevalence of ASD increased almost 3.5 fold among 2-17 year olds, mainly due to an eightfold increase of ASD without ID. In contrast, the prevalence of ASD with ID increased only slightly during this period. The recent increase in ASD prevalence has attracted research interest toward risk factors for ASD that have increased in a parallel manner, such as parental age and weight. In study III, we found that higher parental age increased the risk of offspring ASD as well as stronger parental age effects for ASD with, than without, ID. We found the risk of ASD to be greater for offspring of older mothers than for those of older fathers. Furthermore, the paternal age effect on ASD risk was only evident among offspring to mothers aged 35 years or younger, while maternal age increased the risk of ASD regardless of paternal age. In the population- based analysis of study IV, we found that maternal overweight increased the risk of ASD, while no such effect was evident in the sibling analysis. In addition to the finding that too much weight gain during pregnancy increases the risk of offspring ASD, this study was the first to report that too little weight gain also constitutes a risk. In conclusion, the prevalence of identified ASD without comorbid ID has increased substantially between 2001 and 2011 in Stockholm, and ASD currently affects more than 2% of teenagers, with important implications for the planning of health and educational services. Changes in diagnostic practice and awareness are likely to be the main drivers of the rise, but an actual true increase in ASD incidence cannot be ruled out. Collectively, these studies confirm the relevance of categorizing ASD according to ID. Finally, the SYC, with its extensive register-based data as well as a valid and thorough ASD case ascertainment constitutes an important resource for ASD research

Anxiety Disorders in Adults with Autism Spectrum Disorder:A Population-Based Study

Anxiety is common in children with ASD; however, the burden of specific anxiety disorders for adults with ASD is under-researched. Using the Stockholm Youth Cohort, we compared anxiety disorder diagnoses among autistic adults (n = 4049), with or without intellectual disability, and population controls (n = 217,645). We conducted additional sibling analyses. Anxiety disorders were diagnosed in 20.1% of adults with ASD compared with 8.7% of controls (RR = 2.62 [95% CI 2.47-2.79]), with greatest risk for autistic people without intellectual disability. Rates of almost all individual anxiety disorders were raised, notably obsessive-compulsive disorder and phobic anxiety disorders. Anxiety disorders were more common in full siblings and half-siblings of people with ASD. The implications of this are explored

Screening for co-occurring conditions in adults with autism spectrum disorder using the strengths and difficulties questionnaire: A pilot study.

Adolescents and adults with autism spectrum disorder (ASD) are at elevated risk of co-occurring mental health problems. These are often undiagnosed, can cause significant impairment, and place a very high burden on family and carers. Detecting co-occurring disorders is extremely important. However, there is no validated screening tool for this purpose. The aim of this pilot study is to test the utility of the strengths and difficulties questionnaire (SDQ) to screen for co-occurring emotional disorders and hyperactivity in adolescents and adults with ASD. The SDQ was completed by 126 parents and 98 individuals with ASD (in 79 cases both parent and self-report were available from the same families). Inter-rater reliability, test-retest stability, internal consistency, and construct validity were examined. SDQ subscales were also compared to clinically utilized measures of emotional disorders and hyperactivity to establish the ability to predict risk of disorder. Inter-rater reliability (r = 0.42), test-retest stability (r = 0.64), internal consistency (α = 0.52-0.81) and construct validity (r = 0.42-0.57) for the SDQ subscales were comparable to general population samples. Parent- and self-report SDQ subscales were significantly associated with measures of anxiety, depression and hyperactivity (62-74% correctly classified). Parent-report performed significantly better than self-report; adults with ASD under-reported difficulties. The SDQ shows promise as a simple and efficient way to screen for emotional disorders and hyperactivity in adolescents and adults with ASD that could help reduce the impact of these disorders on individuals and their families. However, further more systematic attempts at validation are warranted. Autism Res 2016, 9: 1353-1363. © 2016 International Society for Autism Research, Wiley Periodicals, Inc

Mode of delivery, order of birth, parental age gap and autism spectrum disorder among Malaysian children: a case-control study

Rising prevalence of autism spectrum disorders (ASD) in the last decades has led research to focus on the diagnosis and identification of factors associated with ASD. This paper sought for possible factors that put children at risk for ASD. In this study, we investigated the association between ASD and parental ages, parental age gaps, birth order and birth delivery method in Malaysian population. In this school-based case control study, 465 children with ASD 464 controls participated. Questionnaires were distributed to the parents of the selected children through the respective principals. Among the tested variables, Caesarean section (OR = 1.63, 95% CI 1.20, 2.20), earlier order of birth in the family (OR = 0.68, 95% CI 0.59, 0.77) and increasing gap in parental ages (OR = 1.04, 95% CI 1.001, 1.07) were significantly associated with ASD. This study concludes that Caesarean section, earlier order of birth in the family and increasing gap in parental age are independent risk factors for developing autism among Malaysian children. *************************************

Sex bias in autism spectrum disorder in neurofibromatosis type 1

BACKGROUND: Despite extensive literature, little is known about the mechanisms underlying sex bias in autism spectrum disorder (ASD). This study investigates the sex differences in ASD associated with neurofibromatosis type 1, a single-gene model of syndromic autism. METHODS: We analysed data from n = 194 children aged 4–16 years with neurofibromatosis type 1. Sex differences were evaluated across the Autism Diagnostic Interview-Revised (ADI-R), Autism Diagnostic Observation Schedule (ADOS), verbal IQ, Social Responsiveness Scale (SRS) and Conners questionnaires. RESULTS: There was 2.68:1 male:female ratio in children meeting ASD criteria on the deep phenotyping measures. On symptom profile, males with neurofibromatosis type 1 (NF1) + ASD were more impaired on reciprocal social interaction and communication domains of the ADI-R but we found no differences on the restricted, repetitive behaviours (RRBs) domain of the ADI-R and no differences on the social on the ADOS. NF1 ASD males and females were comparable on verbal IQ, and the inattention/hyperactivity domains of the Conners questionnaire. CONCLUSIONS: There is a significant male bias in the prevalence of ASD in NF1. The phenotypic profile of NF1 + ASD cases includes greater social communication impairment in males. We discuss the implications of our findings and the rationale for using NF1 as a model for investigating sex bias in idiopathic ASD

Sex Differences in Social Attention in Infants at Risk for Autism

We studied visual attention to emotional faces in 10-month-old infant siblings of children with ASD (ASD-sibs; N = 70) and a siblings of typically developing children (N = 29) using static stimuli. Contrary to our predictions, we found no evidence for atypical gaze behavior in ASD-sibs when boys and girls were analyzed together. However, a sex difference was found in ASD-sibs' visual attention to the mouth. Male ASD-sibs looked more at the mouth across emotions compared to male controls and female ASD-sibs. In contrast, female ASD-sibs looked less at the mouth compared to female controls. These findings suggest that some aspects of early emerging atypical social attention in ASD-sibs may be sex specific

Overview of the Role of Environmental Factors in Neurodevelopmental Disorders

Evidence implicates environmental factors in the pathogenesis of diverse complex neurodevelopmental disorders. However, the identity of specific environmental chemicals that confer risk for these disorders, and the mechanisms by which environmental chemicals interact with genetic susceptibilities to influence adverse neurodevelopmental outcomes remain significant gaps in our understanding of the etiology of most neurodevelopmental disorders. It is likely that many environmental chemicals contribute to the etiology of neurodevelopmental disorders but their influence depends on the genetic substrate of the individual. Research into the pathophysiology and genetics of neurodevelopmental disorders may inform the identification of environmental susceptibility factors that promote adverse outcomes in brain development. Conversely, understanding how low-level chemical exposures influence molecular, cellular, and behavioral outcomes relevant to neurodevelopmental disorders will provide insight regarding gene-environment interactions and possibly yield novel intervention strategies

Advanced paternal age effects in neurodevelopmental disorders?review of potential underlying mechanisms

Multiple epidemiological studies suggest a relationship between advanced paternal age (APA) at conception and adverse neurodevelopmental outcomes in offspring, particularly with regard to increased risk for autism and schizophrenia. Conclusive evidence about how age-related changes in paternal gametes, or age-independent behavioral traits affect neural development is still lacking. Recent evidence suggests that the origins of APA effects are likely to be multidimensional, involving both inherited predisposition and de novo events. Here we provide a review of the epidemiological and molecular findings to date. Focusing on the latter, we present the evidence for genetic and epigenetic mechanisms underpinning the association between late fatherhood and disorder in offspring. We also discuss the limitations of the APA literature. We propose that different hypotheses relating to the origins of the APA effects are not mutually exclusive. Instead, multiple mechanisms likely contribute, reflecting the etiological complexity of neurodevelopmental disorders