Investigation of autism and GABA receptor subunit genes in multiple ethnic groups

Autism is a neurodevelopmental disorder of complex genetics, characterized by impairment in social interaction and communication, as well as repetitive behavior. Multiple lines of evidence, including alterations in levels of GABA and GABA receptors in autistic patients, indicate that the GABAergic system, which is responsible for synaptic inhibition in the adult brain, may be involved in autism. Previous studies in our lab indicated association of noncoding single nucleotide polymorphisms (SNPs) within a GABA receptor subunit gene on chromosome 4, GABRA4, and interaction between SNPs in GABRA4 and GABRB1 (also on chromosome 4), within Caucasian autism patients. Studies of genetic variation in African-American autism families are rare. Analysis of 557 Caucasian and an independent population of 54 African-American families with 35 SNPs within GABRB1 and GABRA4 strengthened the evidence for involvement of GABRA4 in autism risk in Caucasians (rs17599165, p=0.0015; rs1912960, p=0.0073; and rs17599416, p=0.0040) and gave evidence of significant association in African-Americans (rs2280073, p=0.0287 and rs16859788, p=0.0253). The GABRA4 and GABRB1 interaction was also confirmed in the Caucasian dataset (most significant pair, rs1912960 and rs2351299; p=0.004). Analysis of the subset of families with a positive history of seizure activity in at least one autism patient revealed no association to GABRA4; however, three SNPs within GABRB1 showed significant allelic association; rs2351299 (p=0.0163), rs4482737 (p=0.0339), and rs3832300 (p=0.0253). These results confirmed our earlier findings, indicating GABRA4 and GABRB1 as genes contributing to autism susceptibility, extending the effect to multiple ethnic groups and suggesting seizures as a stratifying phenotype

Global prevalence of autism and other pervasive developmental disorders

We provide a systematic review of epidemiological surveys of autistic disorder and pervasive developmental disorders (PDDs) worldwide. A secondary aim was to consider the possible impact of geographic, cultural/ethnic, and socioeconomic factors on prevalence estimates and on clinical presentation of PDD. Based on the evidence reviewed, the median of prevalence estimates of autism spectrum disorders was 62/10 000. While existing estimates are variable, the evidence reviewed does not support differences in PDD prevalence by geographic region nor of a strong impact of ethnic/cultural or socioeconomic factors. However, power to detect such effects is seriously limited in existing data sets, particularly in low-income countries. While it is clear that prevalence estimates have increased over time and these vary in different neighboring and distant regions, these findings most likely represent broadening of the diagnostic concets, diagnostic switching from other developmental disabilities to PDD, service availability, and awareness of autistic spectrum disorders in both the lay and professional public. The lack of evidence from the majority of the world's population suggests a critical need for further research and capacity building in low- and middle-income countries

Validation of the Arabic version of the Social Communication Questionnaire

Validated screening and diagnostic tools for autism spectrum disorder for use in Arabic-speaking individuals are scarce. This study validated the Arabic version of the Social Communication Questionnaire. The total study sample included 206 children with autism spectrum disorder and 206 typically developing children (73.8% male; mean age: 8.5 (standard deviation = 2.6) years). The mean Social Communication Questionnaire total score was significantly higher in autism spectrum disorder children than in typically developing children (p < 0.0001). Scores on the three Social Communication Questionnaire subscales also differed significantly between the groups (p < 0.001). Of the 39 items, 37 were endorsed significantly more often in the autism spectrum disorder group. The total Social Communication Questionnaire score did not vary by age or gender. Internal consistency was excellent (alpha = 0.92). In the receiver operating characteristic analysis, the area under the curve for the total score showed excellent discrimination between autism spectrum disorder and typically developing children (area under the curve = 0.95; 95% confidence interval: 0.93–0.97). The areas under the curve for the scale subscores were 0.923 (95% confidence interval: 0.898–0.949) for the social interaction score, 0.872 (95% confidence interval: 0.838–0.905) for the communication score, and 0.856 (95% confidence interval: 0.819–0.893) for the repetitive behaviors score. The findings support the use of the Arabic Social Communication Questionnaire to successfully differentiate children with clinically diagnosed autism spectrum disorder using the established cutoff value for the English version.The authors would like to thank all the staff of the autism centers and schools who contributed in distributing and collecting the SCQ forms. They also would like to thank Western Psychological Services (WPS) staff for their help during the process of translating and reviewing the Arabic SCQ. They acknowledge Jennifer Holmes, ELS, for medical editing. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The study was funded by the Qatar National Research Fund (NPRP 6-093-3-024)

Regression, developmental trajectory and associated problems in disorders in the autism spectrum: the SNAP study

We report rates of regression and associated findings in a population derived group of 255 children aged 9-14 years, participating in a prevalence study of autism spectrum disorders (ASD); 53 with narrowly defined autism, 105 with broader ASD and 97 with non-ASD neurodevelopmental problems, drawn from those with special educational needs within a population of 56,946 children. Language regression was reported in 30% with narrowly defined autism, 8% with broader ASD and less than 3% with developmental problems without ASD. A smaller group of children were identified who underwent a less clear setback. Regression was associated with higher rates of autistic symptoms and a deviation in developmental trajectory. Regression was not associated with epilepsy or gastrointestinal problems

Prevalence and correlates of autism spectrum disorder in Qatar: a national study

Background Few epidemiological data on autism spectrum disorders (ASD) exist for Arabic countries. We conducted the first survey of ASD in Qatar, a population with high consanguinity level. Methods This cross‐sectional survey was conducted from 2015 to 2018 in Qatar school‐age children (N = 176,960) from national and immigrant families. Children diagnosed with ASD were identified through medical centers and special needs schools. Records were abstracted and supplemented by parental interviews. Additionally, children attending 93 schools were screened; ASD case status was confirmed in random samples of screen‐positive and screen‐negative children. Prevalence was estimated after taking into account different sampling fractions and participation rates at each survey phase. Results One thousand three hundred and ninety‐three children already diagnosed with ASD were identified. Among 9,074 school survey participants, 760 screen‐negative children and 163 screen‐positive children were evaluated; 17 were confirmed to have ASD including five children newly diagnosed. Prevalence was 1.14% (95% CI: 0.89–1.46) among 6‐ to 11‐year‐olds. ASD was reported in full siblings/extended relatives in 5.9% (95% CI: 0.042–0.080)/11.8% (95% CI: 0.095–0.146) families. First‐degree consanguinity in Qatari cases (45%) was comparable to known population levels. Among 844 ASD cases (mean age: 7.2 years; 81% male), most children experienced language delay (words: 75.1%; phrase speech: 91.4%), and 19.4% reported developmental regression. At the time of the survey, persisting deficits in expressive language (19.4%) and peer interactions (14.0%) were reported in conjunction with behavioral problems (ADHD: 30.2%; anxiety: 11.0%). In multivariate logistic regression, ASD severity was associated with parental consanguinity, gestational diabetes, delay in walking, and developmental regression. Conclusions ASD prevalence in Qatar is consistent with recent international studies. The methods employed in this study should help designing comparable surveys in the region. We estimated that 187,000 youths under age 20 have ASD in Gulf countries. This figure should assist in planning health and educational services for a young, fast‐growing population.The study was supported by the Qatar National Research Fund. The sponsor had no role in the design and conduct of the study, or the collection, management, analysis, and interpretation of the data, or in the preparation, review, or approval of the manuscript, and in the decision to submit the manuscript for publication. The authors thank all the independent and private schools that have participated in the SCQ screening phase. The authors thank the Ministry of Public Health and the Ministry of Education for providing their team with the data required throughout the study. The authors would like to express our gratitude to the psychological services team at the Shafallah Center for Children with Disabilities, as well as Dr. Irshad Shafeullah and Dr. Zakariah Al-Sayed for their support in patient recruitment. The authors also thank our colleagues from QBRI: Dr. Hatem Al-Shanti for his assistance in patient phenotyping, and Mr. Yasser Al-Sarraj and Ms. Hamda AlMutawwa for their support with patient recruitment. The authors thank Dr. Hanaa Massoud for assisting with patient recruitment through the clinic at the Child Development Center in Rumailah Hospital. The authors would also like to express their appreciation to the QBRI administration team for their assistance with planning and logistics pertaining to research-related training sessions and research collaborator visits. Additionally, the authors would like to thank all of the special needs centers and clinics which collaborated with us to provide data needed for the high probability cases; Shafallah Center for Children with Disabilities, Hamad Medical Corporation, Child Development Center ? Rumailah Hospital, Child Development Center-Private, Renad Academy, Al-Tamakun school, Step by Step Center, Qatar Institute for Speech and Hearing, and Hope Center. The authors also thank the HBKU Sponsored Research Office for the support provided throughout the research funding period.?K.R. and the OHSU Biostatistics & Design Program was partially supported by the Oregon Clinical and Translational Research Institute (OCTRI) through OHSU Clinical & Translational Science Awards (CTSA UL1TR0002369) National Consortium. The authors are immensely grateful to the families and their children for their time and participation in any of the phases of the research. F.A. and E.F. designed the research plan. F.A., M.A., and E.F. applied for funding. F.A., H.A., S.E., I.G., M.T., M.A., M.K., N.A.A., M.A., A.H.S., and L.D. organized the data collection. F.A., H.A., S.E., and I.G. completed data entry and cleaning, and performed initial data analyses with M.A. E.F. performed data and statistical analyses. K.R. provided biostatistical advice. E.F., F.A., and I.G. wrote the manuscript. All authors reviewed and approved the manuscript. The authors have declared that they have no competing or potential conflicts of interest.Scopu

Association between labour market trends and trends in young people's mental health in ten European countries 1983-2005

<p>Abstract</p> <p>Background</p> <p>Mental health problems have become more common among young people over the last twenty years, especially in certain countries. The reasons for this have remained unclear. The hypothesis tested in this study is that national trends in young people's mental health are associated with national trends in young people's labour market.</p> <p>Methods</p> <p>National secular changes in the proportion of young people with mental health problems and national secular labour market changes were studied from 1983 to 2005 in Austria, Belgium, Denmark, Finland, Hungary, Norway, Spain, Sweden, Switzerland and the United Kingdom.</p> <p>Results</p> <p>The correlation between the national secular changes in the proportion of young people not in the labour force and the national secular changes in proportion of young people with mental health symptoms was 0.77 for boys and 0.92 for girls.</p> <p>Conclusion</p> <p>Labour market trends may have contributed to the deteriorating trend in mental health among young people. A true relationship, should other studies confirm it, would be an important aspect to take into account when forming labour market policies or policies concerning the delivery of higher education.</p

Defining the cognitive phenotype of autism

Although much progress has been made in determining the cognitive profile of strengths and weaknesses that characterise individuals with autism spectrum disorders (ASDs), there remain a number of outstanding questions. These include how universal strengths and deficits are; whether cognitive subgroups exist; and how cognition is associated with core autistic behaviours, as well as associated psychopathology. Several methodological factors have contributed to these limitations in our knowledge, including: small sample sizes, a focus on single domains of cognition, and an absence of comprehensive behavioural phenotypic information. To attempt to overcome some of these limitations, we assessed a wide range of cognitive domains in a large sample (N = 100) of 14- to 16-year-old adolescents with ASDs who had been rigorously behaviourally characterised. In this review, we will use examples of some initial findings in the domains of perceptual processing, emotion processing and memory, both to outline different approaches we have taken to data analysis and to highlight the considerable challenges to better defining the cognitive phenotype(s) of ASDs. Enhanced knowledge of the cognitive phenotype may contribute to our understanding of the complex links between genes, brain and behaviour, as well as inform approaches to remediation

Socioeconomic Inequality in the Prevalence of Autism Spectrum Disorder: Evidence from a U.S. Cross-Sectional Study

This study was designed to evaluate the hypothesis that the prevalence of autism spectrum disorder (ASD) among children in the United States is positively associated with socioeconomic status (SES).A cross-sectional study was implemented with data from the Autism and Developmental Disabilities Monitoring Network, a multiple source surveillance system that incorporates data from educational and health care sources to determine the number of 8-year-old children with ASD among defined populations. For the years 2002 and 2004, there were 3,680 children with ASD among a population of 557,689 8-year-old children. Area-level census SES indicators were used to compute ASD prevalence by SES tertiles of the population.Prevalence increased with increasing SES in a dose-response manner, with prevalence ratios relative to medium SES of 0.70 (95% confidence interval [CI] 0.64, 0.76) for low SES, and of 1.25 (95% CI 1.16, 1.35) for high SES, (P<0.001). Significant SES gradients were observed for children with and without a pre-existing ASD diagnosis, and in analyses stratified by gender, race/ethnicity, and surveillance data source. The SES gradient was significantly stronger in children with a pre-existing diagnosis than in those meeting criteria for ASD but with no previous record of an ASD diagnosis (p<0.001), and was not present in children with co-occurring ASD and intellectual disability.The stronger SES gradient in ASD prevalence in children with versus without a pre-existing ASD diagnosis points to potential ascertainment or diagnostic bias and to the possibility of SES disparity in access to services for children with autism. Further research is needed to confirm and understand the sources of this disparity so that policy implications can be drawn. Consideration should also be given to the possibility that there may be causal mechanisms or confounding factors associated with both high SES and vulnerability to ASD

Childhood loneliness as a predictor of adolescent depressive symptoms: an 8-year longitudinal study

Childhood loneliness is characterised by children’s perceived dissatisfaction with aspects of their social relationships. This 8-year prospective study investigates whether loneliness in childhood predicts depressive symptoms in adolescence, controlling for early childhood indicators of emotional problems and a sociometric measure of peer social preference. 296 children were tested in the infant years of primary school (T1 5 years of age), in the upper primary school (T2 9 years of age) and in secondary school (T3 13 years of age). At T1, children completed the loneliness assessment and sociometric interview. Their teachers completed externalisation and internalisation rating scales for each child. At T2, children completed a loneliness assessment, a measure of depressive symptoms, and the sociometric interview. At T3, children completed the depressive symptom assessment. An SEM analysis showed that depressive symptoms in early adolescence (age 13) were predicted by reports of depressive symptoms at age 8, which were themselves predicted by internalisation in the infant school (5 years). The interactive effect of loneliness at 5 and 9, indicative of prolonged loneliness in childhood, also predicted depressive symptoms at age 13. Parent and peer-related loneliness at age 5 and 9, peer acceptance variables, and duration of parent loneliness did not predict depression. Our results suggest that enduring peer-related loneliness during childhood constitutes an interpersonal stressor that predisposes children to adolescent depressive symptoms. Possible mediators are discussed

Precursors to social and communication difficulties in infants at-risk for autism: gaze following and attentional engagement

Whilst joint attention (JA) impairments in autism have been widely studied, little is known about the early development of gaze following, a precursor to establishing JA. We employed eye-tracking to record gaze following longitudinally in infants with and without a family history of autism spectrum disorder (ASD) at 7 and 13 months. No group difference was found between at-risk and low-risk infants in gaze following behaviour at either age. However, despite following gaze successfully at 13 months, at-risk infants with later emerging socio-communication difficulties (both those with ASD and atypical development at 36 months of age) allocated less attention to the congruent object compared to typically developing at-risk siblings and low-risk controls. The findings suggest that the subtle emergence of difficulties in JA in infancy may be related to ASD and other atypical outcomes