| 1. |
- Anney, Richard, et al.
(författare)
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A genome-wide scan for common alleles affecting risk for autism.
- 2010
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 19:20, s. 4072-4082
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Tidskriftsartikel (refereegranskat)abstract
- Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10(-8). When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10(-8) threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
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| 2. |
- Barnevik Olsson, Martina, et al.
(författare)
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Prevalence of autism in children of Somali origin living in Stockholm: brief report of an at-risk population.
- 2010
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Ingår i: Developmental Medicine and Child Neurology. - : Wiley. - 0012-1622. ; 52:12, s. 1167-1168
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Tidskriftsartikel (refereegranskat)abstract
- This work was a follow-up study (birth years 1999–2003) of the prevalence of autism in children of Somali background living in the county of Stockholm, Sweden. In a previous study (birth years 1988–98), the prevalence of autismassociated with learning disability* was found to be three to four times higher among Somali children compared with other ethnicities in Stockholm. We examined all records of children of Somali background, born from 1999 to 2003, registered at the centre for schoolchildren with autism and learning disability. The census day was 31 December 2009. The prevalence of autismand PDDNOS (with learning disability) was 0.98% (18 ⁄ 1836) in the Somali group and 0.21% (232 ⁄ 111 555) in the group of children of non-Somali origin (p<0.001). The increased prevalence remained and was now between four and five times higher in children of Somali background. A clinical observation was that more than 80%, in addition to autismand learning disability, had a profound hyperactivity. The findings accord with many other studies reporting higher prevalence rates of autism in children of immigrantmothers.We discuss the need for further research of underlyingmechanisms.
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| 3. |
- Cederlund, Mats, 1962, et al.
(författare)
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Asperger syndrome in adolescent and young adult males. Interview, self- and parent assessment of social, emotional, and cognitive problems.
- 2010
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Ingår i: Research in Developmental Disabilities. - : Elsevier BV. - 0891-4222. ; 31:2, s. 287-298
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Tidskriftsartikel (refereegranskat)abstract
- Descriptive and comparative follow-up studies of young adult males with Asperger syndrome (AS) diagnosed in childhood, using both interview, self- and parent assessment instruments for the study of aspects of emotional well-being, social functioning, and cognitive-practical skills have not been performed in the past. One-hundred males with AS diagnosed in childhood were approached for the assessment using the Asperger Syndrome Diagnostic Interview (ASDI), (personal and parent interview), the Leiter-R-Questionnaires, the Beck Depression Inventory (BDI), and the Dysexecutive Questionnaire (DEX). About 75% of the targeted group participated. The ASDI results came out significantly different at personal vs parent interviews in several key domains. In contrast, the Leiter-R-Questionnaires, showed no significant differences across the individuals with AS and their parents in the scoring of cognitive/social and emotional/adaptive skills. The BDI proved to be an adequate screening instrument for depression in that it correctly identified the vast majority of cases with clinical depression in the AS group. The DEX results suggested an executive function deficit problem profile in males with AS as severe as that reported in groups of individuals with traumatic brain injury and schizophrenia. Interviews (personal and collateral), and self-rating and parent-rating questionnaires all have a role in the comprehensive diagnostic process in AS and other autism spectrum disorders, and could be used as adjuncts when evaluating whether or not individuals meeting diagnostic symptom criteria for the condition have sufficient problems in daily life to warrant a clinical diagnosis of AS.
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| 4. |
- Chaste, Pauline, et al.
(författare)
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Identification of pathway-biased and deleterious melatonin receptor mutants in autism spectrum disorders and in the general population.
- 2010
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Ingår i: PloS One. - : Public Library of Science (PLoS). - 1932-6203. ; 5:7
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Tidskriftsartikel (refereegranskat)abstract
- Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration of the melatonin pathway has been reported in circadian disorders, diabetes and autism spectrum disorders (ASD). However, very little is known about the genetic variability of melatonin receptors in humans. Here, we sequenced the melatonin receptor MTNR1A and MTNR1B, genes coding for MT1 and MT2 receptors, respectively, in a large panel of 941 individuals including 295 patients with ASD, 362 controls and 284 individuals from different ethnic backgrounds. We also sequenced GPR50, coding for the orphan melatonin-related receptor GPR50 in patients and controls. We identified six non-synonymous mutations for MTNR1A and ten for MTNR1B. The majority of these variations altered receptor function. Particularly interesting mutants are MT1-I49N, which is devoid of any melatonin binding and cell surface expression, and MT1-G166E and MT1-I212T, which showed severely impaired cell surface expression. Of note, several mutants possessed pathway-selective signaling properties, some preferentially inhibiting the adenylyl cyclase pathway, others preferentially activating the MAPK pathway. The prevalence of these deleterious mutations in cases and controls indicates that they do not represent major risk factor for ASD (MTNR1A case 3.6% vs controls 4.4%; MTNR1B case 4.7% vs 3% controls). Concerning GPR50, we detected a significant association between ASD and two variations, Delta502-505 and T532A, in affected males, but it did not hold up after Bonferonni correction for multiple testing. Our results represent the first functional ascertainment of melatonin receptors in humans and constitute a basis for future structure-function studies and for interpreting genetic data on the melatonin pathway in patients.
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| 5. |
- Delorme, Richard, et al.
(författare)
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Mutation screening of NOS1AP gene in a large sample of psychiatric patients and controls.
- 2010
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 11:1:108
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The gene encoding carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase (NOS1AP) is located on chromosome 1q23.3, a candidate region for schizophrenia, autism spectrum disorders (ASD) and obsessive-compulsive disorder (OCD). Previous genetic and functional studies explored the role of NOS1AP in these psychiatric conditions, but only a limited number explored the sequence variability of NOS1AP. METHODS: We analyzed the coding sequence of NOS1AP in a large population (n = 280), including patients with schizophrenia (n = 72), ASD (n = 81) or OCD (n = 34), and in healthy volunteers controlled for the absence of personal or familial history of psychiatric disorders (n = 93). RESULTS: Two non-synonymous variations, V37I and D423N were identified in two families, one with two siblings with OCD and the other with two brothers with ASD. These rare variations apparently segregate with the presence of psychiatric conditions. CONCLUSIONS: Coding variations of NOS1AP are relatively rare in patients and controls. Nevertheless, we report the first non-synonymous variations within the human NOS1AP gene that warrant further genetic and functional investigations to ascertain their roles in the susceptibility to psychiatric disorders.
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| 6. |
- Fernell, Elisabeth, 1948, et al.
(författare)
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Autism spectrum disorder diagnoses in Stockholm preschoolers.
- 2010
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Ingår i: Research in Developmental Disabilities. - : Elsevier BV. - 0891-4222. ; 31:3, s. 680-685
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Tidskriftsartikel (refereegranskat)abstract
- The aims of this study were to estimate prevalence rates of children with autism spectrum disorder (ASD) diagnoses in a cohort of 6-year-old children with birth year 2002, referred to the Autism Centre for Young Children, serving the whole of Stockholm county and on the basis of the available data discuss clinical aspects of assessment, habilitation and follow-up. Records of 142 of a total of 147 (123 boys and 24 girls) identified children with ASD diagnoses were scrutinised with respect to type of diagnosis, cognitive level, other developmental disorders and medical/neurological disorders. The overall prevalence of such disorders was 6.2/1000 (95% confidence interval 5.2-7.2/1000). The rates of learning disability/mental retardation, developmental delay without a specified cognitive level and normal intelligence constituted about one third, respectively. AS and atypical autism tended to be diagnosed more often at age 5-6 years while AD with learning disability/mental retardation was more often diagnosed at age 3-4 years. The awareness of ASDs has resulted in increasing numbers of children being diagnosed at young ages. We conclude that it is important to take into account these children's broader developmental profiles, need for repeated assessment of cognitive functions and follow-up over time and also the requirement for medical/neurological consideration and work-up.
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| 7. |
- Fernell, Elisabeth, 1948, et al.
(författare)
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Developmental profiles in preschool children with autism spectrum disorders referred for intervention.
- 2010
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Ingår i: Research in Developmental Disabilities. - : Elsevier BV. - 0891-4222 .- 1873-3379. ; 31:3, s. 790-799
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Tidskriftsartikel (refereegranskat)abstract
- The aim was to characterize the panorama of developmental disorders in 208 preschool children with a clinical diagnosis of autism spectrum disorder (ASD), referred to a specialized centre, the Autism Centre for Young Children (ACYC), for intervention. At the centre, a research team examined all children according to structured protocols and interviews. All available test data from their assessments prior to referral were scrutinized. The boy:girl ratio was 5.5:1. In 22% of the total group a period of regression, including speech and language, had occurred. Epilepsy had been diagnosed in 6% of the children. In 38% of the children there was a definite or highly suspected learning disability/mental retardation according to cognitive test results. About the same proportion had a developmental delay that at the time of assessment could not be definitely classified and in 23% there were clear indications of a normal intellectual function. About 40% of the group exhibited hyperactivity. Differences in expressive vocabulary and adaptive functioning were strongly related to cognitive level. About 20% of the group had AD as the dominating developmental disorder, i.e., they represented a clinical picture of "classic" autism. The majority in this group also had learning disability. Another 20%, had ASD combined with a normal intellectual level, some of these conformed to the clinical picture of Asperger syndrome. In a relatively large group (more than half) learning disability or a general developmental delay was as evident as the ASD. In a smaller group (8%) ASD criteria were questionably met. In this group attention deficits in connection with speech and language problems were prominent. The highly individual developmental profiles seen in children with ASDs have to be taken into account when planning intervention and follow-up. The children's medical characteristics also vary considerably and will be detailed in a further report.
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| 8. |
- Fernell, Elisabeth, 1948, et al.
(författare)
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Serum levels of 25-hydroxyvitamin D in mothers of Swedish and of Somali origin who have children with and without autism.
- 2010
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Ingår i: Acta Paediatrica. - : Wiley. - 0803-5253 .- 1651-2227. ; 99:5, s. 743-747
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To analyse serum levels of 25-hydroxyvitamin D in mothers of Somali origin and those of Swedish origin who have children with and without autism as there is a growing evidence that low vitamin D impacts adversely on brain development. Method: Four groups of mothers were invited to participate; 20 with Somali origin with at least one child with autism, 20 with Somali origin without a child with autism, 20 of Swedish origin with at least one child with autism and 20 with Swedish origin without a child with autism. Two blood samples were collected from each individual; during autumn and spring. Results: Between 12 and 17 mothers from the different groups accepted to participate, both groups of mothers of Somali origin had significantly lower values of 25-hydroxyvitamin D compared with Swedish mothers. The difference of 25-hydroxyvitamin D between mothers of Somali origin with and without a child with autism was not significant. Conclusion: Our findings of low vitamin D levels in Somali women entail considerable consequences in a public health perspective. The observed tendency, i.e. the lowest values in mothers of Somali origin with a child with autism was in the predicted direction, supporting the need for further research of vitamin D levels in larger samples of Somali mothers of children with and without autism.
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| 9. |
- Gillberg, Christopher, 1950, et al.
(författare)
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Autism and Epilepsy: Comorbidity, Coexistence or Coincidence?
- 2010
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Ingår i: In M. Bax, & C. Gillberg (Eds.), Comorbidities in Developmental Disorders. Clinics in Developmental Medicine no. 187. - London, United Kingdom : Mac Keith Press. - 9781907655005 ; , s. 89-100
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 10. |
- Gillberg, Christopher, 1950, et al.
(författare)
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Mortality in autism: a prospective longitudinal community-based study.
- 2010
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Ingår i: Journal of Autism and Developmental Disorders. - : Springer Science and Business Media LLC. - 0162-3257 .- 1573-3432. ; 40:3, s. 352-357
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Tidskriftsartikel (refereegranskat)abstract
- The purposes of the present study were to establish the mortality rate in a representative group of individuals (n = 120) born in the years 1962-1984, diagnosed with autism/atypical autism in childhood and followed up at young adult age (>/=18 years of age), and examine the risk factors and causes of death. The study group, which constituted a total population sample of children with these diagnoses, were followed up in Swedish registers. Nine (7.5%) of the 120 individuals with autism had died at the time of follow-up, a rate 5.6 times higher than expected. The mortality rate was significantly higher among the females. Associated medical disorders (including epilepsy with cognitive impairment) and accidents accounted for most of the deaths, and it was not possible to determine whether autism "per se" actually carries an increased mortality risk.
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