| 11. |
- Beggiato, Anita, et al.
(författare)
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Gender differences in autism spectrum disorders: Divergence among specific core symptoms.
- 2017
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Ingår i: Autism research : official journal of the International Society for Autism Research. - : Wiley. - 1939-3806 .- 1939-3792. ; 10:4
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Tidskriftsartikel (refereegranskat)abstract
- Community-based studies have consistently shown a sex ratio heavily skewed towards males in autism spectrum disorders (ASD). The factors underlying this predominance of males are largely unknown, but the way girls score on standardized categorical diagnostic tools might account for the underrecognition of ASD in girls. Despite the existence of different norms for boys and girls with ASD on several major screening tests, the algorithm of the Autism Diagnosis Interview-Revised (ADI-R) has not been reformulated. The aim of our study was to investigate which ADI-R items discriminate between males and females, and to evaluate their weighting in the final diagnosis of autism. We then conducted discriminant analysis (DA) on a sample of 594 probands including 129 females with ASD, recruited by the Paris Autism Research International Sibpair (PARIS) Study. A replication analysis was run on an independent sample of 1716 probands including 338 females with ASD, recruited through the Autism Genetics Resource Exchange (AGRE) program. Entering the raw scores for all ADI-R items as independent variables, the DA correctly classified 78.9% of males and 72.9% of females (P < 0.001) in the PARIS cohort, and 72.2% of males and 68.3% of females (P < 0.0001) in the AGRE cohort. Among the items extracted by the stepwise DA, four belonged to the ADI-R algorithm used for the final diagnosis of ASD. In conclusion, several items of the ADI-R that are taken into account in the diagnosis of autism significantly differentiates between males and females. The potential gender bias thus induced may participate in the underestimation of the prevalence of ASD in females. Autism Res 2016,. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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| 12. |
- Billstedt, Eva, 1961, et al.
(författare)
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Aspects of quality of life in adults diagnosed with autism in childhood: a population-based study.
- 2011
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Ingår i: Autism. - : SAGE Publications. - 1362-3613 .- 1461-7005. ; 15:1, s. 7-20
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Tidskriftsartikel (refereegranskat)abstract
- The present study is a long-term prospective follow-up study of a population-based cohort of 120 individuals diagnosed with autism in childhood, followed into late adolescence/early adulthood. Specific aims of the study were to attempt to measure and study social aspects/quality of life in those 108 individuals with autism alive and available for study at the time of follow-up (13-22 years after original diagnosis). A newly constructed scale for rating 'autism-friendly environment'/quality of life was used alongside a structured parent/carer interview assessing current occupation, educational history, services provided, accommodation type, and recreational activities. The majority of the group with autism remained dependent on parents/caregivers for support in education, accommodation and occupational situations. In spite of this, the estimation of the study group's general quality of life was encouragingly positive. Nevertheless, there was an obvious need for improvements in the areas of occupation and recreational activities. Future studies need to look in more depth at the concept of an autism-friendly environment and develop more detailed quality of life assessment tools relevant for people in the autism spectrum.
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| 13. |
- Billstedt, Eva, 1961, et al.
(författare)
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Autism after adolescence: population-based 13- to 22-year follow-up study of 120 individuals with autism diagnosed in childhood.
- 2005
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Ingår i: Journal of Autism and Developmental Disorders. - : Springer Science and Business Media LLC. - 0162-3257 .- 1573-3432. ; 35:3, s. 351-360
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Prospective population-based follow-up study of 120 individuals with autism followed from childhood to adulthood. METHODS: Individuals with autism, diagnosed in childhood, were followed prospectively for a period of 13-22 years and re-evaluated at ages 17-40 years. The instruments used at follow-up were the DISCO, WAIS-R, WISC-III, Vineland Adaptive Behavior Scales, psychiatric-medical examination and GAF-scale. A set of criteria was used for the classification of outcomes, taking into consideration employment, higher education/vocational training, independent living and peer relations. RESULTS: Six of the 120 (5%) had died at the time of follow-up, and six declined participation. Overall outcome was poor in 78% of cases. Only four individuals were independent albeit leading fairly isolated lives. Childhood IQ-level was positively correlated with better adult outcome, as was the existence of some communicative phrase speech at age six years. CONCLUSIONS: Children with autism as diagnosed in the 1960s, 1970s, and 1980s may have an even worse psychosocial outcome than previously believed.
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| 14. |
- Billstedt, Eva, 1961, et al.
(författare)
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Autism in adults: symptom patterns and early childhood predictors. Use of the DISCO in a community sample followed from childhood.
- 2007
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Ingår i: Journal of Child Psychology and Psychiatry, and Allied Disciplines. - : Wiley. - 0021-9630 .- 1469-7610. ; 48:11, s. 1102-1110
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Few studies have looked at the very long-term outcome of individuals with autism who were diagnosed in childhood. METHODS: A longitudinal, prospective, community-based follow-up study of adults who had received the diagnosis of autism (classic and atypical) in childhood (n = 105) was conducted. A structured interview (the Diagnostic Interview for Social and COmmunication disorders--the DISCO) was used in order to evaluate symptoms and symptom patterns 13-22 years after original diagnosis. Childhood measures, including IQ-level at time of childhood diagnosis and communicative speech registered before age 5 years, were studied in relation to the presence of autism symptoms at follow-up. RESULTS: The classical and atypical autism groups were fairly homogeneously impaired in terms of symptoms in the social interaction category whereas other common childhood autism symptoms, including maladaptive and stereotyped behaviours, were more variable in the study group at follow-up. Odd responses to sensory stimuli were still extremely common. Speech before 5 years of age, IQ, gender, diagnosed medical disorder and onset of epilepsy before 5 years were variables that correlated to outcome on the DISCO algorithm for autistic spectrum disorders (Wing & Gould, 1979) concerning style and quality of social interaction, communication style and pattern of self-chosen activities. CONCLUSIONS: Social interaction problems were still present in the vast majority of adults with autism/atypical autism, but behavioural impairments were much more variable in adulthood. Almost all cases were reported to show persistent perceptual problems. Certain childhood measures were found to prospectively predict adult social interaction style, communication type, and pattern of self-chosen activities, which still met diagnostic criteria for autism/atypical autism in adulthood.
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| 15. |
- Buxbaum, Joseph D, et al.
(författare)
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Mutation screening of the PTEN gene in patients with autism spectrum disorders and macrocephaly.
- 2007
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Ingår i: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. - : Wiley. - 1552-4841 .- 1552-485X. ; 144B:4, s. 484-491
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in the PTEN gene are associated with a broad spectrum of disorders, including Cowden syndrome (CS), Bannayan-Riley-Ruvalcaba syndrome, Proteus syndrome, and Lhermitte-Duclos disease. In addition, PTEN mutations have been described in a few patients with autism spectrum disorders (ASDs) and macrocephaly. In this study, we screened the PTEN gene for mutations and deletions in 88 patients with ASDs and macrocephaly (defined as >or=2 SD above the mean). Mutation analysis was performed by direct sequencing of all exons and flanking regions, as well as the promoter region. Dosage analysis of PTEN was carried out using multiplex ligation-dependent probe amplification (MLPA). No partial or whole gene deletions were observed. We identified a de novo missense mutation (D326N) in a highly conserved amino acid in a 5-year-old boy with autism, mental retardation, language delay, extreme macrocephaly (+9.6 SD) and polydactyly of both feet. Polydactyly has previously been described in two patients with Lhermitte-Duclos disease and CS and is thus likely to be a rare sign of PTEN mutations. Our findings suggest that PTEN mutations are a relatively infrequent cause of ASDs with macrocephaly. Screening of PTEN mutations is warranted in patients with autism and pronounced macrocephaly, even in the absence of other features of PTEN-related tumor syndromes.
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| 16. |
- Casey, Jillian P, et al.
(författare)
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A novel approach of homozygous haplotype sharing identifies candidate genes in autism spectrum disorder.
- 2012
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Ingår i: Human Genetics. - : Springer Science and Business Media LLC. - 0340-6717 .- 1432-1203. ; 131:4, s. 565-579
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Tidskriftsartikel (refereegranskat)abstract
- Autism spectrum disorder (ASD) is a highly heritable disorder of complex and heterogeneous aetiology. It is primarily characterized by altered cognitive ability including impaired language and communication skills and fundamental deficits in social reciprocity. Despite some notable successes in neuropsychiatric genetics, overall, the high heritability of ASD (~90%) remains poorly explained by common genetic risk variants. However, recent studies suggest that rare genomic variation, in particular copy number variation, may account for a significant proportion of the genetic basis of ASD. We present a large scale analysis to identify candidate genes which may contain low-frequency recessive variation contributing to ASD while taking into account the potential contribution of population differences to the genetic heterogeneity of ASD. Our strategy, homozygous haplotype (HH) mapping, aims to detect homozygous segments of identical haplotype structure that are shared at a higher frequency amongst ASD patients compared to parental controls. The analysis was performed on 1,402 Autism Genome Project trios genotyped for 1 million single nucleotide polymorphisms (SNPs). We identified 25 known and 1,218 novel ASD candidate genes in the discovery analysis including CADM2, ABHD14A, CHRFAM7A, GRIK2, GRM3, EPHA3, FGF10, KCND2, PDZK1, IMMP2L and FOXP2. Furthermore, 10 of the previously reported ASD genes and 300 of the novel candidates identified in the discovery analysis were replicated in an independent sample of 1,182 trios. Our results demonstrate that regions of HH are significantly enriched for previously reported ASD candidate genes and the observed association is independent of gene size (odds ratio 2.10). Our findings highlight the applicability of HH mapping in complex disorders such as ASD and offer an alternative approach to the analysis of genome-wide association data.
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| 17. |
- Castellheim, Albert, et al.
(författare)
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The role of general anesthesia on traits of neurodevelopmental disorders in a Swedish cohort of twins.
- 2018
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Ingår i: Journal of child psychology and psychiatry, and allied disciplines. - : Wiley. - 1469-7610 .- 0021-9630. ; 59:9, s. 966-972
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Tidskriftsartikel (refereegranskat)abstract
- The role of general anesthetics as a risk factor for possible neurodevelopmental disorders (NDDs) in humans is unresolved. The investigation of the role of anesthetics in the development of postgeneral anesthesia (anesthesia onward) NDDs has proven to be complicated, partly because of the inherent confounding in clinical cohort studies, and partly by the fact that anesthetics are only one part in the complex process of anesthesia-surgery.Utilizing the Swedish databases Child and Adolescent Twins Study in Sweden (CATSS) and National Patient Register (NPR), we investigated twins discordant for anesthesia, born between 1997 and 2004 for traits of NDDs. We identified 68 twin pairs discordant for anesthesia and explored traits of Attention-Deficit/Hyperactivity Disorder (ADHD), Learning Disability (LD), and Autism Spectrum Disorder (ASD) in them while simultaneously taking congenital abnormalities and systemic disorders (CSDs) into account. We analyzed the possible effect of anesthesia on neurodevelopmental problems, and we analyzed the within-pair differences using conditional linear regression.Twins with a recorded episode of anesthesia had higher traits of NDDs than twins without; similarly twins with CSDs had higher mean scores on all traits than twins without CSDs. The within-pair analyses suggested that exposure to anesthesia was associated with higher scores of ADHD (regression coefficient 1.02 and 95% confidence intervals: 0.27-1.78) in monozygotic (MZ) twins discordant for anesthesia. This effect remained when adjusting for congenital abnormalities.Our finding that traits of ADHD were slightly associated with anesthesia in a genetically sensitive design is in need of replication and warrants further investigation. Future studies should aim to elucidate mechanisms behind this possible association (e.g. anesthetics doses, age at exposure, exposure duration).
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| 18. |
- Cederlund, Mats, 1962, et al.
(författare)
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Asperger syndrome and autism: a comparative longitudinal follow-up study more than 5 years after original diagnosis.
- 2008
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Ingår i: Journal of Autism and Developmental Disorders. - : Springer Science and Business Media LLC. - 0162-3257 .- 1573-3432. ; 38:1, s. 72-85
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Tidskriftsartikel (refereegranskat)abstract
- Prospective follow-up study of 70 males with Asperger syndrome (AS), and 70 males with autism more than 5 years after original diagnosis. Instruments used at follow-up included overall clinical assessment, the Diagnostic Interview for Social and Communication Disorders, Wechsler Intelligence Scales, Vineland Adaptive Behavior Scales, and Global Assessment of Functioning Scale. Specific outcome criteria were used. Outcome in AS was good in 27% of cases. However, 26% had a very restricted life, with no occupation/activity and no friends. Outcome in the autism group was significantly worse. Males with AS had worse outcomes than expected given normal to high IQ. However, outcome was considerably better than for the comparison group of individuals with autism.
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| 19. |
- Chaste, Pauline, et al.
(författare)
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Genetic variations of the melatonin pathway in patients with attention-deficit and hyperactivity disorders.
- 2011
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Ingår i: Journal of Pineal Research. - 0742-3098 .- 1600-079X. ; 51:4, s. 394-399
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Tidskriftsartikel (refereegranskat)abstract
- Melatonin is a powerful antioxidant and a synchronizer of many physiological processes. Alteration in melatonin signaling has been reported in a broad range of diseases, but little is known about the genetic variability of this pathway in humans. Here, we sequenced all the genes of the melatonin pathway -AA-NAT, ASMT, MTNR1A, MTNR1B and GPR50 - in 321 individuals from Sweden including 101 patients with attention-deficit/hyperactivity disorder (ADHD) and 220 controls from the general population. We could find several damaging mutations in patients with ADHD, but no significant enrichment compared with the general population. Among these variations, we found a splice site mutation in ASMT (IVS5+2T>C) and one stop mutation in MTNR1A (Y170X) - detected exclusively in patients with ADHD - for which biochemical analyses indicated that they abolish the activity of ASMT and MTNR1A. These genetic and functional results represent the first comprehensive ascertainment of melatonin signaling deficiency in ADHD.
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| 20. |
- 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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