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  • Hansson, Sara Lina, et al. (författare)
  • The Autism--Tics, AD/HD and other Comorbidities (A-TAC) telephone interview: convergence with the Child Behavior Checklist (CBCL).
  • 2010
  • Ingår i: Nordic Journal of Psychiatry. - 0803-9488. ; 64:3, s. 218-224
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective: To compare telephone interview screening for child psychiatric/neuropsychiatric disorders using the inventory of Autism-Tics, Attention deficit/hyperactivity disorder (AD/HD) and other Comorbidities (A-TAC) with results from the Child Behavior Checklist (CBCL). Background: The A-TAC is a parent telephone interview focusing on autism spectrum disorders (ASDs) and co-existing problems, developed for lay interviewers. Subjects and methods: A-TAC telephone interviews and CBCL questionnaires were obtained from parents of 106 Swedish twin pairs aged 9 and 12 years. Results: Correlations between A-TAC modules and CBCL scales aimed at measuring similar concepts were generally significant albeit modest, with correlation coefficients ranging from 0.30 through 0.55. Conclusion: The A-TAC has convergent validity with the CBCL in several problem areas, but the A-TAC also provides more detailed and specific assessments of ASD symptoms and related neuropsychiatric problems.
  • Henningsson, Susanne, et al. (författare)
  • Possible association between the androgen receptor gene and autism spectrum disorder.
  • 2009
  • Ingår i: Psychoneuroendocrinology. - 0306-4530. ; 34:5, s. 752-761
  • Tidskriftsartikel (refereegranskat)abstract
    • Autism is a highly heritable disorder but the specific genes involved remain largely unknown. The higher prevalence of autism in men than in women, in conjunction with a number of other observations, has led to the suggestion that prenatal brain exposure to androgens may be of importance for the development of this condition. Prompted by this hypothesis, we investigated the potential influence of variation in the androgen receptor (AR) gene on the susceptibility for autism. To this end, 267 subjects with autism spectrum disorder and 617 controls were genotyped for three polymorphisms in exon I of the AR gene: the CAG repeat, the GGN repeat and the rs6152 SNP. In addition, parents and affected siblings were genotyped for 118 and 32 of the cases, respectively. Case-control comparisons revealed higher prevalence of short CAG alleles as well as of the A allele of the rs6152 SNP in female cases than in controls, but revealed no significant differences with respect to the GGN repeat. Analysis of the 118 families using transmission disequilibrium test, on the other hand, suggested an association with the GGN polymorphism, the rare 20-repeat allele being undertransmitted to male cases and the 23-repeat allele being overtransmitted to female cases. Sequencing of the AR gene in 46 patients revealed no mutations or rare variants. The results tend some support for an influence of the studied polymorphisms on the susceptibility for autism, but argue against the possibility that mutations in the AR gene are common in subjects with this condition. (C) 2008 Elsevier Ltd. All rights reserved.
  • Larson, Tomas, et al. (författare)
  • The autism--tics, AD/HD and other comorbidities inventory (A-TAC): further validation of a telephone interview for epidemiological research.
  • 2010
  • Ingår i: BMC Psychiatry. - 1471-244X. ; 10
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Reliable, valid, and easy-to-administer instruments to identify possible caseness and to provide proxies for clinical diagnoses are needed in epidemiological research on child and adolescent mental health. The aim of this study is to provide further validity data for a parent telephone interview focused on Autism - Tics, Attention-deficit/hyperactivity disorder (AD/HD), and other Comorbidities (A-TAC), for which reliability and preliminary validation data have been previously reported. Methods: Parents of 91 children clinically diagnosed at a specialized Child Neuropsychiatric Clinic, 366 control children and 319 children for whom clinical diagnoses had been previously assigned were interviewed by the A-TAC over the phone. Interviewers were blind to clinical information. Different scores from the A-TAC were compared to the diagnostic outcome. Results: Areas under ROC curves for interview scores as predictors of clinical diagnoses were around 0.95 for most disorders, including autism spectrum disorders (ASDs), attention deficit/hyperactivity disorder (AD/HD), tic disorders, developmental coordination disorders (DCD) and learning disorders, indicating excellent screening properties. Screening cut-off scores with sensitivities above 0.90 (0.95 for ASD and AD/HD) were established for most conditions, as well as cut-off scores to identify proxies to clinical diagnoses with specificities above 0.90 (0.95 for ASD and AD/HD). Conclusions: The previously reported validity of the A-TAC was supported by this larger replication study using broader scales from the A-TAC-items and a larger number of diagnostic categories. Short versions of algorithms worked as well as larger. Different cut-off levels for screening versus identifying proxies for clinical diagnoses are warranted. Data on the validity for mood problems and oppositional defiant/conduct problems are still lacking. Although the A-TAC is principally intended for epidemiological research and general investigations, the instrument may be useful as a tool to collect information in clinical practice as well.
  • Anckarsäter, Henrik, et al. (författare)
  • The sociocommunicative deficit subgroup in anorexia nervosa: autism spectrum disorders and neurocognition in a community-based, longitudinal study.
  • 2012
  • Ingår i: Psychological Medicine. - 0033-2917. ; 42:9, s. 1957-1967
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A subgroup of persons with anorexia nervosa (AN) have been proposed to have sociocommunicative problems corresponding to autism spectrum disorders [ASDs, i.e. DSM-IV pervasive developmental disorders (PDDs): autistic disorder, Asperger's disorder, PDD not otherwise specified (NOS)]. Here, clinical problems, personality traits, cognitive test results and outcome are compared across 16 subjects (32%) with teenage-onset AN who meet or have met ASD criteria (AN+ASD), 34 ASD-negative AN subjects and matched controls from a longitudinal Swedish study including four waves of independent assessments from the teens to the early thirties.MethodThe fourth wave included the Structured Clinical Interview for DSM-IV (SCID)-I and the SCID-II (cluster C, i.e. 'anxious' PDs) interviews, the Asperger Syndrome Diagnostic Interview, self-assessments by the Autism Spectrum Quotient and the Temperament and Character Inventory, neurocognitive tests by subscales from the Wechsler scales, continuous performance tests, Tower of London, and Happé's cartoons. RESULTS: The ASD assessments had substantial inter-rater reliability over time (Cohen's κ between 0.70 and 0.80 with previous assessments), even if only six subjects had been assigned a diagnosis of an ASD in all four waves of the study, including retrospective assessments of pre-AN neurodevelopmental problems. The AN+ASD group had the highest prevalence of personality disorders and the lowest Morgan-Russell scores. The non-ASD AN group also differed significantly from controls on personality traits related to poor interpersonal functioning and on neurocognitive tests. CONCLUSIONS: A subgroup of subjects with AN meet criteria for ASDs. They may represent the extreme of neurocognitive and personality problems to be found more generally in AN.
  • Beggiato, Anita, et al. (författare)
  • Gender differences in autism spectrum disorders: Divergence among specific core symptoms
  • 2017
  • Ingår i: Autism Research. - John Wiley and Sons Inc.. - 1939-3806. ; 10:4, s. 680-689
  • 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.
  • Castellheim, Albert, et al. (författare)
  • The role of general anesthesia on traits of neurodevelopmental disorders in a Swedish cohort of twins.
  • 2018
  • Ingår i: Journal of child psychology and psychiatry, and allied disciplines. - 1469-7610. ; 59:9, s. 966-972
  • 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).
  • Chaste, Pauline, et al. (författare)
  • Identification of pathway-biased and deleterious melatonin receptor mutants in autism spectrum disorders and in the general population.
  • 2010
  • Ingår i: PloS One. - 1932-6203. ; 5:7
  • 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.
  • Gillberg, Christopher, et al. (författare)
  • The Asperger Syndrome (and high-functioning autism) Diagnostic Interview (ASDI): a preliminary study of a new structured clinical interview
  • 2001
  • Ingår i: Autism. - 1362-3613 (Print). ; 5:1, s. 57-66
  • Tidskriftsartikel (refereegranskat)abstract
    • The development of the Asperger Syndrome (and highfunctioning autism) Diagnostic Interview (ASDI) is described. Preliminary data from a clinical study suggest that inter-rater reliability and test–retest stability may be excellent, with kappas exceeding 0.90 in both instances. The validity appears to be relatively good. No attempt was made in the present study to validate the instrument as regards the distinction between Asperger syndrome and high-functioning autism.
  • Gong, Ziaohong, et al. (författare)
  • Analysis of X chromosome inactivation in autism spectrum disorders.
  • 2008
  • Ingår i: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics. - 1552-485X. ; 147B:6, s. 830-835
  • Tidskriftsartikel (refereegranskat)abstract
    • Autism spectrum disorders (ASD) are complex genetic disorders more frequently observed in males. Skewed X chromosome inactivation (XCI) is observed in heterozygous females carrying gene mutations involved in several X-linked syndromes. In this study, we aimed to estimate the role of X-linked genes in ASD susceptibility by ascertaining the XCI pattern in a sample of 543 informative mothers of children with ASD and in a sample of 163 affected girls. The XCI pattern was also determined in two control groups (144 adult females and 40 young females) with a similar age distribution to the mothers sample and affected girls sample, respectively. We observed no significant excess of skewed XCI in families with ASD. Interestingly, two mothers and one girl carrying known mutations in X-linked genes (NLGN3, ATRX, MECP2) showed highly skewed XCI, suggesting that ascertainment of XCI could reveal families with X-linked mutations. Linkage analysis was carried out in the subgroup of multiplex families with skewed XCI (80:20) and a modest increased allele sharing was obtained in the Xq27-Xq28 region, with a peak Z-score of 1.75 close to rs719489. In summary, our results suggest that there is no major X-linked gene subject to XCI and expressed in blood cells conferring susceptibility to ASD. However, the possibility that rare mutations in X-linked genes could contribute to ASD cannot be excluded. We propose that the XCI profile could be a useful criteria to prioritize families for mutation screening of X-linked candidate genes.
  • Hadjikhani, Nouchine, 1966-, et al. (författare)
  • Emotional contagion for pain is intact in autism spectrum disorders.
  • 2014
  • Ingår i: Translational psychiatry. - 2158-3188. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • Perceiving others in pain generally leads to empathic concern, consisting of both emotional and cognitive processes. Empathy deficits have been considered as an element contributing to social difficulties in individuals with autism spectrum disorders (ASD). Here, we used functional magnetic resonance imaging and short video clips of facial expressions of people experiencing pain to examine the neural substrates underlying the spontaneous empathic response to pain in autism. Thirty-eight adolescents and adults of normal intelligence diagnosed with ASD and 35 matched controls participated in the study. In contrast to general assumptions, we found no significant differences in brain activation between ASD individuals and controls during the perception of pain experienced by others. Both groups showed similar levels of activation in areas associated with pain sharing, evidencing the presence of emotional empathy and emotional contagion in participants with autism as well as in controls. Differences between groups could be observed at a more liberal statistical threshold, and revealed increased activations in areas involved in cognitive reappraisal in ASD participants compared with controls. Scores of emotional empathy were positively correlated with brain activation in areas involved in embodiment of pain in ASD group only. Our findings show that simulation mechanisms involved in emotional empathy are preserved in high-functioning individuals with autism, and suggest that increased reappraisal may have a role in their apparent lack of caring behavior.
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