| 1. |
- Depienne, Christel, et al.
(författare)
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Screening for genomic rearrangements and methylation abnormalities of the 15q11-q13 region in autism spectrum disorders.
- 2009
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Ingår i: Biological Psychiatry. - : Elsevier BV. - 0006-3223. ; 66:4, s. 349-359
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Maternally derived duplications of the 15q11-q13 region are the most frequently reported chromosomal aberrations in autism spectrum disorders (ASD). Prader-Willi and Angelman syndromes, caused by 15q11-q13 deletions or abnormal methylation of imprinted genes, are also associated with ASD. However, the prevalence of these disorders in ASD is unknown. The aim of this study was to assess the frequency of 15q11-q13 rearrangements in a large sample of patients ascertained for ASD. METHODS: A total of 522 patients belonging to 430 families were screened for deletions, duplications, and methylation abnormalities involving 15q11-q13 with multiplex ligation-dependent probe amplification (MLPA). RESULTS: We identified four patients with 15q11-q13 abnormalities: a supernumerary chromosome 15, a paternal interstitial duplication, and two subjects with Angelman syndrome, one with a maternal deletion and the other with a paternal uniparental disomy. CONCLUSIONS: Our results show that abnormalities of the 15q11-q13 region are a significant cause of ASD, accounting for approximately 1% of cases. Maternal interstitial 15q11-q13 duplications, previously reported to be present in 1% of patients with ASD, were not detected in our sample. Although paternal duplications of chromosome 15 remain phenotypically silent in the majority of patients, they can give rise to developmental delay and ASD in some subjects, suggesting that paternally expressed genes in this region can contribute to ASD, albeit with reduced penetrance compared with maternal duplications. These findings indicate that patients with ASD should be routinely screened for 15q genomic imbalances and methylation abnormalities and that MLPA is a reliable, rapid, and cost-effective method to perform this screening.
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| 2. |
- Johansson, Maria E I, 1961, et al.
(författare)
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Autism spectrum disorder and underlying brain mechanism in the oculoauriculovertebral spectrum.
- 2007
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Ingår i: Developmental Medicine and Child Neurology. - : Wiley. - 0012-1622 .- 1469-8749. ; 49:4, s. 280-288
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Tidskriftsartikel (refereegranskat)abstract
- As part of a multidisciplinary study, the rate of autism spectrum disorder (ASD), learning disability (LD), and brain abnormalities was examined in 20 participants (12 males, 8 females; age range 8mo-17y, mean age 8y 1mo) diagnosed as falling within the oculoauriculovertebral spectrum (OAV). A neuropsychiatric examination was performed, including standardized autism diagnostic interviews. Two individuals met diagnostic criteria for autism, one for autistic-like condition, and five for autistic traits. Four patients had mild LD, three severe LD, two profound LD, and two borderline intellectual functioning. Neuroimaging indicated cerebral abnormalities in more than half of the patients. Abnormalities of white/grey matter were found in more than half of examined individuals; enlargement of ventricles in more than a third. Results indicate that at least a subgroup of ASD may be associated with errors in early embryonic brain development. Awareness of the coexistence of OAV/ASD is important in habilitation care of individuals with OAV.
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| 3. |
- Johansson, Maria E I, 1961, et al.
(författare)
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Autism spectrum disorders and underlying brain pathology in CHARGE association.
- 2006
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Ingår i: Developmental Medicine and Child Neurology. - 0012-1622. ; 48:1, s. 40-50
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Tidskriftsartikel (refereegranskat)abstract
- The rate of autism spectrum disorders (ASDs) and brain abnormalities was analyzed in 31 individuals (15 males, 16 females; age range 1mo to 31y, mean age 8y 11mo) with CHARGE association, as part of a multidisciplinary study. A meticulous neuropsychiatric examination was performed, including standardized autism diagnostic interviews. Judgement regarding ASDs was impossible in three infants and three patients who were deaf and blind. Five individuals met diagnostic criteria for autism, five for an autistic-like condition, and seven for autistic traits. Brain abnormalities were indicated in almost three-quarters of examined individuals, and midline abnormalities of the forebrain in one-third. Awareness of the coexistence of CHARGE and ASDs is important in habilitation care in CHARGE. Moreover, the results indicate that a subgroup of ASDs may be associated with errors in early embryonic brain development.
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| 4. |
- Anckarsäter, Henrik, 1966, et al.
(författare)
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Autism spectrum disorders in institutionalized subjects.
- 2008
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Ingår i: Nordic Journal of Psychiatry. - : Informa UK Limited. - 0803-9488 .- 1502-4725. ; 62:2, s. 160-167
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Tidskriftsartikel (refereegranskat)abstract
- What do we know about the prevalence and the specific features of autism spectrum disorders (ASDs) among subjects in forensic psychiatry and special youth centres? A clinical case series consisting of 42 subjects with ASD, recruited from three well-characterized populations in forensic psychiatry and special youth care, was used to determine: 1) the prevalence of ASD in these institutions (at least 13%), 2) the distribution of diagnostic criteria in this special population (mostly social interaction and communication problems, few or atypical flexibility problems), 3) the degree of comorbidity (the rule rather than the exception), 4) neuropsychological test profiles (lowered IQ with uneven profiles), 5) types of crimes and offences (very heterogeneous, often stress-related with dissociated features), 6) mental health care needs (high), and 7) special clinical features (especially expressions of flexibility deficits in non-classical areas and proneness to dissociation). This descriptive study indicates that ASD is a clinically relevant problem among forensic populations that has to be considered in diagnostics, assessments of needs and treatment planning.
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| 5. |
- Anckarsäter, Henrik, 1966, et al.
(författare)
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Child neurodevelopmental and behavioural problems are intercorrelated and dimensionally distributed in the general population
- 2008
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Ingår i: The Open Psychiatry Journal. - : Bentham Science Publishers Ltd.. - 1874-3544. ; 2, s. 5-11
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Tidskriftsartikel (refereegranskat)abstract
- The Autism – Tics, AD/HD, and other Comorbidities inventory (A-TAC) is a comprehensive interview for evaluating problems related to autism spectrum disorders (ASD), tic disorders, attention-deficit/hyperactivity disorder (AD/HD), and common comorbid conditions in children and adolescents. A-TAC telephone interviews were administered to parents of 2,957 children aged nine- or twelve-years, representing one in each twin pair included in the population- based Child and Adolescent Twin Study in Sweden (CATSS). A total of 16.4% were screen-positive for one or several of the targeted disorder, 1.3% for ASD and 5.6% for AD/HD. All types of problems were more common among boys, with the exception of those related to “eating habits”. They were all dimensionally/continuously distributed, highly inter-correlated, and overlapped across types. They aggregated in three ba- sic factors corresponding to externalizing/disruptiveness, socio-communicative problems, and compulsiveness. Population-based data on problems in children thus challenge current categorical diagnostic definitions, calling for dimen- sional and complementary models of problem descriptions.
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| 6. |
- Anckarsäter, Henrik, 1966, et al.
(författare)
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Prevalences and configurations of mental disorders among institutionalized adolescents.
- 2007
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Ingår i: Developmental Neurorehabilitation. - : Informa UK Limited. - 1751-8423 .- 1751-8431. ; 10:1, s. 57-65
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To assess prevalence figures for psychiatric disorders among institutionalized adolescents due to behavioural problems and/or delinquency. METHOD: Participants were recruited from consecutive referrals to/or treated at two Swedish adolescent units, SIS1 (n = 60) and SIS2 (n = 70) with ranging age of 12-20.3 years (mean age = 16.2; SD = 1.8) during 1 year. Clinical and diagnostic information was used to generate DSM-IV diagnoses. RESULTS: One or several neuropsychiatric disorders were diagnosed in 53% of all subjects: 39% met DSM-IV diagnostic criteria for attention deficit/hyperactivity disorder (AD/HD), 15% for a pervasive developmental disorder (referred to as autism spectrum disorders, ASDs) and 8% had a mental retardation (referred to as a learning disability, LD). The collapsed prevalence for psychiatric disorders requiring specialist attention was 66%, counting severe depression and psychotic disorders but not substance use. About one in three of all adolescents in the study were given psychopharmacological treatment. CONCLUSION: Published studies and this clinical survey clearly indicate that systematic studies of mental health needs among institutionalized adolescents are warranted to form the basis of adequate treatment and support measures.
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| 7. |
- Anckarsäter, Henrik, 1966, et al.
(författare)
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The impact of ADHD and autism spectrum disorders on temperament, character, and personality development.
- 2006
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Ingår i: The American Journal of Psychiatry. - 0002-953X .- 1535-7228. ; 163:7, s. 1239-1244
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: The authors describe personality development and disorders in relation to symptoms of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorders. METHOD: Consecutive adults referred for neuropsychiatric investigation (N=240) were assessed for current and lifetime ADHD and autism spectrum disorders and completed the Temperament and Character Inventory. In a subgroup of subjects (N=174), presence of axis II personality disorders was also assessed with the Structured Clinical Interview for DSM-IV Personality Disorders (SCID-II). RESULTS: Patients with ADHD reported high novelty seeking and high harm avoidance. Patients with autism spectrum disorders reported low novelty seeking, low reward dependence, and high harm avoidance. Character scores (self-directedness and cooperativeness) were extremely low among subjects with neuropsychiatric disorders, indicating a high overall prevalence of personality disorders, which was confirmed with the SCID-II. Cluster B personality disorders were more common in subjects with ADHD, while cluster A and C disorders were more common in those with autism spectrum disorders. The overlap between DSM-IV personality disorder categories was high, and they seem less clinically useful in this context. CONCLUSIONS: ADHD and autism spectrum disorders are associated with specific temperament configurations and an increased risk of personality disorders and deficits in character maturation.
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| 8. |
- Buschard, Karsten, et al.
(författare)
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Low serum concentration of sulfatide and presence of sulfated lactosylceramid are associated with Type 2 diabetes. The Skaraborg Project
- 2005
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Ingår i: Diabetic Medicine. - : Wiley. - 0742-3071 .- 1464-5491. ; 22:9, s. 1190-8
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: The glycosphingolipid sulfatide (sulfated galactosyl-ceramide) increases exocytosis of beta-cell secretory granules, activates K(ATP)-channels and is thereby able to influence insulin secretion through its presence in the islets. A closely related compound, sulfated lactosylceramide (sulf-lac-cer), is present in the islets during fetal and neonatal life when, as in Type 2 diabetes, insulin is secreted autonomically without the usual first phase response to glucose. The aim was to examine whether serum concentrations of these glycolipids are associated with Type 2 diabetes. METHODS: A case-control study, comprising 286 women and 283 men, was designed using a population-based sample of patients with Type 2 diabetes and a population survey. RESULTS: Low serum concentrations of sulfatide were associated with Type 2 diabetes, independent of traditional risk factors for diabetes in a sex-specific analysis: odds ratio (OR) 2.1 (95% confidence interval 1.1, 3.9) in men, and 2.3 (1.2, 4.3) in women, comparing the lowest and the highest tertiles. Type 2 diabetes was also associated with detectable amounts of sulf-lac-cer in serum: OR 1.7 (0.9, 3.4) in men, and 7.6 (3.8, 15.2) in women. After adjustment for confounding from other diabetes risk factors, these associations remained basically unchanged. The connections between sulfatide and Type 2 diabetes, and sulf-lac-cer and Type 2 diabetes were independent of each other. Insulin resistance (HOMA-IR) was negatively correlated with sulfatide concentration and positively correlated with sulf-lac-cer (both P < 0.0001, independently). CONCLUSIONS: We report a new, robust and highly significant independent association between Type 2 diabetes and serum concentrations of sulfatide in both sexes, and sulf-lac-cer in females. The associations were also independent of other known diabetes risk factors.
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| 9. |
- Buxbaum, Joseph. D., et al.
(författare)
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Mutation analysis of the NSD1 gene in patients with autism spectrum disorders and macrocephaly.
- 2007
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Ingår i: BMC Medical Genetics. - : Springer Science and Business Media LLC. - 1471-2350. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- ABSTRACT: BACKGROUND: Sotos syndrome is an overgrowth syndrome characterized by macrocephaly, advanced bone age, characteristic facial features, and learning disabilities, caused by mutations or deletions of the NSD1 gene, located at 5q35. Sotos syndrome has been described in a number of patients with autism spectrum disorders, suggesting that NSD1 could be involved in other cases of autism and macrocephaly. METHODS: We screened the NSD1 gene for mutations and deletions in 88 patients with autism spectrum disorders and macrocephaly (head circumference 2 standard deviations or more above the mean). Mutation analysis was performed by direct sequencing of all exons and flanking regions. Dosage analysis of NSD1 was carried out using multiplex ligation-dependent probe amplification. RESULTS: We identified three missense variants (R604L, S822C and E1499G) in one patient each, but none is within a functional domain. In addition, segregation analysis showed that all variants were inherited from healthy parents and in two cases were also present in unaffected siblings, indicating that they are probably nonpathogenic. No partial or whole gene deletions/duplications were observed. CONCLUSIONS: Our findings suggest that Sotos syndrome is a rare cause of autism spectrum disorders and that screening for NSD1 mutations and deletions in patients with autism and macrocephaly is not warranted in the absence of other features of Sotos syndrome.
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| 10. |
- 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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