Strong association of de novo copy number mutations with autism.
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We tested the hypothesis that de novo copy number variation (CNV) is associated with autism spectrum disorders (ASDs). We performed comparative genomic hybridization (CGH) on the genomic DNA of patients and unaffected subjects to detect copy number variants not present in their respective parents. Candidate genomic regions were validated by higher-resolution CGH, paternity testing, cytogenetics, fluorescence in situ hybridization, and microsatellite genotyping. Confirmed de novo CNVs were significantly associated with autism (P = 0.0005). Such CNVs were identified in 12 out of 118 (10%) of patients with sporadic autism, in 2 out of 77 (3%) of patients with an affected first-degree relative, and in 2 out of 196 (1%) of controls. Most de novo CNVs were smaller than microscopic resolution. Affected genomic regions were highly heterogeneous and included mutations of single genes. These findings establish de novo germline mutation as a more significant risk factor for ASD than previously recognized. (+info)
Impairment of quality of life in parents of children and adolescents with pervasive developmental disorder.
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BACKGROUND: Little is known about the Quality of Life (QOL) in parents of children with developmental diseases as compared to other severe neurological or psychiatric disorders. Aims of the present study were: to evaluate QOL in parents of children affected by Pervasive Development Disorder (PDDs), Cerebral Palsy (CP) or Mental Retardation (MR) as compared to a control group (CG); to evaluate QOL of parents of patients with different types of PDDs, namely Autistic Disorder (AD), High Function Autism/Asperger Syndromes (HFA/AS) and Pervasive Developmental Disorder Not Otherwise Specified (PPD-NOS); and to compare the level of impairment in QOL of mothers and fathers within PDDs, CP, MR groups and between AD, HFA/AS, PDD-NOS sub-groups. METHODS: The sample consisted of 212 parents (115 mothers and 97 fathers) of 135 children or adolescents affected by PDDs, MR or CP. An additional sample of 77 parents (42 mothers and 35 fathers) of 48 healthy children was also included and used as a control group. QOL was assessed by the WHOQOL-BREF questionnaire. RESULTS: Compared with parents of healthy children, parents in the PDDs group reported impairment in physical activity (p = 0.0001) and social relationships (p = 0.0001) and worse overall perception of their QOL (p = 0.0001) and health (p = 0.005). Scores in the physical (p = 0.0001), psychological (p = 0.0001) and social relationships domains (p = 0.0001) and in the physical (p = 0.0001) and social relationships (p = 0.0001) domains were lower compared to the MR group CP group respectively. Little differences were observed between MR, CP and control groups. The level of impairment of physical (p = 0.001) and psychological (p = 0.03) well-being were higher in mothers than in fathers in the PDDs and CP groups respectively; in the other groups, and across all the other domains of QQL impairment was similar. There were no statistically significant differences in the scores between the AD, HFA/AS and PDD-NOS sub-groups, but parents in the HFA/AS sub-group seemed to display a lower QOL compared to the AD sub-group. CONCLUSION: Parents of children with PDDs seem to display a higher burden, probably for a combination of environmental and genetic factors. Within this group of parents also those of HFA or AS people have higher stress. These finding must be taken into account in policy making to provide better and more specific supports and interventions for this group of diseases. (+info)
Mitochondrial myopathy associated with a novel mutation in mtDNA.
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A 6-year-old boy had progressive muscle weakness since age 4 and emotional problems diagnosed as Asperger syndrome. His mother and two older siblings are in good health and there is no family history of neuromuscular disorders. Muscle biopsy showed ragged-red and cytochrome coxidase (COX)-negative fibers. Respiratory chain activities were reduced for all enzymes containing mtDNA-encoded subunits, especially COX. Sequence analysis of the 22 tRNA genes revealed a novel G10406A base substitution, which was heteroplasmic in multiple tissues of the patient by RFLP analysis (muscle, 96%; urinary sediment, 94%; cheek mucosa, 36%; blood, 29%). The mutation was not detected in any accessible tissues from his mother or siblings. It appears that this mutation arose de novo in the proband, probably early in embryogenesis. (+info)
Improving written language performance of adolescents with Asperger syndrome.
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The effects of a multicomponent intervention involving self-regulated strategy development delivered via video self-modeling on the written language performance of 3 students with Asperger syndrome were examined. During intervention sessions, each student watched a video of himself performing strategies for increasing the number of words written and the number of functional essay elements. He then wrote a persuasive essay. The number of words written and number of functional essay elements included in each essay were measured. Each student demonstrated gains in the number of words written and number of functional essay elements. Maintenance of treatment effects at follow-up varied across targets and participants. Implications for future research are suggested. (+info)
Abnormal adaptive face-coding mechanisms in children with autism spectrum disorder.
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In low-level vision, exquisite sensitivity to variation in luminance is achieved by adaptive mechanisms that adjust neural sensitivity to the prevailing luminance level. In high-level vision, adaptive mechanisms contribute to our remarkable ability to distinguish thousands of similar faces [1]. A clear example of this sort of adaptive coding is the face-identity aftereffect [2, 3, 4, 5], in which adaptation to a particular face biases perception toward the opposite identity. Here we investigated face adaptation in children with autism spectrum disorder (ASD) by asking them to discriminate between two face identities, with and without prior adaptation to opposite-identity faces. The ASD group discriminated the identities with the same precision as did the age- and ability-matched control group, showing that face identification per se was unimpaired. However, children with ASD showed significantly less adaptation than did their typical peers, with the amount of adaptation correlating significantly with current symptomatology, and face aftereffects of children with elevated symptoms only one third those of controls. These results show that although children with ASD can learn a simple discrimination between two identities, adaptive face-coding mechanisms are severely compromised, offering a new explanation for previously reported face-perception difficulties [6, 7, 8] and possibly for some of the core social deficits in ASD [9, 10]. (+info)
Affective neuroscience and psychiatry.
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Affective neuroscience addresses the brain mechanisms underlying emotional behaviour. In psychiatry, affective neuroscience finds application not only in understanding the neurobiology of mood disorders, but also by providing a framework for understanding the neural control of interpersonal and social behaviour and processes that underlie psychopathology. By providing a coherent conceptual framework, affective neuroscience is increasingly able to provide a mechanistic explanatory understanding of current therapies and is driving the development of novel therapeutic approaches. (+info)
Women with autistic-spectrum disorder: magnetic resonance imaging study of brain anatomy.
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BACKGROUND: Our understanding of anatomical differences in people with autistic-spectrum disorder, is based on mixed-gender or male samples. AIMS: To study regional grey-matter and white-matter differences in the brains of women with autistic-spectrum disorder. METHOD: We compared the brain anatomy of 14 adult women with autistic-spectrum disorder with 19 controls using volumetric magnetic resonance imaging and voxel-based morphometry. RESULTS: Women with autistic-spectrum disorder had a smaller density bilaterally of grey matter in the fronto-temporal cortices and limbic system, and of white matter in the temporallobes (anterior) and pons. In contrast, they had a larger white-matter density bilaterally in regions of the association and projection fibres of the frontal, parietal, posterior temporal and occipital lobes, in the commissural fibres of the corpus callosum (splenium) and cerebellum (anterior lobe). Further, we found a negative relationship between reduced grey-matter density in right limbic regions and social communication ability. CONCLUSIONS: Women with autistic-spectrum disorder have significant differences in brain anatomy from controls, in brain regions previously reported as abnormal in adult men with the disorder. Some anatomical differences may be related to clinical symptoms. (+info)
Proton MR spectroscopy: higher right anterior cingulate N-acetylaspartate/choline ratio in Asperger syndrome compared with healthy controls.
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BACKGROUND AND PURPOSE: One former study reported higher prefrontal N-acetylaspartate (NAA) levels in patients with Asperger syndrome (AS). The objective of the current study was to test the hypothesis that patients with AS would have higher dorsolateral prefrontal and anterior cingulate cortex NAA/creatine (Cr) and that NAA/Cr would be correlated with symptom severity. MATERIALS AND METHODS: NAA/choline (Cho), NAA/Cr, and Cho/Cr values revealed by (1)H-MR spectroscopy in 14 right-handed male patients with AS (6 medicated with risperidone), 17-38 years of age, diagnosed by the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria were compared with those of 21 right-handed male controls frequency-matched by age and intelligence quotient scores. RESULTS: Patients with AS had significantly higher anterior cingulate NAA/Cho levels (z = -2.18, P = .028); there was a statistical trend for higher anterior cingulate NAA/Cr (z = -1.81, P = .069) that was significant when only the unmedicated patients with AS were taken into account (z = -1.95, P = .050). There were no significant differences in dorsolateral prefrontal MR spectroscopy values. CONCLUSIONS: Our findings show that individuals with AS had higher NAA/Cho levels in the right anterior cingulate compared with healthy controls and that higher anterior cingulate NAA/Cho levels were correlated with higher Yale-Brown Obsessive Compulsive Scale total scores. (+info)