Autism

About: Autism is a research topic. Over the lifetime, 54700 publications have been published within this topic receiving 2039777 citations. The topic is also known as: autistic disorder & autistic disorder of childhood onset.

Methyl‐CpG‐binding protein 2 polymorphisms and vulnerability to autism

Abstract: Autism is a neurodevelopmental disorder characterized by social and communication impairments, coupled with stereotyped and repetitive behaviours. It is far more common in males (4–10:1 male:female ratio; Folstein & Rosen-Sheidley 2001). Linkage studies have provided only weak evidence for the involvement of X-linked loci but have limited power to detect those of small effect size (Freitag 2007). Gauthier et al. (2006) have provided some evidence for the involvement of a locus at Xq27-q28 in the disorder employing both linkage and association, and rare mutations in X-linked genes such as neuroligin 3 (NLGN3) and neuroligin 4 (NLGN4) have also been reported to be associated with autism (Jamain et al. 2003). Rett syndrome (RTT) is an X-linked neurodevelopmental disorder, with a prevalence of around 1 per 10 000–15 000 (Hagberg 1985; Hagberg & Hagberg 1997; Leonard et al. 1997). Many symptoms, including impaired language, stereotypic behaviours, high frequency of seizures and sleep abnormalities as well as the developmental timing are common to both RTT and autism. Indeed, misdiagnosis of RTT individuals as autistic can occur (Abdul-Rahman & Hudgins 2006; Moretti et al. 2005). Both disorders are grouped under the heading of pervasive developmental disorders (PDD) in Diagnostic and Statistical Manual of Disorders-IV (DSM-IV). The MECP2 gene (Xq28) encodes the methyl-CpG-binding protein 2 (MECP2), and mutations in the gene are reported to be responsible for around 75% of cases of classical RTT. Methyl-CpG-binding protein 2 protein binds to methylated CpGs and is believed to repress the transcription of downstream genes, e.g. Bdnf in mice (Chen et al. 2003; Lewis et al. 1992; Meehan et al. 1992; Moretti & Zoghbi 2006); however, there is evidence that the situation is more complex with opposite directions of regulation existing in different tissues (LaSalle 2007). MECP2 comprises four exons, with the coding sequence shared among exons 2, 3 and 4 and a highly conserved 3′ untranslated region (UTR) of 8.5 kb (Coy et al. 1999). Both increases and decreases in MECP2 expression have been implicated in a range of PDDs including autism suggesting that a common pathway may be involved in these disorders (Samaco et al. 2004, 2005; Van Esch et al. 2005). Although they are rare, mutations in the coding region of MECP2 have been observed in autistic individuals (Beyer et al. 2002; Carney et al. 2003; Lam et al. 2000; Lobo-Menendez et al. 2003; Vourc’h et al. 2001). Other studies by Shibayama et al. (2004) detected one missense and two 3′ UTR variants in 24 autism patients vs. only one missense mutation in 144 ethnically matched individuals without autism. Recently, Liu and Francke (2006) showed that certain sequence motifs, distributed over a distance of 130 kb in and around the MECP2 gene, make up a ‘functional expression module’ containing enhancers and silencers. These interact with the MECP2 promoter and affect the tissue-specific, developmental stage-specific or splice-variant-specific control of MECP2 protein expression. Thus, variations throughout the coding and non-coding regions of the MECP2 gene, as well as flanking regions, could be important factors contributing to the complex disorder of autism. This study was designed to investigate a series of polymorphic variants in the MECP2 gene, including flanking and intronic regions, as potential markers for the disorder by transmission disequilibrium tests (TDTs) in two series of autistic families.

Neuroimaging in Child and Adolescent Neuropsychiatric Disorders

Abstract: Objective To review the major findings and pathophysiological implications of imaging studies of neuropsychiatric disorders that onset in childhood or adolescence. Method More than 200 neuroimaging studies were selected for review from Medline searches if the studies concerned developmental neuropsychiatric disorders such as autism, fragile X syndrome, Down syndrome, schizophrenia, obsessive-compulsive disorder, Tourette's syndrome, attention-deficit hyperactivity disorder, and dyslexia. Results Disordered central nervous system development may produce evidence of cortical neuronal migration abnormalities in autism, smaller cortical structures in Down syndrome, frontal lobe deficits and larger basal ganglia in schizophrenia, hypoplastic basal ganglia in Tourette's syndrome, aberrancies of the planum temporale in dyslexia, and hypoplastic cerebellar structures in numerous developmental disorders. Normal cerebral asymmetries appear to be disrupted in a number of disorders, including schizophrenia, Tourette's syndrome, attention deficit disorder, and dyslexia. Conclusions Neuroimaging data regarding pathological central nervous system development in childhood are still sparse, and many of the findings in developmental disorders of childhood onset concern the study of adult subjects with those disorders. Nevertheless, imaging modalities previously used only in adults are with increasing frequency being applied to the study of children, which will likely continue to contribute to the understanding of pathological brain structure and function throughout childhood and to the improved treatment of these disorders.

Autism: Two-way Interplay between Research and Clinical Work

Abstract: The two-way interplay between research and clinical practice in relation to autism is reviewed with respect to: (1) diagnosis and syndrome delineation; (2) the nature of the disorder; (3) intervention studies; and (4) aetiology, as manifest during four time periods; (a) the 1950s and 1960s; (b) the 1970s into the mid 1980s; (c) the late 1980s and early 1990s; and (d) the late 1990s. It is concluded that clinical practice has changed out of all recognition during the last 50 years and that research findings have been crucial in bringing about that change. It has not, however, been a one-way traffic. Many key advances were prompted by astute clinical observations and some extravagant research claims were given a more balanced perspective through the light of clinical experience. Crucial research and clinical tasks remain but the means to meet them are there if the opportunities are taken and attention is paid to the lessons of the past.

Brief Report: Perceptual Load and the Autism Spectrum in Typically Developed Individuals.

Abstract: A fundamental task of the cognitive system is to prioritize behaviourally relevant sensory inputs for processing at the expense of irrelevant inputs. In a study of neurotypical participants (n = 179), we utilized a brief flanker interference task while varying the perceptual load of the visual display. Typically, increasing perceptual load (i.e., with greater numbers of search items) reduces interference from a competing peripheral distractor. We show that individuals who score above average on the Autism Spectrum Quotient (AQ) show stronger interference at high perceptual load than individuals with below-average AQ scores. This is consistent with recent findings in individuals with autism spectrum conditions, and supports the idea that the cognitive style of the autistic brain is reflected in a broader phenotype across the population.