1. Aziz A, Harrop SP, Bishop NE. {{DIA1R Is an X-Linked Gene Related to Deleted In Autism-1}}. {PLoS One};2011;6(1):e14534.
BACKGROUND: AUTISM SPECTRUM DISORDERS (ASDS) ARE FREQUENTLY OCCURRING DISORDERS DIAGNOSED BY DEFICITS IN THREE CORE FUNCTIONAL AREAS: social skills, communication, and behaviours and/or interests. Mental retardation frequently accompanies the most severe forms of ASDs, while overall ASDs are more commonly diagnosed in males. Most ASDs have a genetic origin and one gene recently implicated in the etiology of autism is the Deleted-In-Autism-1 (DIA1) gene. METHODOLOGY/PRINCIPAL FINDINGS: Using a bioinformatics-based approach, we have identified a human gene closely related to DIA1, we term DIA1R (DIA1-Related). While DIA1 is autosomal (chromosome 3, position 3q24), DIA1R localizes to the X chromosome at position Xp11.3 and is known to escape X-inactivation. The gene products are of similar size, with DIA1 encoding 430, and DIA1R 433, residues. At the amino acid level, DIA1 and DIA1R are 62% similar overall (28% identical), and both encode signal peptides for targeting to the secretory pathway. Both genes are ubiquitously expressed, including in fetal and adult brain tissue. CONCLUSIONS/SIGNIFICANCE: Examination of published literature revealed point mutations in DIA1R are associated with X-linked mental retardation (XLMR) and DIA1R deletion is associated with syndromes with ASD-like traits and/or XLMR. Together, these results support a model where the DIA1 and DIA1R gene products regulate molecular traffic through the cellular secretory pathway or affect the function of secreted factors, and functional deficits cause disorders with ASD-like symptoms and/or mental retardation.
2. Reed P, Clark C. {{Impact of intervening learning on resurgence in humans with Autism Spectrum Disorders}}. {Learn Behav};2010 (Dec 29)
In the present study, we investigated the degree to which responding would resurge in children diagnosed with Autism Spectrum Disorders (ASD) following an intervening training period comprising different schedules of reinforcement. Twenty-four children of the ages 7-15, with a diagnosis of an ASD, were taught a play a sequence on a variable ratio- (VR) 3 schedule of reinforcement, during a 30-min session. The play sequence was then extinguished before the participants were taught a second play sequence, using a VR-4 schedule for 30 min, a VR-4 schedule for 60 min, or a VR-2 schedule for 30 min. A 5-min extinction session was then conducted to determine the impact that the intervening schedules had on the resurgence of the original behavior. The original sequence resurged to a greater extent for Group VR-4 30 min than it did for the other two groups. The results provide evidence that the length of time between initial training and testing is not a prime determinant of the level of resurgence, but that the amount of conditioning may play a stronger role: The greater the number of reinforcers received, the smaller the resurgence effect.
3. Reichelt AC, Rodgers RJ, Clapcote SJ. {{The role of neurexins in schizophrenia and autistic spectrum disorder}}. {Neuropharmacology};2011 (Jan 21)
Schizophrenia and autistic spectrum disorder (ASD) are common, chronic mental conditions with both genetic and environmental components to their aetiology. The identification of genes influencing susceptibility to these disorders offers a rational route towards a clearer understanding of the neurobiology, and with this the prospect of treatment and prevention strategies tailored towards the remediation of the altered pathways. Copy number variants (CNVs) underlie many serious illnesses, including neurological and neurodevelopmental syndromes. Recent studies assessing copy number variation in ASD and schizophrenia have repeatedly observed heterozygous deletions eliminating exons of the neurexin-1alpha gene (but not the neurexin-1beta gene) in patients with ASD and schizophrenia. The neurexins are synaptic adhesion proteins that are known to play a key role in synaptic formation and maintenance. The functional significance of the recurrent deletion is poorly understood, but the availability of mice with deletion of the promoter and first exon of neurexin-1alpha provides direct access to the biological effects of neurexin-1alpha disruption on phenotypes relevant to ASD and schizophrenia. We review the evidence for the role of neurexin-1alpha in schizophrenia and ASD, and consider how genetic disruption of neurexin-1alpha may underpin the neuropathology contributing to these distinct neurodevelopmental disorders.
4. Rossignol DA, Frye RE. {{Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis}}. {Mol Psychiatry};2011 (Jan 25)
A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population ( approximately 0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD.Molecular Psychiatry advance online publication, 25 January 2011; doi:10.1038/mp.2010.136.
5. Windham GC, Anderson MC, Croen LA, Smith KS, Collins J, Grether JK. {{Birth Prevalence of Autism Spectrum Disorders in the San Francisco Bay Area by Demographic and Ascertainment Source Characteristics}}. {J Autism Dev Disord};2010 (Dec 14)
Using standardized methods for multi-source surveillance, we calculated the prevalence of autism spectrum disorders (ASD) among children born in a racially diverse region in 1994 or 1996 as 4.7/1000 live births. Children with ASD before age 9 were identified through chart abstraction at health-related sources; three-quarters were being served by the state-wide Department of Developmental Services. In adjusted models, we found a male:female ratio of 6:1, a doubling of ASD prevalence among children of older mothers (40+), and lower prevalence with lower paternal education. Children of Black or Hispanic mothers had lower prevalence than those of White, non-Hispanic mothers, but these differences were attenuated after adjustment. Prevalence in children of Asian mothers was similar to Whites. Potential under-counting is discussed.
