1. Becker KG. {{Autism, immune dysfunction and Vitamin D}}. {Acta Psychiatr Scand};2011 (Mar 13)
2. Corrigan NM, Shaw DW, Richards TL, Estes AM, Friedman SD, Petropoulos H, Artru AA, Dager SR. {{Proton Magnetic Resonance Spectroscopy and MRI Reveal No Evidence for Brain Mitochondrial Dysfunction in Children with Autism Spectrum Disorder}}. {J Autism Dev Disord};2011 (Mar 15)
Brain mitochondrial dysfunction has been proposed as an etiologic factor in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopic imaging ((1)HMRS) and MRI were used to assess for evidence of brain mitochondrial dysfunction in longitudinal samples of children with ASD or developmental delay (DD), and cross-sectionally in typically developing (TD) children at 3-4, 6-7 and 9-10 years-of-age. A total of 239 studies from 130 unique participants (54ASD, 22DD, 54TD) were acquired. (1)HMRS and MRI revealed no evidence for brain mitochondrial dysfunction in the children with ASD. Findings do not support a substantive role for brain mitochondrial abnormalities in the etiology or symptom expression of ASD, nor the widespread use of hyperbaric oxygen treatment that has been advocated on the basis of this proposed relationship.
3. Froehlich W. {{Making a Case to Continue Considering Treatment with Selective Serotonin Reuptake Inhibitors for Children with Autism Spectrum Disorders}}. {Curr Psychiatry Rep};2011 (Mar 15)
4. Lokhandwala T, Khanna R, West-Strum D. {{Hospitalization Burden Among Individuals with Autism}}. {J Autism Dev Disord};2011 (Mar 15)
The objective of this study was to assess the inpatient care burden among individuals with autism using the 2007 Health Care Utilization Project Nationwide Inpatient Sample [HCUP-NIS]). There were ~26,000 hospitalizations among individuals with autism in 2007, with an overall rate of 65.6/100,000 admissions. Rates of hospitalizations were the highest among individuals with autism aged 10-20 years, males, having household income >$63,000, and with private insurance, respectively. In terms of hospital characteristics, rates were the highest in hospitals in large urban areas, located in the Northeast region, and with teaching status, respectively. Individuals with autism had significantly higher LOS (6.5 vs. 4.2; p < 0.0001) and total charges ($24,862 vs. $23,225; p < 0.0001) as compared to those without autism.
5. Meehan TF, Carr CJ, Jay JJ, Bult CJ, Chesler EJ, Blake JA. {{Autism Candidate Genes via Mouse Phenomics}}. {J Biomed Inform};2011 (Mar 10)
Autism spectrum disorders (ASD) represent a group of developmental disabilities with a strong genetic basis. The laboratory mouse is increasingly used as a model organism for ASD, and MGI, the Mouse Genome Informatics resource, is the primary model organism database for the laboratory mouse. MGI uses the Mammalian Phenotype (MP) ontology to describe mouse models of human diseases. Using bioinformatics tools including Phenologs, MouseNET, and the Ontological Discovery Environment, we tested data associated with MP terms to characterize new gene-phenotype associations related to ASD. Our integrative analysis using these tools identified numerous mouse genotypes that are likely to have previously uncharacterized autistic-like phenotypes. The genes implicated in these mouse models had considerable overlap with a set of over 300 genes recently associated with ASD due to small, rare copy number variation (Pinto D. et al, 2010). Prediction and characterization of autistic mutant mouse alleles assists researchers in studying the complex nature of ASD and provides a generalizable approach to candidate gene prioritization.
6. Numis AL, Major P, Montenegro MA, Muzykewicz DA, Pulsifer MB, Thiele EA. {{Identification of risk factors for autism spectrum disorders in tuberous sclerosis complex}}. {Neurology};2011 (Mar 15);76(11):981-987.
OBJECTIVE: The purpose of this study was to assess the prevalence of and to identify epidemiologic, genetic, electrophysiologic, and neuroanatomic risk factors for autism spectrum disorders (ASD) in a cohort of patients with tuberous sclerosis complex (TSC). METHODS: A total of 103 patients with TSC were evaluated for ASD. A retrospective review of patients’ records was performed, including mutational analysis. EEG reports were analyzed for the presence of ictal and interictal epileptiform features. Brain MRI scans were evaluated for TSC neuropathology, including tuber burden. RESULTS: Of the 103 patients with TSC, 40%were diagnosed with an ASD. On univariate analysis, patients with ASD were less likely to have mutations in the TSC1 gene. Patients with ASD also had an earlier age at seizure onset and more frequent seizures. On EEG, those with ASD had a significantly greater amount of interictal epileptiform features in the left temporal lobe only. On MRI, there were no differences in the regional distribution of tuber burden, although those with TSC2 and ASD had a higher prevalence of cyst-like tubers. CONCLUSIONS: The development of ASD in TSC is not well understood. Given our findings, ASD may be associated with persistent seizure activity early in development in particular brain regions, such as those responsible for social perception and communication in the left temporal lobe. The presence of cyst-like tubers on MRI could provide a structural basis or marker for ASD pathology in TSC, although studies assessing their effect on cortical function are needed.
7. Reichow B. {{Overview of Meta-Analyses on Early Intensive Behavioral Intervention for Young Children with Autism Spectrum Disorders}}. {J Autism Dev Disord};2011 (Mar 15)
This paper presents an overview of 5 meta-analyses of early intensive behavioral intervention (EIBI) for young children with autism spectrum disorders (ASDs) published in 2009 and 2010. There were many differences between meta-analyses, leading to different estimates of effect and overall conclusions. The weighted mean effect sizes across meta-analyses for IQ and adaptive behavior ranged from g = .38-1.19 and g = .30-1.09, respectively. Four of five meta-analyses concluded EIBI was an effective intervention strategy for many children with ASDs. A discussion highlighting potential confounds and limitations of the meta-analyses leading to these discrepancies and conclusions about the efficacy of EIBI as an intervention for young children with ASDs are provided.
8. Ricciardi S, Boggio EM, Grosso S, Lonetti G, Forlani G, Stefanelli G, Calcagno E, Morello N, Landsberger N, Biffo S, Pizzorusso T, Giustetto M, Broccoli V. {{Reduced AKT/mTOR signaling and protein synthesis dysregulation in a Rett syndrome animal model}}. {Hum Mol Genet};2011 (Mar 15);20(6):1182-1196.
Rett syndrome (RTT) is a neurodevelopmental disorder with no efficient treatment that is caused in the majority of cases by mutations in the gene methyl-CpG binding-protein 2 (MECP2). RTT becomes manifest after a period of apparently normal development and causes growth deceleration, severe psychomotor impairment and mental retardation. Effective animal models for RTT are available and show morphofunctional abnormalities of synaptic connectivity. However, the molecular consequences of MeCP2 disruption leading to neuronal and synaptic alterations are not known. Protein synthesis regulation via the mammalian target of the rapamycin (mTOR) pathway is crucial for synaptic organization, and its disruption is involved in a number of neurodevelopmental diseases. We investigated the phosphorylation of the ribosomal protein (rp) S6, whose activation is highly dependent from mTOR activity. Immunohistochemistry showed that rpS6 phosphorylation is severely affected in neurons across the cortical areas of Mecp2 mutants and that this alteration precedes the severe symptomatic phase of the disease. Moreover, we found a severe defect of the initiation of protein synthesis in the brain of presymptomatic Mecp2 mutant that was not restricted to a specific subset of transcripts. Finally, we provide evidence for a general dysfunction of the Akt/mTOR, but not extracellular-regulated kinase, signaling associated with the disease progression in mutant brains. Our results indicate that defects in the AKT/mTOR pathway are responsible for the altered translational control in Mecp2 mutant neurons and disclosed a novel putative biomarker of the pathological process. Importantly, this study provides a novel context of therapeutic interventions that can be designed to successfully restrain or ameliorate the development of RTT.
9. Ruta L, Ingudomnukul E, Taylor K, Chakrabarti B, Baron-Cohen S. {{Increased serum androstenedione in adults with autism spectrum conditions}}. {Psychoneuroendocrinology};2011 (Mar 11)
Molecular and behavioural evidence points to an association between sex-steroid hormones and autism spectrum conditions (ASC) and/or autistic traits. Prenatal androgen levels are associated with autistic traits, and several genes involved in steroidogenesis are associated with autism, Asperger Syndrome and/or autistic traits. Furthermore, higher rates of androgen-related conditions (such as Polycystic Ovary Syndrome, hirsutism, acne and hormone-related cancers) are reported in women with autism spectrum conditions. A key question therefore is if serum levels of gonadal and adrenal sex-steroids (particularly testosterone, estradiol, dehydroepiandrosterone sulfate and androstenedione) are elevated in individuals with ASC. This was tested in a total sample of n=166 participants. The final eligible sample for hormone analysis comprised n=128 participants, n=58 of whom had a diagnosis of Asperger Syndrome or high functioning autism (33 males and 25 females) and n=70 of whom were age- and IQ-matched typical controls (39 males and 31 females). ASC diagnosis (without any interaction with sex) strongly predicted androstenedione levels (p<0.01), and serum androstenedione levels were significantly elevated in the ASC group (Mann-Whitney W=2677, p=0.002), a result confirmed by permutation testing in females (permutation-corrected p=0.02). This result is discussed in terms of androstenedione being the immediate precursor of, and being converted into, testosterone, dihydrotestosterone, or estrogens in hormone-sensitive tissues and organs.
10. Semrud-Clikeman M, Fine J. {{Presence of Cysts on Magnetic Resonance Images (MRIs) in Children With Asperger Disorder and Nonverbal Learning Disabilities}}. {J Child Neurol};2011 (Mar 11)
The main purpose of this study was to report the existence of previously unidentified brain cysts or lesions in children with nonverbal learning disabilities, Asperger syndrome, or controls. The authors compared the incidence of cysts or lesions on magnetic resonance images (MRIs) in 28 children with nonverbal learning disability, 26 children with Asperger syndrome, and 24 typical controls for abnormalities. In this study, the authors found 25% of children previously diagnosed with nonverbal learning disability to have unsuspected brain abnormalities generally including cysts or lesions in the occipital region, compared with approximately 4% in the Asperger syndrome or control group. The cysts/lesions were found mainly in the occipital lobe, an area responsible for visual/spatial reasoning. It is appropriate to speculate that there might be a connection between anomalous brain development and skill differences among these groups.
