1. Kaat AJ, Gadow KD, Lecavalier L. {{Psychiatric Symptom Impairment in Children with Autism Spectrum Disorders}}. {J Abnorm Child Psychol};2013 (Apr 20)
The general aim of this study was to examine the relation of psychiatric symptom-induced impairment with other common parameters of mental health in children with autism spectrum disorder (ASD). Prevalence rates are used to illustrate the implications of different criteria for caseness. Parents/teachers completed DSM-IV-referenced rating scales for 6-12 year old children with ASD (N = 115), the majority of whom were boys (86 %). Most children were rated by parents (81 %) or teachers (86 %) as being socially or academically impaired by symptoms of at least one psychiatric disorder. The most common impairing conditions (parent/teacher) were attention-deficit/hyperactivity disorder (67 %/71 %), oppositional defiant disorder (35 %/33 %), and anxiety disorder (47 %/34 %), and the combined rates based on either informant were generally much higher. Agreement between symptom cutoff and impairment cutoff was acceptable for most disorders. A larger percentage of youth were impaired by psychiatric symptoms than met symptom cutoff criteria, and the discrepancy between impairment cutoff and clinical cutoff (impairment cutoff plus symptom cutoff) was even greater. Impairment was moderately to highly correlated with both number and severity of symptoms. Parents’ and teachers’ ratings indicated little agreement as to whether a child was impaired. Findings for youth with ASD were similar to non ASD child psychiatry outpatient referrals, but clearly different in several ways from comparable studies of community-based samples.
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2. Li W, Pozzo-Miller L. {{BDNF deregulation in Rett syndrome}}. {Neuropharmacology};2013 (Apr 15)
BDNF is the best-characterized neurotrophin in terms of its gene structure and modulation, secretion processing, and signaling cascades following its release. In addition to diverse features at the genetic and molecular levels, the abundant expression in several regions of the central nervous system has implicated BDNF as a potent modulator in many aspects of neuronal development, as well as synaptic transmission and plasticity. Impairments in any of these critical functions likely contribute to a wide array of neurodevelopmental, neurodegenerative, and neuropsychiatric diseases. In this review, we focus on a prevalent neurodevelopmental disorder, Rett syndrome (RTT), which afflicts 1:15,000 women world-wide. We describe the consequences of loss-of-function mutations in the gene encoding the transcription factor methyl-CpG binding protein 2 (MeCP2) in RTT, and then elaborate on the current understanding of how MeCP2 controls BDNF expression. Finally, we discuss the literature regarding alterations in BDNF levels in RTT individuals and MeCP2-based mouse models, as well as recent progress in searching for rational therapeutic interventions.
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3. Shi L, Zhang X, Golhar R, Otieno FG, He M, Hou C, Kim C, Keating B, Lyon GJ, Wang K, Hakonarson H. {{Whole-genome sequencing in an autism multiplex family}}. {Mol Autism};2013 (Apr 18);4(1):8.
BACKGROUND: Autism spectrum disorders (ASDs) represent a group of childhood neurodevelopmental disorders that affect 1 in 88 children in the US. Previous exome sequencing studies on family trios have implicated a role for rare, de-novo mutations in the pathogenesis of autism. METHODS: To examine the utility of whole-genome sequencing to identify inherited disease candidate variants and genes, we sequenced two probands from a large pedigree, including two parents and eight children. We evaluated multiple analytical strategies to identify a prioritized list of candidate genes. RESULTS: By assuming a recessive model of inheritance, we identified seven candidate genes shared by the two probands. We also evaluated a different analytical strategy that does not require the assumption of disease model, and identified a list of 59 candidate variants that may increase susceptibility to autism. Manual examination of this list identified ANK3 as the most likely candidate gene. Finally, we identified 33 prioritized non-coding variants such as those near SMG6 and COQ5, based on evolutionary constraint and experimental evidence from ENCODE. Although we were unable to confirm rigorously whether any of these genes indeed contribute to the disease, our analysis provides a prioritized shortlist for further validation studies. CONCLUSIONS: Our study represents one of the first whole-genome sequencing studies in autism leveraging a large family-based pedigree. These results provide for a discussion on the relative merits of finding de-novo mutations in sporadic cases versus finding inherited mutations in large pedigrees, in the context of neuropsychiatric and neurodevelopmental diseases.
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4. Siniscalco D, Antonucci N. {{Possible use of Trichuris suis ova in autism spectrum disorders therapy}}. {Med Hypotheses};2013 (Apr 15)
Autism and autism spectrum disorders (ASDs) are heterogeneous, severe neurodevelopmental pathologies. The main core symptoms are: dysfunctions in social interactions and communication skills, restricted interests, repetitive and stereotypic verbal and non-verbal behaviors. Several biochemical processes are associated with ASDs: oxidative stress; endoplasmic reticulum stress; decreased methylation capacity; limited production of glutathione; mitochondrial dysfunction; intestinal dysbiosis; increased toxic metal burden; immune dysregulation. Current available treatments for ASDs can be divided into behavioral, nutritional and medical approaches, although no defined standard approach exists. Current drugs fail to benefit the ASD core symptoms and can have marked adverse effects, are mainly palliative and only sometimes efficacy in attenuating specific autistic behaviors. Helminthic therapy shows potential for application as anti-inflammatory agent. Several human diseases can be treated by helminths (i.e. inflammatory bowel disease, asthma, multiple sclerosis and autoimmune diabetes). Trichuris suis ova (TSO) show strong immunomodulatory properties. Authors hypothesize that TSO could be useful in addressing ASD immune dysregulations. TSO could be a novel therapeutic option for ASD management.
