1. Balestrieri E, Arpino C, Matteucci C, Sorrentino R, Pica F, Alessandrelli R, Coniglio A, Curatolo P, Rezza G, Macciardi F, Garaci E, Gaudi S, Sinibaldi-Vallebona P. {{HERVs Expression in Autism Spectrum Disorders}}. {PLoS One}. 2012; 7(11): e48831.
BACKGROUND: Autistic Spectrum Disorder (ASD) is a heterogeneous neurodevelopmental disorder, resulting from complex interactions among genetic, genomic and environmental factors. Here we have studied the expression of Human Endogenous Retroviruses (HERVs), non-coding DNA elements with potential regulatory functions, and have tested their possible implication in autism. METHODS: The presence of retroviral mRNAs from four HERV families (E, H, K and W), widely implicated in complex diseases, was evaluated in peripheral blood mononuclear cells (PBMCs) from ASD patients and healthy controls (HCs) by qualitative RT-PCR. We also analyzed the expression of the env sequence from HERV-H, HERV-W and HERV-K families in PBMCs at the time of sampling and after stimulation in culture, in both ASD and HC groups, by quantitative Real-time PCR. Differences between groups were evaluated using statistical methods. RESULTS: The percentage of HERV-H and HERV-W positive samples was higher among ASD patients compared to HCs, while HERV-K was similarly represented and HERV-E virtually absent in both groups. The quantitative evaluation shows that HERV-H and HERV-W are differentially expressed in the two groups, with HERV-H being more abundantly expressed and, conversely, HERV-W, having lower abundance, in PBMCs from ASDs compared to healthy controls. PMBCs from ASDs also showed an increased potential to up-regulate HERV-H expression upon stimulation in culture, unlike HCs. Furthermore we report a negative correlation between expression levels of HERV-H and age among ASD patients and a statistically significant higher expression in ASD patients with Severe score in Communication and Motor Psychoeducational Profile-3. CONCLUSIONS: Specific HERV families have a distinctive expression profile in ASD patients compared to HCs. We propose that HERV-H expression be explored in larger samples of individuals with autism spectrum in order to determine its utility as a novel biological trait of this complex disorder.
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2. Jones RM, Lord C. {{Diagnosing autism in neurobiological research studies}}. {Behav Brain Res}. 2012.
Autism Spectrum Disorder (ASD) is by definition a complex and heterogeneous disorder. Variation in factors such as developmental level, language ability and IQ further complicate the presentation of symptoms. Clinical research and basic science must continue to inform each other’s questions to help address the heterogeneity inherent to the disorder. This review uses a clinical perspective to outline the common tools and best practices for diagnosing and characterizing ASD in a research setting. We discuss considerations for classifying research populations, including language ability and IQ and examine the advantages and disadvantages of different psychometric measurements. Ultimately, the contribution of multiple sources of data representing different perspectives is crucial for interpreting and understanding the ASD phenotype.
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3. Nuytens K, Gantois I, Stijnen P, Iscru E, Laeremans A, Serneels L, Van Eylen L, Liebhaber SA, Devriendt K, Balschun D, Arckens L, Creemers JW, D’Hooge R. {{Haploinsufficiency of the autism candidate gene Neurobeachin induces autism-like behaviors and affects cellular and molecular processes of synaptic plasticity in mice}}. {Neurobiol Dis}. 2012.
Neurobeachin (NBEA), a brain-enriched multidomain scaffolding protein involved in neurotransmitter release and synaptic functioning, has been identified as a candidate gene for autism spectrum disorder (ASD) in four unrelated patients haploinsufficient for NBEA. The aim of this study was to map the behavioral phenotype of Nbea(+/-) mice in order to understand its contribution to the pathogenesis of ASD. ASD-like behavioral variables of Nbea(+/-) mice were related to basal neuronal activity in different brain regions by in situ hybridizations and extracellular field recordings of synaptic plasticity in hippocampal cornu ammonis 1 (CA1) region. Levels of BDNF and phosphorylated cAMP response element-binding protein (CREB) were measured in an attempt to investigate putatively underlying changes in these neuromolecules. Nbea(+/-) mice exhibit several ASD-like features, including changes in self-grooming behavior, social behaviors, conditioned fear responses, and spatial learning and memory, which coincided with enhanced long-term potentiation (LTP) in their CA1 region. The observed alterations in learning and memory and hippocampal LTP are concomitant with decreased expression of the immediate early gene zif268 in dorsomedial stratiatum and hippocampal CA1 region, increased CREB phosphorylation, and increased hippocampal BDNF expression. These findings indicate that Nbea haploinsufficiency leads to various molecular and cellular changes that affect neuroplasticity and behavioral functions in mice, and could thus underlie the ASD symptomatology in NBEA deficient humans.
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4. Vorstman JA, Breetvelt EJ, Thode KI, Chow EW, Bassett AS. {{Expression of autism spectrum and schizophrenia in patients with a 22q11.2 deletion}}. {Schizophr Res}. 2012.
BACKGROUND: Copy number variants (CNVs) associated with neuropsychiatric disorders are increasingly being identified. While the initial reports were relatively specific, i.e. implicating vulnerability for a particular neuropsychiatric disorder, subsequent studies suggested that most of these CNVs can increase the risk for more than one neuropsychiatric disorder. Possibly, the different neuropsychiatric phenotypes associated with a single genetic variant are really distinct phenomena, indicating pleiotropy. Alternatively, seemingly different disorders could represent the same phenotype observed at different developmental stages or the same underlying pathogenesis with different phenotypic expressions. AIMS: To examine the relation between autism and schizophrenia in patients sharing the same CNV. METHOD: We interviewed parents of 78 adult patients with the 22q11.2 deletion (22q11.2DS) to examine if autistic symptoms during childhood were associated with psychosis in adulthood. We used Chi-square, T-tests and logistic regression while entering cognitive level, gender and age as covariates. RESULTS: The subgroup of 22q11.2DS patients with probable ASD during childhood did not show an increased risk for psychosis in adulthood. The average SRS scores were highly similar between those with and those without schizophrenia. CONCLUSIONS: ASD and schizophrenia associated with 22q11.2DS should be regarded as two unrelated, distinct phenotypic manifestations, consistent with true neuropsychiatric pleiotropy. 22q11.2DS can serve as a model to examine the mechanisms associated with neuropsychiatric pleiotropy associated with other CNVs.
