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Measuring Sensory Reactivity in Autism Spectrum Disorder: Application and Simplification of a Clinician-Administered Sensory Observation Scale.

August 16, 2016 - 8:43am
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Measuring Sensory Reactivity in Autism Spectrum Disorder: Application and Simplification of a Clinician-Administered Sensory Observation Scale.

J Autism Dev Disord. 2016 Jan;46(1):287-93

Authors: Tavassoli T, Bellesheim K, Siper PM, Wang AT, Halpern D, Gorenstein M, Grodberg D, Kolevzon A, Buxbaum JD

Abstract
Sensory reactivity is a new DSM-5 criterion for autism spectrum disorder (ASD). The current study aims to validate a clinician-administered sensory observation in ASD, the Sensory Processing Scale Assessment (SPS). The SPS and the Short Sensory Profile (SSP) parent-report were used to measure sensory reactivity in children with ASD (n = 35) and typically developing children (n = 27). Sixty-five percent of children with ASD displayed sensory reactivity symptoms on the SPS and 81.1 % on the SSP. SPS scores significantly predicted SSP scores. We next identified the five SPS tasks that best differentiated groups. Our results indicate that a combination of parent-report and at least the five most differentiating observational tasks may be most sensitive in identifying the presence of sensory reactivity issues.

PMID: 26340959 [PubMed - indexed for MEDLINE]

Recent Advances in Understanding and Managing Autism Spectrum Disorders.

August 16, 2016 - 8:43am
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Recent Advances in Understanding and Managing Autism Spectrum Disorders.

J Child Neurol. 2015 Dec;30(14):1887-920

Authors: Germain B, Eppinger MA, Mostofsky SH, DiCicco-Bloom E, Maria BL

Abstract
Autism spectrum disorder in children is a group of neurodevelopmental disorders characterized by difficulties with social communication and behavior. Growing scientific evidence in addition to clinical practice has led the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) to categorize several disorders into the broader category of autism spectrum disorder. As more is learned about how autism spectrum disorder manifests, progress has been made toward better clinical management including earlier diagnosis, care, and when specific interventions are required. The 2014 Neurobiology of Disease in Children symposium, held in conjunction with the 43rd annual meeting of the Child Neurology Society, aimed to (1) describe the clinical concerns involving diagnosis and treatment, (2) review the current status of understanding in the pathogenesis of autism spectrum disorder, (3) discuss clinical management and therapies for autism spectrum disorder, and (4) define future directions of research. The article summarizes the presentations and includes an edited transcript of question-and-answer sessions.

PMID: 26336201 [PubMed - indexed for MEDLINE]

Altered plasma levels of chemokines in autism and their association with social behaviors.

August 12, 2016 - 11:35am

Altered plasma levels of chemokines in autism and their association with social behaviors.

Psychiatry Res. 2016 Aug 2;244:300-305

Authors: Shen Y, Oua J, Liu M, Shi L, Li Y, Xiao L, Dong H, Zhang F, Xia K, Zhao J

Abstract
Autism Spectrum Disorder (ASD) is a group of neurodevelopment disorders with an unclear etiology. Chemokines have been implicated in the etiology and pathogenesis of ASD. The current study investigated the plasma levels of seven chemokines (RANTES, Eotaxin, MIP-1 α, MIP-1 β, MCP-1, IP-10, and MIG) in 42 young autistic patients and 35 age-matched typically developing (TD) children. The study also tested the association between these chemokine levels and social behaviors, as measured by the Social Responsiveness Scale (SRS). Compared to the TD children, RANTES, MIP-1α, and MIP-1β were higher, while IP-10 and MIG were lower in the autistic patients, after correcting for multiple comparisons. Among these seven chemokines, MIP-1α, MIP-1β and IP-10 levels were found to be associated with social behaviors in all the participants. Moreover, MIP-1α and IP-10 were found to be independent predictors of social behaviors. The results of our study support the hypothesis that altered chemokine levels are involved in the pathophysiology of ASD and they indicate that chemokines plasma levels could be potential biomarkers for ASD.

PMID: 27512919 [PubMed - as supplied by publisher]

Support Vector Machine Model of Developmental Brain Gene Expression Data for Prioritization of Autism Risk Gene Candidates.

August 11, 2016 - 11:32am

Support Vector Machine Model of Developmental Brain Gene Expression Data for Prioritization of Autism Risk Gene Candidates.

Bioinformatics. 2016 Aug 9;

Authors: Cogill S, Wang L

Abstract
MOTIVATION: Autism spectrum disorders (ASD) are a group of neurodevelopmental disorders with clinical heterogeneity and a substantial polygenic component. High-throughput methods for ASD risk gene identification produce numerous candidate genes that are time-consuming and expensive to validate. Prioritization methods can identify high-confidence candidates. Previous ASD gene prioritization methods have focused on a priori knowledge, which excludes genes with little functional annotation or no protein product such as long non-coding RNAs (lncRNAs).
RESULTS: We have developed a support vector machine (SVM) model, trained using brain developmental gene expression data, for the classification and prioritization of ASD risk genes. The selected feature model had a mean accuracy of 76.7%, mean specificity of 77.2%, and mean sensitivity of 74.4%. Gene lists comprised of an ASD risk gene and adjacent genes were ranked using the model's decision function output. The known ASD risk genes were ranked on average in the 77.4(th), 78.4(th), and 80.7(th) percentile for sets of 101, 201, and 401 genes respectively. Of 10,840 lncRNA genes, 63 were classified as ASD-associated candidates with a confidence greater than 0.95. Genes previously associated with brain development and neurodevelopmental disorders were prioritized highly within the lncRNA gene list.
CONTACT: liangjw@clemson.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID: 27506227 [PubMed - as supplied by publisher]

Mutation of the CH1 Domain in the Histone Acetyltransferase CREBBP Results in Autism-Relevant Behaviors in Mice.

August 11, 2016 - 11:32am
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Mutation of the CH1 Domain in the Histone Acetyltransferase CREBBP Results in Autism-Relevant Behaviors in Mice.

PLoS One. 2016;11(1):e0146366

Authors: Zheng F, Kasper LH, Bedford DC, Lerach S, Teubner BJ, Brindle PK

Abstract
Autism spectrum disorders (ASDs) are a group of neurodevelopmental afflictions characterized by repetitive behaviors, deficits in social interaction, and impaired communication skills. For most ASD patients, the underlying causes are unknown. Genetic mutations have been identified in about 25 percent of ASD cases, including mutations in epigenetic regulators, suggesting that dysregulated chromatin or DNA function is a critical component of ASD. Mutations in the histone acetyltransferase CREB binding protein (CBP, CREBBP) cause Rubinstein-Taybi Syndrome (RTS), a developmental disorder that includes ASD-like symptoms. Recently, genomic studies involving large numbers of ASD patient families have theoretically modeled CBP and its paralog p300 (EP300) as critical hubs in ASD-associated protein and gene interaction networks, and have identified de novo missense mutations in highly conserved residues of the CBP acetyltransferase and CH1 domains. Here we provide animal model evidence that supports this notion that CBP and its CH1 domain are relevant to autism. We show that mice with a deletion mutation in the CBP CH1 (TAZ1) domain (CBPΔCH1/ΔCH1) have an RTS-like phenotype that includes ASD-relevant repetitive behaviors, hyperactivity, social interaction deficits, motor dysfunction, impaired recognition memory, and abnormal synaptic plasticity. Our results therefore indicate that loss of CBP CH1 domain function contributes to RTS, and possibly ASD, and that this domain plays an essential role in normal motor function, cognition and social behavior. Although the key physiological functions affected by ASD-associated mutation of epigenetic regulators have been enigmatic, our findings are consistent with theoretical models involving CBP and p300 in ASD, and with a causative role for recently described ASD-associated CBP mutations.

PMID: 26730956 [PubMed - indexed for MEDLINE]

Muscle and brain: a dyad with important diagnostic and therapeutic implications.

August 11, 2016 - 11:32am
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Muscle and brain: a dyad with important diagnostic and therapeutic implications.

Dev Med Child Neurol. 2016 Jan;58(1):13

Authors: Hendriksen JG, Vles JS

PMID: 26456166 [PubMed - indexed for MEDLINE]

Improving Treatment Trial Outcomes for Rett Syndrome: The Development of Rett-specific Anchors for the Clinical Global Impression Scale.

August 11, 2016 - 11:32am
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Improving Treatment Trial Outcomes for Rett Syndrome: The Development of Rett-specific Anchors for the Clinical Global Impression Scale.

J Child Neurol. 2015 Nov;30(13):1743-8

Authors: Neul JL, Glaze DG, Percy AK, Feyma T, Beisang A, Dinh T, Suter B, Anagnostou E, Snape M, Horrigan J, Jones NE

Abstract
Rett syndrome is a genetically based neurodevelopmental disorder. Although the clinical consequences of Rett syndrome are profound and lifelong, currently no approved drug treatments are available specifically targeted to Rett symptoms. High quality outcome measures, specific to the core symptoms of a disorder are a critical component of well-designed clinical trials for individuals with neurodevelopmental disorders. The Clinical Global Impression Scale is a measure of global clinical change with strong face validity that has been widely used as an outcome measure in clinical trials of central nervous system disorders. Despite its favorable assay sensitivity in clinical trials, as a global measure, the Clinical Global Impression Scale is not specific to the signs and symptoms of the disorder under study. Development of key anchors for the scale, specific to the disorder being assessed, holds promise for enhancing the validity and reliability of the measure for disorders such as Rett syndrome.

PMID: 25895911 [PubMed - indexed for MEDLINE]

Prevalence of autism and attention-deficit-hyperactivity disorder in Down syndrome: a population-based study.

August 10, 2016 - 8:29am

Prevalence of autism and attention-deficit-hyperactivity disorder in Down syndrome: a population-based study.

Dev Med Child Neurol. 2016 Aug 9;

Authors: Oxelgren UW, Myrelid Å, Annerén G, Ekstam B, Göransson C, Holmbom A, Isaksson A, Åberg M, Gustafsson J, Fernell E

Abstract
AIM: To investigate the prevalence of autism spectrum disorder (ASD) and attention-deficit-hyperactivity disorder (ADHD) in a population-based group of children and adolescents with Down syndrome, and to relate the findings to level of intellectual disability and to medical conditions.
METHOD: From a population-based cohort of 60 children and adolescents with Down syndrome, 41 individuals (29 males, 12 females; mean age 11y, age range 5-17y) for whom parents gave consent for participation were clinically assessed with regard to ASD and ADHD. The main instruments used were the Autism Diagnostic Interview-Revised, Autism Diagnostic Observation Schedule, Swanson, Nolan, and Pelham-IV Rating Scale, and the Adaptive Behavior Assessment System-II.
RESULTS: High rates of ASD and ADHD were found: 17 (42%) and 14 (34%) of the 41 children met DSM criteria for ASD and ADHD respectively.
INTERPRETATION: Children with Down syndrome and coexisting neurodevelopmental/neuropsychiatric disorders in addition to intellectual disability and medical disorders constitute a severely disabled group. Based on the results, we suggest that screening is implemented for both ASD and ADHD, at the age of 3 to 5 years and early school years respectively, to make adequate interventions possible.

PMID: 27503703 [PubMed - as supplied by publisher]

Neurodevelopmental, emotional, and behavioural problems in Duchenne muscular dystrophy in relation to underlying dystrophin gene mutations.

August 10, 2016 - 8:29am
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Neurodevelopmental, emotional, and behavioural problems in Duchenne muscular dystrophy in relation to underlying dystrophin gene mutations.

Dev Med Child Neurol. 2016 Jan;58(1):77-84

Authors: Ricotti V, Mandy WP, Scoto M, Pane M, Deconinck N, Messina S, Mercuri E, Skuse DH, Muntoni F

Abstract
AIM: Duchenne muscular dystrophy (DMD) is associated with neuropsychiatric disorders. The aim of the study was to characterize the DMD neuropsychiatric profile fully and to explore underlying genotype/phenotype associations.
METHOD: One hundred and thirty males with DMD (mean age 9y 10mo, range 5-17y) in four European centres were included and completed IQ assessment and a neurodevelopmental-screening questionnaire. Of these, 87 underwent comprehensive neuropsychiatric assessment using structured diagnostic interview and parent-reported questionnaires.
RESULTS: The overall mean score on the neurodevelopmental questionnaire was significantly abnormal compared with the general population of children (p<0.001). On average, intelligence was below the population mean, with intellectual disability observed in 34 males (26%). Autistic spectrum disorder was identified in 18 (21%), hyperactivity in 21 (24%), and inattention in 38 (44%). Clinical levels of internalizing and externalizing problems were observed in 21 (24%) and 13 (15%) respectively. Over a third of males scored more than two measures of emotional, behavioural, or neurodevelopmental problems. Males with mutations at the 3' end of the DMD gene affecting all protein isoforms had higher rates of intellectual disability and clusters of symptoms.
INTERPRETATION: Males with DMD are at very high risk of neuropsychiatric disturbance, and this risk appears to increase with mutations at the 3' end of the gene. Patterns of symptom clusters suggest a DMD neuropsychiatric syndrome, which may require prompt evaluation and early intervention.

PMID: 26365034 [PubMed - indexed for MEDLINE]

From estimating activation locality to predicting disorder: A review of pattern recognition for neuroimaging-based psychiatric diagnostics.

August 10, 2016 - 8:29am
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From estimating activation locality to predicting disorder: A review of pattern recognition for neuroimaging-based psychiatric diagnostics.

Neurosci Biobehav Rev. 2015 Oct;57:328-49

Authors: Wolfers T, Buitelaar JK, Beckmann CF, Franke B, Marquand AF

Abstract
Psychiatric disorders are increasingly being recognised as having a biological basis, but their diagnosis is made exclusively behaviourally. A promising approach for 'biomarker' discovery has been based on pattern recognition methods applied to neuroimaging data, which could yield clinical utility in future. In this review we survey the literature on pattern recognition for making diagnostic predictions in psychiatric disorders, and evaluate progress made in translating such findings towards clinical application. We evaluate studies on many criteria, including data modalities used, the types of features extracted and algorithm applied. We identify problems common to many studies, such as a relatively small sample size and a primary focus on estimating generalisability within a single study. Furthermore, we highlight challenges that are not widely acknowledged in the field including the importance of accommodating disease prevalence, the necessity of more extensive validation using large carefully acquired samples, the need for methodological innovations to improve accuracy and to discriminate between multiple disorders simultaneously. Finally, we identify specific clinical contexts in which pattern recognition can add value in the short to medium term.

PMID: 26254595 [PubMed - indexed for MEDLINE]

[Structural variations of the genome in autistic spectrum disorders with intellectual disability].

August 9, 2016 - 8:26am

[Structural variations of the genome in autistic spectrum disorders with intellectual disability].

Zh Nevrol Psikhiatr Im S S Korsakova. 2016;116(7):50-54

Authors: Yurov IY, Vorsanova SG, Korostelev SA, Vasin KS, Zelenova MA, Kurinnaya OS, Yurov YB

Abstract
AIM: To analyze structural variations in the genome in children with autism and intellectual disability.
MATERIAL AND METHODS: Using high-resolution karyotyping (AffymetrixCytoScan HD Array) and original bioinformatic technology, 200 children with autism and intellectual disability were studied.
RESULTS AND CONCLUSION: Data on structural variations in the genome in children with autism and intellectual disability are provided. Causative genomic pathology (chromosome abnormalities and copy number variations - CNV) was determined in 97 cases (48.5%). Based on these RESULTS: 24 candidate genes for autism with intellectual disability were selected. In 16 cases (8%), the chromosome mosaicism manifested as aneuploidy of whole autosomes and sex chromosomes (gonosomes) was identified. In 87 children (43.5%), there were genomic variations, which are characteristic of the so-called «grey zone» of genetic pathology in mental illnesses. Bioinformatic analysis showed that these genomic variations had a pleiotropic effect on the phenotype.

PMID: 27500877 [PubMed - as supplied by publisher]

Insulin-Independent GABAA Receptor-Mediated Response in the Barrel Cortex of Mice with Impaired Met Activity.

August 9, 2016 - 8:26am
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Insulin-Independent GABAA Receptor-Mediated Response in the Barrel Cortex of Mice with Impaired Met Activity.

J Neurosci. 2016 Mar 30;36(13):3691-7

Authors: Lo FS, Erzurumlu RS, Powell EM

Abstract
UNLABELLED: Autism spectrum disorder (ASD) is a neurodevelopmental disorder caused by genetic variants, susceptibility alleles, and environmental perturbations. The autism associated geneMETtyrosine kinase has been implicated in many behavioral domains and endophenotypes of autism, including abnormal neural signaling in human sensory cortex. We investigated somatosensory thalamocortical synaptic communication in mice deficient in Met activity in cortical excitatory neurons to gain insights into aberrant somatosensation characteristic of ASD. The ratio of excitation to inhibition is dramatically increased due to decreased postsynaptic GABAAreceptor-mediated inhibition in the trigeminal thalamocortical pathway of mice lacking active Met in the cerebral cortex. Furthermore, in contrast to wild-type mice, insulin failed to increase GABAAreceptor-mediated response in the barrel cortex of mice with compromised Met signaling. Thus, lacking insulin effects may be a risk factor in ASD pathogenesis.
SIGNIFICANCE STATEMENT: A proposed common cause of neurodevelopmental disorders is an imbalance in excitatory neural transmission, provided by the glutamatergic neurons, and the inhibitory signals from the GABAergic interneurons. Many genes associated with autism spectrum disorders impair synaptic transmission in the expected cell type. Previously, inactivation of the autism-associated Met tyrosine kinase receptor in GABAergic interneurons led to decreased inhibition. In thus report, decreased Met signaling in glutamatergic neurons had no effect on excitation, but decimated inhibition. Further experiments indicate that loss of Met activity downregulates GABAAreceptors on glutamatergic neurons in an insulin independent manner. These data provide a new mechanism for the loss of inhibition and subsequent abnormal excitation/inhibition balance and potential molecular candidates for treatment or prevention.

PMID: 27030755 [PubMed - indexed for MEDLINE]

Prenatal minocycline treatment alters synaptic protein expression, and rescues reduced mother call rate in oxytocin receptor-knockout mice.

August 9, 2016 - 8:26am
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Prenatal minocycline treatment alters synaptic protein expression, and rescues reduced mother call rate in oxytocin receptor-knockout mice.

Biochem Biophys Res Commun. 2016 Apr 1;472(2):319-23

Authors: Miyazaki S, Hiraoka Y, Hidema S, Nishimori K

Abstract
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impaired communication, difficulty in companionship, repetitive behaviors and restricted interests. Recent studies have shown amelioration of ASD symptoms by intranasal administration of oxytocin and demonstrated the association of polymorphisms in the oxytocin receptor (Oxtr) gene with ASD patients. Deficient pruning of synapses by microglial cells in the brain has been proposed as potential mechanism of ASD. Other researchers have shown specific activation of microglial cells in brain regions related to sociality in patients with ASD. Although the roles of Oxtr and microglia in ASD are in the spotlight, the relationship between them remains to be elucidated. In this study, we found abnormal activation of microglial cells and a reduction of postsynaptic density protein PSD95 expression in the Oxtr-deficient brain. Moreover, pharmacological inhibition of microglia during development can alter the expression of PSD95 and ameliorate abnormal mother-infant communication in Oxtr-deficient mice. Our results suggest that microglial abnormality is a potential mechanism of the development of Oxt/Oxtr mediated ASD-like phenotypes.

PMID: 26926566 [PubMed - indexed for MEDLINE]

AMPA Receptors as Therapeutic Targets for Neurological Disorders.

August 9, 2016 - 8:26am
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AMPA Receptors as Therapeutic Targets for Neurological Disorders.

Adv Protein Chem Struct Biol. 2016;103:203-61

Authors: Lee K, Goodman L, Fourie C, Schenk S, Leitch B, Montgomery JM

Abstract
Almost every neurological disease directly or indirectly affects synapse function in the brain. However, these diseases alter synapses through different mechanisms, ultimately resulting in altered synaptic transmission and/or plasticity. Glutamate is the major neurotransmitter that mediates excitatory synaptic transmission in the brain through activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors. These receptors have therefore been identified as a target for the development of therapeutic treatments for neurological disorders including epilepsy, neurodegenerative diseases, autism, and drug addiction. The fact that AMPA receptors play a dominant role throughout the brain raises the significant challenge of selectively targeting only those regions affected by disease, and clinical trials have raised doubt regarding the feasibility of specifically targeting AMPA receptors for new therapeutic options. Benzamide compounds that act as positive allosteric AMPA receptor modulators, known as AMPAkines, can act on specific brain regions and were initially proposed to revolutionize the treatment of cognitive deficits associated with neurological disorders. Their therapeutic potential has since declined due to inconsistent results in clinical trials. However, recent advances in basic biomedical research are significantly increasing our knowledge of AMPA receptor structure, binding sites, and interactions with auxiliary proteins. In particular, the large complex of postsynaptic proteins that interact with AMPA receptor subunits have been shown to control AMPA receptor insertion, location, pharmacology, synaptic transmission, and plasticity. These proteins are now being considered as alternative therapeutic target sites for modulating AMPA receptors in neurological disorders.

PMID: 26920691 [PubMed - indexed for MEDLINE]

Evaluation of the neuroactive steroid ganaxolone on social and repetitive behaviors in the BTBR mouse model of autism.

August 9, 2016 - 8:26am
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Evaluation of the neuroactive steroid ganaxolone on social and repetitive behaviors in the BTBR mouse model of autism.

Psychopharmacology (Berl). 2016 Jan;233(2):309-23

Authors: Kazdoba TM, Hagerman RJ, Zolkowska D, Rogawski MA, Crawley JN

Abstract
RATIONALE: Abnormalities in excitatory/inhibitory neurotransmission are hypothesized to contribute to autism spectrum disorder (ASD) etiology. BTBR T (+) Itpr3 (tf) /J (BTBR), an inbred mouse strain, displays social deficits and repetitive self-grooming, offering face validity to ASD diagnostic symptoms. Reduced GABAergic neurotransmission in BTBR suggests that GABAA receptor positive allosteric modulators (PAMs) could improve ASD-relevant BTBR phenotypes. The neuroactive steroid ganaxolone acts as a PAM, displaying anticonvulsant properties in rodent epilepsy models and an anxiolytic-like profile in the elevated plus-maze.
OBJECTIVES: We evaluated ganaxolone in BTBR and C57BL/6J mice in standardized assays for sociability and repetitive behaviors. Open field and anxiety-related behaviors were tested as internal controls and for comparison with the existing neuroactive steroid literature.
RESULTS: Ganaxolone improved aspects of social approach and reciprocal social interactions in BTBR, with no effect on repetitive self-grooming, and no detrimental effects in C57BL/6J. Ganaxolone increased overall exploratory activity in BTBR and C57BL/6J in the open field, social approach, and elevated plus-maze, introducing a confound for the interpretation of social improvements. Allopregnanolone and diazepam similarly increased total entries in the elevated plus-maze, indicating that behavioral activation may be a general property of GABAA receptor PAMs in these strains.
CONCLUSIONS: Ganaxolone shows promise for improving sociability. In addition, ganaxolone, as well as other GABAA receptor PAMs, enhanced overall BTBR activity. The translational implications of specific sociability improvements and nonspecific behavioral activation by ganaxolone in the BTBR model remain to be determined. Future studies to explore whether PAMs provide a novel profile with unique benefits for ASD treatment will be worthwhile.

PMID: 26525567 [PubMed - indexed for MEDLINE]

Genetic architecture, epigenetic influence and environment exposure in the pathogenesis of Autism.

August 9, 2016 - 8:26am
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Genetic architecture, epigenetic influence and environment exposure in the pathogenesis of Autism.

Sci China Life Sci. 2015 Oct;58(10):958-67

Authors: Yu L, Wu Y, Wu BL

Abstract
Autism spectrum disorder (ASD) is a spectral neurodevelopment disorder affecting approximately 1% of the population. ASD is characterized by impairments in reciprocal social interaction, communication deficits and restricted patterns of behavior. Multiple factors, including genetic/genomic, epigenetic/epigenomic and environmental, are thought to be necessary for autism development. Recent reviews have provided further insight into the genetic/genomic basis of ASD. It has long been suspected that epigenetic mechanisms, including DNA methylation, chromatin structures and long non-coding RNAs may play important roles in the pathology of ASD. In addition to genetic/genomic alterations and epigenetic/epigenomic influences, environmental exposures have been widely accepted as an important role in autism etiology, among which immune dysregulation and gastrointestinal microbiota are two prominent ones.

PMID: 26490976 [PubMed - indexed for MEDLINE]

Autism spectrum disorder model mice: Focus on copy number variation and epigenetics.

August 9, 2016 - 8:26am
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Autism spectrum disorder model mice: Focus on copy number variation and epigenetics.

Sci China Life Sci. 2015 Oct;58(10):976-84

Authors: Nakai N, Otsuka S, Myung J, Takumi T

Abstract
Autism spectrum disorder (ASD) is gathering concerns in socially developed countries. ASD is a neuropsychiatric disorder of genetic origin with high prevalence of 1%-2%. The patients with ASD characteristically show impaired social skills. Today, many genetic studies identify numerous susceptible genes and genetic loci associated with ASD. Although some genetic factors can lead to abnormal brain function linked to ASD phenotypes, the pathogenic mechanism of ASD is still unclear. Here, we discuss a new mouse model for ASD as an advanced tool to understand the mechanism of ASD.

PMID: 26335737 [PubMed - indexed for MEDLINE]

CACNB2: An Emerging Pharmacological Target for Hypertension, Heart Failure, Arrhythmia and Mental Disorders.

August 9, 2016 - 8:26am
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CACNB2: An Emerging Pharmacological Target for Hypertension, Heart Failure, Arrhythmia and Mental Disorders.

Curr Mol Pharmacol. 2015;8(1):32-42

Authors: Soldatov NM

Abstract
The voltage-gated Cav1.2 calcium channels respond to membrane depolarization by increasing the membrane permeability to Ca(2+), a major signal for cardiac muscle contraction, regulation of vascular tone and CREB-dependent transcriptional activation. CACNB2 is one of the four homologous genes coding for the auxiliary Cavβ subunits, which are important modulators of the Ca(2+) channel activity. Five serious mental disorders - autism spectrum disorder, attention deficit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia, - and three major cardiovascular diseases - hypertension, heart failure and sudden cardiac death, - have recently been linked to the CACNB2 gene coding for the Cavβ2 subunits. Here I will focus on the Cavβ2-specific molecular determinant β2-CED as an emerging pharmacological target.

PMID: 25966706 [PubMed - indexed for MEDLINE]

Regulation of neuronal migration, an emerging topic in autism spectrum disorders.

August 7, 2016 - 11:22am
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Regulation of neuronal migration, an emerging topic in autism spectrum disorders.

J Neurochem. 2016 Feb;136(3):440-56

Authors: Reiner O, Karzbrun E, Kshirsagar A, Kaibuchi K

Abstract
Autism spectrum disorders (ASD) encompass a group of neurodevelopmental diseases that demonstrate strong heritability, however, the inheritance is not simple and many genes have been associated with these disorders. ASD is regarded as a neurodevelopmental disorder, and abnormalities at different developmental stages are part of the disease etiology. This review provides a general background on neuronal migration during brain development and discusses recent advancements in the field connecting ASD and aberrant neuronal migration. We propose that neuronal migration impairment may be an important common pathophysiology in autism spectrum disorders (ASD). This review provides a general background on neuronal migration during brain development and discusses recent advancements in the field connecting ASD and aberrant neuronal migration.

PMID: 26485324 [PubMed - indexed for MEDLINE]

Schizophrenia genetics complements its mechanistic understanding.

August 5, 2016 - 8:19am
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Schizophrenia genetics complements its mechanistic understanding.

Nat Neurosci. 2016 Apr;19(4):523-5

Authors: Ruzzo EK, Geschwind DH

PMID: 26998600 [PubMed - indexed for MEDLINE]

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