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Valproate and autism

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https://www.readbyqxmd.com/read/29046483/deficiency-of-shank2-causes-mania-like-behavior-that-responds-to-mood-stabilizers
#1
Andrea L Pappas, Alexandra L Bey, Xiaoming Wang, Mark Rossi, Yong Ho Kim, Haidun Yan, Fiona Porkka, Lara J Duffney, Samantha M Phillips, Xinyu Cao, Jin-Dong Ding, Ramona M Rodriguiz, Henry H Yin, Richard J Weinberg, Ru-Rong Ji, William C Wetsel, Yong-Hui Jiang
Genetic defects in the synaptic scaffolding protein gene, SHANK2, are linked to a variety of neuropsychiatric disorders, including autism spectrum disorders, schizophrenia, intellectual disability, and bipolar disorder, but the molecular mechanisms underlying the pleotropic effects of SHANK2 mutations are poorly understood. We generated and characterized a line of Shank2 mutant mice by deleting exon 24 (Δe24). Shank2Δe24-/- mice engage in significantly increased locomotor activity, display abnormal reward-seeking behavior, are anhedonic, have perturbations in circadian rhythms, and show deficits in social and cognitive behaviors...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/28729328/comparative-safety-of-antiepileptic-drugs-for-neurological-development-in-children-exposed-during-pregnancy-and-breast-feeding-a-systematic-review-and-network-meta-analysis
#2
Areti Angeliki Veroniki, Patricia Rios, Elise Cogo, Sharon E Straus, Yaron Finkelstein, Ryan Kealey, Emily Reynen, Charlene Soobiah, Kednapa Thavorn, Brian Hutton, Brenda R Hemmelgarn, Fatemeh Yazdi, Jennifer D'Souza, Heather MacDonald, Andrea C Tricco
OBJECTIVES: Compare the safety of antiepileptic drugs (AEDs) on neurodevelopment of infants/children exposed in utero or during breast feeding. DESIGN AND SETTING: Systematic review and Bayesian random-effects network meta-analysis (NMA). MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched until 27 April 2017. Screening, data abstraction and quality appraisal were completed in duplicate by independent reviewers. PARTICIPANTS: 29 cohort studies including 5100 infants/children...
July 20, 2017: BMJ Open
https://www.readbyqxmd.com/read/28641949/reduced-protein-expressions-of-cytomembrane-gabaar%C3%AE-3-at-different-postnatal-developmental-stages-of-rats-exposed-prenatally-to-valproic-acid
#3
Yixin Li, Yang Zhou, Li Peng, Yong Zhao
Decreased inhibition plays an extremely important role in pathogenesis of autism spectrum disorder (ASD). Therefore, we aimed to determine whether expression levels of the γ-aminobutyric acid type A receptor β3 subunit (GABAARβ3), K(+)-Cl(-) cotransporter 2 (KCC2), and Na(+)-K(+)-Cl(-) cotransporter 1 (NKCC1) related to inhibition transmission are changed in a sodium valproate-induced rat model of ASD. Decreased expression levels of membrane GABAARβ3 (m-GABAARβ3) and KCC2 as well as increased endocytosis of GABAARs were found in the model group...
June 19, 2017: Brain Research
https://www.readbyqxmd.com/read/28635121/exposure-to-sodium-valproate-during-pregnancy-facial-features-and-signs-of-autism
#4
Rachel Stadelmaier, Hanah Nasri, Curtis K Deutsch, Margaret Bauman, Anne Hunt, Christopher J Stodgell, Jane Adams, Lewis B Holmes
BACKGROUND: Valproic acid (VPA) is the most teratogenic anticonvulsant drug in clinical use today. Children exposed prenatally to VPA have previously been shown to have dysmorphic craniofacial features, identified subjectively but not by anthropometric methods. Exposure to VPA has also been associated with an increased frequency of autism spectrum disorder (ASD). An increased cephalic index (the ratio of the cranial lateral width to the cranial anterior-posterior length) has been observed in children with ASD...
August 15, 2017: Birth Defects Research
https://www.readbyqxmd.com/read/28584888/autism-spectrum-disorder-neuropathology-and-animal-models
#5
REVIEW
Merina Varghese, Neha Keshav, Sarah Jacot-Descombes, Tahia Warda, Bridget Wicinski, Dara L Dickstein, Hala Harony-Nicolas, Silvia De Rubeis, Elodie Drapeau, Joseph D Buxbaum, Patrick R Hof
Autism spectrum disorder (ASD) has a major impact on the development and social integration of affected individuals and is the most heritable of psychiatric disorders. An increase in the incidence of ASD cases has prompted a surge in research efforts on the underlying neuropathologic processes. We present an overview of current findings in neuropathology studies of ASD using two investigational approaches, postmortem human brains and ASD animal models, and discuss the overlap, limitations, and significance of each...
October 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28424947/neurodevelopmental-effects-of-antiepileptic-drugs
#6
Marissa Kellogg, Kimford J Meador
Increasing evidence suggests that exposure to certain antiepileptic drugs (AEDs) during critical periods of development may induce transient or long-lasting neurodevelopmental deficits across cognitive, motor and behavioral domains. The developing nervous system may endure prolonged chronic exposure to AEDs during pregnancy (in utero) or during childhood, which can lead to neurodevelopmental defects such as congenital neural tube defects, lower IQ, language deficits, autism and ADHD. To date, valproate is the most widely recognized AED to significantly negatively affect neurodevelopment, and demonstrates greater adverse effects than any other AEDs that have been assessed...
July 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28230711/asperger-syndrome-and-early-onset-schizophrenia-associated-with-a-novel-mecp2-deleterious-missense-variant
#7
Aurore Curie, Gaëtan Lesca, Gérald Bussy, Sabine Manificat, Valérie Arnaud, Sibylle Gonzalez, Olivier Revol, Alain Calender, Daniel Gérard, Vincent des Portes
Methyl-CpG-binding protein 2 (MECP2) deleterious variants, which are responsible for Rett syndrome in girls, are involved in a wide spectrum of developmental disabilities in males. A neuropsychiatric phenotype without intellectual disability is uncommon in patients with MECP2 deleterious variants. We report on two dizygotic twins with an MECP2-related psychiatric disorder without intellectual disability. Neuropsychological and psychiatric phenotype assessments were performed, and a genetic analysis was carried out...
June 2017: Psychiatric Genetics
https://www.readbyqxmd.com/read/27984170/autism-genes-are-selectively-targeted-by-environmental-pollutants-including-pesticides-heavy-metals-bisphenol-a-phthalates-and-many-others-in-food-cosmetics-or-household-products
#8
REVIEW
C J Carter, R A Blizard
The increasing incidence of autism suggests a major environmental influence. Epidemiology has implicated many candidates and genetics many susceptibility genes. Gene/environment interactions in autism were analysed using 206 autism susceptibility genes (ASG's) from the Autworks database to interrogate ∼1 million chemical/gene interactions in the comparative toxicogenomics database. Any bias towards ASG's was statistically determined for each chemical. Many suspect compounds identified in epidemiology, including tetrachlorodibenzodioxin, pesticides, particulate matter, benzo(a)pyrene, heavy metals, valproate, acetaminophen, SSRI's, cocaine, bisphenol A, phthalates, polyhalogenated biphenyls, flame retardants, diesel constituents, terbutaline and oxytocin, inter alia showed a significant degree of bias towards ASG's, as did relevant endogenous agents (retinoids, sex steroids, thyroxine, melatonin, folate, dopamine, serotonin)...
October 27, 2016: Neurochemistry International
https://www.readbyqxmd.com/read/27732918/evidence-for-spared-attention-to-faces-in-7-month-old-infants-after-prenatal-exposure-to-antiepileptic-drugs
#9
Mari Videman, Susanna Stjerna, Reina Roivainen, Taina Nybo, Sampsa Vanhatalo, Eija Gaily, Jukka M Leppänen
INTRODUCTION: Prenatal antiepileptic drug (AED) exposure is associated with an increased risk of cognitive impairment and autism spectrum disorders detected mainly at the age of two to six years. We examined whether the developmental aberrations associated with prenatal AED exposure could be detected already in infancy and whether effects on visual attention can be observed at this early age. MATERIAL AND METHODS: We compared a prospective cohort of infants with in utero exposure to AED (n=56) with infants without drug exposures (n=62)...
November 2016: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/27708559/does-prenatal-valproate-interact-with-a-genetic-reduction-in-the-serotonin-transporter-a-rat-study-on-anxiety-and-cognition
#10
Bart A Ellenbroek, Caren August, Jiun Youn
There is ample evidence that prenatal exposure to valproate (or valproic acid, VPA) enhances the risk of developing Autism Spectrum Disorders (ASD). In line with this, a single injection of VPA induces a multitude of ASD-like symptoms in animals, such as rats and mice. However, there is equally strong evidence that genetic factors contribute significantly to the risk of ASD and indeed, like most other psychiatric disorders, ASD is now generally thought to results from an interaction between genetic and environmental factors...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27701827/beneficial-effects-of-co-ultramicronized-palmitoylethanolamide-luteolin-in-a-mouse-model-of-autism-and-in-a-case-report-of-autism
#11
Bartolomeo Bertolino, Rosalia Crupi, Daniela Impellizzeri, Giuseppe Bruschetta, Marika Cordaro, Rosalba Siracusa, Emanuela Esposito, Salvatore Cuzzocrea
AIMS: Autism spectrum disorder (ASD) is a condition defined by social communication deficits and repetitive restrictive behaviors. Association of the fatty acid amide palmitoylethanolamide (PEA) with the flavonoid luteolin displays neuroprotective and antiinflammatory actions in different models of central nervous system pathologies. We hypothesized that association of PEA with luteolin might have therapeutic utility in ASD, and we employed a well-recognized autism animal model, namely sodium valproate administration, to evaluate cognitive and motor deficits...
January 2017: CNS Neuroscience & Therapeutics
https://www.readbyqxmd.com/read/27692350/-epigenetics-implication-in-autism-spectrum-disorders-a-review
#12
M Hamza, S Halayem, R Mrad, S Bourgou, F Charfi, A Belhadj
BACKGROUND: The etiology of autism spectrum disorders (ASD) is complex and multifactorial, and the roles of genetic and environmental factors in its emergence have been well documented. Current research tends to indicate that these two factors act in a synergistic manner. The processes underlying this interaction are still poorly known, but epigenetic modifications could be the mediator in the gene/environment interface. The epigenetic mechanisms have been implicated in susceptibility to stress and also in the pathogenesis of psychiatric disorders including depression and schizophrenia...
September 27, 2016: L'Encéphale
https://www.readbyqxmd.com/read/27616580/-the-cerebellum-as-a-major-player-in-motor-disturbances-related-to-autistic-syndrome-disorders
#13
REVIEW
M Jaber
SCIENTIFIC BACKGROUND: Autism spectrum disorders (ASD) are neurodevelopmental disorders associated with disturbances in communication, social interactions, cognition and affect. ASD are also accompanied by complex movement disorders, including ataxia. A special focus of recent research in this area is made on the striatum and the cerebellum, two structures known not only to control movement but also to be involved in cognitive functions such as memory and language. Dysfunction within the motor system may be associated with abnormal movements in ASD that are translated into ataxia, abnormal pattern of righting, gait sequencing, development of walking, and hand positioning...
April 2017: L'Encéphale
https://www.readbyqxmd.com/read/27430241/prenatal-valproate-treatment-produces-autistic-like-behavior-and-increases-metabotropic-glutamate-receptor%C3%A2-1a-immunoreactivity-in-the-hippocampus-of-juvenile-rats
#14
Francisco Peralta, Constanza Fuentealba, Jenny Fiedler, Esteban Aliaga
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by deficits in social communication and social interaction, and repetitive and stereotypical patterns of behavior. Previously, a common physiopathological pathway, involving the control of synaptic protein synthesis, was proposed as a convergence point in ASD. In particular, a role for local mRNA translation activated by class I metabotropic glutamate receptor type 5 (mGluR5) was suggested in genetic syndromes with autistic signs and in the prenatal exposition to the valproate model of autism...
September 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27423376/prenatal-exposure-to-sodium-valproate-alters-androgen-receptor-expression-in-the-developing-cerebellum-in-a-region-and-age-specific-manner-in-male-and-female-rats
#15
Miguel Perez-Pouchoulen, Marta Miquel, Paul Saft, Brenda Brug, Rebeca Toledo, Maria Elena Hernandez, Jorge Manzo
Valproic acid (VPA) is an anti-epileptic drug with teratogenicity activity that has been related to autism. In rodents, exposure to VPA in utero leads to brain abnormalities similar than those reported in the autistic brain. Particularly, VPA reduces the number of Purkinje neurons in the rat cerebellum parallel to cerebellar abnormalities found in autism. Thus, we injected pregnant females on embryonic day 12 either with VPA (600mg/kg, i.p.) or 0.9% saline solution and obtained the cerebellum from their offspring at different postnatal time points...
October 2016: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/27356971/psychoactive-pharmaceuticals-at-environmental-concentrations-induce-in-vitro-gene-expression-associated-with-neurological-disorders
#16
Gaurav Kaushik, Yu Xia, Luobin Yang, Michael A Thomas
BACKGROUND: A number of researchers have speculated that neurological disorders are mostly due to the interaction of common susceptibility genes with environmental, epigenetic and stochastic factors. Genetic factors such as mutations, insertions, deletions and copy number variations (CNVs) are responsible for only a small subset of cases, suggesting unknown environmental contaminants play a role in triggering neurological disorders like idiopathic autism. Psychoactive pharmaceuticals have been considered as potential environmental contaminants as they are detected in the drinking water at very low concentrations...
June 29, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27320472/pi3k-akt-mtor-mediated-autophagy-in-the-development-of-autism-spectrum-disorder
#17
Jun Zhang, Ji-Xiang Zhang, Qin-Liang Zhang
AIM: To investigate the association between PI3K/AKT/mTOR-mediated autophagy and the pathogenesis of autism spectrum disorder (ASD). METHODS: A sodium valproate (VPA)-induced baby rat model of ASD was built. Nine pregnant rats were randomly assigned into three groups, with three rats for each group: healthy control group, VPA group and mTOR inhibition group, receiving different drug administrations. Baby rats were grouped according to the maternal rats. Social interaction of baby rats (35days after birth) was observed and their bilateral hippocampes were sliced...
July 2016: Brain Research Bulletin
https://www.readbyqxmd.com/read/27264355/distinct-defects-in-synaptic-differentiation-of-neocortical-neurons-in-response-to-prenatal-valproate-exposure
#18
Yoko Iijima, Katharina Behr, Takatoshi Iijima, Barbara Biemans, Josef Bischofberger, Peter Scheiffele
Autism spectrum disorders (ASDs) are a heterogeneous group of neurodevelopmental disorders characterized by impairments in social interactions and stereotyped behaviors. Valproic acid (VPA) is frequently used to treat epilepsy and bipolar disorders. When taken during pregnancy, VPA increases the risk of the unborn child to develop an ASD. In rodents, in utero VPA exposure can precipitate behavioral phenotypes related to ASD in the offspring. Therefore, such rodent models may allow for identification of synaptic pathophysiology underlying ASD risk...
2016: Scientific Reports
https://www.readbyqxmd.com/read/26979855/-a-girl-with-foetal-valproate-syndrome-and-autism-spectrum-disorder
#19
I Solignac
We study the case of a 12-year-old girl who, following intra-uterine exposure to valproate, was diagnosed with foetal valproate syndrome, characterised at birth by dysmorphic features. The use of valproate during pregnancy (because of epilepsy or bipolar disorder) can cause not only structural defects in the growing foetus, but also problems in cognitive development and in adaptive and emotional/behavioural functioning in later life. We evaluate these domains of development in our discussion and suggest several other drugs, less harmful than valproate, which can be used to treat epilepsy or bipolar disorder during pregnancy...
2016: Tijdschrift Voor Psychiatrie
https://www.readbyqxmd.com/read/26951404/a-7-year-old-boy-with-intractable-seizures-and-snoring
#20
Casandra Arevalo, Lourdes M DelRosso, Ilya Khaytin, Lawrence Brown
No abstract text is available yet for this article.
June 15, 2016: Journal of Clinical Sleep Medicine: JCSM: Official Publication of the American Academy of Sleep Medicine
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