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Valproate and autism

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
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)...
October 9, 2016: Epilepsy & Behavior: E&B
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
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
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
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...
September 8, 2016: L'Encéphale
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
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
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...
2016: BMC Genomics
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
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
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
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
William Mandy, Meng-Chuan Lai
BACKGROUND: Although autism spectrum condition (ASC) is strongly genetic in origin, accumulating evidence points to the critical roles of various environmental influences on its emergence and subsequent developmental course. METHODS: A developmental psychopathology framework was used to synthesise literature on environmental factors associated with the onset and course of ASC (based on a systematic search of the literature using PubMed, PsychInfo and Google Scholar databases)...
March 2016: Journal of Child Psychology and Psychiatry, and Allied Disciplines
O V Burenkova, E A Aleksandrova, I Yu Zarayskaya
Sodium valproate is a widely used antiepileptic drug at high dosage levels, but it has been shown to produce a variety of toxic side-effects when used during perinatal period. These effects include increased risk of congenital anomalies and autism. For this reason, valproate is commonly employed in animal model of autism. Sodium valproate has multiple molecular targets including histone deacetylases. Therefore valproate can be utilized as a tool for the modulation of epigenetic modifications of the genome via inhibition of histone deacetylases...
April 2015: Patologicheskaia Fiziologiia i èksperimental'naia Terapiia
Peter Ranger, Bart A Ellenbroek
Valproic acid or valproate (VPA) is an anti-convulsant and mood stabiliser effective in treating epilepsy and bipolar disorders. Although in adults VPA is well tolerated and safe, there is convincing evidence that it has teratogenic properties, ranging from mild neurodevelopmental changes to severe congenital malformations. In particular, studies involving humans and other animals have shown that prenatal exposure to VPA can induce developmental abnormalities reminiscent of autism spectrum disorder (ASD). In this chapter, we discuss the connection between VPA and ASD, evaluate the VPA animal model of ASD, and describe the possible molecular mechanisms underlying VPA's teratogenic properties...
2016: Current Topics in Behavioral Neurosciences
Natascia Brondino, Laura Fusar-Poli, Cristina Panisi, Stefano Damiani, Francesco Barale, Pierluigi Politi
Autism spectrum disorders are an emerging health problem worldwide, but little is known about their pathogenesis. It has been hypothesized that autism may result from an imbalance between excitatory glutamatergic and inhibitory GABAergic pathways. Commonly used medications such as valproate, acamprosate, and arbaclofen may act on the GABAergic system and be a potential treatment for people with ASD. The present systematic review aimed at evaluating the state-of-the-art of clinical trials of GABA modulators in autism...
March 2016: Journal of Autism and Developmental Disorders
Sandeep Grover, Ajit Avasthi
Management of bipolar during pregnancy and postpartum is very challenging. The treating clinicians have to take into account various factors like current mental state, longitudinal history of the patient, past history of relapse while off medication, response to medication, time of pregnancy at which patient presents to the clinician, etc. The choice of drug should depend on the balance between safety and efficacy profile. Whenever patient is on psychotropic medication, close and intensive monitoring should be done...
July 2015: Indian Journal of Psychiatry
Miyuki Yasue, Akiko Nakagami, Taku Banno, Keiko Nakagaki, Noritaka Ichinohe, Nobuyuki Kawai
Autism is characterized by deficits in social interaction and social recognition. Although animal models of autism have demonstrated that model animals engage less in social interaction or attend less to conspecifics than control animals, no animal model has yet replicated the deficit in recognition of complex social interaction as is seen in humans with autism. Here, we show that marmosets discriminated between human actors who reciprocated in social exchanges and those who did not; however, marmosets with foetal exposure to valproic acid (VPA marmosets) did not...
October 1, 2015: Behavioural Brain Research
Amanda G Wood, Caroline Nadebaum, Vicki Anderson, David Reutens, Sarah Barton, Terence J O'Brien, Frank Vajda
PURPOSE: The association between autism spectrum disorders (ASDs) and prenatal anticonvulsant exposure is increasingly investigated, but comprehensive, blinded assessment using a validated instrument for autism within a well-characterized prospective cohort has not been conducted. Thus, existing studies may represent an underestimate of the true risk. Herein we present a prospective cohort study in children exposed to anticonvulsants during pregnancy, with all assessments conducted by examiners who were blinded to drug-exposure status...
July 2015: Epilepsia
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