In utero exposure to valproic acid and autism — A current review of clinical and animal studies

Roullet, Florence; Lai, Jonathan; Foster, Jane A.

doi:10.1016/j.ntt.2013.01.004

Cited by 365 publications

(321 citation statements)

References 82 publications

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“…A recent study revealed that some of ASD may be caused by maternal antibodies to fetal brain antigens such as cypin, which, along with PSD-95, can regulate dendritic branching of hippocampal neurons (Braunschweig et al, 2013). Sodium valproate, an anticonvulsant and a mood stabilizer, induces fetal neurodevelopment aberration in animals, including humans, higher incidence of ASD in humans, and ASD-like phenotypes such as reduced social interaction and increased repetitive behaviors in rodents (Roullet et al, 2013). There are many prenatal and postnatal risk factors, as follows: maternal medication use, C-reactive protein levels, hypertension, hemorrhage, infection, depressive symptomatology, food, gestational diabetes, parental age at birth, prolonged labor, fetal distress, birth injury or trauma, multiple birth, low birth weight, etc.…”

Section: Asd and Neuroinflammationmentioning

confidence: 99%

Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia

Nakagawa¹,

Chiba²

2016

Journal of Pharmacology and Experimental Therapeutics

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Development of social cognition, a unique and high-order function, depends on brain maturation from childhood to adulthood in humans. Autism spectrum disorder (ASD) and schizophrenia have similar social cognitive deficits, although age of onset in each disorder is different. Pathogenesis of these disorders is complex and contains several features, including genetic risk factors, environmental risk factors, and sites of abnormalities in the brain. Although several hypotheses have been postulated, they seem to be insufficient to explain how brain alterations associated with symptoms in these disorders develop at distinct developmental stages. Development of ASD appears to be related to cerebellar dysfunction and subsequent thalamic hyperactivation in early childhood. By contrast, schizophrenia seems to be triggered by thalamic hyperactivation in late adolescence, whereas hippocampal aberration has been possibly initiated in childhood. One of the possible culprits is metal homeostasis disturbances that can induce dysfunction of blood-cerebrospinal fluid barrier. Thalamic hyperactivation is thought to be induced by microglia-mediated neuroinflammation and abnormalities of intracerebral environment. Consequently, it is likely that the thalamic hyperactivation triggers dysregulation of the dorsolateral prefrontal cortex for lower brain regions related to social cognition. In this review, we summarize the brain aberration in ASD and schizophrenia and provide a possible mechanism underlying social cognitive deficits in these disorders based on their distinct ages of onset.

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Section: Asd and Neuroinflammationmentioning

confidence: 99%

Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia

Nakagawa¹,

Chiba²

2016

Journal of Pharmacology and Experimental Therapeutics

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“…It should be noted, however, that remarkable changes in the gut microbiota composition and associated intestinal abnormalities have also been identified in another experimental model of neurodevelopmental disease, namely prenatal exposure to valproic acid (VPA) in mice (34). Similar to the polyI:C model (83), the VPA model is frequently used to induce autism-related brain and behavioral abnormalities in experimental rodents (123). Thus, it appears that prenatal exposure to distinct environmental factors does not only induce overlapping neurobehavioral phenotypes, but further induce similar changes in GI functions and microbiota.…”

Section: Gastrointestinal Abnormalities and Dysbiosismentioning

confidence: 99%

Long-term pathological consequences of prenatal infection: beyond brain disorders

Labouesse

Langhans

Meyer

2015

American Journal of Physiology-Regulatory, Integrative and Comp

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“…In a recent comprehensive review of both clinical and animal studies on the topic of VPA and autism (13), it appears that rats can be made less sociable and will produce much fewer ultrasonic vocalizations when exposed to VPA in utero, therefore comprising an autistic rat (my favorite kind). Unlike the human data, a very specific timing of vulnerability is present-embryonic day 12.…”

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confidence: 99%

In Utero Valproate Exposure and Autism: Long Suspected, Finally Proven

Harden¹

2013

Epilepsy Curr

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CommentaryThe cognitive teratogenic activity of valproate (VPA) is crystallizing with the latest report on the association of in utero VPA exposure and the risk of autism determined from a population-based study utilizing Danish national medical databases. Children born between 1996 and 2006 were followed for the documented occurrence of autism up to 14 years of age, with a mean follow-up of 9 years. The astounding results were that for children born to mothers who took VPA during pregnancy, the risk of childhood autism increased 3-fold and the risk of autism spectrum disorder (ASD) increased 5-fold over the general population risk. The authors make the point that the absolute risk to VPA-exposed children remains low at less than 5%, although the upper 95% confidence interval (CI) limit for ASD was 7.49%. There was no contribution of maternal epilepsy to the risk of VPA use.In contrast to the structural teratogenesis with VPA, which manifests with hypospadias and spina bifida and occurs with first trimester exposure (1), the autism risk was present in this study with VPA exposure starting at any trimester during pregnancy. The first report to show an effect of the timing of antiepileptic drug (AED) exposure during pregnancy on adverse cognitive outcomes was an evaluation of phenobarbital

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In utero exposure to valproic acid and autism — A current review of clinical and animal studies

Cited by 365 publications

References 82 publications

Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia

Involvement of Neuroinflammation during Brain Development in Social Cognitive Deficits in Autism Spectrum Disorder and Schizophrenia

Long-term pathological consequences of prenatal infection: beyond brain disorders

In Utero Valproate Exposure and Autism: Long Suspected, Finally Proven

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