1. Gordon I, Vander Wyk BC, Bennett RH, Cordeaux C, Lucas MV, Eilbott JA, Zagoory-Sharon O, Leckman JF, Feldman R, Pelphrey KA. {{Oxytocin enhances brain function in children with autism}}. {Proc Natl Acad Sci U S A};2013 (Dec 2)
Following intranasal administration of oxytocin (OT), we measured, via functional MRI, changes in brain activity during judgments of socially (Eyes) and nonsocially (Vehicles) meaningful pictures in 17 children with high-functioning autism spectrum disorder (ASD). OT increased activity in the striatum, the middle frontal gyrus, the medial prefrontal cortex, the right orbitofrontal cortex, and the left superior temporal sulcus. In the striatum, nucleus accumbens, left posterior superior temporal sulcus, and left premotor cortex, OT increased activity during social judgments and decreased activity during nonsocial judgments. Changes in salivary OT concentrations from baseline to 30 min postadministration were positively associated with increased activity in the right amygdala and orbitofrontal cortex during social vs. nonsocial judgments. OT may thus selectively have an impact on salience and hedonic evaluations of socially meaningful stimuli in children with ASD, and thereby facilitate social attunement. These findings further the development of a neurophysiological systems-level understanding of mechanisms by which OT may enhance social functioning in children with ASD.
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2. Kirsten TB, Lippi LL, Bevilacqua E, Bernardi MM. {{LPS Exposure Increases Maternal Corticosterone Levels, Causes Placental Injury and Increases IL-1Beta Levels in Adult Rat Offspring: Relevance to Autism}}. {PLoS One};2013;8(12):e82244.
Maternal immune activation can induce neuropsychiatric disorders, such as autism and schizophrenia. Previous investigations by our group have shown that prenatal treatment of rats on gestation day 9.5 with lipopolysaccharide (LPS; 100 mug/kg, intraperitoneally), which mimics infections by gram-negative bacteria, induced autism-like behavior in male rats, including impaired communication and socialization and induced repetitive/restricted behavior. However, the behavior of female rats was unchanged. Little is known about how LPS-induced changes in the pregnant dam subsequently affect the developing fetus and the fetal immune system. The present study evaluated the hypothalamic-pituitary-adrenal (HPA) axis activity, the placental tissue and the reproductive performance of pregnant Wistar rats exposed to LPS. In the adult offspring, we evaluated the HPA axis and pro-inflammatory cytokine levels with or without a LPS challenge. LPS exposure increased maternal serum corticosterone levels, injured placental tissue and led to higher post-implantation loss, resulting in fewer live fetuses. The HPA axis was not affected in adult offspring. However, prenatal LPS exposure increased IL-1beta serum levels, revealing that prenatal LPS exposure modified the immune response to a LPS challenge in adulthood. Increased IL-1beta levels have been reported in several autistic patients. Together with our previous studies, our model induced autistic-like behavioral and immune disturbances in childhood and adulthood, indicating that it is a robust rat model of autism.
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3. Naigles LR. {{Input and language development in children with autism}}. {Semin Speech Lang};2013 (Nov);34(4):237-248.
The social deficits associated with autism spectrum disorders (ASD) have been implicated in the language delays and deficits of children with ASD. Consequently, the extent to which children with ASD utilize their language-related interactions and input in the same ways as typically developing children is only just beginning to be investigated. The current article summarizes the role of input for typically developing children learning language, and then reviews in some detail recent studies demonstrating influential effects of maternal responsivity (e.g., following in on children’s focus of attention) and aspects of maternal speech (e.g., word frequency, word diversity, structural complexity) on the language production and comprehension of young children with ASD. Maternal responsivity appears to play a particularly influential role with children who are minimally verbal whereas the content and structure of maternal speech facilitate language in children who are already verbal.
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4. Yang JC, Simon C, Schneider A, Seritan AL, Hamilton L, Hagerman PJ, Hagerman RJ, Olichney JM. {{Abnormal Semantic Processing in Females with Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS)}}. {Genes Brain Behav};2013 (Dec 2)
FXTAS, a neurodegenerative disorder, affects Fragile X (FMR1) gene premutation carriers in late-life. Studies have shown cognitive impairments in FXTAS including executive dysfunction, working memory, and visuospatial deficits. However, less is known about cognition in females with FXTAS. Thus, we examined semantic processing and verbal memory in female FXTAS patients with event-related potentials (ERPs) and neuropsychological testing. 61 females (34 FXTAS Mage = 62.7, 27 controls Mage = 60.4) were studied with 32-channel ERPs during a category judgment task in which semantically congruous (50%) and incongruous items were repeated ~10-140s later. N400 and P600 amplitude data were submitted to ANCOVA. Neuropsychological testing demonstrated lower performance in verbal learning and executive function in females with FXTAS. ERP analyses revealed a significant reduction of the N400 congruity effect (incongruous – congruous) in the FXTAS group. The N400 congruity effect reduction in females with FXTAS was mainly due to increased N400 amplitude to congruous new words. No significant abnormalities of the N400 repetition effect or the P600 repetition effect were found, indicating preserved implicit memory and verbal memory, respectively, in females with FXTAS. The decreased N400 congruity effect suggests abnormal semantic expectancy and/or semantic network disorganization in female FXTAS patients. The enhanced N400 amplitude to congruous new words may reflect decreased cognitive flexibility among FXTAS women, making access to less typical category exemplar words more difficult.
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5. Yoo J, Bakes J, Bradley C, Collingridge GL, Kaang BK. {{Shank mutant mice as an animal model of autism}}. {Philos Trans R Soc Lond B Biol Sci};2014;369(1633):20130143.
In this review, we focus on the role of the Shank family of proteins in autism. In recent years, autism research has been flourishing. With genetic, molecular, imaging and electrophysiological studies being supported by behavioural studies using animal models, there is real hope that we may soon understand the fundamental pathology of autism. There is also genuine potential to develop a molecular-level pharmacological treatment that may be able to deal with the most severe symptoms of autism, and clinical trials are already underway. The Shank family of proteins has been strongly implicated as a contributing factor in autism in certain individuals and sits at the core of the alleged autistic pathway. Here, we analyse studies that relate Shank to autism and discuss what light this sheds on the possible causes of autism.
