1. Allard MJ, Bergeron JD, Baharnoori M, Srivastava LK, Fortier LC, Poyart C, Sebire G. {{A sexually dichotomous, autistic-like phenotype is induced by Group B Streptococcus maternofetal immune activation}}. {Autism research : official journal of the International Society for Autism Research}. 2016 May 25.
Group B Streptococcus (GBS) is a commensal bacterium present in the lower genital tract of 15-30% of healthy pregnant women. GBS is the leading cause of chorioamnionitis and cerebral injuries in newborns, occurring most often in the absence of maternofetal pathogen translocation. Despite GBS being the most frequent bacterium colonizing pregnant women, no preclinical studies have investigated the impact of end-gestational maternal GBS exposure on the offspring’s brain development and its behavioral correlates. Our hypothesis is that GBS-induced gestational infection/inflammation has a deleterious neurodevelopmental impact on uninfected offspring. Our goal was to study the impact of maternal GBS infection on the placental and neurodevelopmental features in the offspring using a new preclinical rat model. GBS-exposed placentas exhibited chorioamnionitis characterized by the presence of Gram-positive cocci and polymorphonuclear cells, with the latter being significantly more prominent in the labyrinth of male offspring. GBS-exposed male offspring had reduced thickness of periventricular white matter. In addition, they exhibited autistic-like behaviors, such as abnormal social interaction and communication, impaired processing of sensory information and hyperactivity. Overall, these data show for the first time that gestational exposure to GBS plays an important role in the generation of neurodevelopmental abnormalities reminiscent of human autism spectrum disorders (ASD). These results provide new evidence in favor of the role of a common and modifiable infectious/inflammatory environmental factor in human ASD pathophysiology. Autism Res 2016,. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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2. Brown HK, Cobigo V, Lunsky Y, Vigod SN. {{Maternal and offspring outcomes in women with intellectual and developmental disabilities: a population-based cohort study}}. {BJOG : an international journal of obstetrics and gynaecology}. 2016 May 24.
OBJECTIVE: To compare the risks for adverse maternal and offspring outcomes in women with and without intellectual and developmental disabilities. DESIGN: Population-based cohort study. SETTING: Ontario, Canada. POPULATION: Singleton obstetrical deliveries to 18- to 49-year-old women with and without intellectual and developmental disabilities (n = 3932 in the exposed cohort, n = 382 774 in the unexposed cohort; 2002-2011 fiscal years). METHODS: Women with intellectual and developmental disabilities were identified based on diagnoses in health administrative data or receipt of disability income support. The unexposed cohort comprised women without intellectual and developmental disabilities. Modified Poisson regression was used to compute adjusted relative risks (aRR) and 95% confidence intervals (CI) comparing the two cohorts. MAIN OUTCOME MEASURES: Primary maternal outcomes were: gestational diabetes, gestational hypertension, pre-eclampsia, eclampsia, and venous thromboembolism. Primary offspring outcomes were: preterm birth, small for gestational age, and large for gestational age. RESULTS: The exposed cohort, compared with the unexposed cohort, had increased risks for pre-eclampsia (aRR 1.47, 95% CI 1.11-1.93) and venous thromboembolism (aRR 1.60, 95% CI 1.17-2.19). Their offspring had increased risks for preterm birth (aRR 1.63, 95% CI 1.47-1.80) and small for gestational age (aRR 1.35, 95% CI 1.25-1.45). CONCLUSIONS: These findings suggest that there is a need to address modifiable risk factors for adverse outcomes among women with intellectual and developmental disabilities prior to and during pregnancy. Moreover, there is a need to enhance monitoring for maternal and offspring complications in this population. TWEETABLE ABSTRACT: Large cohort study: intellectual and developmental disabilities predispose women/babies to adverse outcomes.
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3. Carson TB, Wilkes BJ, Patel K, Pineda JL, Ko JH, Newell KM, Bodfish JW, Schubert MC, Radonovich K, White KD, Lewis MH. {{Vestibulo-ocular reflex function in children with high-functioning autism spectrum disorders}}. {Autism research : official journal of the International Society for Autism Research}. 2016 May 25.
Sensorimotor processing alterations are a growing focus in the assessment and treatment of Autism Spectrum Disorders (ASD). The rotational vestibulo-ocular reflex (rVOR), which functions to maintain stable vision during head movements, is a sensorimotor system that may be useful in understanding such alterations and their underlying neurobiology. In this study, we assessed post-rotary nystagmus elicited by continuous whole body rotation among children with high-functioning ASD and typically developing children. Children with ASD exhibited increased rVOR gain, the ratio of eye velocity to head velocity, indicating a possible lack of cerebellar inhibitory input to brainstem vestibular nuclei in this population. The ASD group also showed less regular or periodic horizontal eye movements as indexed by greater variance accounted for by multiple higher frequency bandwidths as well as greater entropy scores compared to typically developing children. The decreased regularity or dysrhythmia in the temporal structure of nystagmus beats in children with ASD may be due to alterations in cerebellum and brainstem circuitry. These findings could potentially serve as a model to better understand the functional effects of differences in these brain structures in ASD. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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4. Clipperton-Allen AE, Chen Y, Page DT. {{Autism-relevant behaviors are minimally impacted by conditional deletion of Pten in oxytocinergic neurons}}. {Autism research : official journal of the International Society for Autism Research}. 2016 May 25.
Germline heterozygous mutations in Pten (phosphatase and tensin homolog) are associated with macrocephaly and autism spectrum disorders (ASD). Pten germline heterozygous (Pten+/- ) mice approximate these mutations, and both sexes show widespread brain overgrowth and impaired social behavior. Strikingly similar behavior phenotypes have been reported in oxytocin (Oxt) and/or oxytocin receptor (OxtR) knockout mice. Thus, we hypothesized that the behavioral phenotypes of germline Pten+/- mice may be caused by reduced Pten function in Oxt-expressing cells. To investigate this, we tested mice in which Pten was conditionally deleted using oxytocin-Cre (Oxt-Cre+ ; PtenloxP/+ , Oxt-Cre+ ; PtenloxP/loxP ) on a battery including assays of social, repetitive, depression-like, and anxiety-like behaviors. Minimal behavioral abnormalities were found; decreased anxiety-like behavior in the open field test in Oxt-Cre+ ; PtenloxP/loxP males was the only result that phenocopied germline Pten+/- mice. However, Oxt cell size was dramatically increased in Oxt-Cre+ ; PtenloxP/loxP mice in adulthood. Thus, conditional deletion of Pten using Oxt-Cre has a profound effect on Oxt cell structure, but not on ASD-relevant behavior. We interpret these results as inconsistent with our starting hypothesis that reduced Pten function in Oxt-expressing cells causes the behavioral deficits observed in germline Pten+/- mice. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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5. Joseph RM, O’Shea TM, Allred EN, Heeren T, Hirtz D, Paneth N, Leviton A, Kuban KC. {{Prevalence and associated features of autism spectrum disorder in extremely low gestational age newborns at age 10 years}}. {Autism research : official journal of the International Society for Autism Research}. 2016 May 25.
We sought to estimate the prevalence of autism spectrum disorder (ASD) in children born extremely preterm relative to the U.S. population risk of 1.5% [CDC, 2014] using the best-available diagnostic procedures and minimizing confounding with other neurodevelopmental impairments. Eight hundred and eighty nine of 966 (92%) 10-year-old children from the Extremely Low Gestational Age Newborn birth cohort, delivered at 23-27 weeks gestation in 2002-2004, participated. Children meeting ASD screening criteria on the Social Communication Questionnaire were evaluated with the Autism Diagnostic Interview-Revised (ADI-R). Those meeting ADI-R criteria were assessed with the Autism Diagnostic Observation Schedule-2 (ADOS-2). A positive ADOS-2 score was the criterion for ASD. Twenty-six participants were not assessed for ASD because of severe sensory or motor impairment. In the remaining sample, 61 children met criteria for ASD, resulting in a prevalence of 7.1% (95% CI = 5.5-9.0). ASD risk decreased with increasing gestational age, from 15.0% (95% CI = 10.0-21.2) for 23-24 weeks, 6.5% (95% CI = 4.2-9.4) for 25-26 weeks, to 3.4% (95% CI = 1.6-6.1) for 27 weeks gestational age, and this association was independent of IQ. Among children with ASD, 40% had intellectual disability. The male-to-female ratio of children with ASD was 2.1:1 (95% CI = 1.2:1-3.5:1), lower than in the general population (4:1). ASD prevalence in the ELGAN cohort was four times higher than in the general population, and was strongly associated with gestational age, underscoring the need for enhanced ASD screening of children born preterm, and suggesting that some risk factors associated with preterm birth may also play a role in the etiology of autism. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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6. Lee YH, Lenhart PD, Lambert SR. {{Cataract secondary to self-inflicted blunt trauma in children with autism spectrum disorder}}. {Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus / American Association for Pediatric Ophthalmology and Strabismus}. 2016 May 17.
We report 3 cases of bilateral cataract secondary to self-inflicted blunt eye trauma in children with autism spectrum disorder (ASD). All 3 children hit their foreheads, orbits, or globes repeatedly for long periods of time and developed cataracts. Clinicians must be aware of this phenomenon to diagnose ocular pathology early and to provide adequate education, counseling, and services to affected patients and their families and to put appropriate postoperative care mechanisms in place to prevent permanent ocular damage.
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7. Nagaoka A, Takehara H, Hayashi-Takagi A, Noguchi J, Ishii K, Shirai F, Yagishita S, Akagi T, Ichiki T, Kasai H. {{Abnormal intrinsic dynamics of dendritic spines in a fragile X syndrome mouse model in vivo}}. {Scientific reports}. 2016;6:26651.
Dendritic spine generation and elimination play an important role in learning and memory, the dynamics of which have been examined within the neocortex in vivo. Spine turnover has also been detected in the absence of specific learning tasks, and is frequently exaggerated in animal models of autistic spectrum disorder (ASD). The present study aimed to examine whether the baseline rate of spine turnover was activity-dependent. This was achieved using a microfluidic brain interface and open-dura surgery, with the goal of abolishing neuronal Ca(2+) signaling in the visual cortex of wild-type mice and rodent models of fragile X syndrome (Fmr1 knockout [KO]). In wild-type and Fmr1 KO mice, the majority of baseline turnover was found to be activity-independent. Accordingly, the application of matrix metalloproteinase-9 inhibitors selectively restored the abnormal spine dynamics observed in Fmr1 KO mice, without affecting the intrinsic dynamics of spine turnover in wild-type mice. Such findings indicate that the baseline turnover of dendritic spines is mediated by activity-independent intrinsic dynamics. Furthermore, these results suggest that the targeting of abnormal intrinsic dynamics might pose a novel therapy for ASD.
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8. Tian Y, Wang L, Jia M, Lu T, Ruan Y, Wu Z, Wang L, Liu J, Zhang D. {{Association of oligodendrocytes differentiation regulator gene DUSP15 with autism}}. {The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry}. 2016 May 25:1-8.
OBJECTIVES: Autism is a pervasive neurodevelopmental disorder with high heritability. Genetic factors play crucial roles in the aetiology of autism. Dual specificity phosphatase 15 (DUSP15) has been recognised as a key regulator gene for oligodendrocytes differentiation. A previous study detected one de novo missense variant (p.Thr107Met) with probable deleterious function in exon 6 of DUSP15 among patients with autism. Therefore, we sequenced this mutation in autistic children and performed an association analysis between DUSP15 polymorphisms and autism. METHODS: We performed a case-control study between 255 children affected with autism and 427 healthy controls. Four tag-single nucleotide polymorphisms (SNPs) were selected. These SNPs and the previously reported mutation in exon 6 of DUSP15 were genotyped via Sanger sequencing. RESULTS: Our results showed that rs3746599 was significantly associated with autism under allelic, additive and dominant models, respectively (chi2 = 9.699, P = 0.0018; chi2 = 16.224, P = 0.001; chi2 = 7.198, P = 0.007). The association remained significant after Bonferroni correction and permutation tests (n = 10,000). We did not detect the missense variant p.Thr107Met reported in previous studies. However, a de novo missense variant of DUSP15 (p.Ala56Thr) with a probable disease-causing effect was detected in one autistic child while absent in healthy controls. CONCLUSIONS: Our findings initially suggest that DUSP15 might be a susceptibility gene for autism in Chinese Han population.
