1. Andrade C. {{Use of acetaminophen (paracetamol) during pregnancy and the risk of autism spectrum disorder in the offspring}}. {J Clin Psychiatry};2016 (Feb);77(2):e152-154.
Acetaminophen (paracetamol) is available over the counter in most countries and is widely considered to be safe for use during pregnancy; studies report gestational exposures to acetaminophen that lie in the 46%-65% range. Acetaminophen influences inflammatory and immunologic mechanisms and may predispose to oxidative stress; these and other effects are hypothesized to have the potential to compromise neurodevelopment in the fetal and infant brain. Two ecological studies suggested that population-level trends in the use of acetaminophen were associated with trends in the incidence/prevalence of autism; one of these studies specifically examined acetaminophen use during pregnancy. One large prospective observational cohort study found that gestational exposure to acetaminophen (especially when the duration of exposure was 28 days or more) was associated with motor milestone delay, gross and fine motor impairments, communication impairment, impairments in internalizing and externalizing behaviors, and hyperactivity, all at age 3 years; however, social and emotional developmental behaviors were mostly unaffected. A very recent large cohort study with a 12.7-year follow-up found that gestational exposure to acetaminophen was associated with an increased risk of autism spectrum disorder, but only when a hyperkinetic disorder was also present. In the light of existing data associating acetaminophen use during pregnancy and subsequent risk of attention-deficit/hyperactivity disorder, this new finding suggests that the predisposition, if any, is toward the hyperkinetic syndrome rather than to autism. In summary, the empirical data are very limited, but whatever empirical data exist do not support the suggestion that the use of acetaminophen during pregnancy increases the risk of autism in the offspring.
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2. Banerjee A, Luong JA, Ho A, Saib AO, Ploski JE. {{Overexpression of Homer1a in the basal and lateral amygdala impairs fear conditioning and induces an autism-like social impairment}}. {Mol Autism};2016;7:16.
BACKGROUND: Autism spectrum disorders (ASDs) represent a heterogeneous group of disorders with a wide range of behavioral impairments including social and communication deficits. Apart from these core symptoms, a significant number of ASD individuals display higher levels of anxiety, and some studies indicate that a subset of ASD individuals have a reduced ability to be fear conditioned. Deciphering the molecular basis of ASD has been considerably challenging and it currently remains poorly understood. In this study we examined the molecular basis of autism-like impairments in an environmentally induced animal model of ASD, where pregnant rats are exposed to the known teratogen, valproic acid (VPA), on day 12.5 of gestation and the subsequent progeny exhibit ASD-like symptoms. We focused our analysis on the basal and lateral nucleus of the amygdala (BLA), a region of the brain found to be associated with ASD pathology. METHODS: We performed whole genome gene expression analysis on the BLA using DNA microarrays to examine differences in gene expression within the amygdala of VPA-exposed animals. We validated one VPA-dysregulated candidate gene (Homer1a) using both quantitative PCR (qRT-PCR) and western blot. Finally, we overexpressed Homer1a within the basal and lateral amygdala of naive animals utilizing adeno-associated viruses (AAV) and subsequently examined these animals in a battery of behavioral tests associated with ASD, including auditory fear conditioning, social interaction and open field. RESULTS: Our microarray data indicated that Homer1a was one of the genes which exhibited a significant upregulation within the amygdala. We observed an increase in Homer1a messenger RNA (mRNA) and protein in multiple cohorts of VPA-exposed animals indicating that dysregulation of Homer1a levels might underlie some of the symptoms exhibited by VPA-exposed animals. To test this hypothesis, we overexpressed Homer1a within BLA neurons utilizing a viral-mediated approach and found that overexpression of Homer1a impaired auditory fear conditioning and reduced social interaction, while having no influence on open-field behavior. CONCLUSIONS: This study indicates that dysregulation of amygdala Homer1a might contribute to some autism-like symptoms induced by VPA exposure. These findings are interesting in part because Homer1a influences the functioning of Shank3, metabotropic glutamate receptors (mGluR5), and Homer1, and these proteins have previously been associated with ASD, indicating that these differing models of ASD may have a similar molecular basis.
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3. Benjamin TE, Lucas-Thompson RG, Little LM, Davies PL, Khetani MA. {{Participation in Early Childhood Educational Environments for Young Children with and Without Developmental Disabilities and Delays: A Mixed Methods Study}}. {Phys Occup Ther Pediatr};2016 (Mar 1):1-21.
AIMS: This mixed methods study examined: 1) how young children with and without developmental disabilities and delays participate in daycare or preschool activities; 2) similarities and differences in environmental factors impacting daycare or preschool participation; and 3) strategies used by parents who desired a change in their child’s participation. METHODS: Data were drawn from 129 parents of young children with and without developmental disabilities and delays (mean age = 49.3 months) residing in North America. Summary and item-level group differences based on disability status were assessed for participation and environmental supports to participation. Narrative data on parental strategies were content coded, transformed into numerical counts, and summarized to identify strategies commonly employed by parents to promote their child’s participation. RESULTS: Moderate to large disability related group differences in participation and environmental support to participation were found even after controlling for confounding effects of child age, child gender, and family income. Parents commonly described strategies focused on « child care tasks » and « child peer groups, » irrespective of the type(s) of change they desired. CONCLUSIONS: Study findings suggest that discrepancies in school participation between young children with and without disabilities and delays can be detected and intervened on during the early childhood period.
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4. Cai J, Ding L, Zhang JS, Xue J, Wang LZ. {{Elevated plasma levels of glutamate in children with autism spectrum disorders}}. {Neuroreport};2016 (Mar 2);27(4):272-276.
Excitatory neurotransmitter signaling through glutamate receptors modulates cognitive functions such as memory and learning, which are usually impaired in autism spectrum disorders (ASD). The aim of this study was to assess the clinical significance of plasma glutamate levels in ASD. Fifty-one children diagnosed with ASD, 51 typically developing children, and 51 children with intellectual disability matched for sex and age were assessed for plasma glutamate at admission. Plasma levels of glutamate were measured by liquid chromatography-tandem mass spectrometry and the severity of ASD was evaluated using the Childhood Autism Rating Scale Score. We found that the mean plasma glutamate levels were significantly (P<0.0001) higher in children with ASD compared with healthy controls and intellectual disability controls [36.1 (SD: 8.3) vs. 23.4 (4.2) vs. 24.7 (4.6) microM; P<0.001, respectively]. Levels of glutamate increased with increasing severity of ASD as defined by the Childhood Autism Rating Scale score. Receiver operating characteristics to diagnose ASD showed areas under the curve of glutamate of 0.92 [95% confidence interval (CI), 0.87-0.96], which was superior to high-sensitivity C-reactive protein [0.64 (95% CI, 0.55-0.75), P<0.001] and homocysteine (area under the curve, 0.72; 95% CI, 0.64-0.81; P<0.000). In multivariate logistic regression analysis, glutamate was an independent diagnosis indicator of ASD with an adjusted odds ratio of 1.362 (95% CI, 1.164-1.512; P<0.0001). The present study shows that autistic children had higher plasma levels of glutamate and elevated plasma glutamate levels may play an important role in the pathogenesis of autism. Further larger studies are required to support our findings. Lien vers le texte intégral (Open Access ou abonnement)
5. Campbell SB, Leezenbaum NB, Mahoney AS, Moore EL, Brownell CA. {{Pretend Play and Social Engagement in Toddlers at High and Low Genetic Risk for Autism Spectrum Disorder}}. {J Autism Dev Disord};2016 (Mar 2)
Toddlers with an older sibling with autism spectrum disorder (ASD) and low risk (LR) toddlers with typically-developing older siblings were observed during free play with a parent and elicited pretend with an examiner at 22-months. Functional and pretend play, children’s social engagement, and parent sensitivity were assessed during free play. Complexity of play was assessed during the elicited pretend task. Toddlers with an ASD diagnosis showed less pretend play across contexts and less social engagement with parents or the examiner than either LR toddlers or high risk toddlers without a diagnosis (HR-noASD). Lower levels of pretend play and social engagement were associated with symptom severity within the high risk group, reflecting emerging ASD in toddlerhood.
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6. Coshway L, Broussard J, Acharya K, Fried K, Msall ME, Lantos JD, Nahata L. {{Medical Therapy for Inappropriate Sexual Behaviors in a Teen With Autism Spectrum Disorder}}. {Pediatrics};2016 (Mar 2)
Teens with autism spectrum disorder often exhibit sexual behaviors in public that are disturbing to parents, teachers, and peers. Some have proposed that such behaviors can be curtailed with hormonal suppression. There is information on the Internet suggesting that such medications work, and some reports in the peer-reviewed medical literature support these claims. Such medications can have serious side effects. In this paper, we present a case in which parents requested such treatment of their teenage son with autism spectrum disorder.
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7. Darbro BW, Singh R, Zimmerman MB, Mahajan VB, Bassuk AG. {{Autism Linked to Increased Oncogene Mutations but Decreased Cancer Rate}}. {PLoS One};2016;11(3):e0149041.
Autism spectrum disorder (ASD) is one phenotypic aspect of many monogenic, hereditary cancer syndromes. Pleiotropic effects of cancer genes on the autism phenotype could lead to repurposing of oncology medications to treat this increasingly prevalent neurodevelopmental condition for which there is currently no treatment. To explore this hypothesis we sought to discover whether autistic patients more often have rare coding, single-nucleotide variants within tumor suppressor and oncogenes and whether autistic patients are more often diagnosed with neoplasms. Exome-sequencing data from the ARRA Autism Sequencing Collaboration was compared to that of a control cohort from the Exome Variant Server database revealing that rare, coding variants within oncogenes were enriched for in the ARRA ASD cohort (p<1.0x10-8). In contrast, variants were not significantly enriched in tumor suppressor genes. Phenotypically, children and adults with ASD exhibited a protective effect against cancer, with a frequency of 1.3% vs. 3.9% (p<0.001), but the protective effect decreased with age. The odds ratio of neoplasm for those with ASD relative to controls was 0.06 (95% CI: 0.02, 0.19; p<0.0001) in the 0 to 14 age group; 0.35 (95% CI: 0.14, 0.87; p = 0.024) in the 15 to 29 age group; 0.41 (95% CI: 0.15, 1.17; p = 0.095) in the 30 to 54 age group; and 0.49 (95% CI: 0.14, 1.74; p = 0.267) in those 55 and older. Both males and females demonstrated the protective effect. These findings suggest that defects in cellular proliferation, and potentially senescence, might influence both autism and neoplasm, and already approved drugs targeting oncogenic pathways might also have therapeutic value for treating autism. Lien vers le texte intégral (Open Access ou abonnement)
8. Fluegge K. {{Environmental factors in the development of autism spectrum disorders: A reply to Sealey et al. (2016)}}. {Environ Int};2016 (Feb 26)
Sealey et al. have reviewed the available evidence on environmental factors that may predispose the development of autism spectrum disorders (ASD) in vulnerable populations. The authors identify exposure to vaccines, pesticides, and air pollutants as potential contributors. The author of this correspondence has previously proposed elsewhere that exposure to increasing levels of the agricultural and environmental pollutant, nitrous oxide (N2O), may be the dominant etiology of ASD and other neurodevelopmental disorders. N2O is thought to target the opioidergic system, including the K-opioid receptor (KOR). Exposure to thimerosal-containing vaccines may disrupt the activity of several endogenous targets as has been shown, principally including mu-opioid receptor (MOR). Given the antagonistic actions of the MOR and KOR, dysregulation of MOR may leave the heightened dynorphin/KOR system unchecked, possibly inducing a negative emotional state that is characteristic of ASD. Future attention may need to be focused on understanding on how early-life mercury exposures, such as in vaccines, may or may not reveal a gestational opiate dependence induced from other ASD-implicated environmental factors.
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9. Gogliotti RG, Klar R, Rook JM, Ghoshal A, Zamorano R, Malosh C, Stauffer SR, Bridges TM, Bartolome JM, Daniels JS, Jones C, Lindsley CW, Conn PJ, Niswender CM. {{mGlu5 Positive Allosteric Modulation Normalizes Synaptic Plasticity Defects and Motor Phenotypes in a Mouse Model of Rett Syndrome}}. {Hum Mol Genet};2016 (Mar 2)
Rett syndrome (RS) is a neurodevelopmental disorder that shares many symptomatic and pathological commonalities with idiopathic autism. Alterations in protein synthesis dependent synaptic plasticity (PSDSP) are a hallmark of a number of syndromic forms of autism; in the present work, we explore the consequences of disruption and rescue of PSDSP in a mouse model of RS. We report that expression of a key regulator of synaptic protein synthesis, the metabotropic glutamate receptor 5 (mGlu5) protein, is significantly reduced in both the brains of RS model mice and in the motor cortex of human RS autopsy samples. Furthermore, we demonstrate that reduced mGlu5 expression correlates with attenuated DHPG induced long term depression (LTD) in the hippocampus of RS model mice, and that administration of a novel mGlu5 positive allosteric modulator (PAM), termed VU0462807, can rescue synaptic plasticity defects. Additionally, treatment of Mecp2-deficient mice with VU0462807 improves motor performance (open field behavior and gait dynamics), corrects repetitive clasping behavior, as well as normalizes cued fear conditioning defects. Importantly, due to the rationale drug discovery approach used in its development, our novel mGlu5 PAM improves RS phenotypes and synaptic plasticity defects without evoking the overt adverse effects commonly associated with potentiation of mGlu5 signaling (i.e. seizures), or affecting cardiorespiratory defects in RS model mice. These findings provide strong support for the continued development of mGlu5 PAMs as potential therapeutic agents for use in RS, and, more broadly, for utility in idiopathic autism.
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10. Hare DJ, Vahey C, Walker S, Wittkowski A. {{Clinical psychologists’ attitudes towards the biology and ‘new genetics’ of intellectual and developmental disabilities: a pilot study using Q-methodology}}. {J Intellect Disabil Res};2016 (Feb 29)
BACKGROUND: The current study investigated how ideas and models from the ‘New Genetics’ and associated fields of developmental neuroscience and behavioural phenotypes are perceived by clinical psychologists working with people with intellectual and developmental disabilities (IDD). As well as examining the take-up and influence of such ideas, it also examines barriers, both personal and institutional, to the widespread adoption of such concepts and research findings in services for people with IDD. METHODS: A Q-methodology study was undertaken with 31 qualified and 16 trainee clinical psychologists in the North West of England using a specifically developed 81-item Q set. RESULTS: Three factors were identified and labelled Integration of social and medical models, Social model of disability is more helpful and Genetic advances in conflict with recognising the value of people with IDD. CONCLUSION: There was a lack of consensus in clinical psychologists working with people with IDD, with amount and type of professional experience affecting the factor loadings, which may need to be considered in developing clinical applications of genetic IDD research.
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11. Harrop C, Green J, Hudry K. {{Play complexity and toy engagement in preschoolers with autism spectrum disorder: Do girls and boys differ?}}. {Autism};2016 (Mar 2)
While sex differences in play have been extensively observed in typical development, only a handful of studies have explored this phenomenon in depth with children with autism spectrum disorders. This study explored sex differences in play complexity and toy engagement within caregiver-child interaction samples for preschool-aged children (2-5 years 11 months) with an autism spectrum disorder who were matched to typically developing children on sex and non-verbal development. Overall we found that girls and boys with autism spectrum disorder were largely equivalent in their play complexity. Despite similar play, girls and boys with autism spectrum disorder differed in a number of ways in their toy engagement, replicating traditional gender differences-girls played more with dolls and domestic items (though at lower rates than typically developing girls) and boys played more with the garage and cars (though at lower rates than typically developing boys). Our findings support the importance and utility of examining sex differences in autism spectrum disorder in light of those observed within typical development.
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12. Kawabe K, Kondo S, Matsumoto M, Seo K, Ochi M, Oka Y, Horiuchi F, Ueno SI. {{Developmental quotient to estimate intelligence in autism spectrum disorder}}. {Pediatr Int};2016 (Mar 2)
BACKGROUND: Autism spectrum disorders (ASD) are characterized by persistent deficits in social communication and social interaction across contexts, and are associated with restricted patterns of behavior. The developmental quotient (DQ) is a quotient based on the developmental age and chronological age of children. This study aimed to investigate the utility of the DQ to estimate cognitive ability in young children with ASD. METHODS: The DQ and intelligence quotient (IQ) were assessed using the Kyoto Scale of Psychological Development 2001 (KSPD) and Wechsler Intelligence Scale for Children-III (WISC-III), respectively. The correlation between the DQ and IQ was then analyzed among children with ASD. RESULTS: We enrolled 18 children with ASD (16 boys, 2 girls; age, 63.6 +/- 9.4 months; age range, 45-83 months). Overall, Cognitive-Adaptive and Language-Social DQ scores were significantly correlated with the IQ scores in the full, verbal, and performance domains. Full IQ and overall DQ showed a linear regression (y = -22.747 + 1.177x, R2 = 0.677, R = 0.823). CONCLUSIONS: The DQ scores obtained using the KSPD were a reasonable estimate of cognitive ability in children with ASD. The KSPD may be a useful variable alternative to the WISC-III for young children with ASD and could facilitate earlier assessment. This article is protected by copyright. All rights reserved.
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13. Kover ST, Edmunds SR, Ellis Weismer S. {{Brief Report: Ages of Language Milestones as Predictors of Developmental Trajectories in Young Children with Autism Spectrum Disorder}}. {J Autism Dev Disord};2016 (Mar 2)
Recognizing early risk markers in young children with autism spectrum disorder (ASD) is critical for timely diagnosis and intervention. The purpose of this study was to extend previous findings regarding language milestones to a longitudinal design, in which ages of expressive language milestones (i.e., first words, first phrases) could serve as predictors of developmental trajectories in a heterogeneous sample of young children with ASD (N = 98; age at first assessment: M = 32 months, SD = 5). Age of first words predicted trajectories of expressive language and adaptive skills; number of words predicted each outcome examined. Because these aspects of early language show promise as potential indicators of later functional outcomes, future research on developmental processes as they relate to individual differences will be particularly informative.
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14. Li P, Zhang C, Yi L. {{Brief Report: Sensitivity of Children with Autism Spectrum Disorders to Face Appearance in Selective Trust}}. {J Autism Dev Disord};2016 (Mar 2)
The current study examined how children with Autism Spectrum Disorders (ASD) could selectively trust others based on three facial cues: the face race, attractiveness, and trustworthiness. In a computer-based hide-and-seek game, two face images, which differed significantly in one of the three facial cues, were presented as two cues for selective trust. Children had to selectively trust the own-race, attractive and trustworthy faces to get the prize. Our findings demonstrate an intact ability of selective trust based on face appearance in ASD compared to typical children: they could selectively trust the informant based on face race and attractiveness. Our results imply that despite their face recognition deficits, children with ASD are still sensitive to some aspects of face appearance.
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15. Li W, Xu X, Pozzo-Miller L. {{Excitatory synapses are stronger in the hippocampus of Rett syndrome mice due to altered synaptic trafficking of AMPA-type glutamate receptors}}. {Proc Natl Acad Sci U S A};2016 (Feb 29)
Deficits in long-term potentiation (LTP) at central excitatory synapses are thought to contribute to cognitive impairments in neurodevelopmental disorders associated with intellectual disability and autism. Using the methyl-CpG-binding protein 2 (Mecp2) knockout (KO) mouse model of Rett syndrome, we show that naive excitatory synapses onto hippocampal pyramidal neurons of symptomatic mice have all of the hallmarks of potentiated synapses. Stronger Mecp2 KO synapses failed to undergo LTP after either theta-burst afferent stimulation or pairing afferent stimulation with postsynaptic depolarization. On the other hand, basal synaptic strength and LTP were not affected in slices from younger presymptomatic Mecp2 KO mice. Furthermore, spine synapses in pyramidal neurons from symptomatic Mecp2 KO are larger and do not grow in size or incorporate GluA1 subunits after electrical or chemical LTP. Our data suggest that LTP is occluded in Mecp2 KO mice by already potentiated synapses. The higher surface levels of GluA1-containing receptors are consistent with altered expression levels of proteins involved in AMPA receptor trafficking, suggesting previously unidentified targets for therapeutic intervention for Rett syndrome and other MECP2-related disorders.
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16. Marion IW, Nelson TM, Sheller B, McKinney CM, Scott JM. {{Dental stories for children with autism}}. {Spec Care Dentist};2016 (Mar 2)
PURPOSE: To investigate caregivers’ preference regarding dental stories to prepare children with autism for dental visits. METHODS: Caregivers of children with autism were allowed use of dental stories available via different media (paper, tablet computer, computer) and image types (comics or drawings, photographs, video). Caregivers completed pre- and postintervention surveys. Fisher’s exact tests were used to determine associations between predictive factors and preferences. RESULTS: Forty initial and 16 follow-up surveys were completed. Subjects were primarily male (85%). Mean child age was 6.7 years. Nine (64%) caregivers found the dental story useful for themselves and their child. Two (14%) caregivers found the aid only helpful for themselves. Preferred media type was associated with language understanding (p = .038) and home media preference (p = .002). CONCLUSIONS: Practitioners should consider using dental stories to help prepare families and children for dental visits. Individual preferences for dental stories vary; using prior history can aid in selection.
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17. Mohamed FE, Zaky EA, Youssef A, Elhossiny R, Zahra S, Khalaf R, Youssef W, Wafiq A, Ibrahim R, Abd-Elhakim R, Obada A, Eldin WS. {{Screening of Egyptian toddlers for autism spectrum disorder using an Arabic validated version of M-CHAT; report of a community-based study (Stage I)}}. {Eur Psychiatry};2016 (Feb 26);34:43-48.
BACKGROUND: Although there is a recommendation that toddlers be screened for Autism spectrum disorder (ASD) during their 18- and 24-month well-care child visits, diagnosis often occurs well after the child turns 4 years old. Such delayed diagnosis hinders the implementation of early intervention thus worsens the long-term prognosis of ASD. OBJECTIVE: The current community-based study in its stage I aimed at early screening of Egyptian toddlers for ASD using an Arabic validated version of Modified Checklist for Autism in Toddlers (M-CHAT). METHODOLOGY: A cross-sectional community-based descriptive study was carried out enrolling 5546 Egyptian toddlers. They were randomly recruited from those attending Primary Health Care Units in six Egyptian governorates with a fair representation of the urban, semi-urban, and rural Egyptian populations. An Arabic validated version of M-CHAT was used as a screening tool for ASD. RESULTS: The current study revealed failure of M-CHAT (suspected to have ASD and needs further evaluation) in 1320 out of the enrolled 5546 Egyptian toddlers (23.8%). CONCLUSION: M-CHAT as a screening tool for ASD has flagged a considerable percent of the enrolled toddlers that necessitates referral for further evaluation (stage II) to settle the diagnosis of ASD in the true positive cases. Perfecting the delicate balance between sensitivity and specificity for ASD screening tools is crucial in order not to miss early detection of ASD cases and at the same time, to avoid over-diagnosis with subsequent abuse of the limited healthcare resources in developing countries.
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18. Raspa M, Sacco P, Candrilli SD, Bishop E, Petrillo J. {{Validity of a condition specific outcome measure for fragile X syndrome: the Aberrant Behaviour Checklist-utility index}}. {J Intellect Disabil Res};2016 (Mar 1)
BACKGROUND: The purpose of this study was to assess the construct validity of the Aberrant Behaviour Checklist-utility index (ABC-UI) by examining the relationship between healthcare resource utilisation by patients with fragile X syndrome (FXS) as well as burden experienced by their caregivers. METHOD: In 2011, a total of 350 US caregivers of individuals with FXS completed a questionnaire that captured information on FXS-related burden as well as the ABC-Community. Using the ABC-UI, a condition-specific outcome measure derived from the ABC-Community, five utility index categories were created: very low (0.00-0.33); low (0.34-0.66); moderate (0.67-0.77); high (0.78-0.89); and very high (0.90-1.00). Multivariable regression models examined the association between the utility value and nine burden-related outcomes. RESULTS: Approximately 2% of individuals with FXS were in the very low utility index category, 31% low, 27% moderate, 38% high and 3% very high. The median utility value was 0.74. Women with FXS and adults 18 years and older had higher values. Regression results indicate that individuals with higher utility values were more likely to have fewer specialist visits, use fewer prescription medications, need fewer hours of unpaid caregiving, inflict fewer caregiver injuries and have caregivers with fewer mental health provider visits. CONCLUSIONS: The ABC-UI appears to function well as condition-specific outcome measure, and as an indicator of health-related quality-of-life and economic burden in individuals with FXS. Among patients with FXS in the US and their caregivers, significant differences in health care resource utilisation and burden exist across health state utility categories.
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19. Signorini C, De Felice C, Leoncini S, Moller RS, Zollo G, Buoni S, Cortelazzo A, Guerranti R, Durand T, Ciccoli L, D’Esposito M, Ravn K, Hayek J. {{MECP2 Duplication Syndrome: Evidence of Enhanced Oxidative Stress. A Comparison with Rett Syndrome}}. {PLoS One};2016;11(3):e0150101.
Rett syndrome (RTT) and MECP2 duplication syndrome (MDS) are neurodevelopmental disorders caused by alterations in the methyl-CpG binding protein 2 (MECP2) gene expression. A relationship between MECP2 loss-of-function mutations and oxidative stress has been previously documented in RTT patients and murine models. To date, no data on oxidative stress have been reported for the MECP2 gain-of-function mutations in patients with MDS. In the present work, the pro-oxidant status and oxidative fatty acid damage in MDS was investigated (subjects n = 6) and compared to RTT (subjects n = 24) and healthy condition (subjects n = 12). Patients with MECP2 gain-of-function mutations showed increased oxidative stress marker levels (plasma non-protein bound iron, intraerythrocyte non-protein bound iron, F2-isoprostanes, and F4-neuroprostanes), as compared to healthy controls (P Lien vers le texte intégral (Open Access ou abonnement)
20. Sun YL, Shao T, Yao YY, Tao HH, Ni LL, Yan SQ, Gu CL, Cao H, Huang K, Tao FB. {{[Pregnancy-related anxiety and subthreshold autism trait in preschool children based a birth cohort study]}}. {Zhonghua Yu Fang Yi Xue Za Zhi};2016 (Feb 6);50(2):118-122.
OBJECTIVE: To analyze the associations between pregnancy-related anxiety and the prevalence of subthreshold autism trait (SAT) in preschool children. METHODS: Baseline data came from the Ma’anshan Birth Cohort Study, a part of the China-Anhui Birth Cohort Study (C-ABCS). All the participants were enrolled among pregnant women who received prenatal health care in 4 municipal medical centers during Oct. 2008 to Oct. 2010. A total of 5 084 pregnant women were recruited at the beginning and 4 669 singleton live births were included until childbirth. The situation about pregnancy-specific anxiety during trimester and third trimester of women were evaluated by Pregnancy-specific Anxiety Questionnaire (PAQ). Between April 2014 and April 2015, the cohort was followed up again, and the Clancy Autism Behavior Scale (CABRS) filled out by parents was used for telling the SAT children from the healthy children among 3 663 preschool children. Univariate and binary regression model was used to estimate associations between the pregnancy-related anxiety during trimester and third trimester and the subthreshold autism trait in children. RESULTS: During the pregnancy, the detected rates of women with pregnancy-specific anxiety in trimester and the third trimester were 25.5%(935/3 663), 13.9%(501/3 592) respectively, and the detected rate of maternal pregnancy-specific anxiety in both periods was 7.7%(278/3 592). There were 290 positive children with SAT and the detection rate was 7.9%. After controlling possible confounding factors including children’s genders, place of residence, supplement folic acid during pregnancy, preterm birth, exposure to second-hand smoke during pregnancy, the father (mother) cultural levels, the father (mother) nature of work and family income, the results of multinomial logistic regression analysis showed that maternal pregnancy-specific anxiety in trimester was the risk factor for SAT in preschool children (OR=1.51, 95%CI: 1.11-2.04), and there was no association between maternal pregnancy-specific anxiety in the third trimester and SAT in preschool children (OR=1.36, 95%CI: 0.82-2.22). Compared with the single function of maternal pregnancy-specific anxiety in trimester or the third trimester for SAT in preschool children, maternal pregnancy-specific anxiety in both periods presented a joint action that increasing the risk for SAT (OR=2.02, 95%CI: 1.36-2.98). CONCLUSION: Maternal pregnancy-related anxiety was a risk factor for subthreshold autism trait in preschooler children. Pregnant women should try to keep a good mental state to create a good environment for fetal growth.
21. Takata A, Ionita-Laza I, Gogos JA, Xu B, Karayiorgou M. {{De Novo Synonymous Mutations in Regulatory Elements Contribute to the Genetic Etiology of Autism and Schizophrenia}}. {Neuron};2016 (Mar 2);89(5):940-947.
We analyze de novo synonymous mutations identified in autism spectrum disorders (ASDs) and schizophrenia (SCZ) with potential impact on regulatory elements using data from whole-exome sequencing (WESs) studies. Focusing on five types of genetic regulatory functions, we found that de novo near-splice site synonymous mutations changing exonic splicing regulators and those within frontal cortex-derived DNase I hypersensitivity sites are significantly enriched in ASD and SCZ, respectively. These results remained significant, albeit less so, after incorporating two additional ASD datasets. Among the genes identified, several are hit by multiple functional de novo mutations, with RAB2A and SETD1A showing the highest statistical significance in ASD and SCZ, respectively. The estimated contribution of these synonymous mutations to disease liability is comparable to de novo protein-truncating mutations. These findings expand the repertoire of functional de novo mutations to include « functional » synonymous ones and strengthen the role of rare variants in neuropsychiatric disease risk.
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22. Zettergren A, Karlsson S, Hovey D, Jonsson L, Melke J, Anckarsater H, Lichtenstein P, Lundstrom S, Westberg L. {{Further investigations of the relation between polymorphisms in sex steroid related genes and autistic-like traits}}. {Psychoneuroendocrinology};2016 (Feb 23);68:1-5.
Autism spectrum disorders (ASDs) are more prevalent in boys than in girls, indicating that high levels of testosterone during early development may be a risk factor. Evidence for this hypothesis comes from studies showing associations between fetal testosterone levels, as well as indirect measures of prenatal androgenization, and ASDs and autistic-like traits (ALTs). In a recent study we reported associations between ALTs and single nucleotide polymorphisms (SNPs) in the genes encoding estrogen receptor 1 (ESR1), steroid-5-alpha-reductase, type 2 (SRD5A2) and sex hormone-binding globulin (SHBG) in a subset (n=1771) from the Child and Adolescent Twin Study in Sweden (CATSS). The aim of the present study was to try to replicate these findings in an additional, larger, sample of individuals from the CATSS (n=10,654), as well as to analyze additional SNPs of functional importance in SHBG and SRD5A2. No associations between the previously associated SNPs in the genes ESR1 and SRD5A2 and ALTs could be seen in the large replication sample. Still, our results show that two non-linked SNPs (rs6259 and rs9901675) at the SHBG gene locus might be of importance for language impairment problems in boys. The results of the present study do not point toward a major role for the investigated SNPs in the genes ESR1 and SRD5A2 in ALTs, but a possible influence of genetic variation in SHBG, especially for language impairment problems in boys, cannot be ruled out.
