1. Bieleninik L, Posserud MB, Geretsegger M, Thompson G, Elefant C, Gold C. {{Tracing the temporal stability of autism spectrum diagnosis and severity as measured by the Autism Diagnostic Observation Schedule: A systematic review and meta-analysis}}. {PLoS One}. 2017; 12(9): e0183160.
BACKGROUND: Exploring ways to improve the trajectory and symptoms of autism spectrum disorder is prevalent in research, but less is known about the natural prognosis of autism spectrum disorder and course of symptoms. The objective of this study was to examine the temporal stability of autism spectrum disorder and autism diagnosis, and the longitudinal trajectories of autism core symptom severity. We furthermore sought to identify possible predictors for change. METHODS: We searched PubMed, PsycInfo, EMBASE, Web of Science, Cochrane Library up to October 2015 for prospective cohort studies addressing the autism spectrum disorder/autism diagnostic stability, and prospective studies of intervention effects. We included people of all ages with autism spectrum disorder/autism or at risk of having autism spectrum disorder, who were diagnosed and followed up for at least 12 months using the Autism Diagnostic Observation Schedule (ADOS). Both continuous ADOS scores and dichotomous diagnostic categories were pooled in random-effects meta-analysis and meta-regression. RESULTS: Of 1443 abstracts screened, 44 were eligible of which 40 studies contained appropriate data for meta-analysis. A total of 5771 participants from 7 months of age to 16.5 years were included. Our analyses showed no change in ADOS scores across time as measured by Calibrated Severity Scores (mean difference [MD] = 0.05, 95% CI -0.26 to 0.36). We observed a minor but statistically significant change in ADOS total raw scores (MD = -1.51, 95% CI -2.70 to -0.32). There was no improvement in restricted and repetitive behaviours (standardised MD [SMD] = -0.04, 95% CI -0.19 to 0.11), but a minor improvement in social affect over time (SMD = -0.31, 95% CI -0.50 to -0.12). No changes were observed for meeting the autism spectrum disorder criteria over time (risk difference [RD] = -0.01, 95% CI -0.03 to 0.01), but a significant change for meeting autism criteria over time (RD = -0.18, 95% CI -0.29 to -0.07). On average, there was a high heterogeneity between studies (I2 range: 65.3% to 93.1%). DISCUSSION: While 18% of participants shifted from autism to autism spectrum disorder diagnosis, the overall autism spectrum disorder prevalence was unchanged. Overall autism core symptoms were remarkably stable over time across childhood indicating that intervention studies should focus on other areas, such as quality of life and adaptive functioning. However, due to high heterogeneity between studies and a number of limitations in the studies, the results need to be interpreted with caution.
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2. Chen CH, Chen HI, Chien WH, Li LH, Wu YY, Chiu YN, Tsai WC, Gau SS. {{High resolution analysis of rare copy number variants in patients with autism spectrum disorder from Taiwan}}. {Sci Rep}. 2017; 7(1): 11919.
Rare genomic copy number variations (CNVs) (frequency <1%) contribute a part to the genetic underpinnings of autism spectrum disorders (ASD). The study aimed to understand the scope of rare CNV in Taiwanese patients with ASD. We conducted a genome-wide CNV screening of 335 ASD patients (299 males, 36 females) from Taiwan using Affymetrix Genome-Wide Human SNP Array 6.0 and compared the incidence of rare CNV with that of 1093 control subjects (525 males, 568 females). We found a significantly increased global burden of rare CNVs in the ASD group compared to the controls as a whole or when the rare CNVs were classified by the size and types of CNV. Further analysis confirmed the presence of several rare CNVs at regions strongly associated with ASD as reported in the literature in our sample. Additionally, we detected several new private pathogenic CNVs in our samples and five patients carrying two pathogenic CNVs. Our data indicate that rare genomic CNVs contribute a part to the genetic landscape of our ASD patients. These CNVs are highly heterogeneous, and the clinical interpretation of the pathogenic CNVs of ASD is not straightforward in consideration of the incomplete penetrance, varied expressivity, and individual genetic background. Lien vers le texte intégral (Open Access ou abonnement)
3. Crunkhorn S. {{Neurological disorders: Reversing Rett syndrome}}. {Nat Rev Drug Discov}. 2017.
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4. Durkin MS, Maenner MJ, Baio J, Christensen D, Daniels J, Fitzgerald R, Imm P, Lee LC, Schieve LA, Van Naarden Braun K, Wingate MS, Yeargin-Allsopp M. {{Autism Spectrum Disorder Among US Children (2002-2010): Socioeconomic, Racial, and Ethnic Disparities}}. {Am J Public Health}. 2017: e1-e9.
OBJECTIVES: To describe the association between indicators of socioeconomic status (SES) and the prevalence of autism spectrum disorder (ASD) in the United States during the period 2002 to 2010, when overall ASD prevalence among children more than doubled, and to determine whether SES disparities account for ongoing racial and ethnic disparities in ASD prevalence. METHODS: We computed ASD prevalence and 95% confidence intervals (CIs) from population-based surveillance, census, and survey data. We defined SES categories by using area-level education, income, and poverty indicators. We ascertained ASD in 13 396 of 1 308 641 8-year-old children under surveillance. RESULTS: The prevalence of ASD increased with increasing SES during each surveillance year among White, Black, and Hispanic children. The prevalence difference between high- and low-SES groups was relatively constant over time (3.9/1000 [95% CI = 3.3, 4.5] in 2002 and 4.1/1000 [95% CI = 3.6, 4.6] in the period 2006-2010). Significant racial/ethnic differences in ASD prevalence remained after stratification by SES. CONCLUSIONS: A positive SES gradient in ASD prevalence according to US surveillance data prevailed between 2002 and 2010, and racial and ethnic disparities in prevalence persisted during this time among low-SES children. (Am J Public Health. Published online ahead of print September 21, 2017: e1-e9. doi:10.2105/AJPH.2017.304032).
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5. Goncalves J, Violante IR, Sereno J, Leitao RA, Cai Y, Abrunhosa A, Silva AP, Silva AJ, Castelo-Branco M. {{Testing the excitation/inhibition imbalance hypothesis in a mouse model of the autism spectrum disorder: in vivo neurospectroscopy and molecular evidence for regional phenotypes}}. {Mol Autism}. 2017; 8: 47.
BACKGROUND: Excitation/inhibition (E/I) imbalance remains a widely discussed hypothesis in autism spectrum disorders (ASD). The presence of such an imbalance may potentially define a therapeutic target for the treatment of cognitive disabilities related to this pathology. Consequently, the study of monogenic disorders related to autism, such as neurofibromatosis type 1 (NF1), represents a promising approach to isolate mechanisms underlying ASD-related cognitive disabilities. However, the NF1 mouse model showed increased gamma-aminobutyric acid (GABA) neurotransmission, whereas the human disease showed reduced cortical GABA levels. It is therefore important to clarify whether the E/I imbalance hypothesis holds true. We hypothesize that E/I may depend on distinct pre- and postsynaptic push-pull mechanisms that might be are region-dependent. METHODS: In current study, we assessed two critical components of E/I regulation: the concentration of neurotransmitters and levels of GABA(A) receptors. Measurements were performed across the hippocampi, striatum, and prefrontal cortices by combined in vivo magnetic resonance spectroscopy (MRS) and molecular approaches in this ASD-related animal model, the Nf1+/- mouse. RESULTS: Cortical and striatal GABA/glutamate ratios were increased. At the postsynaptic level, very high receptor GABA(A) receptor expression was found in hippocampus, disproportionately to the small reduction in GABA levels. Gabaergic tone (either by receptor levels change or GABA/glutamate ratios) seemed therefore to be enhanced in all regions, although by a different mechanism. CONCLUSIONS: Our data provides support for the hypothesis of E/I imbalance in NF1 while showing that pre- and postsynaptic changes are region-specific. All these findings are consistent with our previous physiological evidence of increased inhibitory tone. Such heterogeneity suggests that therapeutic approaches to address neurochemical imbalance in ASD may need to focus on targets where convergent physiological mechanisms can be found.
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6. Hotier S, Leroy F, Boisgontier J, Laidi C, Mangin JF, Delorme R, Bolognani F, Czech C, Bouquet C, Toledano E, Bouvard M, Petit J, Mishchenko M, d’Albis MA, Gras D, Gaman A, Scheid I, Leboyer M, Zalla T, Houenou J. {{Social cognition in autism is associated with the neurodevelopment of the posterior superior temporal sulcus}}. {Acta Psychiatr Scand}. 2017.
OBJECTIVE: The posterior superior temporal sulcus (pSTS) plays a critical role in the ‘social brain’. Its neurodevelopment and relationship with the social impairment in autism spectrum disorders (ASD) are not well understood. We explored the relationship between social cognition and the neurodevelopment of the pSTS in ASD. METHOD: We included 44 adults with high-functioning ASD and 36 controls. We assessed their performances on the ‘Reading the mind in the eyes’ test (for 34 of 44 subjects with ASD and 30 of 36 controls), their fixation time on the eyes with eye tracking (for 35 of 44 subjects with ASD and 30 of 36 controls) and the morphology of the caudal branches of the pSTS (length and depth), markers of the neurodevelopment, with structural MRI. RESULTS: The right anterior caudal ramus of the pSTS was significantly longer in patients with ASD compared with controls (52.6 mm vs. 38.3 mm; P = 1.4 x 10-3 ; Cohen’s d = 0.76). Its length negatively correlated with fixation time on the eyes (P = 0.03) in the ASD group and with the ‘Reading the mind in the eyes’ test scores in both groups (P = 0.03). CONCLUSION: Our findings suggest that the neurodevelopment of the pSTS is related to the ASD social impairments.
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7. Kida H, Takahashi T, Nakamura Y, Kinoshita T, Hara M, Okamoto M, Okayama S, Nakamura K, Kosai KI, Taniwaki T, Yamashita Y, Matsuishi T. {{Pathogenesis of Lethal Aspiration Pneumonia in Mecp2-null Mouse Model for Rett Syndrome}}. {Sci Rep}. 2017; 7(1): 12032.
Rett syndrome (RTT) is a neurodevelopmental disorder mainly caused by mutations in the gene encoding the transcriptional regulator Methyl-CpG-binding protein 2 (MeCP2), located on the X chromosome. Many RTT patients have breathing abnormalities, such as apnea and breathing irregularity, and respiratory infection is the most common cause of death in these individuals. Previous studies showed that MeCP2 is highly expressed in the lung, but its role in pulmonary function remains unknown. In this study, we found that MeCP2 deficiency affects pulmonary gene expression and structures. We also found that Mecp2-null mice, which also have breathing problems, often exhibit inflammatory lung injury. These injuries occurred in specific sites in the lung lobes. In addition, polarizable foreign materials were identified in the injured lungs of Mecp2-null mice. These results indicated that aspiration might be a cause of inflammatory lung injury in Mecp2-null mice. On the other hand, MeCP2 deficiency affected the expression of several neuromodulator genes in the lower brainstem. Among them, neuropeptide substance P (SP) immunostaining was reduced in Mecp2-null brainstem. These findings suggest that alteration of SP expression in brainstem may be involved in autonomic dysregulation, and may be one of the causes of aspiration in Mecp2-null mice.
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8. Laidi C, Boisgontier J, Chakravarty MM, Hotier S, d’Albis MA, Mangin JO, Devenyi GA, Delorme R, Bolognani F, Czech C, Bouquet C, Toledano E, Bouvard M, Gras D, Petit J, Mishchenko M, Gaman A, Scheid I, Leboyer M, Zalla T, Houenou J. {{Cerebellar anatomical alterations and attention to eyes in autism}}. {Sci Rep}. 2017; 7(1): 12008.
The cerebellum is implicated in social cognition and is likely to be involved in the pathophysiology of autism spectrum disorder (ASD). The goal of our study was to explore cerebellar morphology in adults with ASD and its relationship to eye contact, as measured by fixation time allocated on the eye region using an eye-tracking device. Two-hundred ninety-four subjects with ASD and controls were included in our study and underwent a structural magnetic resonance imaging scan. Global segmentation and cortical parcellation of the cerebellum were performed. A sub-sample of 59 subjects underwent an eye tracking protocol in order to measure the fixation time allocated to the eye region. We did not observe any difference in global cerebellar volumes between ASD patients and controls; however, regional analyses found a decrease of the volume of the right anterior cerebellum in subjects with ASD compared to controls. There were significant correlations between fixation time on eyes and the volumes of the vermis and Crus I. Our results suggest that cerebellar morphology may be related to eye avoidance and reduced social attention. Eye tracking may be a promising neuro-anatomically based stratifying biomarker of ASD.
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9. Liu J, Liu X, Xiong XQ, Yang T, Cui T, Hou NL, Lai X, Liu S, Guo M, Liang XH, Cheng Q, Chen J, Li TY. {{Effect of vitamin A supplementation on gut microbiota in children with autism spectrum disorders – a pilot study}}. {BMC Microbiol}. 2017; 17(1): 204.
BACKGROUND: Dysbiosis of gut microbiota are commonly reported in autism spectrum disorder (ASD) and may contribute to behavioral impairment. Vitamin A (VA) plays a role in regulation of gut microbiota. This study was performed to investigate the role of VA in the changes of gut microbiota and changes of autism functions in children with ASD. RESULTS: Sixty four, aged 1 to 8 years old children with ASD completed a 6-month follow-up study with VA intervention. High-performance liquid chromatography was used to assess plasma retinol levels. The Autism Behaviour Checklist (ABC), Childhood Autism Rating Scale (CARS) and Social Responsiveness Scale (SRS) were used to assess autism symptoms. CD38 and acid-related orphan receptor alpha (RORA) mRNA levels were used to assess autism-related biochemical indicators’ changes. Evaluations of plasma retinol, ABC, CARS, SRS, CD38 and RORA mRNA levels were performed before and after 6 months of intervention in the 64 children. Illumina MiSeq for 16S rRNA genes was used to compare the differences in gut microbiota before and after 6 months of treatment in the subset 20 of the 64 children. After 6 months of intervention, plasma retinol, CD38 and RORA mRNA levels significantly increased (all P < 0.05); the scores of ABC, CARS and SRS scales showed no significant differences (all P > 0.05) in the 64 children. Meanwhile, the proportion of Bacteroidetes/Bacteroidales significantly increased and the proportion of Bifidobacterium significantly decreased in the subgroup of 20 (all false discovery rate (FDR) q < 0.05). CONCLUSIONS: Bacteroidetes/Bacteroidales were the key taxa related to VA. Moreover, VA played a role in the changes in autism biomarkers. It remains unclear whether the VA concentration is associated with autism symptoms. TRIAL REGISTRATION: The study protocol was peer reviewed and approved by the institutional review board of Children's Hospital, Chongqing Medical University in 2013 and retrospectively registered in Chinese Clinical Trial Registry (ChiCTR) on November 6, 2014 (TRN: ChiCTR-ROC-14005442 ). Lien vers le texte intégral (Open Access ou abonnement)
10. Martinez-Gonzalez AE, Piqueras JA. {{Validation of the Repetitive Behavior Scale-Revised in Spanish-Speakers Participants with Autism Spectrum Disorder}}. {J Autism Dev Disord}. 2017.
Restricted and repetitive behavior (RRB) is one of the two key diagnostic features of autism spectrum disorder (ASD). DSM-5 highlights the importance of severity-based diagnostic modifiers assigned on the basis of intensity of needed supports. Therefore, there is a need for available measures that assess the severity of RRB. The repetitive behavior scale-revised (RBS-R) is probably the most used informant-based rating scale for the assessment of RRB and interests observed in ASD. The present study examined the psychometric properties of the Spanish version of the RBS-R in a sample of 233 participants with ASD, aged 3 to 63 years. Results revealed a six-factor model, good internal consistency, and concurrent-divergent validity. These findings suggest the utility of the Spanish version of RBS-R.
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11. Matsuzaki J, Kagitani-Shimono K, Sugata H, Hanaie R, Nagatani F, Yamamoto T, Tachibana M, Tominaga K, Hirata M, Mohri I, Taniike M. {{Delayed Mismatch Field Latencies in Autism Spectrum Disorder with Abnormal Auditory Sensitivity: A Magnetoencephalographic Study}}. {Front Hum Neurosci}. 2017; 11: 446.
Although abnormal auditory sensitivity is the most common sensory impairment associated with autism spectrum disorder (ASD), the neurophysiological mechanisms remain unknown. In previous studies, we reported that this abnormal sensitivity in patients with ASD is associated with delayed and prolonged responses in the auditory cortex. In the present study, we investigated alterations in residual M100 and MMFs in children with ASD who experience abnormal auditory sensitivity. We used magnetoencephalography (MEG) to measure MMF elicited by an auditory oddball paradigm (standard tones: 300 Hz, deviant tones: 700 Hz) in 20 boys with ASD (11 with abnormal auditory sensitivity: mean age, 9.62 +/- 1.82 years, 9 without: mean age, 9.07 +/- 1.31 years) and 13 typically developing boys (mean age, 9.45 +/- 1.51 years). We found that temporal and frontal residual M100/MMF latencies were significantly longer only in children with ASD who have abnormal auditory sensitivity. In addition, prolonged residual M100/MMF latencies were correlated with the severity of abnormal auditory sensitivity in temporal and frontal areas of both hemispheres. Therefore, our findings suggest that children with ASD and abnormal auditory sensitivity may have atypical neural networks in the primary auditory area, as well as in brain areas associated with attention switching and inhibitory control processing. This is the first report of an MEG study demonstrating altered MMFs to an auditory oddball paradigm in patients with ASD and abnormal auditory sensitivity. These findings contribute to knowledge of the mechanisms for abnormal auditory sensitivity in ASD, and may therefore facilitate development of novel clinical interventions.
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12. Mullegama SV, Klein SD, Nguyen DC, Kim A, Signer R, Fox M, Dorrani N, Hendershot A, Mardach R, Suddath R, Dipple K, Vilain E, Wong DA, Deignan JL, S DC, Grody WW, Martinez-Agosto JA. {{Is it time to retire fragile X testing as a first-tier test for developmental delay, intellectual disability, and autism spectrum disorder?}}. {Genet Med}. 2017.
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13. Operto FF, Martino F, Rinaldi A, Cerracchio A, Salvati G, Orza M, Lembo C, Panzarino G, Di Paolantonio C, Verrotti A, Farello G, Coppola G. {{Long-term outcome of autistic spectrum disorder: a retrospective case study in a southern italian region}}. {Ital J Pediatr}. 2017; 43(1): 83.
BACKGROUND: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder, characterized by impaired social communication and restricted and repetitive behaviours, as well as associated features including intellectual disability and impaired sensorimotor function. Despite a growing interest in this devastating disorder for families and young parents, there are no certainties as regards its aetiology, although a significant genetic background is considered to be important. Since there is little information about the social adaptation and quality of life of patients with Autism Spectrum Disorder, we decided to study and evaluate the long-term outcome and quality of life in a sample of children, adolescent and young adults. METHODS: This is a case study of subjects diagnosed with ASD and followed by clinics and rehabilitation centers in Campania region, in the south of Italy. The study sample was composed by 110 patients (83 males, 27 females), aged between 8.1 and 28.0 years (mean 20.6; median 21.2; SD +/- 4.85), recruited in 8 rehabilitation centers of Campania region. A follow-up interview was performed by means of a questionnaire administered to the parents/caregivers of patients at a mean age of their son/daughter of 20.6 years (median 21.2 years; range 8.1-28.0). RESULTS: Reports from parents or caregivers show an overall improvement with regard to social and adaptive abilities in a group of teen-agers and young adults with ASD. Major concerns on significant quality of life parameters such as independent living, work experiences, friendships and relationships, accommodation type, recreational activities and personal autonomy were persisting. CONCLUSIONS: The present study shows an overall improvement with regard to social and adaptive abilities in a large number of subjects. Considerable problems are related to autonomy, employment opportunities and social relationships of these patients. Parents need more recreational activities and continuous support with facilities for families.
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14. Perez Repetto L, Jasmin E, Fombonne E, Gisel E, Couture M. {{Longitudinal Study of Sensory Features in Children with Autism Spectrum Disorder}}. {Autism Res Treat}. 2017; 2017: 1934701.
BACKGROUND: Between 45 and 95% of children with Autism Spectrum Disorder (ASD) present sensory features that affect their daily functioning. However, the data in the scientific literature are not conclusive regarding the evolution of sensory features in children with ASD. The main objective of this study was to analyze the sensory features of children within the age of 3-4 (T1) when they received their ASD diagnosis and two years later (T2) when they started school. METHODS: We conducted a prospective cohort study to assess sensory features in 34 children with ASD over time. The data were collected using a standardized assessment tool, the Sensory Profile. RESULTS: Our analyses show that sensory features in children with ASD are stable from the age of three to six years. The stability of sensory scores is independent of correction by covariates, such as cognitive level and autism severity scores. CONCLUSIONS: Children with ASD have sensory features that persist from the time of diagnosis at the age of 3 to 4 years to school age. This persistence of sensory features from an early age underscores the need to support these children and their parents. Sensory features should be detected early and managed to improve functional and psychosocial outcomes.
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15. Rescorla LA, Winder-Patel BM, Paterson SJ, Pandey J, Wolff JJ, Schultz RT, Piven J. {{Autism spectrum disorder screening with the CBCL/1(1/2)-5: Findings for young children at high risk for autism spectrum disorder}}. {Autism}. 2017: 1362361317718482.
The screening power of the CBCL/1(1/2)-5’s Withdrawn and Diagnostic and Statistical Manual of Mental Disorders-Pervasive Developmental Problems (DSM-PDP) scales to identify children diagnosed with autism spectrum disorder at 24 months was tested in a longitudinal, familial high-risk study. Participants were 56 children at high risk for autism spectrum disorder due to an affected older sibling (high-risk group) and 26 low-risk children with a typically developing older sibling (low-risk group). At 24 months, 13 of the 56 high-risk children were diagnosed with autism spectrum disorder, whereas the other 43 were not. The high-risk children diagnosed with autism spectrum disorder group had significantly higher scores on the CBCL/1(1/2)-5’s Diagnostic and Statistical Manual of Mental Disorders-Pervasive Developmental Problems and Withdrawn scales than children in the low-risk and high-risk children not diagnosed with autism spectrum disorder groups [Formula: see text]. Receiver operating characteristic analyses yielded very high area under the curve values (0.91 and 0.89), and a cut point of T 60 yielded sensitivity of 77% and specificity of 97% to 99% between the high-risk children diagnosed with autism spectrum disorder and the combination of low-risk and high-risk children not diagnosed with autism spectrum disorder. Consistent with several previous studies, the CBCL/1(1/2)-5’s Diagnostic and Statistical Manual of Mental Disorders-Pervasive Developmental Problems scale and the Withdrawn syndrome differentiated well between children diagnosed with autism spectrum disorder and those not diagnosed.
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16. Schmidt RJ, Kogan V, Shelton JF, Delwiche L, Hansen RL, Ozonoff S, Ma CC, McCanlies EC, Bennett DH, Hertz-Picciotto I, Tancredi DJ, Volk HE. {{Combined Prenatal Pesticide Exposure and Folic Acid Intake in Relation to Autism Spectrum Disorder}}. {Environ Health Perspect}. 2017; 125(9): 097007.
BACKGROUND: Maternal folic acid (FA) protects against developmental toxicity from certain environmental chemicals. OBJECTIVE: We examined combined exposures to maternal FA and pesticides in relation to autism spectrum disorder (ASD). METHODS: Participants were California children born from 2000-2007 who were enrolled in the Childhood Autism Risks from Genetics and the Environment (CHARGE) case-control study at age 2-5 y, were clinically confirmed to have ASD (n=296) or typical development (n=220), and had information on maternal supplemental FA and pesticide exposures. Maternal supplemental FA and household pesticide product use were retrospectively collected in telephone interviews from 2003-2011. High vs. low daily FA intake was dichotomized at 800mug (median). Mothers’ addresses were linked to a statewide database of commercial applications to estimate agricultural pesticide exposure. RESULTS: High FA intake (>/=800mug) during the first pregnancy month and no known pesticide exposure was the reference group for all analyses. Compared with this group, ASD was increased in association with <800mug FA and any indoor pesticide exposure {adjusted odds ratio [OR]=2.5 [95% confidence interval (CI): 1.3, 4.7]} compared with low FA [OR=1.2 (95% CI: 0.7, 2.2)] or indoor pesticides [OR=1.7 (95% CI: 1.1, 2.8)] alone. ORs for the combination of low FA and regular pregnancy exposure (>/=6 mo) to pet pesticides or to outdoor sprays and foggers were 3.9 (95% CI: 1.4, 11.5) and 4.1 (95% CI: 1.7, 10.1), respectively. ORs for low maternal FA and agricultural pesticide exposure 3 mo before or after conception were 2.2 (95% CI: 0.7, 6.5) for chlorpyrifos, 2.3 (95% CI: 0.98, 5.3) for organophosphates, 2.1 (95% CI: 0.9, 4.8) for pyrethroids, and 1.5 (95% CI: 0.5, 4.8) for carbamates. Except for carbamates, these ORs were approximately two times greater than those for either exposure alone or for the expected ORs for combined exposures under multiplicative or additive models. CONCLUSIONS: In this study population, associations between pesticide exposures and ASD were attenuated among those with high versus low FA intake during the first month of pregnancy. Confirmatory and mechanistic studies are needed. https://doi.org/10.1289/EHP604.
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17. Smith-Hicks CL, Gupta S, Ewen JB, Hong M, Kratz L, Kelley R, Tierney E, Vaurio R, Bibat G, Sanyal A, Yenokyan G, Brereton N, Johnston MV, Naidu S. {{Randomized open-label trial of dextromethorphan in Rett syndrome}}. {Neurology}. 2017.
OBJECTIVE: To determine safety and perform a preliminary assessment of dose-dependent efficacy of dextromethorphan in normalizing electrographic spikes, clinical seizures, and behavioral and cognitive functions in girls with Rett syndrome. METHODS: We used a prospective randomized, open-label trial in fast metabolizers of dextromethorphan to examine the effect of dextromethorphan on core clinical features of Rett syndrome. Interictal spike activity and clinical seizures were determined using EEG and parent reporting. Cognitive data were obtained using the Mullen Scales of Early Learning and Vineland Adaptive Behavior Scales, while behavioral data were obtained from parent-completed checklists, the Aberrant Behavior Checklist-Community Version, and the Screen for Social Interaction. Anthropometric data were obtained according to the National Health and Nutrition Examination Survey. The Rett Syndrome Severity Scale provided a clinical global impression of the effect of dextromethorphan on clinical severity. RESULTS: Dextromethorphan is safe for use in 3- to 15-year-old girls with Rett syndrome. Thirty-five girls were treated with 1 of 3 doses of dextromethorphan over a period of 6 months. Statistically significant dose-dependent improvements were seen in clinical seizures, receptive language, and behavioral hyperactivity. There was no significant improvement in global clinical severity as measured by the Rett Syndrome Severity Scale. CONCLUSIONS: Dextromethorphan is a potent noncompetitive antagonist of the NMDA receptor channel that is safe for use in young girls with Rett syndrome. Preliminary evidence suggests that dextromethorphan may improve some core features of Rett syndrome. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that dextromethorphan at various doses does not change EEG spike counts over 6 months, though precision was limited to exclude an important effect.
