1. Davis MAC, Spriggs A, Rodgers A, Campbell J. {{The Effects of a Peer-Delivered Social Skills Intervention for Adults with Comorbid Down Syndrome and Autism Spectrum Disorder}}. {J Autism Dev Disord};2017 (Dec 22)
Deficits in social skills are often exhibited in individuals with comorbid Down syndrome (DS) and autism spectrum disorder (ASD), and there is a paucity of research to help guide intervention for this population. In the present study, a multiple probe study across behaviors, replicated across participants, assessed the effectiveness of peer-delivered simultaneous prompting in teaching socials skills to adults with DS-ASD using visual analysis techniques and Tau-U statistics to measure effect. Peer-mediators with DS and intellectual disability (ID) delivered simultaneous prompting sessions reliably (i.e., > 80% reliability) to teach social skills to adults with ID and a dual-diagnoses of DS-ASD with small (Tau Weighted = .55, 90% CI [.29, .82]) to medium effects (Tau Weighted = .75, 90% CI [.44, 1]). Statistical and visual analysis findings suggest a promising social skills intervention for individuals with DS-ASD as well as reliable delivery of simultaneous prompting procedures by individuals with DS.
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2. Farley M, Cottle KJ, Bilder D, Viskochil J, Coon H, McMahon W. {{Mid-life social outcomes for a population-based sample of adults with ASD}}. {Autism Res};2017 (Dec 20)
Adults with autism spectrum disorders (ASD) fall short of social outcomes of non-ASD peers in mid-life, as documented by currently published research. The aim of the current study was to extend what is known about social functioning, employment, independent living, and use of social services by examining details of the current life status for a population-based sample of adults with ASD (mean age = 35.5 years, range = 22.2-51.4). We collected outcome data via direct assessment and informant report for 169 individuals. Three-fourths of the sample had cognitive abilities in the intellectually disabled range. Social functioning outcomes, as a single measure, mirror those reported previously for other samples, including samples with a high proportion of individuals with normal range intellectual abilities, with 20% achieving the most independent outcomes and 46% requiring high levels of support across most life areas. Participant subgroups who achieved maximal outcomes represented a range of social and intellectual abilities for several outcome metrics. Participants used high levels of public and private supports, yet specific areas of clear, unmet need were also identified. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This paper describes the social functioning outcomes for 169 adults with autism spectrum disorders in mid-life. Adult participants spanned the full range of functional and cognitive ability levels, with over 75% functioning in the cognitively impaired range. While summary descriptions of outcomes for this sample were similar to those reported for other groups of adults, this report provides detailed information regarding employment outcomes, social relationships, leisure activities, participation in the community, residential situations, public service use, and involvement with law enforcement.
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3. Gibbard CR, Ren J, Skuse DH, Clayden JD, Clark CA. {{Structural connectivity of the amygdala in young adults with autism spectrum disorder}}. {Hum Brain Mapp};2017 (Dec 19)
Autism spectrum disorder (ASD) is characterized by impairments in social cognition, a function associated with the amygdala. Subdivisions of the amygdala have been identified which show specificity of structure, connectivity, and function. Little is known about amygdala connectivity in ASD. The aim of this study was to investigate the microstructural properties of amygdala-cortical connections and their association with ASD behaviours, and whether connectivity of specific amygdala subregions is associated with particular ASD traits. The brains of 51 high-functioning young adults (25 with ASD; 26 controls) were scanned using MRI. Amygdala volume was measured, and amygdala-cortical connectivity estimated using probabilistic tractography. An iterative ‘winner takes all’ algorithm was used to parcellate the amygdala based on its primary cortical connections. Measures of amygdala connectivity were correlated with clinical scores. In comparison with controls, amygdala volume was greater in ASD (F(1,94) = 4.19; p = .04). In white matter (WM) tracts connecting the right amygdala to the right cortex, ASD subjects showed increased mean diffusivity (t = 2.35; p = .05), which correlated with the severity of emotion recognition deficits (rho = -0.53; p = .01). Following amygdala parcellation, in ASD subjects reduced fractional anisotropy in WM connecting the left amygdala to the temporal cortex was associated with with greater attention switching impairment (rho = -0.61; p = .02). This study demonstrates that both amygdala volume and the microstructure of connections between the amygdala and the cortex are altered in ASD. Findings indicate that the microstructure of right amygdala WM tracts are associated with overall ASD severity, but that investigation of amygdala subregions can identify more specific associations.
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4. Grimm RP, Solari EJ, McIntyre NS, Zajic M, Mundy PC. {{Comparing growth in linguistic comprehension and reading comprehension in school-aged children with autism versus typically developing children}}. {Autism Res};2017 (Dec 21)
Many children with autism spectrum disorders (ASD) struggle with reading comprehension. Linguistic comprehension is an important predictor of reading comprehension, especially as children progress through elementary school and later grades. Yet, there is a dearth of research examining longitudinal relations between linguistic comprehensions in school-age children with ASD compared to typically-developing peers (TD). This study compared the developmental trajectories of linguistic and reading comprehension in samples of children with ASD and age-matched TD peers. Both groups were administered measures of linguistic and reading comprehension multiple times over a 30-month period. Latent growth curve modeling demonstrated children with ASD performed at significantly lower levels on both measures at the first timepoint and these deficits persisted across time. Children with ASD exhibited growth in both skills comparable to their TD peers, but this was not sufficient to enable them to eventually achieve at a level similar to the TD group. Due to the wide age range of the sample, age was controlled and displayed significant effects. Findings suggest linguistic comprehension skills are related to reading comprehension in children with ASD, similar to TD peers. Further, intervention in linguistic comprehension skills for children with ASD should begin early and there may be a finite window in which these skills are malleable, in terms of improving reading comprehension skills. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: There is relatively little research concerning reading comprehension development in children with ASD and how they compare to TD peers. This study found children with ASD began at lower achievement levels of linguistic comprehension and reading comprehension than TD peers, but the skills developed at a similar rate. Intervening early and raising initial levels of linguistic and reading comprehension may enable children with ASD to perform similarly to TD peers over time.
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5. Lai X, Wu X, Hou N, Liu S, Li Q, Yang T, Miao J, Dong Z, Chen J, Li T. {{Vitamin A Deficiency Induces Autistic-Like Behaviors in Rats by Regulating the RARbeta-CD38-Oxytocin Axis in the Hypothalamus}}. {Mol Nutr Food Res};2017 (Dec 21)
SCOPE: Vitamin A (VA) is an essential nutrient for the development of the brain. We previously found that children with autism spectrum disorder (ASD) have a significant rate of VA deficiency (VAD). In the current study, we aim to determine whether VAD is a risk factor for the generation of autistic-like behaviors via the transcription factor retinoic acid receptor beta (RARbeta)-regulated cluster of differentiation 38 (CD38)-oxytocin (OXT) axis. METHODS AND RESULTS: Gestational VAD or VA supplementation (VAS) rat models were established, and the autistic-like behaviors in the offspring rats were investigated. The different expression levels of RARbeta and CD38 in hypothalamic tissue and serum retinol and OXT concentration were tested. Primary cultured rat hypothalamic neurons were treated with all trans retinoic acid (atRA) and recombinant adenoviruses carrying the rat RARbeta (AdRARbeta) or RNA interference virus RARbeta-siRNA (siRARbeta) were used to infect neurons to change RARbeta signal. Western blotting, chromatin immunoprecipitation (ChIP) and intracellular Ca(2+) detections were used to investigate the primary regulatory mechanism of RARbeta in the CD38-OXT signaling pathway. We found that gestational VAD increased autistic-like behaviors and decreased the expression levels of hypothalamic RARbeta and CD38 and serum OXT levels in the offspring. VAS ameliorated these autistic-like behaviors and increased the expression levels of RARbeta, CD38 and OXT in the gestational VAD pups. In vitro, atRA increased the Ca(2+) excitability of neurons, which might further promote the release of OXT. Different CD38 levels were induced in the neurons by infection with different RARbeta adenoviruses. Furthermore, atRA enhanced the binding of RARbeta to the proximal promoter of CD38, indicating a potential up-regulation of CD38 transcriptional activity by RARbeta. CONCLUSIONS: Gestational VAD might be a risk factor for autistic-like behaviors due to the RARbeta signal suppression of CD38 expression in the hypothalamus of the offspring, which improved with VAS during the early-life period. The nutritional status during pregnancy and the early-life period is important in rats. This article is protected by copyright. All rights reserved.
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6. Lauber E, Filice F, Schwaller B. {{Parvalbumin neurons as a hub in autism spectrum disorders}}. {J Neurosci Res};2017 (Dec 22)
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7. Leaf JB, Leaf R, McEachin J, Cihon JH, Ferguson JL. {{Advantages and Challenges of a Home- and Clinic-Based Model of Behavioral Intervention for Individuals Diagnosed with Autism Spectrum Disorder}}. {J Autism Dev Disord};2017 (Dec 20)
Researchers have demonstrated that comprehensive behavioral intervention can result in significant improvements in the lives of individuals diagnosed with autism spectrum disorder (ASD; e.g.; Lovaas, Journal of Consulting and Clinical Psychology 55(1):3-9, 1987; McEachin et al., American Journal of Mental Retardation 97(4):359-372, 1993). This intervention has occurred in a variety of settings (e.g., school, home, and clinic). Even though procedures based upon the principles of applied behavior analysis (ABA) can be implemented across a variety of settings, there is often confusion about the differences and relative advantages of home- versus clinic-based settings. The purpose of this paper is to provide a discussion of home- and clinic-based intervention within the context of a progressive approach to ABA and discus possible advantages of each type of setting.
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8. Lekovich J, Man L, Xu K, Canon C, Lilienthal D, Stewart JD, Pereira N, Rosenwaks Z, Gerhardt J. {{CGG repeat length and AGG interruptions as indicators of fragile X-associated diminished ovarian reserve}}. {Genet Med};2017 (Dec 21)
PurposeFragile X premutation (PM) carriers may experience difficulties conceiving a child probably due to fragile X-associated diminished ovarian reserve (FXDOR). We investigated which subgroups of carriers with a PM are at higher risk of FXDOR, and whether the number of AGG interruptions within the repeat sequence further ameliorates the risk.MethodsWe compared markers of ovarian reserve, including anti-Mullerian hormone, antral follicle count, and number of oocytes retrieved between different subgroups of patients with a PM.ResultsWe found that carriers with midrange repeats size (70-90 CGG) demonstrate significantly lower ovarian reserve. Additionally, the number of AGG interruptions directly correlated with parameters of ovarian reserve. Patients with longer uninterrupted CGG repeats post-AGG interruptions had the lowest ovarian reserve.ConclusionThis study connects AGG interruptions and certain CGG repeat length to reduced ovarian reserve in carriers with a PM. A possible explanation for our findings is the proposed gonadotoxicity of the FMR1 transcripts. Reduction of AGG interruptions could increase the likelihood that secondary RNA structures in the FMR1 messenger RNA are formed, which could cause cell dysfunction within the ovaries. These findings may provide women with guidance regarding their fertility potential and accordingly assist with their family planning.GENETICS in MEDICINE advance online publication, 21 December 2017; doi:10.1038/gim.2017.220.
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9. Mash LE, Reiter MA, Linke AC, Townsend J, Muller RA. {{Multimodal approaches to functional connectivity in autism spectrum disorders: An integrative perspective}}. {Dev Neurobiol};2017 (Dec 21)
Atypical functional connectivity has been implicated in autism spectrum disorders (ASDs). However, the literature to date has been largely inconsistent, with mixed and conflicting reports of hypo- and hyper-connectivity. These discrepancies are partly due to differences between various neuroimaging modalities. Functional magnetic resonance imaging (fMRI), electroencephalography (EEG), and magnetoencephalography (MEG) measure distinct indices of functional connectivity (e.g., blood-oxygenation level-dependent [BOLD] signal vs. electrical activity). Furthermore, each method has unique benefits and disadvantages with respect to spatial and temporal resolution, vulnerability to specific artifacts, and practical implementation. Thus far, functional connectivity research on ASDs has remained almost exclusively unimodal; therefore, interpreting findings across modalities remains a challenge. Multimodal integration of fMRI, EEG, and MEG data is critical in resolving discrepancies in the literature, and working toward a unifying framework for interpreting past and future findings. This review aims to provide a theoretical foundation for future multimodal research on ASDs. First, we will discuss the merits and shortcomings of several popular theories in ASD functional connectivity research, using examples from the literature to date. Next, the neurophysiological relationships between imaging modalities, including their relationship with invasive neural recordings, will be reviewed. Finally, methodological approaches to multimodal data integration will be presented, and their future application to ASDs will be discussed. Analyses relating transient patterns of neural activity (« states ») are particularly promising. This strategy provides a comparable measure across modalities, captures complex spatiotemporal patterns, and is a natural extension of recent dynamic fMRI research in ASDs. (c) 2017 Wiley Periodicals, Inc. Develop Neurobiol, 2017.
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10. Meiri G, Azoulay H, Menashe I. {{Characteristics Associated with Drug Prescription and Compliance Among Young Children with Autism Spectrum Disorder}}. {J Child Adolesc Psychopharmacol};2017 (Dec 21)
OBJECTIVES: Psychotropic drugs are prescribed to people with autism spectrum disorder (ASD) usually as a means to alleviate comorbidities associated with the disorder. However, despite the uncertainty regarding the efficacy of these treatments for ASD, their prevalence is continuously increasing. The goal of this study was to understand the characteristics associated with drug prescription and compliance among young children with ASD. MATERIALS AND METHODS: We studied patterns of drug utilization in a population-based sample of 211 young children with ASD in Southern Israel. Data regarding drug prescription and compliance (percentage of purchased drugs out of total prescriptions) were acquired from the electronic records of these patients. Compliance rates (CRs) were calculated as percentage of purchased drugs of the total number of prescriptions. RESULTS: A total of 122 prescriptions were made for 75 children in our sample. Drug prescription was significantly associated with the severity of ASD and the types of comorbidity (p < 0.05). Atypical antipsychotic drugs were the most prevalent drugs (49 children; 23.2%), followed by stimulants (28 children; 13.2%) and first-generation antipsychotic drugs (16 children; 7.6%). The average CR in our sample was 75% +/- 3% with about half of the children demonstrating full compliance, and less than fifth of them not complying at all with their drug prescription. CR had a positively linear association with ASD severity at a marginal statistical significance of p = 0.06. No other variables were statistically associated with drug compliance in our study. CONCLUSIONS: Our results highlight the significant effect of ASD severity on both the prescription and CRs of drugs among young children with ASD. Further examination of drug utilization for longer periods and larger samples will help confirming our findings and test the effects of other variables on these pharmaceutical parameters. Lien vers le texte intégral (Open Access ou abonnement)
11. Ming S, Mulhern T, Stewart I, Moran L, Bynum K. {{Training class inclusion responding in typically-developing children and individuals with autism}}. {J Appl Behav Anal};2017 (Dec 19)
In a class inclusion task, a child must respond to stimuli as being involved in two different though hierarchically related categories. This study used a Relational Frame Theory (RFT) paradigm to assess and train this ability in three typically developing preschoolers and three individuals with autism spectrum disorder, all of whom had failed class inclusion tests. For all subjects, relational training successfully established the target repertoire and subsequent testing demonstrated both maintenance and generalization. Limitations and future research directions are discussed.
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12. Song Y, Hakoda Y. {{Selective Impairment of Basic Emotion Recognition in People with Autism: Discrimination Thresholds for Recognition of Facial Expressions of Varying Intensities}}. {J Autism Dev Disord};2017 (Dec 22)
Autism spectrum disorders (ASD) are characterized by early onset qualitative impairments in reciprocal social development. However, whether individuals with ASD exhibit impaired recognition of facial expressions corresponding to basic emotions is debatable. To investigate subtle deficits in facial emotion recognition, we asked 14 children diagnosed with high-functioning autism (HFA)/AS and 17 typically developing peers to complete a new highly sensitive test of facial emotion recognition. The test stimuli comprised faces expressing increasing degrees of emotional intensity that slowly changed from a neutral to a full-intensity happiness, sadness, surprise, anger, disgust, or fear expression. We assessed individual differences in the intensity of stimuli required to make accurate judgments about emotional expressions. We found that, different emotions had different identification thresholds and the two groups were generally similar in terms of the sequence of discrimination threshold of six basic expressions. It was easier for individuals in both groups to identify emotions that were relatively fully expressed (e.g., intensity > 50%). Compared with control participants, children with ASD generally required stimuli with significantly greater intensity for the correct identification of anger, disgust, and fear expressions. These results suggest that individuals with ASD do not have a general but rather a selective impairment in basic emotion recognition.
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13. Thevenet M, Donde C, Machabert R, Ancona L, Jost C, Georgieff N. {{[A mentalization-based perspective on childhood autism treatment]}}. {Encephale};2017 (Dec 22)
Mentalization is a process by which a subject makes sense of both his own mental representations and of those around him. Disturbances in the mentalization process are found in several psychiatric disorders, notably borderline personality disorders for which mentalization-based treatments (MBT) have been developed and evaluated. Children with Autism Spectrum Disorder (ASD) display a theory of mind impairments, which corresponds to disturbances in the mentalization process. Although no MBT protocol for patients with ASD has been described in the literature, such treatment appears promising to improve theory of mind and functional outcome of these children. In this paper, we propose to discuss the theoretical ground of MBT therapeutic effect in children with ASD without intellectual disabilities and to describe a clinical protocol to test this perspective.
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14. Yang Y, Tian J, Yang B. {{Targeting gut microbiome: A novel and potential therapy for autism}}. {Life Sci};2017 (Dec 22)
Autism spectrum disorder (ASD) is a severely neurodevelopmental disorder that impairs a child’s ability to communicate and interact with others. Children with neurodevelopmental disorder, including ASD, are regularly affected by gastrointestinal problems and dysbiosis of gut microbiota. On the other hand, humans live in a co-evolutionary association with plenty of microorganisms that resident on the exposed and internal surfaces of our bodies. The microbiome, refers to the collection of microbes and their genetic material, confers a variety of physiologic benefits to the host in many key aspects of life as well as being responsible for some diseases. A large body of preclinical literature indicates that gut microbiome plays an important role in the bidirectional gut-brain axis that communicates between the gut and central nervous system. Moreover, accumulating evidences suggest that the gut microbiome is involved in the pathogenesis of ASD. The present review introduces the increasing evidence suggesting the reciprocal interaction network among microbiome, gut and brain. It also discusses the possible mechanisms by which gut microbiome influences the etiology of ASD via altering gut-brain axis. Most importantly, it highlights the new findings of targeting gut microbiome, including probiotic treatment and fecal microbiota transplant, as novel and potential therapeutics for ASD diseases.
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15. Silva LC, Teixeira M, Ribeiro EL, Paula CS. {{Impact of a provider training program on the treatment of children with autism spectrum disorder at psychosocial care units in Brazil}}. {Rev Bras Psiquiatr};2017 (Dec 18):0.
OBJECTIVE: To develop, implement, and verify the impact of a training program for health care providers working with children with autism spectrum disorder (ASD) in psychosocial care centers for children and adolescents (Centro de Atencao Psicossocial a Infancia e a Adolescencia – CAPSi) in Sao Paulo, Brazil. METHODS: This quasi-experimental study was conducted with 14 professionals from four CAPSi units. The training program consisted of six phases: 1) pre-intervention observation; 2) meeting with staff to assess the main needs of the training program; 3) developing materials for training and evaluation; 4) meetings to discuss program implementation; 5) a final meeting for case discussion and evaluation; and 6) distance supervision. Three measures were used to evaluate the training program: i) the Knowledge, Attitudes, and Practices (KAP) questionnaire; ii) videos containing questions designed to assess program comprehension; and iii) a satisfaction survey. RESULTS: Thirteen videos were produced to as visual aids for use during the training program, and a further 26 videos were developed to evaluate it. The program was well evaluated by the participants. The video responses and KAP questionnaire scores suggest that staff knowledge and attitudes improved after training. CONCLUSION: The positive findings of this study suggest that the tested training program is feasible for use with multidisciplinary teams working in the CAPSi environment.
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16. Dale B, Modi BM, Jilderda S, McConnell B, Hoang N, Swaroop P, Falcon J, Thiruvahindrapuram B, Walker S, Scherer SW, Stavropoulos DJ, Drmic IE, Carter MT. {{Atypical autism in a boy with double duplication of 22q11.2: implications of increasing dosage}}. {NPJ Genom Med};2017;2:28.
Duplication of chromosome 22q11.2 (LCR A-D) has been reported at higher frequencies in clinical samples than the general population, but phenotypes vary widely. Triplication (4 copies) is rare, but studying the associated phenotype may provide insight into dosage-sensitivity of the genes in this chromosomal interval. We describe a proband with a triplication, specifically a « double duplication » (two copies per chromosome) of the 22q11.2 region, while his parents and two siblings each have a single duplication (3 copies). The proband had a heart malformation, dysmorphic features, and learning and socialization deficits, whereas the other family members did not. This family illustrates that while duplication of the 22q11.2 may not be sufficient to cause clinically significant neurodevelopmental or health-related phenotypes, triplication of the same region may result in a phenotype characterized by a mild neurodevelopmental disorder, facial dysmorphism, and possibly cardiac anomalies.
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17. Dell’Osso L, Carpita B, Gesi C, Cremone IM, Corsi M, Massimetti E, Muti D, Calderani E, Castellini G, Luciano M, Ricca V, Carmassi C, Maj M. {{Subthreshold autism spectrum disorder in patients with eating disorders}}. {Compr Psychiatry};2017 (Nov 28);81:66-72.
AIM: Increasingly data suggest a possible overlap between psychopathological manifestations of eating disorders (EDs) and autism spectrum disorders (ASD). The aim of the present study was to assess the presence of subthreshold autism spectrum symptoms, by means of a recently validated instrument, in a sample of participants with EDs, particularly comparing participants with or without binge eating behaviours. METHODS: 138 participants meeting DSM-5 criteria for EDs and 160 healthy control participants (HCs), were recruited at 3 Italian University Departments of Psychiatry and assessed by the SCID-5, the Adult Autism Subthreshold Spectrum (AdAS Spectrum) and the Eating Disorders Inventory, version 2 (EDI-2). ED participants included: 46 with restrictive anorexia (AN-R); 24 with binge-purging type of Anorexia Nervosa (AN-BP); 34 with Bulimia Nervosa (BN) and 34 with Binge Eating Disorder (BED). The sample was split in two groups: participants with binge eating behaviours (BEB), in which were included participants with AN-BP, BN and BED, and participants with restrictive behaviours (AN-R). RESULTS: participants with EDs showed significantly higher AdAS Spectrum total scores than HCs. Moreover, EDs participants showed significantly higher scores on all AdAS Spectrum domains with the exception of Non verbal communication and Hyper-Hypo reactivity to sensory input for AN-BP participants, and Childhood/Adolescence domain for AN-BP and BED participants. Participants with AN-R scored significantly higher than participants with BEB on the AdAS Spectrum total score, and on the Inflexibility and adherence to routine and Restricted interest/rumination AdAS Spectrum domain scores. Significant correlations emerged between the Interpersonal distrust EDI-2 sub-scale and the Non verbal communication and the Restricted interest and rumination AdAS Spectrum domains; as well as between the Social insecurity EDI-2 sub-scale and the Inflexibility and adherence to routine and Restricted interest and rumination domains in participants with EDs. CONCLUSIONS: Our data corroborate the presence of higher subthreshold autism spectrum symptoms among ED participants with respect to HCs, with particularly higher levels among restrictive participants. Relevant correlations between subthreshold autism spectrum symptoms and EDI-2 Subscale also emerged.
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18. Calhoun JD, Vanoye CG, Kok F, George AL, Jr., Kearney JA. {{Characterization of a KCNB1 variant associated with autism, intellectual disability, and epilepsy}}. {Neurol Genet};2017 (Dec);3(6):e198.
Objective: To perform functional characterization of a potentially pathogenic KCNB1 variant identified by clinical exome sequencing of a proband with a neurodevelopmental disorder that included epilepsy and centrotemporal spikes on EEG. Methods: Whole-exome sequencing identified the KCNB1 variant c.595A>T (p.Ile199Phe). Biochemical and electrophysiologic experiments were performed to determine whether this variant affected protein expression, trafficking, and channel functional properties. Results: Biochemical characterization of the variant suggested normal protein expression and trafficking. Functional characterization revealed biophysical channel defects in assembled homotetrameric and heterotetrameric channels. Conclusions: The identification of the KCNB1 variant c.595A>T (p.Ile199Phe) in a neurodevelopmental disorder that included epilepsy with centrotemporal spikes expands the phenotypic spectrum of epilepsies associated with KCNB1 variants. The KCNB1-I199F variant exhibited partial loss of function relative to the wild-type channel. This defect is arguably less severe than previously reported KCNB1 variants, suggesting the possibility that the degree of KCNB1 protein dysfunction may influence disease severity.
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19. Yang F, Chen J, Miao MH, Yuan W, Li L, Liang H, Ehrenstein V, Li J. {{Risk of autism spectrum disorder in offspring following paternal use of selective serotonin reuptake inhibitors before conception: a population-based cohort study}}. {BMJ Open};2017 (Dec 22);7(12):e016368.
OBJECTIVE: The present study aimed to examine the association between paternal selective serotonin reuptake inhibitor (SSRI) use before conception and the risk of autism spectrum disorder (ASD) in offspring. DESIGN: A population-based cohort study. METHODS: We conducted a cohort study of 669 922 children born from 1998 to 2008, with follow-up throughout 2013. Based on Danish national registers, we linked information on paternal use of SSRIs, ASD diagnosed in children and a range of potential confounders. The children whose fathers used SSRIs during the last 3 months prior to conception were identified as the exposed. Cox regression model was used to estimate the HR for ASD in children. RESULTS: Compared with unexposed children, the exposed had a 1.62-fold higher risk of ASD (95% CI 1.33 to 1.96) and the risk attenuated after adjusting for potential confounders, especially fathers’ psychiatric conditions (HR=1.43, 95% CI 1.18 to 1.74). When extending the exposure window to 1 year before conception, the increased risk persisted in children of fathers using SSRIs only from the last year until the last 3 months prior to conception (HR=1.54, 95% CI 1.21 to 1.94) but not in children of fathers using SSRIs only during the last 3 months prior to conception (HR=1.17, 95% CI 0.75 to 1.82). We also performed stratified analyses according to paternal history of affective disorders and observed no increased ASD risk among children whose father had affective disorders. Besides, the sibling analysis showed that the ASD risk did not increase among exposed children compared with their unexposed siblings. CONCLUSIONS: The mildly increased risk of ASD in the offspring associated with paternal SSRI use before conception may be attributable to paternal underlying psychiatric indications related to SSRI use or other unmeasured confounding factors.
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20. Dona O, Hall GB, Noseworthy MD. {{Temporal fractal analysis of the rs-BOLD signal identifies brain abnormalities in autism spectrum disorder}}. {PLoS One};2017;12(12):e0190081.
BACKGROUND: Brain connectivity in autism spectrum disorders (ASD) has proven difficult to characterize due to the heterogeneous nature of the spectrum. Connectivity in the brain occurs in a complex, multilevel and multi-temporal manner, driving the fluctuations observed in local oxygen demand. These fluctuations can be characterized as fractals, as they auto-correlate at different time scales. In this study, we propose a model-free complexity analysis based on the fractal dimension of the rs-BOLD signal, acquired with magnetic resonance imaging. The fractal dimension can be interpreted as measure of signal complexity and connectivity. Previous studies have suggested that reduction in signal complexity can be associated with disease. Therefore, we hypothesized that a detectable difference in rs-BOLD signal complexity could be observed between ASD patients and Controls. METHODS AND FINDINGS: Anatomical and functional data from fifty-five subjects with ASD (12.7 +/- 2.4 y/o) and 55 age-matched (14.1 +/- 3.1 y/o) healthy controls were accessed through the NITRC database and the ABIDE project. Subjects were scanned using a 3T GE Signa MRI and a 32-channel RF-coil. Axial FSPGR-3D images were used to prescribe rs-BOLD (TE/TR = 30/2000ms) where 300 time points were acquired. Motion correction was performed on the functional data and anatomical and functional images were aligned and spatially warped to the N27 standard brain atlas. Fractal analysis, performed on a grey matter mask, was done by estimating the Hurst exponent in the frequency domain using a power spectral density approach and refining the estimation in the time domain with de-trended fluctuation analysis and signal summation conversion methods. Voxel-wise fractal dimension (FD) was calculated for every subject in the control group and in the ASD group to create ROI-based Z-scores for the ASD patients. Voxel-wise validation of FD normality across controls was confirmed, and non-Gaussian voxels were eliminated from subsequent analysis. To maintain a 95% confidence level, only regions where Z-score values were at least 2 standard deviations away from the mean (i.e. where |Z| > 2.0) were included in the analysis. We found that the main regions, where signal complexity significantly decreased among ASD patients, were the amygdala (p = 0.001), the vermis (p = 0.02), the basal ganglia (p = 0.01) and the hippocampus (p = 0.02). No regions reported significant increase in signal complexity in this study. Our findings were correlated with ADIR and ADOS assessment tools, reporting the highest correlation with the ADOS metrics. CONCLUSIONS: Brain connectivity is best modeled as a complex system. Therefore, a measure of complexity as the fractal dimension of fluctuations in brain oxygen demand and utilization could provide important information about connectivity issues in ASD. Moreover, this technique can be used in the characterization of a single subject, with respect to controls, without the need for group analysis. Our novel approach provides an ideal avenue for personalized diagnostics, thus providing unique patient specific assessment that could help in individualizing treatments.
