1. Angelakos CC, Watson AJ, O’Brien WT, Krainock KS, Nickl-Jockschat T, Abel T. {{Hyperactivity and male-specific sleep deficits in the 16p11.2 deletion mouse model of autism}}. {Autism Res};2016 (Oct 14)
Sleep disturbances and hyperactivity are prevalent in several neurodevelopmental disorders, including autism spectrum disorders (ASDs) and attention deficit-hyperactivity disorder (ADHD). Evidence from genome-wide association studies indicates that chromosomal copy number variations (CNVs) are associated with increased prevalence of these neurodevelopmental disorders. In particular, CNVs in chromosomal region 16p11.2 profoundly increase the risk for ASD and ADHD, disorders that are more common in males than females. We hypothesized that mice hemizygous for the 16p11.2 deletion (16p11.2 del/+) would exhibit sex-specific sleep and activity alterations. To test this hypothesis, we recorded activity patterns using infrared beam breaks in the home-cage of adult male and female 16p11.2 del/+ and wildtype (WT) littermates. In comparison to controls, we found that both male and female 16p11.2 del/+ mice exhibited robust home-cage hyperactivity. In additional experiments, sleep was assessed by polysomnography over a 24-hr period. 16p11.2 del/+ male, but not female mice, exhibited significantly more time awake and significantly less time in non-rapid-eye-movement (NREM) sleep during the 24-hr period than wildtype littermates. Analysis of bouts of sleep and wakefulness revealed that 16p11.2 del/+ males, but not females, spent a significantly greater proportion of wake time in long bouts of consolidated wakefulness (greater than 42 min in duration) compared to controls. These changes in hyperactivity, wake time, and wake time distribution in the males resemble sleep disturbances observed in human ASD and ADHD patients, suggesting that the 16p11.2 del/+ mouse model may be a useful genetic model for studying sleep and activity problems in human neurodevelopmental disorders. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
2. Brodhead MT, Rispoli MJ. {{Using videos to assess preference for novel stimuli in children with autism}}. {Dev Neurorehabil};2016 (Oct 14):1-5.
A primary effort of preference assessment research has been to develop strategies to identify potential reinforcers for educational, social, and behavioral programming for individuals with disabilities, including children with autism. However, little attention has been paid to the identification of preferred stimuli children with autism may not have previous experience with. The purpose of this study was to evaluate the extent to which a video-based preference assessment may accurately identify preference for novel stimuli. We compared the results of the video-based preference assessment with no access to novel stimuli to the results of a preference assessment conducted in a tangible format with access. We then conducted the same video-based preference assessment a second time to evaluate the extent to which exposure to stimuli affected assessment results. The results provide preliminary support that a video-based preference assessment may accurately identify preference for novel stimuli. Implications and future directions are discussed.
Lien vers le texte intégral (Open Access ou abonnement)
3. Cox AD, Virues-Ortega J, Julio F, Martin TL. {{Establishing motion control in children with autism and intellectual disability: Applications for anatomical and functional MRI}}. {J Appl Behav Anal};2016 (Oct 14)
Excessive motion makes magnetic resonance imaging (MRI) extremely challenging among children with autism spectrum disorder (ASD). The medical risks of sedation establish the need for behavioral interventions to promote motion control among children with ASD undergoing MRI scans. We present a series of experiments aimed at establishing both tolerance of the MRI environment and a level of motion control that would be compatible with a successful MRI. During Study 1, we evaluated the effects of prompting and contingent reinforcement on compliance with a sequence of successive approximations to an MRI using a mock MRI. During Study 2, we used prompting and progressive differential reinforcement of other behaviors (DRO) to promote motion control in a mock MRI for increasing periods of time. Finally, during Study 3, some of the participants underwent a real MRI scan while a detailed in-session motion analysis informed the quality of the images captured.
Lien vers le texte intégral (Open Access ou abonnement)
4. DeFilippis M, Wagner KD. {{Treatment of Autism Spectrum Disorder in Children and Adolescents}}. {Psychopharmacol Bull};2016 (Aug 15);46(2):18-41.
Autism spectrum disorder is a diagnosis that includes significant social communication deficits/delays along with restricted patterns of interests and behaviors. The prevalence of this diagnosis has increased over the past few decades, and it is unclear whether this is solely attributable to the increased awareness of milder forms of the disorder among medical providers. The current treatment options for the core symptoms of autism are limited to psychosocial therapies, such as applied behavior analysis. Medications have been most effective in treating the associated behavioral symptoms of autism, though studies have examined potential benefits in some of the core symptoms of autism with certain medications, especially the repetitive behaviors often seen with this diagnosis. Risperidone and aripiprazole are currently the only medications FDA approved for symptoms associated with autism spectrum disorders, targeting the irritability often seen with this diagnosis. Children and adolescents with autism spectrum disorder appear to be more susceptible to adverse effects with medications; therefore, initiation with low doses and titrating very slowly is recommended. Some complementary alternative treatments have been researched as possible treatments in autism, though evidence supporting many of these is very limited.
5. Erickson CA, Ray B, Wink LK, Bayon BL, Pedapati EV, Shaffer R, Schaefer TL, Lahiri DK. {{Initial analysis of peripheral lymphocytic extracellular signal related kinase activation in autism}}. {J Psychiatr Res};2016 (Sep 9);84:153-160.
BACKGROUND: Dysregulation of extracellular signal-related kinase (ERK) activity has been potentially implicated in the pathophysiology of autistic disorder (autism). ERK is part of a central intracellular signaling cascade responsible for a myriad of cellular functions. ERK is expressed in peripheral blood lymphocytes, and measurement of activated (phosphorylated) lymphocytic ERK is commonly executed in many areas of medicine. We sought to conduct the first study of ERK activation in humans with autism by utilizing a lymphocytic ERK activation assay. We hypothesized that ERK activation would be enhanced in peripheral blood lymphocytes from persons with autism compared to those of neurotypical control subjects. METHOD: We conducted an initial study of peripheral lymphocyte ERK activation in 45 subjects with autism and 26 age- and gender-matched control subjects (total n = 71). ERK activation was measured using a lymphocyte counting method (primary outcome expressed as lymphocytes staining positive for cytosolic phosphorylated ERK divided by total cells counted) and additional Western blot analysis of whole cell phosphorylated ERK adjusted for total ERK present in the lymphocyte lysate sample. RESULTS: Cytosolic/nuclear localization of pERK activated cells were increased by almost two-fold in the autism subject group compared to matched neurotypical control subjects (cell count ratio of 0.064 +/- 0.044 versus 0.034 +/- 0.031; p = 0.002). Elevated phosphorylated ERK levels in whole cell lysates also showed increased activated ERK in the autism group compared to controls (n = 54 total) in Western blot analysis. CONCLUSIONS: The results of this first in human ERK activation study are consistent with enhanced peripheral lymphocytic ERK activation in autism, as well as suggesting that cellular compartmentalization of activated ERK may be altered in this disorder. Future work will be required to explore the impact of concomitant medication use and other subject characteristics such as level of cognitive functioning on ERK activation. TRIAL REGISTRATION: Not applicable.
Lien vers le texte intégral (Open Access ou abonnement)
6. Levy A, DeLeon IG, Martinez CK, Fernandez N, Gage NA, Sigurdsson SO, Frank-Crawford MA. {{A quantitative review of overjustification effects in persons with intellectual and developmental disabilities}}. {J Appl Behav Anal};2016 (Oct 14)
The overjustification hypothesis suggests that extrinsic rewards undermine intrinsic motivation. Extrinsic rewards are common in strengthening behavior in persons with intellectual and developmental disabilities; we examined overjustification effects in this context. A literature search yielded 65 data sets permitting comparison of responding during an initial no-reinforcement phase to a subsequent no-reinforcement phase, separated by a reinforcement phase. We used effect sizes to compare response levels in these two no-reinforcement phases. Overall, the mean effect size did not differ from zero; levels in the second no-reinforcement phase were equally likely to be higher or lower than in the first. However, in contrast to the overjustification hypothesis, levels were higher in the second no-reinforcement phase when comparing the single no-reinforcement sessions immediately before and after reinforcement. Outcomes consistent with the overjustification hypothesis were somewhat more likely when the target behavior occurred at relatively higher levels prior to reinforcement.
Lien vers le texte intégral (Open Access ou abonnement)
7. Lounds Taylor J, Adams RE, Bishop SL. {{Social participation and its relation to internalizing symptoms among youth with autism spectrum disorder as they transition from high school}}. {Autism Res};2016 (Oct 14)
In this study, we examined how unstructured (e.g., spending time with friends or co-workers) and structured (e.g., attending social events at a place of workshop, sports teams) social participation changed from before to after high school for youth with autism spectrum disorders (ASD), as well as the longitudinal and concurrent relations between social participation and internalizing symptoms. Participants included 36 families of youth with ASD who were all in their last year of high school at the first time point of data collection, and who were out of high school for an average of 9 months at the second time point. Social participation and internalizing symptoms were determined using parental report. There was no average change in the amount of unstructured social participation after high school exit, although substantial individual variability was observed. Participation in structured social activities significantly declined after high school exit. Youth who had more structured social participation while in high school were significantly more likely to have gains in their unstructured social participation after high school exit. Turning to relationships between internalizing and social activities, more internalizing symptoms while youth with ASD were in high school significantly predicted increasing social isolation after high school exit (both in terms of structured and unstructured activities). Results point to the likely need for additional supports during the transition to adulthood for youth with ASD who have internalizing problems. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
8. Lyall K, Anderson M, Kharrazi M, Windham GC. {{Neonatal thyroid hormone levels in association with autism spectrum disorder}}. {Autism Res};2016 (Oct 14)
Thyroid hormones (TH) are critical in early neurodevelopment, but few studies have examined whether neonatal TH levels influence risk of autism spectrum disorder (ASD). This study linked California neonatal screening data with live birth and Department of Developmental Services records to examine newborn TH levels in relation to ASD. Thyroxine (T4) and thyroid-stimulating hormone (TSH) levels were measured in newborn bloodspots as part of routine screening, in 1996 and 2002, respectively. Mean levels of T4 and TSH were compared between ASD cases and non-cases. Four hundred forty-seven thousand, fifty-nine screened, singleton births from 1996 and 446,424 from 2002 were examined, including 4,818 ASD cases. Binomial regression, using categories of T4 and TSH percentiles was used to calculate crude and adjusted risk ratios (RR). Covariates included maternal and child factors, gestational age, and age at blood draw. No significant associations were found with TSH levels and ASD in crude or adjusted analyses. ASD cases had significantly lower mean T4 levels than non-cases, but this association was no longer significant in adjusted analyses (RR in individuals in lowest 5th percentile of T4 levels = 1.13, 95% 0.93-1.37). However, this association appeared stronger in certain subgroup analyses, particularly among neonates with blood draw >/=48 hr from birth (RR = 1.67, 95% CI 1.08, 2.60), when TH levels become more stable. Thus, results from this large, population-based study did not suggest strong associations between neonatal TH and ASD, but certain subgroups of newborns with the lowest T4 levels may have modestly increased ASD risk. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
9. Lynn AC, Padmanabhan A, Simmonds D, Foran W, Hallquist MN, Luna B, O’Hearn K. {{Functional connectivity differences in autism during face and car recognition: underconnectivity and atypical age-related changes}}. {Dev Sci};2016 (Oct 16)
Face recognition abilities improve between adolescence and adulthood over typical development (TD), but plateau in autism, leading to increasing face recognition deficits in autism later in life. Developmental differences between autism and TD may reflect changes between neural systems involved in the development of face encoding and recognition. Here, we focused on whole-brain connectivity with the fusiform face area (FFA), a well-established face-preferential brain region. Older children, adolescents, and adults with and without autism completed the Cambridge Face Memory Test, and a matched car memory test, during fMRI scanning. We then examined task-based functional connectivity between the FFA and the rest of the brain, comparing autism and TD groups during encoding and recognition of face and car stimuli. The autism group exhibited underconnectivity, relative to the TD group, between the FFA and frontal and primary visual cortices, independent of age. Underconnectivity with the medial and rostral lateral prefrontal cortex was face-specific during encoding and recognition, respectively. Conversely, underconnectivity with the L orbitofrontal cortex was evident for both face and car encoding. Atypical age-related changes in connectivity emerged between the FFA and the R temporoparietal junction, and R dorsal striatum for face stimuli only. Similar differences in age-related changes in autism emerged for FFA connectivity with the amygdala across both face and car recognition. Thus, underconnectivity and atypical development of functional connectivity may lead to a less optimal face-processing network in the context of increasing general and social cognitive deficits in autism.
Lien vers le texte intégral (Open Access ou abonnement)
10. McAuliffe T, Vaz S, Falkmer T, Cordier R. {{A comparison of families of children with autism spectrum disorders in family daily routines, service usage, and stress levels by regionality}}. {Dev Neurorehabil};2016 (Oct 14):1-8.
PURPOSE: To explore whether family routines, service usage, and stress levels in families of children with autism spectrum disorder differ as a function of regionality. METHODS: Secondary analysis of data was undertaken from 535 surveys. Univariate and multivariate analyses were performed to investigate differences between families living in densely populated (DP) areas and less densely populated (LDP) areas. RESULTS: Families living in LDP areas were found to: (1) have reduced employment hours (a two-parent household: Exp (B) = 3.48, p < .001, a single-parent household: Exp (B) = 3.32, p = .011); (2) travel greater distance to access medical facilities (Exp (B) = 1.27, p = .006); and (3) report less severe stress levels (Exp (B) = 0.22, p = .014). CONCLUSIONS: There were no differences in family routines; however, flexible employment opportunities and travel distance to medical services need to be considered in families living in LDP areas. Lien vers le texte intégral (Open Access ou abonnement)
11. Moulton E, Bradbury K, Barton M, Fein D. {{Factor Analysis of the Childhood Autism Rating Scale in a Sample of Two Year Olds with an Autism Spectrum Disorder}}. {J Autism Dev Disord};2016 (Oct 14)
The Childhood Autism Rating Scale (CARS), (Schopler et al. in J Autism Dev Disord 10(1):91-103, 1980) is a 15-item observation-based rating scale that yields a total score reflective of autism symptom severity. This study investigated the factor structure of the CARS in a sample of 2-year-old children with DSM-IV-TR (American Psychiatric Association in Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Publishing, Washington, 2000) diagnoses of AD or PDD-NOS. Following a preliminary internal cross-validation, principal axis factor analysis was completed (N = 282). The results indicate a three-factor solution: Social Communication, Stereotyped Behaviors and Sensory Sensitivities, and Emotional Reactivity. The factors are meaningful, with the first two reflective of DSM-5 symptom domains. This study supports the continued relevance of the CARS in ASD assessment, and extends its utility in 2-year-old children.
Lien vers le texte intégral (Open Access ou abonnement)
12. Shelton AL, Cornish K, Clough M, Gajamange S, Kolbe S, Fielding J. {{Disassociation between brain activation and executive function in fragile X premutation females}}. {Hum Brain Mapp};2016 (Oct 14)
Executive dysfunction has been demonstrated among premutation (PM) carriers (55-199 CGG repeats) of the Fragile X mental retardation 1 (FMR1) gene. Further, alterations to neural activation patterns have been reported during memory and comparison based functional magnetic resonance imaging (fMRI) tasks in these carriers. For the first time, the relationships between fMRI neural activation during an interleaved ocular motor prosaccade/antisaccade paradigm, and concurrent task performance (saccade measures of latency, accuracy and error rate) in PM females were examined. Although no differences were found in whole brain activation patterns, regions of interest (ROI) analyses revealed reduced activation in the right ventrolateral prefrontal cortex (VLPFC) during antisaccade trials for PM females. Further, a series of divergent and group specific relationships were found between ROI activation and saccade measures. Specifically, for control females, activation within the right VLPFC and supramarginal gyrus correlated negatively with antisaccade latencies, while for PM females, activation within these regions was found to negatively correlate with antisaccade accuracy and error rate (right VLPFC only). For control females, activation within frontal and supplementary eye fields and bilateral intraparietal sulci correlated with prosaccade latency and accuracy; however, no significant prosaccade correlations were found for PM females. This exploratory study extends previous reports of altered prefrontal neural engagement in PM carriers, and clearly demonstrates dissociation between control and PM females in the transformation of neural activation into overt measures of executive dysfunction. Hum Brain Mapp, 2016. (c) 2016 Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
13. Takahashi H, Nakahachi T, Stickley A, Ishitobi M, Kamio Y. {{Stability of the acoustic startle response and its modulation in children with typical development and those with autism spectrum disorders: A one-year follow-up}}. {Autism Res};2016 (Oct 14)
Auditory hyper-reactivity is a common sensory-perceptual abnormality that interrupts behavioral adaptations in autism spectrum disorders (ASD). Recently, prolonged acoustic startle response (ASR) latency and hyper-reactivity to weak acoustic stimuli were reported in children with ASD. Indexes of ASR and its modulation are known to be stable biological markers for translational research in the adult population. However, little is known about the stability of these indexes in children. Thus, the objective of our study was to investigate the stability of neurophysiological ASR indexes in children with ASD and typical development (TD). Participants included 12 children with ASD and 24 with TD. Mean startle magnitudes to acoustic stimuli presented at 65-105 dB in increments of 10 dB were analyzed. Average peak startle latency (PSL), ASR modulation of habituation, and prepulse inhibition were also analyzed. These startle measures were examined after a follow-up period of 15.7 +/- 5.1 months from baseline. At both baseline and in the follow-up period, children with ASD had significantly greater startle magnitudes to weak stimuli of 65-85 dB and more prolonged PSL compared with controls. Intraclass correlation coefficients for these ASR measures between both periods were 0.499-0.705. None of the ASR measures differed significantly between the two periods. Our results suggest that prolonged PSL and greater startle magnitudes to weak stimuli in children with ASD might serve as moderately stable neurophysiological indexes of ASD. Autism Res 2016. (c) 2016 International Society for Autism Research, Wiley Periodicals, Inc.
Lien vers le texte intégral (Open Access ou abonnement)
14. Tanaka S, Oi M, Fujino H, Kikuchi M, Yoshimura Y, Miura Y, Tsujii M, Ohoka H. {{Characteristics of communication among Japanese children with autism spectrum disorder: A cluster analysis using the Children’s Communication Checklist-2}}. {Clin Linguist Phon};2016 (Oct 14):1-16.
Some overlap has been suggested among the subtypes of autism spectrum disorder (ASD) in children. The Japanese version of the Children’s Communication Checklist-2 (CCC-2) is a useful measure for identifying profiles in relation to communication impairments in children with ASD. The aim of this study was to investigate whether the CCC-2 could identify subtypes in relation to communication impairments in Japanese children with ASD. The study participants were 113 children with ASD but without intellectual disabilities aged 3-12 years. Parents were given the Japanese version of the CCC-2 and asked to rate their children, who were then classified into two groups based on statistical analysis. Significant differences were found between clusters in mean CCC-2 subscales. These results suggest that one subtype was associated with low language competence and strong characteristics of autism, while the other was associated with relatively high language competence and milder characteristics of autism.
Lien vers le texte intégral (Open Access ou abonnement)
15. Yerys BE, Nissley-Tsiopinis J, de Marchena A, Watkins MW, Antezana L, Power TJ, Schultz RT. {{Evaluation of the ADHD Rating Scale in Youth with Autism}}. {J Autism Dev Disord};2016 (Oct 13)
Scientists and clinicians regularly use clinical screening tools for attention deficit/hyperactivity disorder (ADHD) to assess comorbidity without empirical evidence that these measures are valid in youth with autism spectrum disorder (ASD). We examined the prevalence of youth meeting ADHD criteria on the ADHD rating scale fourth edition (ADHD-RS-IV), the relationship of ADHD-RS-IV ratings with participant characteristics and behaviors, and its underlying factor structure in 386, 7-17 year olds with ASD without intellectual disability. Expected parent prevalence rates, relationships with age and externalizing behaviors were observed, but confirmatory factor analyses revealed unsatisfactory fits for one-, two-, three-factor models. Exploratory analyses revealed several items cross-loading on multiple factors. Implications of screening ADHD in youth with ASD using current diagnostic criteria are discussed.
Lien vers le texte intégral (Open Access ou abonnement)
16. Yin J, Schaaf CP. {{Autism genetics – an overview}}. {Prenat Diagn};2016 (Oct 15)
Autism spectrum disorder (ASD) a highly heritable, clinically diverse group of neurodevelopmental disorders. Its genetic heterogeneity is remarkable, with more than 800 ASD predisposition genes identified to date. They are involved in various biological processes, including chromatin remodeling and gene transcription regulation, cell growth and proliferation, ubiquitination, and neuronal-specific processes, such as synaptic organization and activity, dendritic morphology and axonogenesis. This review aims to discuss basic autism genetics, ways to investigate ASD in model systems, highlight some key genes and their molecular pathways, and introduce novel theories of ASD pathogenesis, such as imbalance of excitatory and inhibitory brain activity, oligogenic heterozygosity, and the female protective model.
Lien vers le texte intégral (Open Access ou abonnement)
17. Yoo HJ, Park M, Kim SA. {{Difference in mitochondrial DNA copy number in peripheral blood cells between probands with autism spectrum disorders and their unaffected siblings}}. {World J Biol Psychiatry};2016 (Oct 14):1-6.
OBJECTIVES: Several reports suggest that mitochondrial dysfunction is involved in the pathophysiology of autism spectrum disorders (ASD). Therefore, mitochondrial DNA (mtDNA) copy number, a common biomarker for mitochondrial dysfunction, might be associated with ASD phenotypes. METHODS: Relative mtDNA copy number in the peripheral blood cells of 100 Korean ASD patients and their unaffected sib-pairs was measured by quantitative polymerase chain reaction (qPCR). RESULTS: ASD patients had significantly higher relative mtDNA copy numbers than their unaffected sibs (P = .042). In addition, there were statistically significant correlations between mtDNA copy number and clinical phenotypes for language and communication in ASD. CONCLUSIONS: Our findings suggest that mitochondrial dysfunction and elevated mtDNA copy number may be a biological subtype of ASD that is related to the phenotype for communication.
