1. Aronoff E, Hillyer R. {{Environmental Enrichment Therapy for Autism: Outcomes with Increased Access}}. {Neural Plast};2016;2016:2734915.
We have previously shown in two randomized clinical trials that environmental enrichment is capable of ameliorating symptoms of autism spectrum disorder (ASD), and in the present study, we determined whether this therapy could be effective under real-world circumstances. 1,002 children were given daily Sensory Enrichment Therapy, by their parents, using personalized therapy instructions given over the Internet. Parents were asked to assess the symptoms of their child every 2 weeks for up to 7 months. An intention-to-treat analysis showed significant overall gains for a wide range of symptoms in these children, including learning, memory, anxiety, attention span, motor skills, eating, sleeping, sensory processing, self-awareness, communication, social skills, and mood/autism behaviors. The children of compliant caregivers were more likely to experience a significant improvement in their symptoms. The treatment was effective across a wide age range and there was equal progress reported for males and females, for USA and international subjects, for those who paid and those who did not pay for the therapy, and for individuals at all levels of initial symptom severity. Environmental enrichment, delivered via an online system, therefore appears to be an effective, low-cost means of treating the symptoms of ASD.
Lien vers le texte intégral (Open Access ou abonnement)
2. Almeida LE, Wang L, Khaibullina A, Quezado ZM. {{Nicotinic cholinergic system alterations and nitrous oxide exposure in a mouse model: a hypothesis for the pathobiology of autism spectrum disorder}}. {Psychopharmacology (Berl)};2016 (Oct 11)
Lien vers le texte intégral (Open Access ou abonnement)
3. Weber RJ, Gadow KD. {{Relation of Psychiatric Symptoms with Epilepsy, Asthma, and Allergy in Youth with ASD vs. Psychiatry Referrals}}. {J Abnorm Child Psychol};2016 (Oct 11)
The present study aimed to characterize the association of psychopathology with the clinical correlates of epilepsy, asthma, and allergy within and between neurobehavioral syndromes. Participants were consecutively evaluated youth (6-18 years, 75 % male) with autism spectrum disorder (ASD; n = 589) and non-ASD outpatient psychiatry referrals (n = 653). Informants completed a background questionnaire (parents) and a psychiatric symptom severity rating scale (parents, teachers). Youth with ASD had higher rates of epilepsy and allergy but not asthma than psychiatry referrals, even when analyses were limited to youth with IQ >/= 70. Somatic conditions evidenced variable associations with medical services utilization, educational interventions, family income, and maternal education. Youth with ASD with versus without epilepsy had more severe ASD social deficits (parents’ ratings) and less severe ASD repetitive behaviors (teachers’ ratings). Epilepsy was associated with more severe depression, mania, and schizophrenia symptoms in youth with ASD. Youth with allergy (psychiatry referrals only) had more severe anxiety and depression symptoms (parents’ ratings) but less severe aggression (teachers’ ratings) thus providing evidence of both context- and diagnostic-specificity. Youth with ASD versus non-ASD psychiatry referrals evidence a variable pattern of relations between somatic conditions and a range of clinical correlates, which suggests that the biologic substrates and psychosocial concomitants of neurodevelopmental disorders and their co-occurring somatic conditions may interact to produce unique clinical phenotypes.
Lien vers le texte intégral (Open Access ou abonnement)
4. Lu P, Chen X, Feng Y, Zeng Q, Jiang C, Zhu X, Fan G, Xue Z. {{Integrated transcriptome analysis of human iPS cells derived from a fragile X syndrome patient during neuronal differentiation}}. {Sci China Life Sci};2016 (Oct 11)
Fragile X syndrome (FXS) patients carry the expansion of over 200 CGG repeats at the promoter of fragile X mental retardation 1 (FMR1), leading to decreased or absent expression of its encoded fragile X mental retardation protein (FMRP). However, the global transcriptional alteration by FMRP deficiency has not been well characterized at single nucleotide resolution, i.e., RNA-seq. Here, we performed in-vitro neuronal differentiation of human induced pluripotent stem (iPS) cells that were derived from fibroblasts of a FXS patient (FXS-iPSC). We then performed RNA-seq and examined the transcriptional misregulation at each intermediate stage during in-vitro differentiation of FXS-iPSC into neurons. After thoroughly analyzing the transcriptomic data and integrating them with those from other platforms, we found up-regulation of many genes encoding TFs for neuronal differentiation (WNT1, BMP4, POU3F4, TFAP2C, and PAX3), down-regulation of potassium channels (KCNA1, KCNC3, KCNG2, KCNIP4, KCNJ3, KCNK9, and KCNT1) and altered temporal regulation of SHANK1 and NNAT in FXS-iPSC derived neurons, indicating impaired neuronal differentiation and function in FXS patients. In conclusion, we demonstrated that the FMRP deficiency in FXS patients has significant impact on the gene expression patterns during development, which will help to discover potential targeting candidates for the cure of FXS symptoms.
Lien vers le texte intégral (Open Access ou abonnement)
5. Betz CL. {{Focus on Autism Spectrum Disorder: Issues and Treatment Approaches}}. {J Pediatr Nurs};2016 (Oct 6)
Lien vers le texte intégral (Open Access ou abonnement)
6. Bessette Gorlin J, McAlpine CP, Garwick A, Wieling E. {{Severe Childhood Autism: The Family Lived Experience}}. {J Pediatr Nurs};2016 (Oct 6)
This research examined the experiences of families living with a child with severe autism. There is limited literature on the experiences of families when a child has severe autism as distinct from milder autism and includes the voices of multiple family members. Van Manen’s phenomenological approach was used for data collection and analysis. This approach allowed for the use of innovative data sources, including unstructured individual and family interviews, observations, and family lifelines (a pictorial, temporal picture with comments of the families lives). This study included 29 interviews with 22 participants from 11 families. All data were creatively triangulated and interpreted. Six essential themes were identified. First, families experienced autism as mysterious and complex because it is an invisible and unpredictable condition with diagnostic challenges. Second, families described severe autism behaviors that often caused self-injury, harm to others and damaged homes. Third, profound communication deficits resulted in isolation between the family and child. Fourth, families discussed the unrelenting stress from lack of sleep, managing the child’s developmental delays, coordinating and financing services, and concern for the child’s future. Fifth, families described consequences of isolation from friends, school, the public, and health providers. Sixth, families portrayed their need for compassionate support and formed ‘hybrid families’ (nuclear, extended families and friends) to gain support. Study results can be utilized to educate nurses/other providers about the unique needs of families with children with severe autism and could influence health care policies to improve the care for families caring for children with severe autism.
Lien vers le texte intégral (Open Access ou abonnement)
7. Zhang B, Seigneur E, Wei P, Gokce O, Morgan J, Sudhof TC. {{Developmental plasticity shapes synaptic phenotypes of autism-associated neuroligin-3 mutations in the calyx of Held}}. {Mol Psychiatry};2016 (Oct 11)
Neuroligins are postsynaptic cell-adhesion molecules that bind to presynaptic neurexins. Mutations in neuroligin-3 predispose to autism, but how such mutations affect synaptic function remains incompletely understood. Here we systematically examined the effect of three autism-associated mutations, the neuroligin-3 knockout, the R451C knockin, and the R704C knockin, on synaptic transmission in the calyx of Held, a central synapse ideally suited for high-resolution analyses of synaptic transmission. Surprisingly, germline knockout of neuroligin-3 did not alter synaptic transmission, whereas the neuroligin-3 R451C and R704C knockins decreased and increased, respectively, synaptic transmission. These puzzling results prompted us to ask whether neuroligin-3 mutant phenotypes may be reshaped by developmental plasticity. Indeed, conditional knockout of neuroligin-3 during late development produced a marked synaptic phenotype, whereas conditional knockout of neuroligin-3 during early development caused no detectable effect, mimicking the germline knockout. In canvassing potentially redundant candidate genes, we identified developmentally early expression of another synaptic neurexin ligand, cerebellin-1. Strikingly, developmentally early conditional knockout of cerebellin-1 only modestly impaired synaptic transmission, whereas in contrast to the individual single knockouts, developmentally early conditional double knockout of both cerebellin-1 and neuroligin-3 severely decreased synaptic transmission. Our data suggest an unanticipated mechanism of developmental compensation whereby cerebellin-1 and neuroligin-3 functionally occlude each other during development of calyx synapses. Thus, although acute manipulations more likely reveal basic gene functions, developmental plasticity can be a major factor in shaping the overall phenotypes of genetic neuropsychiatric disorders.Molecular Psychiatry advance online publication, 11 October 2016; doi:10.1038/mp.2016.157.
Lien vers le texte intégral (Open Access ou abonnement)
8. D’Cruz AM, Mosconi MW, Ragozzino ME, Cook EH, Sweeney JA. {{Alterations in the functional neural circuitry supporting flexible choice behavior in autism spectrum disorders}}. {Transl Psychiatry};2016 (Oct 11);6(10):e916.
Restricted and repetitive behaviors, and a pronounced preference for behavioral and environmental consistency, are distinctive characteristics of autism spectrum disorder (ASD). Alterations in frontostriatal circuitry that supports flexible behavior might underlie this behavioral impairment. In an functional magnetic resonance imaging study of 17 individuals with ASD, and 23 age-, gender- and IQ-matched typically developing control participants, reversal learning tasks were used to assess behavioral flexibility as participants switched from one learned response choice to a different response choice when task contingencies changed. When choice outcome after reversal was uncertain, the ASD group demonstrated reduced activation in both frontal cortex and ventral striatum, in the absence of task performance differences. When the outcomes of novel responses were certain, there was no difference in brain activation between groups. Reduced activation in frontal cortex and ventral striatum suggest problems in decision-making and response planning, and in processing reinforcement cues, respectively. These processes, and their integration, are essential for flexible behavior. Alterations in these systems may therefore contribute to a rigid adherence to preferred behavioral patterns in individuals with an ASD. These findings provide an additional impetus for the use of reversal learning paradigms as a translational model for treatment development targeting the domain of restricted and repetitive behaviors in ASD.
Lien vers le texte intégral (Open Access ou abonnement)
9. Sawicka K, Pyronneau A, Chao M, Bennett MV, Zukin RS. {{Elevated ERK/p90 ribosomal S6 kinase activity underlies audiogenic seizure susceptibility in fragile X mice}}. {Proc Natl Acad Sci U S A};2016 (Oct 11);113(41):E6290-e6297.
Fragile X syndrome (FXS) is the most common heritable cause of intellectual disability and a leading genetic form of autism. The Fmr1 KO mouse, a model of FXS, exhibits elevated translation in the hippocampus and the cortex. ERK (extracellular signal-regulated kinase) and mTOR (mechanistic target of rapamycin) signaling regulate protein synthesis by activating downstream targets critical to translation initiation and elongation and are known to contribute to hippocampal defects in fragile X. Here we show that the effect of loss of fragile X mental retardation protein (FMRP) on these pathways is brain region specific. In contrast to the hippocampus, ERK (but not mTOR) signaling is elevated in the neocortex of fragile X mice. Phosphorylation of ribosomal protein S6, typically a downstream target of mTOR, is elevated in the neocortex, despite normal mTOR activity. This is significant in that S6 phosphorylation facilitates translation, correlates with neuronal activation, and is altered in neurodevelopmental disorders. We show that in fragile X mice, S6 is regulated by ERK via the « alternative » S6 kinase p90-ribosomal S6 kinase (RSK), as evidenced by the site of elevated phosphorylation and the finding that ERK inhibition corrects elevated RSK and S6 activity. These findings indicate that signaling networks are altered in the neocortex of fragile X mice such that S6 phosphorylation receives aberrant input from ERK/RSK. Importantly, an RSK inhibitor reduces susceptibility to audiogenic seizures in fragile X mice. Our findings identify RSK as a therapeutic target for fragile X and suggest the therapeutic potential of drugs for the treatment of FXS may vary in a brain-region-specific manner.
Lien vers le texte intégral (Open Access ou abonnement)
10. Vo LC, Snyder C, McCracken C, McDougle CJ, McCracken JT, Aman MG, Tierney E, Arnold LE, Levi D, Kelleman M, Carroll D, Morrissey J, Vitiello B, Scahill L. {{No Apparent Cardiac Conduction Effects of Acute Treatment with Risperidone in Children with Autism Spectrum Disorder}}. {J Child Adolesc Psychopharmacol};2016 (Oct 11)
OBJECTIVES: Risperidone is approved for the treatment of serious behavioral problems in children with autism spectrum disorder (ASD). This study examined the effects of risperidone on cardiac conduction in children with ASD. METHODS: Data were collected from an 8-week, five-site trial conducted by the Research Units on Pediatric Psychopharmacology Autism Network. Children (age 5-17 years) were randomly assigned to risperidone (n = 49) or placebo (n = 52) under double-blind conditions. Risperidone was superior to placebo in reducing serious behavioral problems. A standard 12-lead, electrocardiogram (ECG) was obtained in most subjects at screening and week 8. A pediatric electrophysiologist blind to treatment assignment reviewed all available ECGs for readability, abnormalities, and cardiac conduction parameters, including QTc. The electrophysiologist measurements were compared to machine readings. A second blinded electrophysiologist examined all available ECGs for abnormalities and a 20% random sample for QTc. RESULTS: Of the 101 randomized subjects in the trial, complete pretreatment and week 8 data were available on 65 subjects (placebo n = 30; risperidone n = 35). The electrophysiologist did not identify any cardiac conduction adverse effects of risperidone and there was no difference in mean change on the QTc compared to placebo. The Bland-Altman plot showed a systematic bias in QTc measurements by the electrophysiologist and machine. Machine readings produced higher values than the electrophysiologist for shorter QTc intervals and machine scoring was lower than electrophysiologist readings for longer QTc values (p = 0.001). Two electrophysiologists had overall percent agreements of 82.9% (95% CI: 76.3 to 89.6) on qualitative assessment and 88.6% (95% CI: 79.3 to 98.0) on QTc interval. CONCLUSION: Using conventional doses during acute treatment in children with ASD and serious behavioral problems, there was no difference in the mean change in QTc between risperidone and placebo. Compared to the electrophysiologist, the machine readings may miss elevated QTc measurements.
Lien vers le texte intégral (Open Access ou abonnement)
11. Conallen K, Reed P. {{Children with autism spectrum disorder: teaching conversation involving feelings about events}}. {J Intellect Disabil Res};2016 (Oct 10)
BACKGROUND: Two procedures were developed to teach individuals with Autism Spectrum Disorders labels (tacts) for various private events (emotions): Study 1 attempted to distinguish them from pure tacts and mands (requests); and Study 2 attempted to train initiating a conversation with grammatically correct subject-verb-comment construction. METHODS: A multiple treatment reversal design was used in both studies, followed by a probe to see if the tacts were used across novel settings. RESULTS: The children were prompted to initiate a series of language exchanges, which resulted in an increased ability to participate in conversations about private events. CONCLUSIONS: Together, the results of both studies suggest that, by providing an effective and reinforcing means of teaching both the function and the form of these tacts, conversations can be successfully initiated by children with ASD.
Lien vers le texte intégral (Open Access ou abonnement)
12. Hall SS, Barnett RP, Hustyi KM. {{Problem behaviour in adolescent boys with fragile X syndrome: relative prevalence, frequency and severity}}. {J Intellect Disabil Res};2016 (Oct 11)
BACKGROUND: A large proportion of boys with fragile X syndrome (FXS), the most common known inherited form of intellectual disability (ID), exhibit problem behaviours (e.g. aggression, self-injury, property destruction and stereotypy) that can negatively impact the health and safety of others as well as the individual concerned. However, data are limited concerning the relative prevalence, frequency and severity of problem behaviours exhibited by boys with FXS compared with those by boys with mixed-aetiology ID who also exhibit problem behaviours. METHOD: As part of a larger study on problem behaviour, we obtained survey data on 85 adolescent boys with FXS and 155 age-matched boys with mixed-aetiology ID who exhibited at least one form of problem behaviour. RESULTS: For boys with FXS, stereotypy was reported to be more prevalent (chi2 = 4.52, P = 0.012), self-injury was reported to more frequent (U = 2525, P = 0.010) and aggression was reported to be less severe (U = 4176, P = 0.029) than for boys with mixed-aetiology ID. Ratings of aggression and property destruction were highly correlated in each group in terms of both frequency and severity (r = 0.60 to 0.71). Examination of the data by age indicated that the relative frequency of self-injury decreased with age in boys with FXS (chi2 = 8.29, P = 0.040). CONCLUSIONS: Taken together, these results refine and extend previous studies concerning the specificity of the behavioural phenotype in FXS and indicate that specific forms of problem behaviour shown by boys with FXS appear to differ from those exhibited by boys with mixed-aetiology ID in terms of prevalence, frequency and severity. Studies employing more objective measures of frequency and severity, including direct observations, are needed to confirm these findings.
Lien vers le texte intégral (Open Access ou abonnement)
13. McCarthy MJ, Behimer G, Anderson JA, Riddle I. {{Caregiving for youth with co-occurring developmental disabilities and behavioral health issues when caregivers face additional health-related stressors: Analysis of risk and protective factors from a national sample}}. {Neural Plast};2016 (Oct 6);59:399-409.
BACKGROUND: Family caregivers of youth with DD and behavioral health issues experience the highest level of caregiving strain. Many must also deal with their own or another family member’s chronic health condition, which may place them at additional risk for poor outcomes. AIMS: (1) Provide a « snapshot » of DD family caregivers based on a national sample; (2) identify risk and protective factors among groups of DD caregivers with graduated levels of health-related stressors; (3) examine the impact of risk and protective factors on strain for DD caregivers. METHODS AND PROCEDURES: We conducted a secondary analysis of data from N=600 DD caregivers recruited through sites across the United States. Risk and protective factors were compared among three groups of caregivers at study enrollment: (1) those focused on providing care for the target youth with DD, without additional health-related stressors with which to contend; (2) those contending with minor additional health-related stressors; and, (3) those contending with major additional health-related stressors. Predictors of caregiving strain at six months post-enrollment were identified. RESULTS: 52% of the overall sample was unemployed and 71% were living at or below poverty. Differences were found among groups on a variety of risk and protective factors. With some exceptions, predictors of caregiving strain were similar to non-DD populations. CONCLUSIONS AND IMPLICATIONS: This study provides valuable information about a population of caregivers who are highly vulnerable to poor outcomes. Findings highlight the importance of considering the needs, strengths, and outcomes of family caregivers.
Lien vers le texte intégral (Open Access ou abonnement)
14. Frain J, Helps S, Toledano M. {{Book Reviews Clinical Communication in Medicine Edited by Jo Brown , Lorraine M Noble , Alexia Papageorgiou , Jane Kidd Wiley Blackwell 2016 Price pound34.99 . Pp 280 ISBN 978 1 118 72824 6 Re-thinking Autism: Diagnosis, Identity and Equality Edited by Katherine Runswick-Cole , Rebecca Mallett , Sami Timimi Jessica Kingsley Publishers 2016 Price pound18.99 . Pp 336 978 1 84905 581 9 A Dictionary of Neurological Signs (4th edn) AJ Larner Springer 2016 Price pound97.00. Pp 347 ISBN 978 3 319 29819 1}}. {Br J Hosp Med (Lond)};2016 (Oct);77(Sup10):605.
