1. Aggernaes B. {{Autism: A transdiagnostic, dimensional, construct of reasoning?}}. {Eur J Neurosci};2017 (Apr 27)
The concept of autism has changed across time, from the Bleulerian concept, which defined it as one of several symptoms of dementia praecox, to the present-day concept representing a pervasive development disorder. The present theoretical contribution to this special issue of EJN on autism introduces new theoretical ideas and discusses them in light of selected prior theories, clinical examples, and recent empirical evidence. The overall aim is to identify some present challenges of diagnostic practice and autism research and to suggest new pathways that may help direct future research. Future research must agree on the definitions of core concepts such as autism and psychosis. A possible redefinition of the concept of autism may be a condition in which the rationale of an individual’s behaviour differs qualitatively from that of the social environment due to characteristic cognitive impairments affecting reasoning. A broad concept of psychosis could focus on deviances in the experience of reality resulting from impairments of reasoning. In this light and consistent with recent empirical evidence, it may be appropriate to redefine dementia praecox as a developmental disorder of reasoning. A future challenge of autism research may be to develop theoretical models that can account for the impact of complex processes acting at the social level in addition to complex neurobiological and psychological processes. Such models could profit from a distinction among processes related to 1) basic susceptibility, 2) adaptive processes and 3) decompensating factors involved in the development of manifest illness. This article is protected by copyright. All rights reserved.
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2. Baker EK, Richdale AL, Hazi A, Prendergast LA. {{Assessing the Dim Light Melatonin Onset in Adults with Autism Spectrum Disorder and No Comorbid Intellectual Disability}}. {J Autism Dev Disord};2017 (Apr 26)
This study assessed melatonin levels and the dim light melatonin onset (DLMO) in adults with Autism Spectrum Disorder (ASD) and also investigated the relationships between melatonin and objectively measured sleep parameters. Sixteen adults with ASD (ASD-Only), 12 adults with ASD medicated for comorbid diagnoses of anxiety and/or depression (ASD-Med) and 32 controls participated in the study. Although, the timing of the DLMO did not differ between the two groups, advances and delays of the melatonin rhythm were observed in individual profiles. Overall mean melatonin levels were lower in the ASD-Med group compared to the two other groups. Lastly, greater increases in melatonin in the hour prior to sleep were associated with greater sleep efficiency in the ASD groups.
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3. Bozzi Y, Provenzano G, Casarosa S. {{Neurobiological bases of autism-epilepsy comorbidity: a focus on excitation/inhibition imbalance}}. {Eur J Neurosci};2017 (Apr 27)
Autism spectrum disorders (ASD) and epilepsy are common neurological diseases of childhood, with an estimated incidence of approximately 0.5 – 1% of the worldwide population. Several genetic, neuroimaging and neuropathological studies clearly showed that both ASD and epilepsy have developmental origins and a substantial degree of heritability. Most importantly, ASD and epilepsy frequently coexist in the same individual, suggesting a common neurodevelopmental basis for these disorders. Genome-wide association studies recently allowed for the identification of a substantial number of genes involved in ASD and epilepsy, some of which are mutated in syndromes presenting both ASD and epilepsy clinical features. At the cellular level, both pre-clinical and clinical studies indicate that the different genetic causes of ASD and epilepsy may converge to perturb the excitation/inhibition (E/I) balance, due to the dysfunction of excitatory and inhibitory circuits in various brain regions. Metabolic and immune dysfunctions, as well as environmental causes also contribute to ASD pathogenesis. Thus, an E/I imbalance resulting from neurodevelopmental deficits of multiple origins might represent a common pathogenic mechanism for both diseases. Here, we will review the most significant studies supporting these hypotheses. A deeper understanding of the molecular and cellular determinants of autism-epilepsy comorbidity will pave the way to the development of novel therapeutic strategies. This article is protected by copyright. All rights reserved.
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4. Gibson AN, Kaplan S, Vardell E. {{A Survey of Information Source Preferences of Parents of Individuals with Autism Spectrum Disorder}}. {J Autism Dev Disord};2017 (Apr 27)
For parents of children with an Autism spectrum disorder (ASD), high quality, easily accessible information and a strong peer network can be the key to raising a happy, healthy child, and maintaining family well-being and emotional resilience. This article reports the findings of an anonymous survey examining the information source preferences for 935 parents of individuals with ASDs in North Carolina. Data indicates that parents show similar information seeking patterns across the age spectrum, that availability of information (as indicated by overall information source selection) decrease as children age. It also shows that parents rely heavily on local sources of information, preferring them to nonlocal sources (such as the internet) for many types of information.
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5. Golding J, Ellis G, Gregory S, Birmingham K, Iles-Caven Y, Rai D, Pembrey M. {{Grand-maternal smoking in pregnancy and grandchild’s autistic traits and diagnosed autism}}. {Sci Rep};2017 (Apr 27);7:46179.
Although there is considerable research into the genetic background of autism spectrum disorders, environmental factors are likely to contribute to the variation in prevalence over time. Rodent experiments indicate that environmental exposures can have effects on subsequent generations, and human studies indicate that parental prenatal exposures may play a part in developmental variation. Here we use the Avon Longitudinal Study of Parents and Children (ALSPAC) to test the hypothesis that if the mother or father (F1) had been exposed to their own mother’s (F0) smoking during pregnancy, the offspring (F2) would be at increased risk of autism. We find an association between maternal grandmother smoking in pregnancy and grand daughters having adverse scores in Social Communication and Repetitive Behaviour measures that are independently predictive of diagnosed autism. In line with this, we show an association with actual diagnosis of autism in her grandchildren. Paternal grandmothers smoking in pregnancy showed no associations.
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6. Gu X, Zhou TJ, Anagnostou E, Soorya L, Kolevzon A, Hof PR, Fan J. {{Heightened Brain Response to Pain Anticipation in High-Functioning Adults with Autism Spectrum Disorder}}. {Eur J Neurosci};2017 (Apr 27)
Autism spectrum disorder (ASD) is marked by both socio-communicative difficulties and abnormalities in sensory processing. Much of the work on sensory deficits in ASD has focused on tactile sensations and the perceptual aspects of somatosensation, such as encoding of stimulus intensity and location. Although aberrant pain processing has often been noted in clinical observations of patients with ASD, it remains largely uninvestigated. Importantly, the neural mechanism underlying higher-order cognitive aspects of pain processing such as pain anticipation also remains unknown. Here we examined both pain perception and anticipation in high functioning adults with ASD and matched healthy controls (HC) using an anticipatory pain paradigm in combination with functional magnetic resonance imaging (fMRI) and concurrent skin conductance response (SCR) recording. Participants were asked to choose a level of electrical stimulation that would feel moderately painful to them. Compared to HC group, ASD group chose a lower level of stimulation prior to fMRI. However, ASD participants showed greater activation in both rostral and dorsal anterior cingulate cortex during the anticipation of stimulation, but not during stimulation delivery. There was no significant group difference in insular activation during either pain anticipation or perception. However, activity in the left anterior insula correlated with SCR during pain anticipation. Taken together, these results suggest that ASD is marked with aberrantly higher level of sensitivity to upcoming aversive stimuli, which may reflect abnormal attentional orientation to nociceptive signals and a failure in interoceptive inference. This article is protected by copyright. All rights reserved.
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7. Kim D, Volk H, Girirajan S, Pendergrass S, Hall MA, Verma SS, Schmidt RJ, Hansen RL, Ghosh D, Ludena-Rodriguez Y, Kim K, Ritchie MD, Hertz-Picciotto I, Selleck SB. {{The joint effect of air pollution exposure and copy number variation on risk for autism}}. {Autism Res};2017 (Apr 27)
Autism spectrum disorder is a complex trait with a high degree of heritability as well as documented susceptibility from environmental factors. In this study the contributions of copy number variation, exposure to air pollutants, and the interaction between the two on autism risk, were evaluated in the population-based case-control Childhood Autism Risks from Genetics and Environment (CHARGE) Study. For the current investigation, we included only those CHARGE children (a) who met criteria for autism or typical development and (b) for whom our team had conducted both genetic evaluation of copy number burden and determination of environmental air pollution exposures based on mapping addresses from the pregnancy and early childhood. This sample consisted of 158 cases of children with autism and 147 controls with typical development. Multiple logistic regression models were fit with and without environmental variable-copy number burden interactions. We found no correlation between average air pollution exposure from conception to age 2 years and the child’s CNV burden. We found a significant interaction in which a 1SD increase in duplication burden combined with a 1SD increase in ozone exposure was associated with an elevated autism risk (OR 3.4, P < 0.005) much greater than the increased risks associated with either genomic duplication (OR 1.85, 95% CI 1.25-2.73) or ozone (OR 1.20, 95% CI 0.93-1.54) alone. Similar results were obtained when CNV and ozone were dichotomized to compare those in the top quartile relative to those having a smaller CNV burden and lower exposure to ozone, and when exposures were assessed separately for pregnancy, the first year of life, and the second year of life. No interactions were observed for other air pollutants, even those that demonstrated main effects; ozone tends to be negatively correlated with the other pollutants examined. While earlier work has demonstrated interactions between the presence of a pathogenic CNV and an environmental exposure [Webb et al., 2016], these findings appear to be the first indication that global copy number variation may increase susceptibility to certain environmental factors, and underscore the need to consider both genomics and environmental exposures as well as the mechanisms by which each may amplify the risks for autism associated with the other. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc. Lien vers le texte intégral (Open Access ou abonnement)
8. Lerner MD, De Los Reyes A, Drabick DAG, Gerber AH, Gadow KD. {{Informant discrepancy defines discrete, clinically useful autism spectrum disorder subgroups}}. {J Child Psychol Psychiatry};2017 (Apr 27)
BACKGROUND: Discrepancy between informants (parents and teachers) in severity ratings of core symptoms commonly arise when assessing autism spectrum disorder (ASD). Whether such discrepancy yields unique information about the ASD phenotype and its clinical correlates has not been examined. We examined whether degree of discrepancy between parent and teacher ASD symptom ratings defines discrete, clinically meaningful subgroups of youth with ASD using an efficient, cost-effective procedure. METHODS: Children with ASD (N = 283; 82% boys; Mage = 10.5 years) were drawn from a specialty ASD clinic. Parents and teachers provided ratings of the three core DSM-IV-TR domains of ASD symptoms (communication, social, and perseverative behavior) with the Child and Adolescent Symptom Inventory-4R (CASI-4R). External validators included child psychotropic medication status, frequency of ASD-relevant school-based services, and the Autism Diagnostic Observation Schedule (ADOS-2). RESULTS: Four distinct subgroups emerged that ranged from large between-informant discrepancy (informant-specific) to relative lack of discrepancy (i.e. informant agreement; cross-situational): Moderate Parent/Low Teacher or Low Parent/Moderate Teacher Severity (Discrepancy), and Moderate or High Symptom Severity (Agreement). Subgroups were highly distinct (mean probability of group assignment = 94%). Relative to Discrepancy subgroups, Agreement subgroups were more likely to receive psychotropic medication, school-based special education services, and an ADOS-2 diagnosis. These differential associations would not have been identified based solely on CASI-4R scores from one informant. CONCLUSIONS: The degree of parent-teacher discrepancy about ASD symptom severity appears to provide more clinically useful information than reliance on a specific symptom domain or informant, and thus yields an innovative, cost-effective approach to assessing functional impairment. This conclusion stands in contrast to existing symptom clustering approaches in ASD, which treat within-informant patterns of symptom severity as generalizable across settings. Within-child variability in symptom expression across settings may yield uniquely useful information for characterizing the ASD phenotype.
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9. Marchezan J, Becker M, Schwartsmann G, Ohlweiler L, Roesler R, Renck LB, Goncalves MMM, Ranzan J, Riesgo RDS. {{A Placebo-Controlled Crossover Trial of Gastrin-Releasing Peptide in Childhood Autism}}. {Clin Neuropharmacol};2017 (May/Jun);40(3):108-112.
OBJECTIVES: The aim of this study was to evaluate the efficacy, safety, and tolerability of gastrin-releasing peptide (GRP) compared with placebo in autism spectrum disorder symptoms. METHODOLOGY: This is a randomized, double-blind, placebo-controlled crossover trial using GRP 160 pmol/kg for 4 consecutive days in 10 children with autism. Outcomes were measured by the Aberrant Behavior Checklist (ABC) scale. RESULTS: All participants were boys, aged between 4 and 9 years. There was a reduction in the scores of the ABC range and its subscales after use GRP and placebo. The reduction was more prominent with GRP, particularly in the subscale « hyperactivity and noncompliance, » but there was no statistical difference between the results (P = 0.334). After a week of infusion, 5 children showed improvement of 25% or greater in the total score of the ABC scale with GRP use and 2 with placebo use; however, there was no statistical difference (P = 0.375). There were no adverse effects, changes in vital signs, or laboratory abnormalities associated with the use of GRP. CONCLUSIONS: The results of this study, despite the small sample size, reinforce previous data on the safety of the GRP in short-term use. There is a need for further research with other designs and a larger sample size to evaluate the efficacy and safety of GRP in children with autism.
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10. Remington A, Fairnie J. {{A sound advantage: Increased auditory capacity in autism}}. {Cognition};2017 (Apr 27)
Autism Spectrum Disorder (ASD) has an intriguing auditory processing profile. Individuals show enhanced pitch discrimination, yet often find seemingly innocuous sounds distressing. This study used two behavioural experiments to examine whether an increased capacity for processing sounds in ASD could underlie both the difficulties and enhanced abilities found in the auditory domain. Autistic and non-autistic young adults performed a set of auditory detection and identification tasks designed to tax processing capacity and establish the extent of perceptual capacity in each population. Tasks were constructed to highlight both the benefits and disadvantages of increased capacity. Autistic people were better at detecting additional unexpected and expected sounds (increased distraction and superior performance respectively). This suggests that they have increased auditory perceptual capacity relative to non-autistic people. This increased capacity may offer an explanation for the auditory superiorities seen in autism (e.g. heightened pitch detection). Somewhat counter-intuitively, this same ‘skill’ could result in the sensory overload that is often reported – which subsequently can interfere with social communication. Reframing autistic perceptual processing in terms of increased capacity, rather than a filtering deficit or inability to maintain focus, increases our understanding of this complex condition, and has important practical implications that could be used to develop intervention programs to minimise the distress that is often seen in response to sensory stimuli.
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11. Robin G, Lopez JR, Espinal GM, Hulsizer S, Hagerman PJ, Pessah IN. {{Calcium dysregulation and Cdk5-ATM pathway involved in a mouse model of Fragile X-associated tremor-ataxia syndrome}}. {Hum Mol Genet};2017 (Apr 21)
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurological disorder that affects premutation carriers with 55-200 CGG-expansion repeats (preCGG) in FMR1, presenting with early alterations in neuronal network formation and function that precede neurodegeneration. Whether intranuclear inclusions containing DNA damage response (DDR) proteins, are causally linked to abnormal synaptic function, neuronal growth and survival are unknown. In a mouse that harbors a premutation CGG expansion (preCGG), cortical and hippocampal FMRP expression is moderately reduced from birth through adulthood, with greater FMRP reductions in the soma than in the neurite, despite several-fold elevation of Fmr1 mRNA levels. Resting cytoplasmic calcium concentration ([Ca2+]i) in cultured preCGG hippocampal neurons is chronically elevated, 3-fold compared to Wt; and elevated ROS and abnormal glutamatergic responses are detected at 14 DIV. Elevated micro-calpain activity and a higher p25/p35 ratio in the cortex of preCGG young adult mice indicate abnormal Cdk5 regulation. In support, the Cdk5 substrate, ATM, is upregulated by 1.5 to 2-fold at P0 and 6 months in preCGG brain, as is p-Ser1981-ATM. Bax:Bcl-2 is 30% higher in preCGG brain, indicating a greater vulnerability to apoptotic activation. Elevated [Ca2+]i, ROS, and DDR signals are normalized with dantrolene. Chronic [Ca2+]i dysregulation amplifies Cdk5-ATM signaling, possibly linking impaired glutamatergic signaling and DDR to neurodegeneration in preCGG brain.
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12. Sourial M, Doering LC. {{Abnormal neural precursor cell regulation in the early postnatal Fragile X mouse hippocampus}}. {Brain Res};2017 (Apr 22)
The regulation of neural precursor cells (NPCs) is indispensable for a properly functioning brain. Abnormalities in NPC proliferation, differentiation, survival, or integration have been linked to various neurological diseases including Fragile X syndrome. Yet, no studies have examined NPCs from the early postnatal Fragile X mouse hippocampus despite the importance of this developmental time point, which marks the highest expression level of FMRP, the protein missing in Fragile X, in the rodent hippocampus and is when hippocampal NPCs have migrated to the dentate gyrus (DG) to give rise to lifelong neurogenesis. In this study, we examined NPCs from the early postnatal hippocampus and DG of Fragile X mice (Fmr1-KO). Immunocytochemistry on neurospheres showed increased Nestin expression and decreased Ki67 expression, which collectively indicated aberrant NPC biology. Intriguingly, flow cytometric analysis of the expression of the antigens CD15, CD24, CD133, GLAST, and PSA-NCAM showed a decreased proportion of neural stem cells (GLAST+CD15+CD133+) and an increased proportion of neuroblasts (PSA-NCAM+CD15+) in the DG of P7 Fmr1-KO mice. This was mirrored by lower expression levels of Nestin and the mitotic marker phospho-histone H3 in vivo in the P9 hippocampus, as well as a decreased proportion of cells in the G2/M phases of the P7 DG. Thus, the absence of FMRP leads to fewer actively cycling NPCs, coinciding with a decrease in neural stem cells and an increase in neuroblasts. Together, these results show the importance of FMRP in the developing hippocampal formation and suggest abnormalities in cell cycle regulation in Fragile X.
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13. Teh EJ, Chan DM, Tan GKJ, Magiati I. {{Continuity and Change in, and Child Predictors of, Caregiver Reported Anxiety Symptoms in Young People with Autism Spectrum Disorder: A Follow-Up Study}}. {J Autism Dev Disord};2017 (Apr 27)
Little is known about continuity, change and predictors of anxiety in ASD. This follow-up study investigated changes in caregiver-reported anxiety in 54 non-referred youth with ASD after 10-19 months. Earlier child predictors of later anxiety were also examined. Anxiety scores were generally stable. Time 1 ASD repetitive behavior symptoms, but not social/communication symptoms, predicted Time 2 total anxiety scores, over and above child age, gender and adaptive functioning scores, but this predictive relationship was fully mitigated by Time 1 anxiety scores when these were included as a covariate in the regression model. Exploring bi-directionality between autism and anxiety symptomatology, Time 1 anxiety scores did not predict Time 2 ASD symptoms. Preliminary clinical implications and possible future directions are discussed.
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14. Williams DL, Minshew NJ, Goldstein G, Mazefsky CA. {{Long-term memory in older children/adolescents and adults with autism spectrum disorder}}. {Autism Res};2017 (Apr 27)
This study extends prior memory reports in autism spectrum disorders (ASD) by investigating memory for narratives after longer recall periods and by examining developmental aspects of narrative memory using a cross-sectional design. Forty-seven older children/adolescents with ASD and 31 youth with typical development (TD) and 39 adults with ASD and 45 TD adults were compared on memory for stories from standardized measures appropriate for each age group at three intervals (immediate, 30 min, and 2 day). Both the youth with and without ASD had difficulty with memory for story details with increasing time intervals. More of the youths with ASD performed in the range of impairment when recalling the stories 2 days later as compared to the TD group. The adults with ASD had more difficulty on memory for story details with increasing delay and were poorer at recall of thematic information (needed to create a gist) across the three delay conditions as compared to the TD group. Analyses of the individual results suggested that memory for details of most of the adults with ASD was not impaired when applying a clinical standard; however, a significant percentage of the adults with ASD did not make use of thematic information to organize the narrative information, which would have helped them to remember the stories. The youth with and without ASD performed similarly when both were at a stage of development when memory for details is the primary strategy. The adults with ASD had difficulty with use organizational strategies to support episodic memory. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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15. Zwart FS, Vissers C, van der Meij R, Kessels RPC, Maes JHR. {{Autism: Too eager to learn? Event related potential findings of increased dependency on intentional learning in a serial reaction time task}}. {Autism Res};2017 (Apr 27)
It has been suggested that people with autism spectrum disorder (ASD) have an increased tendency to use explicit (or intentional) learning strategies. This altered learning may play a role in the development of the social communication difficulties characterizing ASD. In the current study, we investigated incidental and intentional sequence learning using a Serial Reaction Time (SRT) task in an adult ASD population. Response times and event related potentials (ERP) components (N2b and P3) were assessed as indicators of learning and knowledge. Findings showed that behaviorally, sequence learning and ensuing explicit knowledge were similar in ASD and typically developing (TD) controls. However, ERP findings showed that learning in the TD group was characterized by an enhanced N2b, while learning in the ASD group was characterized by an enhanced P3. These findings suggest that learning in the TD group might be more incidental in nature, whereas learning in the ASD group is more intentional or effortful. Increased intentional learning might serve as a strategy for individuals with ASD to control an overwhelming environment. Although this led to similar behavioral performances on the SRT task, it is very plausible that this intentional learning has adverse effects in more complex social situations, and hence contributes to the social impairments found in ASD. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
