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. Anand N, Cohen JE, Cohen RB, Khandehroo B, Kahwaty S, Baron E. {{Comparison of a Newer Versus Older Protocol for Circumferential Minimally Invasive Surgical (CMIS) Correction of Adult Spinal Deformity (ASD)-Evolution Over a 10-Year Experience}}. {Spine Deform};2017 (May);5(3):213-223.
STUDY DESIGN: Retrospective. OBJECTIVES: Compare circumferential minimally invasive surgical (CMIS) correction outcomes of patients treated for adult spinal deformity (ASD) with a newer versus older protocol SUMMARY OF BACKGROUND DATA: CMIS techniques have become increasingly popular. Increasing experience and learning curve may help improve outcomes. METHODS: A prospectively collected database was queried for all patients who underwent CMIS correction of ASD (Cobb angle >20 degrees or sagittal vertical axis [SVA] >50 mm or pelvic incidence-lumbar lordosis mismatch >10) at 3+ levels. Those without a full-length radiograph or 2-year follow-up were excluded. Patients were compared based on treatment using our original or newer protocol. RESULTS: The original protocol had 76 patients with an average age of 66.99 years (range 46-81, standard deviation [SD] 9.03), and the new protocol had 53 patients with average age of 65.85 years (range 48-85, SD 8.08). Preoperative and latest visual analog scale (VAS) scores in the original were 6.85 and 3.45 (p = .001) and in the new were 6.19 and 2.27 (p = .004). Delta-VAS scores were 3.27 and 4.27. The Oswestry disability index (ODI) reduced from 45.84 to 32.91 (p = .041) in the original and from 44.21 to 25.39 (p = .017) in the new. Average delta-ODIs were 22.25 and 24.01. Preoperative, latest, and delta-SF physical component scores for the original were 35.38, 42.42, and 10.06 and for the new, 30.89, 39.49, and 11.93. SF mental component scores were 50.96, 55.19, and 12.84 and 50.12, 52.99, and 8.85. The original and new protocols had latest Cobb angles of 11.54 degrees and 11.12 degrees (p = .789), delta-Cobb angles of 14.51 degrees and 20.03 degrees (p < .05), latest SVAs of 42.85 and 30.58 mm (p < .05) and latest PI-LL mismatch of 15.49 and 9.00 mm (p < .05). In the original and the new, the average preoperative SVAs that reliably achieved a postoperative SVA of 50 mm or less were 84 and 119 mm, respectively, and the maximum delta-SVAs were 89 and 120 mm. The new protocol had fewer surgical complications (p < .05). CONCLUSION: Improvements in radiographic scores, functional outcomes, and limits of SVA correction and lower complication rates suggest that the new protocol may help improve outcomes. These findings may be a reflection of our 10-year experience and advances in the learning curve. LEVEL OF EVIDENCE: Level IV. Lien vers le texte intégral (Open Access ou abonnement)
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. Galpin J, Barratt P, Ashcroft E, Greathead S, Kenny L, Pellicano E. {{‘The dots just don’t join up’: Understanding the support needs of families of children on the autism spectrum}}. {Autism};2017 (Apr 01):1362361316687989.
Much research has documented the elevated levels of stress experienced by families of autistic children. Yet remarkably little research has examined the types of support that these families perceive to be beneficial to their lives. This study, co-produced by researchers and school-based professionals, sought to establish these families’ support needs from their own perspectives. In total, 139 parents of autistic children with additional intellectual disabilities and limited spoken communication, all attending an inner-city London school, participated in an initial survey examining parental wellbeing, self-efficacy and the extent to which they felt supported. Semi-structured interviews were conducted with a subgroup of parents ( n = 17), some of whom reported in the survey that they felt unsupported, in order to gain their in-depth perspectives. The results from both the survey and the interviews suggested that existing support (particularly from formal support services) was not meeting parents’ needs, which ultimately made them feel isolated and alienated. Parents who were interviewed called for service provision that adopted a relational, family-centred approach – one that understands the specific needs of the whole family, builds a close working relationship with them and ensures that they are supported at times when the parents and families feel they need it most.
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5. 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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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. Keller R, Basta R, Salerno L, Elia M. {{Autism, epilepsy, and synaptopathies: a not rare association}}. {Neurol Sci};2017 (Apr 28)
Autism spectrum disorders (ASD) are neurodevelopmental disorders typically diagnosed in childhood, characterized by core social dysfunction, rigid and repetitive behaviors, restricted interests, and abnormal sensorial sensitivity. ASD belong to multifactorial diseases: both genetic and environmental factors have been considered as potential risk factors for their onset. ASD are often associated with neurological conditions: the co-occurrence of epilepsy is well documented and there is also evidence of a higher prevalence of EEG abnormalities with 4-86% of individuals with ASD presenting epileptiform or not epileptiform EEG abnormalities. The presence of epilepsy in people with ASD may be determined by several structural alterations, genetic conditions, or metabolic dysfunctions, known to play a role in the emergence of both epilepsy and autism. The purpose of this article is to discuss precisely such latter cause of the autism-epilepsy association, focusing specifically on those « synaptic genes, » whose mutation predisposes to both the diseases.
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8. Landa RK, Hansen B, Alice Shillingsburg M. {{Teaching mands for information using ‘when’ to children with autism}}. {J Appl Behav Anal};2017 (Apr 28)
Previous research has evaluated contrived motivating operations to teach mands for information. However, literature evaluating acquisition of the mand when? is comparatively limited. As an extension of Shillingsburg, Bowen, Valentino, & Pierce (2014), we taught three children with autism to engage in mands for information using when under alternating conditions in which a contrived establishing operation was present (EOP) or absent (EOA). Following training with a constant prompt delay, all participants acquired the mand for information and demonstrated correct use of the provided information and a decrease in inappropriate attempts to access restricted items.
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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. Rosa M, Puig O, Lazaro L, Valles V, Lera S, Sanchez-Gistau V, Calvo R. {{Broad Cognitive Profile in Children and Adolescents with HF-ASD and in Their Siblings: Widespread Underperformance and its Clinical and Adaptive Correlates}}. {J Autism Dev Disord};2017 (Apr 28)
Despite evidence supporting the presence of cognitive deficits in children and adolescents with high-functioning autism spectrum disorder (HF-ASD), the nature of these deficits and their clinical and adaptive correlates remain unclear. Moreover, there are few cognitive studies of ASD siblings as a high risk population. We compared 50 children and adolescents with HF-ASD, 22 unaffected siblings of the HF-ASD sample and 34 community controls using an extensive neuropsychological battery. Planning, cognitive flexibility, verbal and working memory, visual local-global processing and emotion recognition are impaired in HF-ASD. Worse cognitive performance, especially in verbal and working memory, was significantly correlated with more severe symptoms and poorer adaptive functioning, also when controlling for intelligence quotient. Results in siblings may suggest an intermediate profile.
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11. Sinclair D, Featherstone R, Naschek M, Nam J, Du A, Wright S, Pance K, Melnychenko O, Weger R, Akuzawa S, Matsumoto M, Siegel SJ. {{GABA-B Agonist Baclofen Normalizes Auditory-Evoked Neural Oscillations and Behavioral Deficits in the Fmr1 Knockout Mouse Model of Fragile X Syndrome}}. {eNeuro};2017 (Jan-Feb);4(1)
Fragile X syndrome is a genetic condition resulting from FMR1 gene mutation that leads to intellectual disability, autism-like symptoms, and sensory hypersensitivity. Arbaclofen, a GABA-B agonist, has shown efficacy in some individuals with FXS but has become unavailable after unsuccessful clinical trials, prompting interest in publicly available, racemic baclofen. The present study investigated whether racemic baclofen can remediate abnormalities of neural circuit function, sensory processing, and behavior in Fmr1 knockout mice, a rodent model of fragile X syndrome. Fmr1 knockout mice showed increased baseline and auditory-evoked high-frequency gamma (30-80 Hz) power relative to C57BL/6 controls, as measured by electroencephalography. These deficits were accompanied by decreased T maze spontaneous alternation, decreased social interactions, and increased open field center time, suggestive of diminished working memory, sociability, and anxiety-like behavior, respectively. Abnormal auditory-evoked gamma oscillations, working memory, and anxiety-related behavior were normalized by treatment with baclofen, but impaired sociability was not. Improvements in working memory were evident predominantly in mice whose auditory-evoked gamma oscillations were dampened by baclofen. These findings suggest that racemic baclofen may be useful for targeting sensory and cognitive disturbances in fragile X syndrome.
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12. Smith T, Iadarola S, Mandell DS, Harwood R, Kasari C. {{Community-Partnered Research with Urban School Districts that Serve Children with Autism Spectrum Disorder}}. {Acad Pediatr};2017 (Apr 25)
OBJECTIVE: To illustrate the process of community-partnered participatory research (CPPR) to develop and evaluate interventions for children with autism in urban school districts METHODS: We formed partnerships of school personnel, parents, and researchers to guide the project. We then conducted focus groups, key informant interviews, and town halls to explore how public schools currently serve students with autism. We used findings from these activities to adapt interventions for public schools. We then tested interventions in randomized clinical trials (RCTs). RESULTS: Community input indicated a particular need for interventions to improve children’s social interaction and instructional supports to promote their success throughout the day. Based on this input, we adapted two interventions: Remaking Recess for improving peer engagement during social times; and Schedules, Tools, and Activities for Transition (STAT) for facilitating successful transitions between activities throughout the daily routine. Results of the RCT of Remaking Recess are not yet available. The RCT of STAT involved 150 children and 56 teachers. Teachers reported high buy-in and increased their proficiency at implementing STAT; children with ASD reduced their disruptive behavior and made progress toward teacher-nominated goals. However, teachers’ implementation remained inconsistent, and children did not reliably improve in academic engagement or independence. CONCLUSIONS: The findings suggest that, although CPPR has limitations, it can assist in selecting interventions to address community priorities and produce some favorable outcomes for children with autism in public schools. An important next step is to evaluate the sustainability of the interventions introduced in this project.
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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. Wong H, Hoeffer C. {{Maternal IL-17A in autism}}. {Exp Neurol};2017 (Apr 25)
Although autism spectrum disorder (ASD) has a strong genetic basis, its etiology is complex, with several genetic factors likely to be involved as well as environmental factors. Immune dysregulation has gained significant attention as a causal mechanism in ASD pathogenesis. ASD has been associated with immune abnormalities in the brain and periphery, including inflammatory disorders and autoimmunity in not only the affected individuals but also their mothers. Prenatal exposure to maternal immune activation (MIA) has been implicated as an environmental risk factor for ASD. In support of this notion, animal models have shown that MIA results in offspring with behavioral, neurological, and immunological abnormalities similar to those observed in ASD. This raises the question of how MIA exposure can lead to ASD in susceptible individuals. Recent evidence points to a potential inflammation pathway linking MIA-associated ASD with the activity of T helper 17 (Th17) lymphocytes and their effector cytokine interleukin-17A (IL-17A). IL-17A has been implicated from human studies and elevated IL-17A levels in the blood have been found to correlate with phenotypic severity in a subset of ASD individuals. In MIA model mice, elevated IL-17A levels also have been observed. Additionally, antibody blockade to inhibit IL-17A signaling was found to prevent ASD-like behaviors in offspring exposed to MIA. Therefore, IL-17A dysregulation may play a causal role in the development of ASD. The source of increased IL-17A in the MIA mouse model was attributed to maternal Th17 cells because genetic removal of the transcription factor RORgammat to selectively inhibit Th17 differentiation in pregnant mice was able to prevent ASD-like behaviors in the offspring. Similar to ASD individuals, the MIA-exposed offspring also displayed cortical dysplasia which could be prevented by inhibition of IL-17A signaling in pregnant mice. This finding reveals one possible cellular mechanism through which ASD-related cognitive and behavioral deficits may emerge following maternal inflammation. IL-17A can exert strong effects on cell survival and differentiation and the activity of signal transduction cascades, which can have important consequences during cortical development on neural function. This review examines IL-17A signaling pathways in the context of both immunity and neural function that may contribute to the development of ASD associated with MIA.
