1. Gallagher S, Varga S. {{Conceptual issues in autism spectrum disorders}}. {Curr Opin Psychiatry}. 2015.
PURPOSE OF REVIEW: To provide an update on recent studies concerning social cognition in autism spectrum disorders (ASDs), to compare different theoretical approaches used to interpret empirical data, and to highlight a number of conceptual issues. RECENT FINDINGS: In regard to social cognition in ASDs, there is an emerging emphasis on early-onset and prolonged sensory-motor problems. Such sensory-motor problems may fit with the theories of social cognition that emphasize the importance of embodied interaction rather than deficits in mindreading, or they may reflect more general aspects of developmental disorders. SUMMARY: Different theoretical frameworks offer alternative perspectives on the central characteristics in ASDs and motivate different ways of conceptualizing diagnosis and intervention. Theory-of-mind approaches continue to appeal to false-belief paradigms, and debate continues about the performance of individuals with autism. Likewise, there is continuing debate and renewed skepticism about the role of simulation and deficits in the mirror system in ASDs. Growing evidence concerning sensory-motor problems, specifically disrupted patterns in re-entrant (afferent and proprioceptive) sensory feedback across the autistic spectrum, may not only provide support for more embodied interactive approaches, but also suggests that a single approach is unlikely able to explain all social cognition problems in autism. A pluralist approach understands ASDs as involving a variant range of cascading disrupted processes.
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2. Gesundheit B, Ashwood P, Keating A, Naor D, Melamed M, Rosenzweig JP. {{Therapeutic properties of mesenchymal stem cells for autism spectrum disorders}}. {Med Hypotheses}. 2014.
Recent studies of autism spectrum disorders (ASD) highlight hyperactivity of the immune system, irregular neuronal growth and increased size and number of microglia. Though the small sample size in many of these studies limits extrapolation to all individuals with ASD, there is mounting evidence of both immune and nervous system related pathogenesis in at least a subset of patients with ASD. Given the disturbing rise in incidence rates for ASD, and the fact that no pharmacological therapy for ASD has been approved by the Food and Drug Administration (FDA), there is an urgent need for new therapeutic options. Research in the therapeutic effects of mesenchymal stem cells (MSC) for other immunological and neurological conditions has shown promising results in preclinical and even clinical studies. MSC have demonstrated the ability to suppress the immune system and to promote neurogenesis with a promising safety profile. The working hypothesis of this paper is that the potentially synergistic ability of MSC to modulate a hyperactive immune system and its ability to promote neurogenesis make it an attractive potential therapeutic option specifically for ASD. Theoretical mechanisms of action will be suggested, but further research is necessary to support these hypothetical pathways. The choice of tissue source, type of cell, and most appropriate ages for therapeutic intervention remain open questions for further consideration. Concern over poor regulatory control of stem cell studies or treatment, and the unique ethical challenges that each child with ASD presents, demands that future research be conducted with particular caution before widespread use of the proposed therapeutic intervention is implemented.
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3. Hagerman RJ, Polussa J. {{Treatment of the psychiatric problems associated with fragile X syndrome}}. {Curr Opin Psychiatry}. 2015.
PURPOSE OF REVIEW: This work reviews recent research regarding treatment of fragile X syndrome (FXS), the most common inherited cause of intellectual disability and autism spectrum disorder. The phenotype includes anxiety linked to sensory hyperarousal, hyperactivity, and attentional problems consistent with attention deficit hyperactivity disorder and social deficits leading to autism spectrum disorder in 60% of boys and 25% of girls with FXS. RECENT FINDINGS: Multiple targeted treatments for FXS have rescued the phenotype of the fmr1 knockout mouse, but few have been beneficial to patients with FXS. The failure of the metabotropic glutamate receptor 5 antagonists falls on the heels of the failure of Arbaclofen’s efficacy in children and adults with autism or FXS. In contrast, efficacy has been demonstrated in a controlled trial of minocycline in children with FXS. Minocycline lowers the abnormally elevated levels of matrix metalloproteinase 9 in FXS. Acamprosate and lovastatin have been beneficial in open-label trials in FXS. The first 5 years of life may be the most efficacious time for intervention when combined with behavioral and/or educational interventions. SUMMARY: Minocycline, acamprosate, lovastatin, and sertraline are treatments that can be currently prescribed and have shown benefit in children with FXS. Use of combined medical and behavioral interventions will likely be most efficacious for the treatment of FXS.
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4. Hill-Yardin EL, Argyropoulos A, Hosie S, Rind G, Anderson P, Hannan AJ, Terence JO. {{Reduced susceptibility to induced seizures in the Neuroligin-3 mouse model of Autism}}. {Neurosci Lett}. 2015.
Epilepsy is a common comorbidity in patients with Autism spectrum disorder (ASD) and several gene mutations are associated with both of these disorders. In order to determine whether a point mutation in the gene for the synaptic protein, neuroligin-3 (Nlgn3, R451C), identified in patients with ASD alters seizure susceptibility, we administered the proconvulsant pentylenetetrazole (PTZ) to adult male Neuroligin-3R451C (NL3R451C) and wild type (WT) mice. It has previously been reported that NL3R451C mice show altered inhibitory GABAergic activity in brain regions relevant to epilepsy, including the hippocampus and somatosensory cortex. PTZ administration induces absence-seizures at low dose, and generalised convulsive seizures at higher dose. Susceptibility to absence seizures was examined by analysing the frequency and duration of spike-and-wave discharge (SWD) events and accompanying motor seizure activity induced by subcutaneous administration of low dosage (20 or 30 mg/kg) PTZ. Susceptibility to generalised convulsive seizures was tested by measuring the response to high dosage (60 mg/kg) PTZ using a modified Racine scale. There was no change in the number of SWD events exhibited by NL3R451C compared to WT mice following administration of both 20 mg/kg PTZ (1.17 +/- 0.31 compared to 16.0 +/- 11.16 events/30 min, NL3R451C vs WT respectively) and 30 mg/kg PTZ (7.5 +/- 6.54 compared with 27.8 +/- 19.9 events/30 min, NL3R451C versus WT respectively). NL3R451C mice were seizure resistant to generalised convulsive seizures induced by high dose PTZ compared to WT littermates (median latency to first > 3 s duration clonic seizure; 14.5 min versus 7.25 min, 95% CI: 1.625-2.375, p = 0.0009, NL3R451C vs WT respectively). These results indicate that the R451C mutation in the Nlgn3 gene, associated with ASD in humans, confers resistance to induced seizures, suggesting dysfunction of PTZ-sensitive GABAergic signalling in this mouse model of ASD.
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5. Lunsky Y, Balogh RS, Cobigo V, Isaacs B, Lin E, Ouellette-Kuntz HM. {{Primary care of adults with developmental disabilities in ontario}}. {Healthc Q}. 2014; 17(3): 11-3.
The health status and healthcare of adults with developmental disabilities have not been well-studied in Ontario, due to the absence of population-based data. To address this deficit, the Health Care Access Research and Developmental Disabilities (H-CARDD) program – a provincial partnership of scientists, policymakers and clinicians – has used existing provincial-level administrative data to provide descriptive information on the health of adults with developmental disabilities and the quality of their primary care relative to other adults. H-CARDD’s findings have revealed many gaps in the care of adults with developmental disabilities. While primary care providers are critical to achieving needed changes, the broader healthcare context and infrastructure also need to be considered.
6. Mezzelani A, Raggi ME, Marabotti A, Milanesi L. {{Ochratoxin A as possible factor trigging autism and its male prevalence via epigenetic mechanism}}. {Nutr Neurosci}. 2015.
The role of dysbiosis causing leaky gut with xenobiotic production and absorption is increasingly demonstrated in autism spectrum disorder (ASD) pathogenesis. Among xenobiotics, we focused on ochratoxin A (one of the major food contaminating mycotoxin), that in vitro and in vivo exerts a male-specific neurotoxicity probably via microRNA modulation of a specific target gene. Among possible targets, we focused on neuroligin4X. Interestingly, this gene carries some SNPs already correlated with the disease and with illegitimate microRNA binding sites and, being located on X-chromosome, could explain the male prevalence. In conclusion, we propose a possible gene-environment interaction triggering ASD explaining the epigenetic neurotoxic mechanism activated by ochratoxin A in genetically predisposed children. This mechanism offers a clue for male prevalence of the disease and may have an important impact on prevention and cure of ASD.
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7. Stahmer AC, Reed S, Lee E, Reisinger EM, Connell JE, Mandell DS. {{Training Teachers to use Evidence-Based Practices for Autism: Examining Procedural Implementation fidelity}}. {Psychol Sch}. 2015; 52(2): 181-95.
The purpose of this study was to examine the extent to which public school teachers implemented evidence-based interventions for students with autism in the way these practices were designed. Evidence-based practices for students with autism are rarely incorporated into community settings, and little is known about the quality of implementation. An indicator of intervention quality is procedural implementation fidelity (the degree to which a treatment is implemented as prescribed). Procedural fidelity likely affects student outcomes. This project examined procedural implementation fidelity of three evidence-based practices used in a randomized trial of a comprehensive program for students with autism in partnership with a large, urban school district. Results indicate that teachers in public school special education classrooms can learn to implement evidence-based strategies; however they require extensive training, coaching, and time to reach and maintain moderate procedural implementation fidelity. Procedural fidelity over time, and across intervention strategies is examined.
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8. Vasa RA, Mazurek MO. {{An update on anxiety in youth with autism spectrum disorders}}. {Curr Opin Psychiatry}. 2015.
PURPOSE OF REVIEW: Anxiety is one of the most common co-occurring psychiatric conditions in youth with autism spectrum disorders (ASDs). This article reviews recent evidence as well as earlier relevant studies regarding the characteristics, assessment, and treatment of anxiety in youth with ASD. RECENT FINDINGS: It is well established that the prevalence of anxiety in youth with an ASD is significantly greater than the prevalence of anxiety in the general population. Recent studies have highlighted the importance of informant, method, and instrument when measuring anxiety in this population. Despite the high prevalence, findings to date have been unable to identify any consistent risk factors for anxiety. New psychological treatments, including modified cognitive behavioral therapy for youth with high functioning ASD and co-occurring anxiety, are emerging. Pharmacological data, however, are scant. Existing studies show that youth with ASD are at increased risk for behavioral activation when taking SSRIs. SUMMARY: Clinicians working with youth with ASD are encouraged to routinely screen for anxiety. Until further data are available, clinical judgment is needed when prescribing treatments, particularly selective serotonin reuptake inhibitors, which require close monitoring of side-effects. Research on risk factors, pathophysiology, and treatment of this condition is needed.
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9. Wegiel J, Flory M, Kuchna I, Nowicki K, Ma S, Imaki H, Frackowiak J, Kolecka B, Wierzba-Bobrowicz T, London E, Wisniewski T, Hof PR, Brown W. {{Neuronal nucleus and cytoplasm volume deficit in children with autism and volume increase in adolescents and adults}}. {Acta Neuropathol Commun}. 2015; 3(1): 2.
IntroductionCharacterization of the type and topography of structural changes and their alterations throughout the lifespan of individuals with autism is essential for understanding the mechanisms contributing to the autistic phenotype. The aim of this stereological study of neurons in 16 brain structures of 14 autistic and 14 control subjects from 4 to 64 years of age was to establish the course of neuronal nuclear and cytoplasmic volume changes throughout the lifespan of individuals with autism.ResultsOur data indicate that a deficit of neuronal soma volume in children with autism is associated with deficits in the volume of the neuronal nucleus and cytoplasm. The significant deficits of neuronal nuclear and cytoplasmic volumes in 13 of 16 examined subcortical structures, archicortex, cerebellum, and brainstem in 4- to 8-year-old autistic children suggest a global nature of brain developmental abnormalities, but with region-specific differences in the severity of neuronal pathology. The observed increase in nuclear volumes in 8 of 16 structures in the autistic teenagers/young adults and decrease in nuclear volumes in 14 of 16 regions in the age-matched control subjects reveal opposite trajectories throughout the lifespan. The deficit in neuronal nuclear volumes, ranging from 7% to 42% in the 16 examined regions in children with autism, and in neuronal cytoplasmic volumes from 1% to 31%, as well as the broader range of interindividual differences for the nuclear than the cytoplasmic volume deficits, suggest a partial distinction between nuclear and cytoplasmic pathology.ConclusionsThe most severe deficit of both neuronal nucleus and cytoplasm volume in 4-to 8-year-old autistic children appears to be a reflection of early developmental alterations that may have a major contribution to the autistic phenotype. The broad range of functions of the affected structures implies that their developmental and age-associated abnormalities contribute not only to the diagnostic features of autism but also to the broad spectrum of clinical alterations associated with autism. Lack of clinical improvement in autistic teenagers and adults indicates that the observed increase in neuron nucleus and cytoplasm volume close to control level does not normalize brain function.
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10. Young NJ, Findling RL. {{An update on pharmacotherapy for autism spectrum disorder in children and adolescents}}. {Curr Opin Psychiatry}. 2015.
PURPOSE OF REVIEW: Although there is no known efficacious pharmacotherapy for core symptoms of autism spectrum disorder (ASD), psychotropic medications are commonly prescribed for behavioral/emotional symptoms associated with ASD. We reviewed current evidence-based pharmacotherapy options and updates from recent noteworthy studies. RECENT FINDINGS: Atypical antipsychotics, particularly risperidone and aripiprazole, are effective in reducing irritability, stereotypy and hyperactivity. Metabolic adverse events, including weight gain and dyslipidemia, are common. Methylphenidate is effective in reducing attention-deficit hyperactivity disorder (ADHD) symptoms. Atomoxetine and alpha-2 agonists appear effective in reducing ADHD symptoms. Selective serotonin reuptake inhibitors are not effective in improving repetitive behaviors in children with ASD, and frequently cause activating adverse events. Efficacy of antiepileptic drugs is inconclusive. Overall, efficacy and tolerability of pharmacotherapy in children with ASD are less favorable than data seen in typically developing children with similar symptoms. Newer agents, including glutamatergic agents and oxytocin, appear promising albeit with mixed results. SUMMARY: Current evidence-based pharmacotherapy options in children with ASD are very limited, and many have substantial adverse events. Clinicians should use pharmacotherapy as a part of comprehensive treatment, and judiciously weigh risks and benefits. New pharmacotherapy options for core symptoms as well as co-occurring symptoms of ASD are in urgent need.
