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- Is a Subtype of Autism an Allergy of the Brain? [JOURNAL ARTICLE]
- Clin Ther 2013 May; 35(5):584-591.
BACKGROUND:Autism spectrum disorders (ASDs) are characterized by deficits in social communication and language and the presence of repetitive behaviors that affect as many as 1 in 50 US children. Perinatal stress and environmental factors appear to play a significant role in increasing the risk for ASDs. There is no definitive pathogenesis, which therefore significantly hinders the development of a cure.
OBJECTIVE:We aimed to identify publications using basic or clinical data that suggest a possible association between atopic symptoms and ASDs, as well as evidence of how such an association could lead to brain disease, that may explain the pathogenesis of ASD.
METHODS:PubMed was searched for articles published since 1995 that reported any association between autism and/or ASDs and any one of the following terms: allergy, atopy, brain, corticotropin-releasing hormone, cytokines, eczema, food allergy, food intolerance, gene mutation, inflammation, mast cells, mitochondria, neurotensin, phenotype, stress, subtype, or treatment.
RESULTS:Children with ASD respond disproportionally to stress and also present with food and skin allergies that involve mast cells. Brain mast cells are found primarily in the hypothalamus, which participates in the regulation of behavior and language. Corticotropin-releasing hormone is secreted from the hypothalamus under stress and, together with neurotensin, stimulates brain mast cells that could result in focal brain allergy and neurotoxicity. Neurotensin is significantly increased in serum of children with ASD and stimulates mast cell secretion of mitochondrial adenosine triphosphate and DNA, which is increased in these children; these mitochondrial components are misconstrued as innate pathogens, triggering an autoallergic response in the brain. Gene mutations associated with higher risk of ASD have been linked to reduction of the phosphatase and tensin homolog, which inhibits the mammalian target of rapamycin (mTOR). These same mutations also lead to mast cell activation and proliferation. Corticotropin-releasing hormone, neurotensin, and environmental toxins could further trigger the already activated mTOR, leading to superstimulation of brain mast cells in those areas responsible for ASD symptoms. Preliminary evidence indicates that the flavonoid luteolin is a stronger inhibitor of mTOR than rapamycin and is a potent mast cell blocker.
CONCLUSION:Activation of brain mast cells by allergic, environmental, immune, neurohormonal, stress, and toxic triggers, especially in those areas associated with behavior and language, lead to focal brain allergies and subsequent focal encephalitis. This possibility is more likely in the subgroup of patients with ASD susceptibility genes that also involve mast cell activation.
- The Relationship of Autism and Gluten. [JOURNAL ARTICLE]
- Clin Ther 2013 May; 35(5):578-583.
BACKGROUND:Autism is now a common condition with a prevalence of 1 in 88 children. There is no known etiology. Speculation about possible treatments for autism or autism spectrum disorders (ASD) has included the use of various dietary interventions, including a gluten-free diet.
OBJECTIVE:The goal of this article was to review the literature available evaluating the use of gluten-free diets in patients with autism to determine if diet should be instituted as a treatment.
METHODS:A literature review was performed, identifying previously published studies in which a gluten-free diet was instituted as an autism treatment. These studies were not limited to randomized controlled trials because only 1 article was available that used a double-blind crossover design. Most publish reports were unblinded, observational studies.
RESULTS:In the only double-blind, crossover study, no benefit of a gluten-free diet was identified. Several other studies did report benefit from gluten-free diet. Controlling for observer bias and what may have represented unrelated progress over time in these studies is not possible. There are many barriers to evaluating treatment benefits for patients with autism. Gluten sensitivity may present in a variety of ways, including gastrointestinal and neurologic symptoms. Although making a diagnosis of celiac disease is easier with new serology and genetic testing, a large number of gluten-sensitive patients do not have celiac disease. Testing to confirm non-celiac gluten sensitivity is not available.
CONCLUSIONS:A variety of symptoms may be present with gluten sensitivity. Currently, there is insufficient evidence to support instituting a gluten-free diet as a treatment for autism. There may be a subgroup of patients who might benefit from a gluten-free diet, but the symptom or testing profile of these candidates remains unclear.
- Environmental Enrichment as an Effective Treatment for Autism: A Randomized Controlled Trial. [JOURNAL ARTICLE]
- Behav Neurosci 2013 May 20.
Enriched sensorimotor environments enable rodents to compensate for a wide range of neurological challenges, including those induced in animal models of autism. Given the sensorimotor deficits in most children with autism, we attempted to translate that approach to their treatment. In a randomized controlled trial, 3-12 year-old children with autism were assigned to either a sensorimotor enrichment group, which received daily olfactory/tactile stimulation along with exercises that stimulated other paired sensory modalities, or to a control group. We administered tests of cognitive performance and autism severity to both groups at the initiation of the study and after 6 months. Severity of autism, as assessed with the Childhood Autism Rating Scale, improved significantly in the enriched group compared to controls. Indeed, 42% of the enriched group and only 7% of the control group had what we considered to be a clinically significant improvement of 5 points on that scale. Sensorimotor enrichment also produced a clear improvement in cognition, as determined by their Leiter-R Visualization and Reasoning scores. At 6 months, the change in average scores for the enriched group was 11.3 points higher than that for the control group. Finally, 69% of parents in the enriched group and 31% of parents in the control group reported improvement in their child over the 6-month study. Environmental enrichment therefore appears to be effective in ameliorating some of the symptoms of autism in children. (PsycINFO Database Record (c) 2013 APA, all rights reserved).
- Opinion: Sex, Gender and the Diagnosis of Autism - A Biosocial View of the Male Preponderance. [JOURNAL ARTICLE]
- Res Autism Spectr Disord 2013 Jun; 7(6):675-679.
- Disruption of TBC1D7, a subunit of the TSC1-TSC2 protein complex, in intellectual disability and megalencephaly. [JOURNAL ARTICLE]
- J Med Genet 2013 May 17.
BACKGROUND:Mutations in TSC1 or TSC2 cause the tuberous sclerosis complex (TSC), a disorder characterised by the development of hamartomas or benign tumours in various organs as well as the variable presence of epilepsy, intellectual disability (ID) and autism. TSC1, TSC2 and the recently described protein TBC1D7 form a complex that inhibits mTORC1 signalling and limits cell growth. Although it has been proposed that mutations in TBC1D7 might also cause TSC, loss of its function has not yet been documented in humans.
METHODS AND RESULTS:We used homozygosity mapping and exome sequencing to study a consanguineous family with ID and megalencephaly but without any specific features of TSC. We identified only one rare coding variant, c.538delT:p.Y180fsX1 in TBC1D7, in the regions of homozygosity shared by the affected siblings. We show that this mutation abolishes TBC1D7 expression and is associated with increased mTORC1 signalling in cells of the affected individuals.
CONCLUSIONS:Our study suggests that disruption of TBC1D7 causes ID but without the other typical features found in TSC. Although megalencephaly is not commonly observed in TSC, it has been associated with mTORC1 activation. Our observation thus reinforces the relationship between this pathway and the development of megalencephaly.
- Deletions of 16p11.2 and 19p13.2 in a Family With Intellectual Disability and Generalized Epilepsy. [JOURNAL ARTICLE]
- Am J Med Genet A 2013 May 17.:0.
Rare copy number variants (CNVs) have been established as an important cause of various neurodevelopmental disorders, including intellectual disability (ID) and epilepsy. In some cases, a second CNV may contribute to a more severe clinical presentation. Here we present two siblings and their mother who have mild ID, short stature, obesity and seizures. Array CGH studies show that each affected individual has two large, rare CNVs. The first is a deletion of chromosome 16p11.2, which has been previously associated with ID and autism. The second is a 0.9 Mb deletion of 19p13.2, which results in the deletion of a cluster of zinc finger genes. We suggest that, while the 16p11.2 deletion is likely the primary cause of the obesity and ID in this family, the 19p13.2 deletion may act as a modifier of the epilepsy phenotype, which is not a core feature of the 16p11.2 deletion syndrome. We investigate the potential role of ZNF44, a gene within the deleted region, in a cohort of patients with generalized epilepsy. © 2013 Wiley Periodicals, Inc.
- Impact of Early Intervention on Children with Autism Spectrum Disorders as Measured by Inclusion and Retention in Mainstream Schools. [JOURNAL ARTICLE]
- Indian J Pediatr 2013 May 18.
OBJECTIVES:To follow up the school/educational status of children with a primary diagnosis of Autism Spectrum Disorders (ASD), who had been enrolled in an Early Intervention (EI) program for 1-3 y, before the age of 6.
METHODS:Data was collected through a questionnaire covering three specific areas-the families' success in following the recommendation given on completion of the EI program, issues in schooling and feedback on the EI program. The contact modes included email, post, telephonic interviews and face-to-face interviews.
RESULTS:One hundred and two of the 296 children responded to the questionnaire. The responses were analyzed to identify, the number of families who had completed the program and were able to follow through with the recommendation given on completion of the EI program, difficulties faced if any, family feedback on the program and the additional help that they would have liked to receive. The reasons for failure to comply with the recommendations were analyzed. Of the 102 children who responded seven had dropped out midway through the program and 10 had discontinued after one year. Of the remaining 85 who completed the program, 71 were advised mainstreaming (83.5 %) and 14 were advised special school (16.5 %). Sixty-five of the 71 children, who were advised to enroll their child in the mainstream, were in regular school. 76.5 % of the children who completed the EI program were integrated in regular schools, 2 to 7 y after having completed the program.
CONCLUSIONS:EI helps in enrolment and retention of substantial numbers of children with ASD in mainstream schools.
- A Clinical Treatment Intervention for Dysphoria: Externalizing Metaphors Therapy. [JOURNAL ARTICLE]
- Clin Psychol Psychother 2013 May 20.
The purpose of this article is to explore a novel, short-term treatment intervention for internalizing behaviours. This intervention is primarily based upon an externalizing process, transforming of metaphoric imagery, and shifting of underlying maladaptive emotional schemas. This article addresses the clinical population of children and youth, specifically through outlining the protocol, externalizing metaphors therapy. A selective review of significant works regarding the efficacy of short-term therapy was conducted, including the process of change within narrative therapy. It is proposed that two specific processes account for the mental health change experienced by clients who receive this new treatment intervention: (1) externalization of problems and (2) purposeful client-generated metaphor manipulation, impacting upon underlying schemas. From these theoretical constructs, the present article outlines a three-session treatment protocol that manualizes these key clinical processes. A case study is presented to illustrate this intervention for anxiety and depression. Further clinical research is underway to address the testable hypotheses resulting from the current theoretical model. Clinical trials in brief psychotherapy are suggested to empirically evaluate the efficacy of this new treatment intervention for dysphoria. Copyright © 2013 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: This article outlines a short-term treatment intervention for anxiety and depression (dysphoira) through a novel 3-session model, where the clinician-practitioner can obtain competency through a one-day workshop. Its relevance for the clinical researcher and the mental health community is in its versatility in addressing internalizing behavior for four clinical populations: (1) children and adolescents; (2) children and adolescents on the autism spectrum; (3) adults in general; and, (4) adults with a dual-diagnosis. The treatment protocol described within is based upon the externalizing and deconstructive properties of Narrative Therapy, and the transformation of metaphoric imagery of Metaphor Therapy; both of which have little empirical support with narrative practices gaining international attention and widespread usage - through brief therapy, long-term therapy, and walk-in clinics in North America. For the first time, the theoretical constructs of the 3-session model are described and a case example illustrates the interlinking concepts.
- A Meta-Analysis of Mentalizing Impairments in Adults With Schizophrenia and Autism Spectrum Disorder. [JOURNAL ARTICLE]
- Schizophr Bull 2013 May 17.
Mentalizing has been examined both in autism spectrum disorder (ASD) and schizophrenia (SCZ) primarily by either cognitive-linguistic (referred to as verbal) or emotion recognition from eyes (referred to as visual) mentalizing tasks. Each type of task is thought to measure different aspects of mentalizing. Differences in clinical features and developmental courses of each disorder may predict distinct patterns of mentalizing performance across dis orders on each type of task. To test this, a meta-analysis was conducted using 37 studies that assessed mentalizing either verbally or visually in adults with SCZ or ASD. We found that the estimated effect sizes of impairments in verbal and visual mentalizing tasks for both clinical groups were statistically large and at a similar level (overall Hedges' g = 0.73-1.05). For each disorder, adults with SCZ showed a trend towards larger impairments on verbal (overall Hedges' g = 0.99) than on visual mentalizing task (overall Hedges' g = 0.73; Qbet = 3.45, p =.06, df =1). Adults with ASD did not show different levels of impairment on the verbal versus visual tasks (Qbet = 0.08, p =.78, df =1). These results suggest that both clinical groups share, at least in part, some common cognitive processing deficits associated with mentalizing impairments.
- Deeper attentional masking by lateral objects in children with autism. [JOURNAL ARTICLE]
- Brain Cogn 2013 May 14; 82(2):213-218.
Autism spectrum disorder (ASD) is often associated with a detail-oriented perception and overselective attention in visual tasks, such as visual search and crowding. These results were obtained manipulating exclusively the spatial properties of the stimuli: few is known about the spatio-temporal dynamics of visual processing in ASD. In this study we employed an attentional masking (AM) paradigm comparing children with ASD and IQ-matched typically developing (TD) controls. The AM effect refers to an impaired identification of a target followed by a competitive masking object at different proximities in space and time. We found that ASD and TD groups did not differ in the AM effect provoked by the competitive object displayed in the same position of the target. In contrast, children with ASD showed a deeper and prolonged interference than the TD group when the masking object was displayed in the lateral position. These psychophysical results suggest that the inefficient attentional selection in ASD depends on the spatio-temporal interaction between competitive visual objects. These evidence are discussed in the light of the ASD altered neural connectivity hypothesis and the reentrant theory of perception.