1. Cai RY, Richdale AL. {{Educational Experiences and Needs of Higher Education Students with Autism Spectrum Disorder}}. {J Autism Dev Disord};2015 (Jul 28)
Little research directly examines the needs of post-secondary students with ASD. The experiences and support needs of 23 students with ASD enrolled in two universities and four colleges, and 15 family members were explored in 15 semi-structured focus groups. Thematic analysis identified five themes: core ASD features, co-morbid conditions, transition, disclosure, and services and support. Most students felt educationally but not socially supported; most families felt support was poor in both areas. Transition from secondary school was often unplanned, and disclosure of diagnosis usually occurred after enrolment, often following a significant problem. Many parents provided substantial student support. Thus disclosure of ASD diagnosis and meeting the individual needs of these students are important considerations as higher education enrolments increase.
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2. Chakrabarti B, Persico A, Battista N, Maccarrone M. {{Endocannabinoid Signaling in Autism}}. {Neurotherapeutics};2015 (Jul 28)
Autism spectrum disorder (ASD) is a complex behavioral condition with onset during early childhood and a lifelong course in the vast majority of cases. To date, no behavioral, genetic, brain imaging, or electrophysiological test can specifically validate a clinical diagnosis of ASD. However, these medical procedures are often implemented in order to screen for syndromic forms of the disorder (i.e., autism comorbid with known medical conditions). In the last 25 years a good deal of information has been accumulated on the main components of the « endocannabinoid (eCB) system », a rather complex ensemble of lipid signals (« endocannabinoids »), their target receptors, purported transporters, and metabolic enzymes. It has been clearly documented that eCB signaling plays a key role in many human health and disease conditions of the central nervous system, thus opening the avenue to the therapeutic exploitation of eCB-oriented drugs for the treatment of psychiatric, neurodegenerative, and neuroinflammatory disorders. Here we present a modern view of the eCB system, and alterations of its main components in human patients and animal models relevant to ASD. This review will thus provide a critical perspective necessary to explore the potential exploitation of distinct elements of eCB system as targets of innovative therapeutics against ASD.
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3. Friedman C, Lulinski A, Rizzolo MC. {{Mental/Behavioral Health Services: Medicaid Home and Community-Based Services 1915(c) Waiver Allocation for People With Intellectual and Developmental Disabilities}}. {Intellect Dev Disabil};2015 (Aug);53(4):257-270.
Research has indicated that people who have intellectual and developmental disabilities (IDD) appear to be more vulnerable to having a co-existing psychiatric diagnosis. This study examined Medicaid 1915(c) Home and Community-Based Services (HCBS) waiver applications for people with IDD to determine the mental/behavioral health services proposed. We found that a large variance exists across states in projected spending for services, spending per participant, annual hours of service per participant, and hourly reimbursement rates. Moreover, compared to overall funding we found a general lack of state commitment to mental/behavioral services. States must shore up the capacity of their HCBS 1915
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4. Gori I, Giuliano A, Muratori F, Saviozzi I, Oliva P, Tancredi R, Cosenza A, Tosetti M, Calderoni S, Retico A. {{Gray Matter Alterations in Young Children with Autism Spectrum Disorders: Comparing Morphometry at the Voxel and Regional Level}}. {J Neuroimaging};2015 (Jul 27)
BACKGROUND AND PURPOSE: Sophisticated algorithms to infer disease diagnosis, pathology progression and patient outcome are increasingly being developed to analyze brain MRI data. They have been successfully implemented in a variety of diseases and are currently investigated in the field of neuropsychiatric disorders, including autism spectrum disorder (ASD). We aim to test the ability to predict ASD from subtle morphological changes in structural magnetic resonance imaging (sMRI). METHODS: The analysis of sMRI of a cohort of male ASD children and controls matched for age and nonverbal intelligence quotient (NVIQ) has been carried out with two widely used preprocessing software packages (SPM and Freesurfer) to extract brain morphometric information at different spatial scales. Then, support vector machines have been implemented to classify the brain features and to localize which brain regions contribute most to the ASD-control separation. RESULTS: The features extracted from the gray matter subregions provide the best classification performance, reaching an area under the receiver operating characteristic curve (AUC) of 74%. This value is enhanced to 80% when considering only subjects with NVIQ over 70. CONCLUSIONS: Despite the subtle impact of ASD on brain morphology and a limited cohort size, results from sMRI-based classifiers suggest a consistent network of altered brain regions.
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5. Hall D, Todorova-Koteva K, Pandya S, Bernard B, Ouyang B, Walsh M, Pounardjian T, Deburghraeve C, Zhou L, Losh M, Leehey M, Berry-Kravis E. {{Neurological and Endocrine Phenotypes of Fragile X Carrier Women}}. {Clin Genet};2015 (Jul 25)
INTRODUCTION: Women who carry fragile X mental retardation 1 (FMR1)gene premutation expansions frequently report neurological or endocrine symptoms and prior studies have predominantly focused on questionnaire report of medical issues. METHODS: Premutation carrier women (n = 33) and non-carrier controls (n = 13) were recruited and evaluated by a neurologist, neuropsychologist, and endocrinologist. Blood and skin biopsies were collected for molecular measures. Scales for movement disorders, neuropathy, cognitive function, psychiatric symptoms, sleep, and quality of life were completed. RESULTS: The average age of the women was 51 years (n = 46) and average CGG repeat size was 91 +/- 24.9 in the FMR1 premutation carrier women. Seventy-percent of the premutation carrier women had an abnormal neurological examination. Premutation carrier women had significantly higher scores on the FXTAS Rating Scale, more neuropathy, and difficulty with tandem gait compared to controls. Central sensitivity syndromes, a neuroticism profile on the NEO Personality Profile, and sleep disorders were also prevalent. Discrepancies between subject report and examination findings were also seen. CONCLUSIONS: This pilot study suggests that women with the FMR1 premutation may have a phenotype that overlaps with that seen in FXTAS. Additional research with larger sample sizes is warranted to better delineate the clinical features.
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6. Hidalgo NJ, Mc IL, Mc WE. {{Sociodemographic differences in parental satisfaction with an autism spectrum disorder diagnosis}}. {J Intellect Dev Disabil};2015;40(2):147-155.
BACKGROUND: The diagnostic process for autism spectrum disorder (ASD) can be difficult for families. Growing evidence suggests that the diagnostic process may vary as a function of sociodemographic factors, such as socioeconomic status. The purpose of this study was to extend findings related to families’ experiences obtaining a diagnosis and accessing services for their young child with ASD. METHOD: A mixed methods approach was used in this study, in which 46 families with children with ASD participated. A chi-square analysis compared ratings of parental satisfaction with the diagnostic process and current services between sociodemographic groups, and this was supplemented by thematic analysis of relevant open-ended questions. RESULTS: Results indicated that satisfaction ratings varied significantly by maternal education and family income levels. Ratings of satisfaction with the child’s paediatrician also differed by family income. Major themes from the open-ended questions are discussed. CONCLUSIONS: Results support assessing satisfaction and barriers in families seeking healthcare and school-based services to facilitate access to services.
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7. Kelly S, Su Y. {{Psychotropic and Anticonvulsant Medication: Individuals With Intellectual and Developmental Disabilities Who Transitioned to the Community From an Institution}}. {Intellect Dev Disabil};2015 (Aug);53(4):289-300.
Influenced by Georgia’s settlement agreement with the United States Department of Justice relating to the enforcement of the Americans with Disabilities Act, an increasing number of individuals with intellectual and developmental disabilities (IDD) are transitioning from institutions to community living. In this study we evaluate the pattern of medication use among individuals who recently transitioned to the community (IRTC), comparing results to the IDD population already residing in the community (comparison group). Average use and prevalence rates were trended over time, between January 1, 2010, and December 31. 2012. Findings indicate a significant increase in medication use in the IRTC and comparison group, with a greater and faster increase in the IRTC population. We suggest the transition process should be examined and revised, ensuring adequate preparation time and training for each person and relevant staff, particularly on medications and challenging behaviors. Several demographic trends were also significant and are discussed.
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8. Kestemont J, Vandekerckhove M, Bulnes LC, Matthys F, Overwalle FV. {{Causal Attribution in Individuals with Subclinical and Clinical Autism Spectrum Disorder: an fMRI Study}}. {Soc Neurosci};2015 (Jul 27)
This neuroimaging study compares brain activation during causal attribution to three different attribution loci (i.e. self, another person and situation) across a typical population without (N = 20) or with subclinical Autism Spectrum symptoms (N = 18) and a clinical population with Autism Spectrum Disorder (ASD; N = 11). While they underwent fMRI, all participants read short sentences describing positive and negative behaviors and thoughts of another person directed towards the participant (i.e., « you »). Participants were then asked to attribute these behaviors to themselves, the other person or the situation. Behavioral measures revealed self-serving attributions (i.e. attributing positive events to the self, while attributing negative events externally from the self) in all three participant groups. Neural measures revealed a great deal of shared activation across the three attribution loci and across the three participant groups in the temporo-parietal junction, the posterior superior sulcus and the precuneus. Comparison between groups revealed more widespread activation in both subclinical and clinical ASD participants, which may be indicative of the extra neural resources these participants invest to compensate their impairments.
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9. Kirsten TB, Chaves-Kirsten GP, Bernardes S, Scavone C, Sarkis JE, Bernardi MM, Felicio LF. {{Lipopolysaccharide Exposure Induces Maternal Hypozincemia, and Prenatal Zinc Treatment Prevents Autistic-Like Behaviors and Disturbances in the Striatal Dopaminergic and mTOR Systems of Offspring}}. {PLoS One};2015;10(7):e0134565.
Autism is characterized by social deficits, repetitive behaviors, and cognitive inflexibility. The risk factors appear to include genetic and environmental conditions, such as prenatal infections and maternal dietary factors. Previous investigations by our group have demonstrated that prenatal exposure to lipopolysaccharide (LPS), which mimics infection by gram-negative bacteria, induces autistic-like behaviors. To understand the causes of autistic-like behaviors, we evaluated maternal serum metal concentrations, which are involved in intrauterine development and infection/inflammation. We identified reduced maternal levels of zinc, magnesium, selenium and manganese after LPS exposure. Because LPS induced maternal hypozincemia, we treated dams with zinc in an attempt to prevent or ease the impairments in the offspring. We evaluated the social and cognitive autistic-like behaviors and brain tissues of the offspring to identify the central mechanism that triggers the development of autism. Prenatal LPS exposure impaired play behaviors and T-maze spontaneous alternations, i.e., it induced autistic-like behaviors. Prenatal LPS also decreased tyrosine hydroxylase levels and increased the levels of mammalian target of rapamycin (mTOR) in the striatum. Thus, striatal dopaminergic impairments may be related to autism. Moreover, excessive signaling through the mTOR pathway has been considered a biomarker of autism, corroborating our rat model of autism. Prenatal zinc treatment prevented these autistic-like behaviors and striatal dopaminergic and mTOR disturbances in the offspring induced by LPS exposure. The present findings revealed a possible relation between maternal hypozincemia during gestation and the onset of autism. Furthermore, prenatal zinc administration appears to have a beneficial effect on the prevention of autism.
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10. Krishnan N, Krishnan K, Connors CR, Choy MS, Page R, Peti W, Van Aelst L, Shea SD, Tonks NK. {{PTP1B inhibition suggests a therapeutic strategy for Rett syndrome}}. {J Clin Invest};2015 (Jul 27)
The X-linked neurological disorder Rett syndrome (RTT) presents with autistic features and is caused primarily by mutations in a transcriptional regulator, methyl CpG-binding protein 2 (MECP2). Current treatment options for RTT are limited to alleviating some neurological symptoms; hence, more effective therapeutic strategies are needed. We identified the protein tyrosine phosphatase PTP1B as a therapeutic candidate for treatment of RTT. We demonstrated that the PTPN1 gene, which encodes PTP1B, was a target of MECP2 and that disruption of MECP2 function was associated with increased levels of PTP1B in RTT models. Pharmacological inhibition of PTP1B ameliorated the effects of MECP2 disruption in mouse models of RTT, including improved survival in young male (Mecp2-/y) mice and improved behavior in female heterozygous (Mecp2-/+) mice. We demonstrated that PTP1B was a negative regulator of tyrosine phosphorylation of the tyrosine kinase TRKB, the receptor for brain-derived neurotrophic factor (BDNF). Therefore, the elevated PTP1B that accompanies disruption of MECP2 function in RTT represents a barrier to BDNF signaling. Inhibition of PTP1B led to increased tyrosine phosphorylation of TRKB in the brain, which would augment BDNF signaling. This study presents PTP1B as a mechanism-based therapeutic target for RTT, validating a unique strategy for treating the disease by modifying signal transduction pathways with small-molecule drugs.
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11. Lerthattasilp T, Charernboon T, Chunsuwan I, Siriumpunkul P. {{Depression and burden among caregivers of children with autistic spectrum disorder}}. {J Med Assoc Thai};2015 (Mar);98 Suppl 2:S45-52.
OBJECTIVE: To study depression prevalence and burden among caregivers of children with autistic spectrum disorder and the related factors. MATERIAL AND METHOD: This is a cross-sectional descriptive study. Measures included questionnaires, CES-D and burden interview. Patients’ diagnoses andfunctions were obtainedfrom childpsychiatrists and developmental pediatricians responsible for the patients. RESULTS: There were 51 participants. The depression prevalence was 5.9%. Concerning the burden, 45.1% ofthe participants reported little or no burden, and 45.1% reported mild to moderate burden. Only 7.8% and 2.0% experienced moderate to severe and severe burdens, respectively. There was a significant positive correlation between depression and burden (p = 0.012). Significant correlations were also observed between burden and months after diagnosed, the number ofpatient’ problems and the number of hours that caregiver spent with patient per day. Moreover the burden was significantly associated with patient’s communication problems and patient’s inappropriate odd repetitive behaviors (p<0. 05). CONCLUSION: The prevalence of depression in and severe burden on caregivers of autistic childrenfrom the present study was low. Factors related to the burden were months after diagnosed, the number of patient’s problems, the number of hours that caregiver spent with patient, patient’s communication problems and inappropriate or odd repetitive behaviors.
12. Nava C, Rupp J, Boissel JP, Mignot C, Rastetter A, Amiet C, Jacquette A, Dupuits C, Bouteiller D, Keren B, Ruberg M, Faudet A, Doummar D, Philippe A, Perisse D, Laurent C, Lebrun N, Guillemot V, Chelly J, Cohen D, Heron D, Brice A, Closs EI, Depienne C. {{Hypomorphic variants of cationic amino acid transporter 3 in males with autism spectrum disorders}}. {Amino Acids};2015 (Jul 28)
Cationic amino acid transporters (CATs) mediate the entry of L-type cationic amino acids (arginine, ornithine and lysine) into the cells including neurons. CAT-3, encoded by the SLC7A3 gene on chromosome X, is one of the three CATs present in the human genome, with selective expression in brain. SLC7A3 is highly intolerant to variation in humans, as attested by the low frequency of deleterious variants in available databases, but the impact on variants in this gene in humans remains undefined. In this study, we identified a missense variant in SLC7A3, encoding the CAT-3 cationic amino acid transporter, on chromosome X by exome sequencing in two brothers with autism spectrum disorder (ASD). We then sequenced the SLC7A3 coding sequence in 148 male patients with ASD and identified three additional rare missense variants in unrelated patients. Functional analyses of the mutant transporters showed that two of the four identified variants cause severe or moderate loss of CAT-3 function due to altered protein stability or abnormal trafficking to the plasma membrane. The patient with the most deleterious SLC7A3 variant had high-functioning autism and epilepsy, and also carries a de novo 16p11.2 duplication possibly contributing to his phenotype. This study shows that rare hypomorphic variants of SLC7A3 exist in male individuals and suggest that SLC7A3 variants possibly contribute to the etiology of ASD in male subjects in association with other genetic factors.
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13. Rosenberg A, Patterson JS, Angelaki DE. {{A computational perspective on autism}}. {Proc Natl Acad Sci U S A};2015 (Jul 28);112(30):9158-9165.
Autism is a neurodevelopmental disorder that manifests as a heterogeneous set of social, cognitive, motor, and perceptual symptoms. This system-wide pervasiveness suggests that, rather than narrowly impacting individual systems such as affection or vision, autism may broadly alter neural computation. Here, we propose that alterations in nonlinear, canonical computations occurring throughout the brain may underlie the behavioral characteristics of autism. One such computation, called divisive normalization, balances a neuron’s net excitation with inhibition reflecting the overall activity of the neuronal population. Through neural network simulations, we investigate how alterations in divisive normalization may give rise to autism symptomatology. Our findings show that a reduction in the amount of inhibition that occurs through divisive normalization can account for perceptual consequences of autism, consistent with the hypothesis of an increased ratio of neural excitation to inhibition (E/I) in the disorder. These results thus establish a bridge between an E/I imbalance and behavioral data on autism that is currently absent. Interestingly, our findings implicate the context-dependent, neuronal milieu as a key factor in autism symptomatology, with autism reflecting a less « social » neuronal population. Through a broader discussion of perceptual data, we further examine how altered divisive normalization may contribute to a wide array of the disorder’s behavioral consequences. These analyses show how a computational framework can provide insights into the neural basis of autism and facilitate the generation of falsifiable hypotheses. A computational perspective on autism may help resolve debates within the field and aid in identifying physiological pathways to target in the treatment of the disorder.
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14. Smith IM. {{Expanding our understanding of behavioural difficulties associated with autism spectrum disorder}}. {Dev Med Child Neurol};2015 (Jul 28)
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15. Tapanadechopone P. {{Childhood disintegrative disorder: a case report}}. {J Med Assoc Thai};2015 (Mar);98 Suppl 2:S158-161.
Childhood Disintegrative Disorder (CDD), a clinical syndrome distinctfrom childhood autism, is a rare unremittingly pervasive developmental disorder resultingfrom disintegration ofmentalfunctions and progressive neurological abnormality. This rare condition is characterized by regression or loss ofpreviously acquired language and social skills after a period of at least 2 years of normal development. This report presenting a case of a 10-year-old boy who presented with normal development until 3-4 years of age followed by gradually developmental deterioration in previously acquired social skills, language and intellectual functions with aberrant behaviors suggestive of childhood disintegrative disorder This case is reported as a very rare case and there is no previous official report in Thailand.
16. Tautz L. {{PTP1B: a new therapeutic target for Rett syndrome}}. {J Clin Invest};2015 (Jul 27):1-4.
Rett syndrome (RTT) is an X-linked neurodevelopmental disorder that is characterized by successive loss of acquired cognitive, social, and motor skills and development of autistic behavior. RTT affects approximately 1 in 10,000 live female births and is the second most common cause of severe mental retardation in females after Down syndrome. Currently, there is no cure or effective therapy for RTT. Approved treatment regimens are presently limited to supportive management of specific physical and mental disabilities. In this issue, Krishnan and colleagues reveal that the protein tyrosine phosphatase PTP1B is upregulated in patients with RTT and in murine models and provide strong evidence that targeting PTP1B has potential as a viable therapeutic strategy for the treatment of RTT.
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17. Wong CT, Wais J, Crawford DA. {{Prenatal exposure to common environmental factors affects brain lipids and increases risk of developing Autism Spectrum Disorders}}. {Eur J Neurosci};2015 (Jul 28)
The prevalence of Autism Spectrum Disorders (ASDs) has been on the rise over recent years. The presence of diverse subsets of candidate genes in each individual with an ASD and the vast variability of phenotypical differences suggest that the interference of an exogenous environmental component may greatly contribute to the development of ASDs. The lipid mediator prostaglandin E2 (PGE2 ) is released from phospholipids of cell membranes and is important in brain development and function; PGE2 is involved in differentiation, synaptic plasticity, and calcium regulation. Our previous review already described extrinsic factors including deficient dietary supplementation and exposure to oxidative stress, infections, and inflammation that can disrupt signalling of the PGE2 pathway and contribute to ASDs. In this review, we describe the structure and establishment of two key protective barriers for the brain during early development: the blood brain barrier and the placental barrier. We then provide the first comprehensive summary of other environmental factors-such as exposure to chemicals in air pollution, pesticides, and consumer products-that can also disturb PGE2 signalling and increase the risk for developing ASDs. We also describe how these exogenous agents are capable of crossing the protective barriers of the brain during critical developmental periods when barrier components are still being formed. This review underlines the importance of avoiding or limiting exposure to these factors during vulnerable periods in development. This article is protected by copyright. All rights reserved.
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18. Xiang AH. {{Maternal Diabetes and Autism in Offspring–Reply}}. {JAMA};2015 (Jul 28);314(4):407.
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19. Zitser B. {{Maternal Diabetes and Autism in Offspring}}. {JAMA};2015 (Jul 28);314(4):407.
