1. Baudouin SJ, Gaudias J, Gerharz S, Hatstatt L, Zhou K, Punnakkal P, Tanaka KF, Spooren W, Hen R, De Zeeuw CI, Vogt K, Scheiffele P. {{Shared Synaptic Pathophysiology in Syndromic and Nonsyndromic Rodent Models of Autism}}. {Science};2012 (Sep 13)
The genetic heterogeneity of autism poses a major challenge for identifying mechanism-based treatments. A number of rare mutations are associated with autism, and it is unclear whether these result in common neuronal alterations. Monogenic syndromes, such as fragile X, include autism as one of their multifaceted symptoms and have revealed specific defects in synaptic plasticity. We discovered an unexpected convergence of synaptic pathophysiology in a nonsyndromic form of autism with those in fragile X syndrome. Neuroligin-3 knockout mice (a model for nonsyndromic autism) exhibited disrupted hetero-synaptic competition and perturbed metabotropic glutamate receptor-dependent synaptic plasticity, a hallmark of fragile X. These phenotypes could be rescued by re-expression of neuroligin-3 in juvenile mice, highlighting the possibility for reverting neuronal circuit alterations in autism after completion of development.
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2. Berry A, Borgi M, Francia N, Alleva E, Cirulli F. {{Use of Assistance and Therapy Dogs for Children with Autism Spectrum Disorders: A Critical Review of the Current Evidence}}. {J Altern Complement Med};2012 (Sep 14)
Abstract Background: Autism spectrum disorders (ASD) are characterized by deficits in social reciprocity and communication, and by unusually restricted, repetitive behaviors. Intervention strategies based on the exploitation of the emotional aspects of human-dog relationships hold the potential to overcome the difficulty of subjects with ASD to relate and interact effectively with others, targeting core symptoms of this disorder. Methods: This review summarizes the results of six published studies on the effects of brief interactions with dogs and the effects of introducing dogs in families with a child diagnosed with ASD, with an emphasis on social behaviors and language use. Furthermore, the possible mechanisms responsible for the beneficial effects observed are discussed. Conclusions: Although the studies described here are encouraging, further research with better designs and using larger samples is needed to strengthen translation of such interventions to the clinic. In addition, potential applications of analyzing child-dog interactions are highlighted to screen for early signs of the disorder.
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3. Bhat AN, Galloway JC, Landa RJ. {{Relation between early motor delay and later communication delay in infants at risk for autism}}. {Infant Behav Dev};2012 (Sep 12);35(4):838-846.
BACKGROUND: Motor delays have been reported in retrospective studies of young infants who later develop Autism Spectrum Disorders (ASDs). OBJECTIVE: In this study, we prospectively compared the gross motor development of a cohort at risk for ASDs; infant siblings of children with ASDs (AU sibs) to low risk typically developing (LR) infants. METHODS: 24 AU sibs and 24 LR infants were observed at 3 and 6 months using a standardized motor measure, the Alberta Infant Motor Scale (AIMS). In addition, as part of a larger study, the AU sibs also received a follow-up assessment to determine motor and communication performance at 18 months using the Mullen Scales of Early Learning. RESULTS: Significantly more AU sibs showed motor delays at 3 and 6 months than LR infants. The majority of the AU sibs showed both early motor delays and later communication delays. LIMITATIONS: Small sample size and limited follow-up. CONCLUSIONS: Early motor delays are more common in AU sibs than LR infants. Communication delays later emerged in 67-73% of the AU sibs who had presented with early motor delays. Overall, early motor delays may be predictive of future communication delays in children at risk for autism.
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4. Crowder SA, Melton DJ. {{Individual and system-related factors associated with the costs of intellectual and developmental disabilities}}. {Tenn Med};2012 (Sep);105(8):49-51.
The factors associated with the cost of intellectual and developmental disabilities are the prevalence of pervasive developmental disorders, limited access to specialized services, the high cost of prescription medication, strained relationships with providers, and not enough latitude when it comes to selection of services. These factors work together to create an environment that is either conducive to or prohibitive of quality patient outcomes and improved perceptions of publicly-provided health care. Improving any of these factors would undoubtedly lower the overall annual cost. However, more research is required to understand how these factors affect both cost and perceptions. The factors addressed in this paper are the difference between mental healthcare and general healthcare; the prevalence of intellectual and developmental disabilities; the sociological impact of Medicaid services; out-of-pocket expenses; use of specialized mental health services; access to specialized services; and patients’ relationship with providers.
5. De Andres-Garcia S, Moya-Albiol L, Gonzalez-Bono E. {{Salivary cortisol and immunoglobulin A: Responses to stress as predictors of health complaints reported by caregivers of offspring with autistic spectrum disorder}}. {Horm Behav};2012 (Aug 15)
In the caregiving model of chronic stress, few studies have been conducted with young middle-aged samples and no data exists about acute stress response in this population. To extend knowledge in this issue, health complaints and psychological, endocrine, and immunological responses to stress have been assessed in a cross-sectional sample of 41 parents of offspring with autistic spectrum disorder (ASD) in comparison with 37 non-caregiver parents. Salivary cortisol and immunoglobulin A (IgA) levels were measured before, during, and after a mental psychosocial stressor, while mood and state anxiety were evaluated before and after the stress. Health complaints, personality traits, socio-economic status, and characteristics of the care recipient were assessed. Caregivers reported more health complaints showing buffered cortisol and IgA responses and greater increases in fatigue to acute stress than the controls. In terms of predictive power of health complaints, IgA levels, care status, and severity of the care recipient are especially relevant for caregivers. Results strongly suggest a dysregulation in the immune and hormonal stress-induced responses in middle-aged caregivers, with immune component and care characteristics as the main modulators of health complaints. A deficit in the adaptive capability of stress response is plausible in this population, emphasizing the need to consider family approaches when planning protocols for assistance to ASD patients.
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6. Depape AM, Hall GB, Tillmann B, Trainor LJ. {{Auditory processing in high-functioning adolescents with autism spectrum disorder}}. {PLoS One};2012;7(9):e44084.
Autism Spectrum Disorder (ASD) is a pervasive developmental disorder including abnormalities in perceptual processing. We measure perception in a battery of tests across speech (filtering, phoneme categorization, multisensory integration) and music (pitch memory, meter categorization, harmonic priming). We found that compared to controls, the ASD group showed poorer filtering, less audio-visual integration, less specialization for native phonemic and metrical categories, and a higher instance of absolute pitch. No group differences were found in harmonic priming. Our results are discussed in a developmental framework where culture-specific knowledge acquired early compared to late in development is most impaired, perhaps because of early-accelerated brain growth in ASD. These results suggest that early auditory remediation is needed for good communication and social functioning.
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7. Ginsberg MR, Rubin RA, Falcone T, Ting AH, Natowicz MR. {{Brain transcriptional and epigenetic associations with autism}}. {PLoS One};2012;7(9):e44736.
BACKGROUND: Autism is a common neurodevelopmental syndrome. Numerous rare genetic etiologies are reported; most cases are idiopathic. METHODOLOGY/PRINCIPAL FINDINGS: To uncover important gene dysregulation in autism we analyzed carefully selected idiopathic autistic and control cerebellar and BA19 (occipital) brain tissues using high resolution whole genome gene expression and whole genome DNA methylation microarrays. No changes in DNA methylation were identified in autistic brain but gene expression abnormalities in two areas of metabolism were apparent: down-regulation of genes of mitochondrial oxidative phosphorylation and of protein translation. We also found associations between specific behavioral domains of autism and specific brain gene expression modules related to myelin/myelination, inflammation/immune response and purinergic signaling. CONCLUSIONS/SIGNIFICANCE: This work highlights two largely unrecognized molecular pathophysiological themes in autism and suggests differing molecular bases for autism behavioral endophenotypes.
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8. Joshi G, Biederman J, Wozniak J, Goldin RL, Crowley D, Furtak S, Lukas SE, Gonenc A. {{Magnetic resonance spectroscopy study of the glutamatergic system in adolescent males with high-functioning autistic disorder: a pilot study at 4T}}. {Eur Arch Psychiatry Clin Neurosci};2012 (Sep 18)
The pilot study aimed at examining the neural glutamatergic activity in autism. Seven adolescent males (mean age: 14 +/- 1.8; age range: 12-17 years) with intact intellectual capacity (mean IQ: 108 +/- 14.26; IQ range: 85-127) suffering from autistic disorder and an equal number of age- and sex-matched healthy controls underwent a two-dimensional magnetic resonance spectroscopy scan at 4T. Results indicated significantly high glutamate (Glu) levels in the anterior cingulate cortex of autistic disorder versus control subjects (paired t test p = 0.01) and a trend for lower Glu in the right medial temporal lobe, which was not statistically different between the groups (paired t test p = 0.06). These preliminary findings support the glutamatergic dysregulation hypothesis in autism and need to be replicated in a larger sample.
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9. Kube DA, Bishop EA, Roth JM, Palmer FB. {{Evaluation of a Parent Led Curriculum in Developmental Disabilities for Pediatric and Medicine/Pediatric Residents}}. {Matern Child Health J};2012 (Sep 18)
Families of children with special health care needs (CSHCN) want to partner with their physicians to provide family-centered care and a medical home for their children. A parent group independently developed a parent-led curriculum to assist in the training of residents for this purpose. The objective of this study was to evaluate pediatric residents’ satisfaction with and perceived relevance of this parent-led curriculum demonstrating the effects a disability has on the child and family. From 2002 to 2009, 188 residents participated in a parent interview and a home visit with families of CSHCN through Project DOCC(SM) (Delivery of Chronic Care), as part of their required developmental disabilities rotation. Residents voluntarily completed anonymous quantitative surveys regarding the parent interview and home visit, rating the Parent Presenters, Information Provided, Depth of Coverage, Relevance to Future Practice, and Overall Satisfaction. Scores were reported on a Likert scale: 1 = Poor, 2 = Fair, 3 = Satisfactory, 4 = Very Good, and 5 = Excellent. Qualitative comments regarding the residents’ experience on the quality and relevance of the curriculum were also received. 112 (60 %) residents completed the survey for the parent interview and 96 (51 %) for the home visit. Average scores and standard deviations were calculated for each variable. Results for the parent interview: Presenters = 4.76 +/- 0.52, Information = 4.40 +/- 0.73, Depth = 4.59 +/- 0.67, Relevance = 4.47 +/- 0.73, and Satisfaction = 4.64 +/- 0.60. Results for the home visit: Presenters = 4.68 +/- 0.62, Information = 4.25 +/- 0.89, Depth = 4.46 +/- 0.82, Relevance = 4.40 +/- 0.75, and Satisfaction = 4.49 +/- 0.74. The overall experience was favorable with qualitative comments such as: excellent, eye opening, humbling, informative, valuable, and relevant. Pediatric residents rated this parent-led curriculum « very good » to « excellent » overall. Residents were highly satisfied with all areas assessed and felt that it was relevant to their future practices. Parent-led curricula regarding care of children with disabilities can be incorporated into and enhance pediatric resident training programs.
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10. Lukas M, Neumann ID. {{Oxytocin and vasopressin in rodent behaviors related to social dysfunctions in autism spectrum disorders}}. {Behav Brain Res};2012 (Aug 17)
Autism spectrum disorders (ASD) and social anxiety disorder involve various forms of social deficits like impaired affiliative behavior, social cognition and social approach. Although the neurobiological underpinnings of these disorders are largely unknown, rodent and human studies suggest an involvement of the evolutionary highly conserved oxytocin (OXT) and vasopressin (AVP), as these neuropeptides modulate various aspects of mammalian social behaviors. In this review we summarize the current knowledge regarding the involvement of brain OXT and AVP in rodent social behaviors related to social dysfunctions in ASD. Starting with an introduction into the neurobiology of the central OXT and AVP systems (neuroanatomy, central release, receptor distribution) we describe the distinct roles OXT and AVP play in basic social behaviors in rodents, i.e. affiliative behavior (pair-bonding and maternal behavior), social cognition (social memory), and social approach (social preference or social avoidance). The regulatory capacity of OXT and AVP to modulate social behaviors in various rodent species implies a high translational potential, in particular that dys-regulations in the brain neuropeptide systems may underlie social dysfunctions in ASD. It also suggests that the brain OXT and AVP systems are promising pharmacotherapeutic targets to improve social behaviors and to reverse social deficits.
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11. Roy S, Watkins N, Heck D. {{Comprehensive analysis of ultrasonic vocalizations in a mouse model of fragile x syndrome reveals limited, call type specific deficits}}. {PLoS One};2012;7(9):e44816.
Fragile X syndrome (FXS) is a well-recognized form of inherited mental retardation, caused by a mutation in the fragile X mental retardation 1 (Fmr1) gene. The gene is located on the long arm of the X chromosome and encodes fragile X mental retardation protein (FMRP). Absence of FMRP in fragile X patients as well as in Fmr1 knockout (KO) mice results, among other changes, in abnormal dendritic spine formation and altered synaptic plasticity in the neocortex and hippocampus. Clinical features of FXS include cognitive impairment, anxiety, abnormal social interaction, mental retardation, motor coordination and speech articulation deficits. Mouse pups generate ultrasonic vocalizations (USVs) when isolated from their mothers. Whether those social ultrasonic vocalizations are deficient in mouse models of FXS is unknown. Here we compared isolation-induced USVs generated by pups of Fmr1-KO mice with those of their wild type (WT) littermates. Though the total number of calls was not significantly different between genotypes, a detailed analysis of 10 different categories of calls revealed that loss of Fmr1 expression in mice causes limited and call-type specific deficits in ultrasonic vocalization: the carrier frequency of flat calls was higher, the percentage of downward calls was lower and that the frequency range of complex calls was wider in Fmr1-KO mice compared to their WT littermates.
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12. Saitovitch A, Bargiacchi A, Chabane N, Brunelle F, Samson Y, Boddaert N, Zilbovicius M. {{Social cognition and the superior temporal sulcus: Implications in autism}}. {Rev Neurol (Paris)};2012 (Sep 13)
The most common clinical sign of autism spectrum disorders (ASD) is social interaction impairment, which is associated with communication deficits and stereotyped behaviors. Based on brain-imaging results, our hypothesis is that abnormalities in the superior temporal sulcus (STS) are highly implicated in ASD. These abnormalities are characterized by decreased grey matter concentration, rest hypoperfusion and abnormal activation during social tasks. STS anatomofunctional anomalies occurring early across brain development could constitute the first step in the cascade of neural dysfunctions underlying autism. It is known that STS is highly implicated on social perception processing, from perception of biological movements, such as body movements or eye gaze, to more complex social cognition processes. Among the impairments that can be described in social perception processing, eye gaze perception is particularly relevant in autism. Gaze abnormalities can now be objectively measured using eye-tracking methodology. In the present work, we will review recent data on STS contributions to normal social cognition and its implication in autism, with particular focus on eye gaze perception.
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13. Shield A, Meier RP. {{Palm reversal errors in native-signing children with autism}}. {J Commun Disord};2012 (Aug 25)
Children with autism spectrum disorder (ASD) who have native exposure to a sign language such as American Sign Language (ASL) have received almost no scientific attention. This paper reports the first studies on a sample of five native-signing children (four deaf children of deaf parents and one hearing child of deaf parents; ages 4;6 to 7;5) diagnosed with ASD. A domain-general deficit in the ability of children with ASD to replicate the gestures of others is hypothesized to be a source of palm orientation reversal errors in sign. In Study 1, naturalistic language samples were collected from three native-signing children with ASD and were analyzed for errors in handshape, location, movement and palm orientation. In Study 2, four native-signing children with ASD were compared to 12 typically developing deaf children (ages 3;7 to 6;9, all born to deaf parents) on a fingerspelling task. In both studies children with ASD showed a tendency to reverse palm orientation on signs specified for inward/outward orientation. Typically developing deaf children did not produce any such errors in palm orientation. We conclude that this kind of palm reversal has a perceptual rather than a motoric source, and is further evidence of a « self-other mapping » deficit in ASD. Learning outcomes:Educational objectives: The reader will: (a) learn about the gesture imitation deficit in autism; (b) be introduced to the four parameters of sign language articulation; and (c) understand how autism affects these parameters in native-signing children.
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14. Smile S, Anagnostou E. {{New Models for Considering the Role of Medication in the Treatment and Elucidation of the Etiology of Autism}}. {Curr Psychiatry Rep};2012 (Sep 18)
Autism spectrum disorder (ASD) is a lifelong neurodevelopmental disorder. Over the past decades, much research has been conducted to elucidate a single etiological factor and effective pharmacotherapuetics to address the core symptom domains of ASD with limited success. Research has changed focus from behavioral observations of ASD to translating findings from animal models, genomic manipulation studies and basic science studies to pharmacological agents with the aim to lessen or reverse core symptoms of ASD. This paper evaluates potential models for translating information from the biology of ASD to pharmacological treatments.
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15. State MW, Sestan N. {{Neuroscience. The emerging biology of autism spectrum disorders}}. {Science};2012 (Sep 14);337(6100):1301-1303.
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16. Torralva T, Gleichgerrcht E, Roca M, Ibanez A, Marenco V, Rattazzi A, Manes F. {{Impaired theory of mind but intact decision-making in Asperger syndrome: Implications for the relationship between these cognitive domains}}. {Psychiatry Res};2012 (Sep 12)
The relationship between decision making and theory of mind (TOM) has been hardly investigated in patients with Asperger Syndrome (AS). Here, we show that the AS group (n=25) exhibited deficits on a complex TOM task, yet were unimpaired in a decision-making test. No association was found between these two domains.
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17. van Balkom ID, Bresnahan M, Vuijk PJ, Hubert J, Susser E, Hoek HW. {{Paternal age and risk of autism in an ethnically diverse, non-industrialized setting: aruba}}. {PLoS One};2012;7(9):e45090.
OBJECTIVE: The aim of this study was to examine paternal age in relation to risk of autism spectrum disorders (ASDs) in a setting other than the industrialized west. DESIGN: A case-control study of Aruban-born children (1990-2003). Cases (N = 95) were identified at the Child and Adolescent Psychiatry Clinic, the only such clinic in Aruba; gender and age matched controls (N = 347) were gathered from public health records. Parental age was defined categorically (</=29, 30-39, 40-49, >/=50y). The analysis was made, using conditional logistic regression. RESULTS: Advanced paternal age was associated with increased risk of ASDs in offspring. In comparison to the youngest paternal age group (</=29y), risk of autism increased 2.18 times for children born from fathers in their thirties, 2.71 times for fathers in their forties, and 3.22 thereafter. CONCLUSION: This study, part of the first epidemiologic study of autism in the Caribbean, contributes additional evidence, from a distinctive sociocultural setting, of the risk of ASD associated with increased paternal age.
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18. Williams PG, Tomchek S, Grau R, Bundy MB, Davis DW, Kleinert H. {{Parent and Physician Perceptions of Medical Home Care for Children With Autism Spectrum Disorders in the State of Kentucky}}. {Clin Pediatr (Phila)};2012 (Sep 13)
The medical home model of care is widely accepted as the ideal for children with autism spectrum disorders (ASDs) but may be very difficult to implement. In this study, parents of children with autism and pediatricians caring for children with autism in Kentucky were surveyed to determine the current status of primary care services for children with ASDs. Results indicated that the majority of families and physicians were comfortable with the routine health care provided to children with ASDs, but had concerns about physician ability to provide information regarding community resources, address comorbid conditions associated with autism, and discuss treatment options. The need for physician education regarding available national and regional autism resources is clear. Creative strategies involving collaboration across medical, educational, and community systems appear to be essential for establishing effective medical homes for children with ASDs.
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19. Yang Y, Shen Y, Wu B. {{Are there two different neural pathways for gender differences in autism spectrum disorders? – A pilot study}}. {Med Hypotheses};2012 (Sep 11)
Many studies have described sex differences in the prevalence of autism spectrum disorders (ASD) which was diagnosed four times more often in boys than in girls. However, there is no unified conclusion about why gender differences exist in ASD. Several theories attempt to elaborate why ASD in boys is more prevalent than that in girls including extreme male brain, failure of accurate diagnosis, endocrinologic mechanism effecting brain development and genetics explanation. Based on previous studies we hypothesize that there may be two different neural pathways existed in boys and girls with ASD. Using de novo copy number variations (CNVs) from boys and girls with ASD, we tested the genes contained in de novo CNVs from boys and girls with ASD by a web database. Two significant different neural pathways were identified. It indicated that a different combination of genes in the neural pathways may be responsible for sex difference of ASD. Then it is favorable to the judgment of the prognosis and influence on the treatment.
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20. Zhang X, Bao X, Zhang J, Zhao Y, Cao G, Pan H, Wei L, Wu X. {{Molecular characteristics of Chinese patients with Rett syndrome}}. {Eur J Med Genet};2012 (Aug 27)
OBJECTIVE: Rett syndrome (RTT) is a neurodevelopmental disorder which affects 1/10,000 girls. The aim of this study is to delineate the molecular characteristics of Rett syndrome in China based on the largest group of Chinese patients ever studied. METHODS: In all, 365 Chinese patients with Rett syndrome were recruited. Clinical information including the family reproductive history was collected through interviewing patients and their parents as well as questionnaires. MECP2, CDKL5, FOXG1 mutational analysis was performed using polymerase chain reaction (PCR), direct sequencing and multiplex ligation-dependent probe amplification (MLPA). The parental origin of mutated MECP2 gene, the MECP2 gene mutation rate in the patients’ mothers, and the X-chromosome inactivation pattern of the mothers who carry the mutation were also analyzed. RESULTS: Almost all of the patients were sporadic cases except one pair of twins. The pregnancy loss in probands’ mothers and sex ratio of offspring in probands(‘) generation were available in 352 families and were comparable to the general population. Out of the 365 cases, 315 had MECP2 gene mutations and 3 had de novo CDKL5 gene mutations. No patients had FOXG1 mutation. Among the 315 cases with MECP2 mutations, 274 were typical cases and 41 were atypical cases. All the 3 cases with CDKL5 gene mutations were atypical RTT with early-onset seizures. The analysis of parental origin of mutated MECP2 gene were performed on 139 cases, 90 (64.7%) cases were informative for the study. The result showed 94.4% cases with mutations from paternal origin and 5.6% from maternal origin. Among the cases with paternal mutation, 90.6% had point mutations. C > T was the most common one, accounting for 85.7% of the point mutations. Only one normal phenotype mother (0.41%) carried the same p.R133C mutation of MECP2 gene as her daughter with mild phenotype. The different patterns of X-chromosome inactivation in the mother and the daughter may explain their different phenotypes. CONCLUSION: The high rate of paternal origin of the mutated MECP2 gene may explain the high occurrence of RTT in female gender. The family cases of RTT are rare and the recurrence risk of RTT is very low in China. Only 0.41% (1/244) mothers carry the pathogenic gene. FOXG1 mutations were not found in this group of Chinese patients.
