1. Al-Ayadhi LY, Mostafa GA. {{Serum antinucleosome-specific antibody as a marker of autoimmunity in children with autism}}. {J Neuroinflammation};2014;11(1):69.
BACKGROUND: Increasing evidence of autoimmune phenomena in some individuals with autism could represent the presence of altered or inappropriate immune responses in this disorder. The role of the nucleosome in the induction of antibody response in some autoimmune-mediated tissue damage may provide novel targets for treatment. Due to the paucity of studies investigating the frequency of systemic auto-antibodies in autism, we are the first to investigate the frequency of antinucleosome-specific antibodies in a group of autistic children. METHODS: Serum antinucleosome-specific antibodies were measured by ELISA in 60 autistic children, between the ages of 3 and 12 years, in comparison to 60 healthy children. Autistic severity was assessed using the Childhood Autism Rating Scale (CARS). RESULTS: Autistic children had significantly higher serum antinucleosome-specific antibodies than healthy children (P <0.001). The seropositivity of antinucleosome-specific antibodies was found in 46.7% of autistic children. Autistic children with a family history of autoimmunity (40%) had a significantly higher frequency of serum antinucleosome-specific antibodies (83.3%) than patients without such a history (22.2%, P <0.001). CONCLUSIONS: Serum levels of antinucleosome-specific antibodies were increased in some autistic children. However, these data should be treated with caution until further investigations are performed with a larger subject population to determine whether these antibodies have a role in the induction of autoimmunity in a subgroup of autistic children. The role of immunotherapy in children with autism should be also studied.
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2. Andersen EF, Baldwin EE, Ellingwood S, Smith R, Lamb AN. {{Xq28 duplication overlapping the int22h-1/int22h-2 region and including RAB39B and CLIC2 in a family with intellectual and developmental disability}}. {Am J Med Genet A};2014 (Apr 3)
Duplications involving terminal Xq28 are a known cause of intellectual disability (ID) in males and in females with unfavorable X-inactivation patterns. Within Xq28, functional disomy of MECP2 causes a severe ID syndrome, however the dosage sensitivity of other Xq28 duplicated genes is less certain. Duplications involving the int22h-1/int22h-2 LCR-flanked region in distal Xq28 have recently been linked to a novel ID-associated phenotype. While evidence for the dosage sensitivity of this region is emerging, the phenotypic contribution of individual genes within the int22h-1/int22h-2-flanked region has yet to be determined. We report a familial case of a novel 774 kb Xq28-qter duplication, detected by cytogenomic microarray analysis, that partially overlaps the int22h-1/int22h-2-flanked region. This duplication and a 570 kb Xpter-p22.33 loss within the pseudoautosomal region were identified in three siblings, one female and two males, who presented with developmental delays/intellectual disability, mild dysmorphic features and short stature. Although unconfirmed, these results are suggestive of maternal inheritance of a recombinant X. We compare our clinical findings to patients with int22h-1/int22h-2-mediated duplications and discuss the potential pathogenicity of genes within the duplicated region, including those within the shared region of overlap, RAB39B and CLIC2. (c) 2014 Wiley Periodicals, Inc.
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3. Bergstrom-Isacsson M, Lagerkvist B, Holck U, Gold C. {{Neurophysiological responses to music and vibroacoustic stimuli in Rett syndrome}}. {Res Dev Disabil};2014 (Mar 29);35(6):1281-1291.
People with Rett syndrome (RTT) have severe communicative difficulties. They have as well an immature brainstem that implies dysfunction of the autonomic nervous system. Music plays an important role in their life, is often used as a motivating tool in a variety of situations and activities, and caregivers are often clear about people with RTTs favourites. The aim of this study was to investigate physiological and emotional responses related to six different musical stimuli in people with RTT. The study included 29 participants with RTT who were referred to the Swedish Rett Center for medical brainstem assessment during the period 2006-2007. 11 children with a typical developmental pattern were used as comparison. A repeated measures design was used, and physiological data were collected from a neurophysiological brainstem assessment. The continuous dependent variables measured were Cardiac Vagal Tone (CVT), Cardiac Sensitivity to Baroreflex (CSB), Mean Arterial Blood Pressure (MAP) and the Coefficient of Variation of Mean Arterial Blood Pressure (MAP-CV). These parameters were used to categorise brainstem responses as parasympathetic (calming) response, sympathetic (activating) response, arousal (alerting) response and unclear response. The results showed that all participants responded to the musical stimuli, but not always in the expected way. It was noticeable that both people with and without RTT responded with an arousal to all musical stimuli to begin with. Even though the initial expressions sometimes changed after some time due to poor control functions of their brainstem, the present results are consistent with the possibility that the RTT participants’ normal responses to music are intact. These findings may explain why music is so important for individuals with RTT throughout life.
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4. Bowler DM, Gaigg SB, Gardiner JM. {{Binding of Multiple Features in Memory by High-Functioning Adults with Autism Spectrum Disorder}}. {J Autism Dev Disord};2014 (Apr 3)
Diminished episodic memory and diminished use of semantic information to aid recall by individuals with autism spectrum disorder (ASD) are both thought to result from diminished relational binding of elements of complex stimuli. To test this hypothesis, we asked high-functioning adults with ASD and typical comparison participants to study grids in which some cells contained drawings of objects in non-canonical colours. Participants were told at study which features (colour, item, location) would be tested in a later memory test. In a second experiment, participants studied similar grids and were told that they would be tested on object-location or object-colour combinations. Recognition of combinations was significantly diminished in ASD, which survived covarying performance on the Color Trails Test (D’Elia et al. Color trails test. Professional manual. Psychological Assessment Resources, Lutz, 1996), a test of executive difficulties. The findings raise the possibility that medial temporal as well as frontal lobe processes are dysfunctional in ASD.
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5. Brett M, McPherson J, Zang ZJ, Lai A, Tan ES, Ng I, Ong LC, Cham B, Tan P, Rozen S, Tan EC. {{Massively Parallel Sequencing of Patients with Intellectual Disability, Congenital Anomalies and/or Autism Spectrum Disorders with a Targeted Gene Panel}}. {PLoS One};2014;9(4):e93409.
Developmental delay and/or intellectual disability (DD/ID) affects 1-3% of all children. At least half of these are thought to have a genetic etiology. Recent studies have shown that massively parallel sequencing (MPS) using a targeted gene panel is particularly suited for diagnostic testing for genetically heterogeneous conditions. We report on our experiences with using massively parallel sequencing of a targeted gene panel of 355 genes for investigating the genetic etiology of eight patients with a wide range of phenotypes including DD/ID, congenital anomalies and/or autism spectrum disorder. Targeted sequence enrichment was performed using the Agilent SureSelect Target Enrichment Kit and sequenced on the Illumina HiSeq2000 using paired-end reads. For all eight patients, 81-84% of the targeted regions achieved read depths of at least 20x, with average read depths overlapping targets ranging from 322x to 798x. Causative variants were successfully identified in two of the eight patients: a nonsense mutation in the ATRX gene and a canonical splice site mutation in the L1CAM gene. In a third patient, a canonical splice site variant in the USP9X gene could likely explain all or some of her clinical phenotypes. These results confirm the value of targeted MPS for investigating DD/ID in children for diagnostic purposes. However, targeted gene MPS was less likely to provide a genetic diagnosis for children whose phenotype includes autism.
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6. Chabani E, Hommel B. {{Visuospatial Processing in Children with Autism: No Evidence for (Training-Resistant) Abnormalities}}. {J Autism Dev Disord};2014 (Apr 3)
Individuals with autism spectrum disorders (ASDs) have been assumed to show evidence of abnormal visuospatial processing, which has been attributed to a failure to integrate local features into coherent global Gestalts and/or to a bias towards local processing. As the available data are based on baseline performance only, which does not provide insight into cognitive/neural plasticity and actual cognitive potential, we investigated how training-resistant possible visuospatial processing differences between children with and without ASD are. In particular, we studied the effect of computerized versus face-to-face visuospatial training in a group of normally intelligent children with ASD and typically developing children as control. Findings show that (a) children with and without ASD do not differ much in visuospatial processing (as assessed by a tangram-like task) and the few differences we observed were all eliminated by training; (b) training can improve visuospatial processing (equally) in both children with ASD and normally developing children; and (c) computer-based and face-to-face training was equally effective.
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7. Dardas LA, Ahmad MM. {{Validation of the World Health Organization’s Quality of Life Questionnaire with Parents of Children with Autistic Disorder}}. {J Autism Dev Disord};2014 (Apr 3)
The World Health Organization’s Quality of Life Questionnaire-BREF (WHOQOL-BREF) has been used in many studies that target parents of children with Autistic Disorder. However, the measure has yet to be validated and adapted to this sample group whose daily experiences are considered substantially different from those of parents of children with typical development and parents of children with other disabilities. Therefore, this study was designed to examine the psychometric properties and the theoretical structure of the WHOQOL-BREF with a sample of 184 parents of children with Autistic Disorder. The factor structure for the WHOQOL-BREF was examined using exploratory and confirmatory factor analyses. Our analyses provided no evidence of a better model than the original 4-domain model. Nevertheless, some items in the measure were re-distributed to different domains based on theoretical meanings and/or clean loading criteria. The new model structure gained the measure’s required validity with parents of children with Autistic Disorder.
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8. Harrington JW. {{Addendum for Clinician’s Guide to Autism}}. {Pediatr Rev};2014 (Apr);35(4):175.
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9. Hunter J, Rivero-Arias O, Angelov A, Kim E, Fotheringham I, Leal J. {{Epidemiology of fragile X syndrome: A systematic review and meta-analysis}}. {Am J Med Genet A};2014 (Apr 3)
Prevalence estimates for fragile X syndrome vary considerably. This systematic review and meta-analysis was conducted to provide an accurate prevalence estimate for this disorder using primary publications in PubMed, Embase, and the Cochrane library. Data were pooled using Bayesian fixed-effects and random-effects models. Primary analyses assessed the frequency of the full mutation and premutation in males and females in the total population (no bias against individuals with intellectual disability) and in female carriers of the premutation in normal populations (biased against individuals with intellectual disability), based on diagnosis by polymerase chain reaction or Southern blotting. A sensitivity analysis included studies using any diagnostic testing method and conference abstracts. Sixty-eight recorded observations provided data for the primary (56 observations) and sensitivity (12 observations) analysis. Using the random-effects model, frequency of the full mutation was 1.4 (95% CI: 0.1-3.1) per 10,000 males and 0.9 (95% CI: 0.0-2.9) per 10,000 females (1:7,143 and 1:11,111, respectively) in the total population. The premutation frequency was 11.7 (95% CI: 6.0-18.7) per 10,000 males and 34.4 (95% CI: 6.3-83.3) per 10,000 for females (1:855 and 1:291, respectively) in the total population. The prevalence of female carriers of the premutation in the normal population was 34.4 (95% CI: 8.9-60.3) per 10,000, or 1:291. Sensitivity analyses resulted in similar prevalence estimates but with wider heterogeneity. Prevalence estimates for the full mutation from this meta-analysis are lower than those in previous reviews of fragile X syndrome epidemiological data. (c) 2014 Wiley Periodicals, Inc.
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10. Juneja M, Jain R, Chakrabarty B, Mishra D, Saboo P. {{Indian Children with Developmental Disabilities: Early versus Late Referral for Intervention}}. {Indian J Pediatr};2014 (Apr 3)
OBJECTIVE: To study the age at referral, of children with neurodevelopmental disabilities to Child Development and Early Intervention Clinic and compare the neuromorbidity and socio-economic profile of the early and late presenters. METHODS: This retrospective observational study was conducted at Child Development and Early Intervention Clinic (CDEIC) located in Northern India. Case records of children enroled at CDEIC in last 5 y; with neurodevelopmental disabilities namely Mental Retardation/Global Developmental Delay, Cerebral Palsy, hearing and vision impairment were separated and studied. RESULTS: Two thousand and twenty cases were included in this study. 62.8 % presented before 3 y of age (early presenters) and 37.1 % presented at 3 y or more (late presenters). There was no difference in the overall rates and severity of mental retardation in early and late presenters. The proportion of children with quadriparetic cerebral palsy, hearing impairment, vision impairment and multiple disabilities was significantly more in early presenters. The early presenters had better parental education status, less number of siblings, better immunization status and more were delivered at a hospital and residing in urban areas. CONCLUSIONS: Large numbers of children with neurodevelopmental disabilities are referred late for intervention services, leading to loss of opportunity for early intervention. Children with purely mental disability are the ones, most likely to be referred late. Socio-economic differences are significantly contributing to these delayed referrals.
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11. Kimhi Y, Shoam-Kugelmas D, Agam Ben-Artzi G, Ben-Moshe I, Bauminger-Zviely N. {{Theory of Mind and Executive Function in Preschoolers with Typical Development Versus Intellectually Able Preschoolers with Autism Spectrum Disorder}}. {J Autism Dev Disord};2014 (Apr 3)
Children with autism spectrum disorder (ASD) have difficulties in theory of mind (ToM) and executive function (EF), which may be linked because one domain (EF) affects the other (ToM). Group differences (ASD vs. typical development) were examined in both cognitive domains, as well as EF’s associations and regressions with ToM. Participants included 29 intellectually able preschoolers with ASD and 30 typical preschoolers, aged 3-6 years. EF tasks included planning and cognitive shifting measures. ToM tasks included predicting and explaining affective and location false-belief tasks. The novelty of this study lies in its in-depth examination of ToM explanation abilities in ASD alongside the role of verbal abilities (VIQ). Significant group differences emerged on most EF and ToM measures, in favor of typically developing children. Overall in the study group, EF-planning skills, EF-cognitive shifting and VIQ significantly contributed to the explained variance of ToM measures. Implications are discussed regarding the social-cognitive deficit in ASD.
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12. Kuo HC, Wu CM, Chang WP, Kuo CN, Yeter D, Lin CY, Pai JT, Chi YC, Lin CH, Wang LJ, Chang WC. {{Association between Kawasaki Disease and Autism: A Population-Based Study in Taiwan}}. {Int J Environ Res Public Health};2014;11(4):3705-3716.
Objective: The association between Kawasaki disease and autism has rarely been studied in Asian populations. By using a nationwide Taiwanese population-based claims database, we tested the hypothesis that Kawasaki disease may increase the risk of autism in Taiwan. Materials and Methods: Our study cohort consisted of patients who had received the diagnosis of Kawasaki disease (ICD-9-CM: 446.1) between 1997 and 2005 (N = 563). For a comparison cohort, five age- and gender-matched control patients for every patient in the study cohort were selected using random sampling (N = 2,815). All subjects were tracked for 5 years from the date of cohort entry to identify whether they had developed autism (ICD-9-CM code 299.0) or not. Cox proportional hazard regressions were then performed to evaluate 5-year autism-free survival rates. Results: The main finding of this study was that patients with Kawasaki disease seem to not be at increased risk of developing autism. Of the total patients, four patients developed autism during the 5-year follow-up period, among whom two were Kawasaki disease patients and two were in the comparison cohort. Further, the adjusted hazard ratios (AHR) (AHR: 4.81; 95% confidence interval: 0.68-34.35; P = 0.117) did not show any statistical significance between the Kawasaki disease group and the control group during the 5-year follow-up. Conclusion: Our study indicated that patients with Kawasaki disease are not at increased risk of autism.
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13. Mammarella IC, Giofre D, Caviola S, Cornoldi C, Hamilton C. {{Visuospatial working memory in children with autism: The effect of a semantic global organization}}. {Res Dev Disabil};2014 (Apr 3);35(6):1349-1356.
It has been reported that individuals with Autism Spectrum Disorders (ASD) perceive visual scenes as a sparse set of details rather than as a congruent and meaningful unit, failing in the extraction of the global configuration of the scene. In the present study, children with ASD were compared with typically developing (TD) children, in a visuospatial working memory task, the Visual Patterns Test (VPT). The VPT array was manipulated to vary the semantic affordance of the pattern, high semantic (global) vs. low semantic; temporal parameters were also manipulated within the change detection protocol. Overall, there was no main effect associated with Group, however there was a significant effect associated with Semantics, which was further qualified by an interaction between the Group and Semantic factors; there was only a significant effect of semantics in the TD group. The findings are discussed in light of the weak central coherence theory where the ASD group are unable to make use of long term memory semantics in order to construct global representations of the array.
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14. Manor-Binyamini I. {{Positive aspects of the coping of mothers of adolescent children with developmental disability in the Bedouin community in Israel}}. {Res Dev Disabil};2014 (Mar 29);35(6):1272-1280.
This research examines the positive aspects of coping experienced by 270 mothers of adolescent children with and without a developmental disability in the Bedouin community. The mothers completed the Sociodemographic Data Questionnaire, the Grandparents Functional Support Assessment, the Gratitude Questionnaire, and the Posttraumatic Growth Inventory. Mothers of adolescent children with developmental disability reported higher levels of social support, gratitude, and personal growth than did mothers of adolescent children without developmental disability. Additionally, mothers demonstrated a higher level of gratitude toward their spouse’s parents. Positive correlation was also found between gratitude and personal growth and between gratitude and support from the husband’s parents. The findings highlight the important need to develop awareness and culturally appropriate intervention programs based on these positive aspects, to enhance these mothers’ coping abilities.
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15. Mastrogiuseppe M, Capirci O, Cuva S, Venuti P. {{Gestural communication in children with autism spectrum disorders during mother-child interaction}}. {Autism};2014 (Apr 3)
Children with autism spectrum disorders display atypical development of gesture production, and gesture impairment is one of the determining factors of autism spectrum disorder diagnosis. Despite the obvious importance of this issue for children with autism spectrum disorder, the literature on gestures in autism is scarce and contradictory. The purpose of this study was to analyze gestural communication in children with autism spectrum disorder during spontaneous mother-child interaction. Participants were children with autism spectrum disorder (n = 20), Down’s syndrome (n = 20), and typical development (n = 20) and their mothers. Children’s mean developmental age was 24.16 months (standard deviation = 1.45 months) and did not differ across the groups. Gestural communication was analyzed with a specific coding scheme allowing a quantitative and qualitative analysis of gestural production. Results showed the following: (a) differences between autism spectrum disorder, typical development, and Down’s syndrome groups in the total number of gestures produced; (b) differences between the three groups in the distribution of gesture types; and (c) specific correlations between gestural production, cognitive development, and autism severity scores. The study of gestures in autism spectrum disorder could help us to identify different phenotypes in autism and could also lead to the development of new therapies.
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16. Nakajima J, Okamoto N, Tohyama J, Kato M, Arai H, Funahashi O, Tsurusaki Y, Nakashima M, Hisashi K, Saitsu H, Matsumoto N, Miyake N. {{De novo EEF1A2 mutations in patients with characteristic facial features, intellectual disability and, autistic behaviors and epilepsy}}. {Clin Genet};2014 (Apr 3)
Eukaryotic elongation factor 1, alpha-2 (eEF1A2) protein is involved in protein synthesis, suppression of apoptosis, and regulation of actin function and cytoskeletal structure. EEF1A2 gene is highly expressed in the central nervous system and Eef1a2 knockout mice show the neuronal degeneration. Until now, only one missense mutation (c.208G>A, p.Gly70Ser) in EEF1A2 has been reported in two independent patients with neurological disease. In this report, we described two patients with de novo mutations (c.754G>C, p.Asp252His and c.364G>A, p.Glu122Lys) in EEF1A2 found by whole exome sequencing. Common clinical features are shared by all four individuals: severe intellectual disability, autistic behavior, absent speech, neonatal hypotonia, epilepsy and progressive microcephaly. Furthermore, the two patients share the similar characteristic facial features including a depressed nasal bridge, tented upper lip, everted lower lip and downturned corners of the mouth. These data strongly indicate that a new recognizable disorder is caused by EEF1A2 mutations.
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17. Rose S, Frye RE, Slattery J, Wynne R, Tippett M, Melnyk S, James SJ. {{Oxidative stress induces mitochondrial dysfunction in a subset of autistic lymphoblastoid cell lines}}. {Transl Psychiatry};2014;4:e377.
There is an increasing recognition that mitochondrial dysfunction is associated with autism spectrum disorders. However, little attention has been given to the etiology of mitochondrial dysfunction and how mitochondrial abnormalities might interact with other physiological disturbances such as oxidative stress. Reserve capacity is a measure of the ability of the mitochondria to respond to physiological stress. In this study, we demonstrate, for the first time, that lymphoblastoid cell lines (LCLs) derived from children with autistic disorder (AD) have an abnormal mitochondrial reserve capacity before and after exposure to reactive oxygen species (ROS). Ten (44%) of 22 AD LCLs exhibited abnormally high reserve capacity at baseline and a sharp depletion of reserve capacity when challenged with ROS. This depletion of reserve capacity was found to be directly related to an atypical simultaneous increase in both proton-leak respiration and adenosine triphosphate-linked respiration in response to increased ROS in this AD LCL subgroup. In this AD LCL subgroup, 48-hour pretreatment with N-acetylcysteine, a glutathione precursor, prevented these abnormalities and improved glutathione metabolism, suggesting a role for altered glutathione metabolism associated with this type of mitochondrial dysfunction. The results of this study suggest that a significant subgroup of AD children may have alterations in mitochondrial function, which could render them more vulnerable to a pro-oxidant microenvironment as well as intrinsic and extrinsic sources of ROS such as immune activation and pro-oxidant environmental toxins. These findings are consistent with the notion that AD is caused by a combination of genetic and environmental factors.
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18. Scheele D, Kendrick KM, Khouri C, Kretzer E, Schlapfer TE, Stoffel-Wagner B, Gunturkun O, Maier W, Hurlemann R. {{An Oxytocin-Induced Facilitation of Neural and Emotional Responses to Social Touch Correlates Inversely with Autism Traits}}. {Neuropsychopharmacology};2014 (Apr 3)
Social communication through touch and mutual grooming can convey highly salient socio-emotional signals and has been shown to involve the neuropeptide oxytocin (OXT) in several species. Less is known about the modulatory influence of OXT on the neural and emotional responses to human interpersonal touch. The present randomized placebo (PLC)-controlled within-subject pharmaco-functional magnetic resonance imaging (fMRI) study was designed to test the hypothesis that a single intranasal dose of synthetic OXT (24 IU) would facilitate both neural and emotional responses to interpersonal touch in a context (female vs male touch) and trait (autistic trait load) specific manner. Specifically, the experimental rationale was to manipulate the reward value of interpersonal touch independent of the intensity and type of actual cutaneous stimulation administered. Thus forty heterosexual males believed they were touched by either a man or a woman, although in fact an identical pattern of touch was always given by the same female experimenter blind to condition type. Our results show that OXT increased the perceived pleasantness of female, but not male touch, and associated neural responses in the insula, precuneus, orbitofrontal and pregenual anterior cingulate cortex. Moreover, the behavioral and neural effects of OXT were negatively correlated with autistic-like traits. Taken together, this is the first study to show that the perceived hedonic value of human heterosexual interpersonal touch is facilitated by OXT in men, but that its behavioral and neural effects in this context are blunted in individuals with autistic traits.Neuropsychopharmacology accepted article peview online, 03 April 2014; doi:10.1038/npp.2014.78.
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19. Smith V, Brown N. {{Prenatal valproate exposure and risk of autism spectrum disorders and childhood autism}}. {Arch Dis Child Educ Pract Ed};2014 (Apr 1)
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20. Stewart AM, Nguyen M, Wong K, Poudel MK, Kalueff AV. {{Developing zebrafish models of autism spectrum disorder (ASD)}}. {Prog Neuropsychopharmacol Biol Psychiatry};2014 (Apr 3);50:27-36.
Autism spectrum disorder (ASD) is a serious neurodevelopmental disorder with complex symptoms and unclear, multi-factorial pathogenesis. Animal (rodent) models of ASD-like behavior are extensively used to study genetics, circuitry and molecular mechanisms of ASD. The evolutionarily conserved nature of social behavior and its molecular pathways suggests that alternative experimental models can be developed to complement and enhance the existing rodent ASD paradigms. The zebrafish (Danio rerio) is rapidly becoming a popular model organism in neuroscience and biological psychiatry to study brain function, model human brain disorders and explore their genetic or pharmacological modulation. Representing highly social animals, zebrafish emerge as a strong potential model organism to study normal and pathological social phenotypes, as well as several other ASD-like symptoms. Here, we discuss the developing utility of zebrafish in modeling ASD as a new emerging field in translational neuroscience and drug discovery.
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21. Uljarevic M, Prior MR, Leekam SR. {{First evidence of sensory atypicality in mothers of children with Autism Spectrum Disorder (ASD)}}. {Mol Autism};2014;5(1):26.
BACKGROUND: Atypical reactions to sensory stimuli show heritability in the general population and are a known risk factor for affective disorders. As sensory problems are highly prevalent in individuals with ASD and their siblings, and the occurrence of affective disorders is elevated in parents of children with ASD, investigating sensory symptoms in parents is important both from clinical and theoretical standpoints.Fifty mothers of children and adolescents with ASD completed the Adolescent and Adult Sensory Profile (AASP). The AASP is a norm-referenced questionnaire that provides scores for four types of responses to sensory stimuli (sensory quadrants): hypo-sensitivity, hyper-sensitivity, sensation seeking, and sensory avoiding. FINDINGS: Mothers’ scores were compared with AASP norms. Ninety eight percent of mothers had sensory scores at least one standard deviation (SD) above the normative mean and 44% were two or more SDs above the mean for at least one sensory quadrant. CONCLUSIONS: This study provides the first evidence for sensory atypicality in parents of children with ASD. Further research is needed to elucidate the contribution of genetic and environmental influences on the expression of sensory problems in ASD.
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22. Verma D, Chakraborti B, Karmakar A, Bandyopadhyay T, Singh AS, Sinha S, Chatterjee A, Ghosh S, Mohanakumar KP, Mukhopadhyay K, Rajamma U. {{Sexual dimorphic effect in the genetic association of monoamine oxidase A (MAOA) markers with autism spectrum disorder}}. {Prog Neuropsychopharmacol Biol Psychiatry};2014 (Apr 3);50:11-20.
Autism spectrum disorders are heritable and behaviorally-defined neurodevelopmental disorders having skewed sex ratio. Serotonin as modulator of behavior and implication of serotonergic dysfunction in ASD etiology corroborates that serotonergic system genes are potential candidates for autism susceptibility. In the current study X-chromosomal gene, MAOA responsible for degradation of serotonin is investigated for possible association with ASD using population-based approach. Study covers analysis of 8 markers in 421 subjects including cases and ethnically-matched controls from West Bengal. MAOA marker, rs6323 and various haplotypes formed between the markers show significant association with the disorder. Stratification on the basis of sex reveals significant genetic effect of rs6323 with low activity T allele posing higher risk in males, but not in females. Haplotypic association results also show differential effect both in males and females. Contrasting linkage disequilibrium pattern between pair of markers involving rs6323 in male cases and controls further supports the sex-bias in genetic association. Bioinformatic analysis shows presence of Y-encoded SRY transcription factor binding sites in the neighborhood of rs1137070. C allele of rs1137070 causes deletion of GATA-2 binding site and GATA-2 is known to interact with SRY. This is the first study highlighting male-specific effect of rs6323 marker and its haplotypes in ASD etiology and it suggests sexual dimorphic effect of MAOA in this disorder. Overall results of this study identify MAOA as a possible ASD susceptibility locus and the differential genetic effect in males and females might contribute to the sex ratio differences and molecular pathology of the disorder.
