1. Bakare MO, Munir KM. {{Excess of non-verbal cases of autism spectrum disorders presenting to orthodox clinical practice in Africa – a trend possibly resulting from late diagnosis and intervention}}. {The South African journal of psychiatry : SAJP : the journal of the Society of Psychiatrists of South Africa}. 2011 Dec;17(4):118-20.
OBJECTIVES: Characteristics of children with autism spectrum disorders (ASDs) in Africa are not known because of unavailability of large-scale epidemiological studies in this region. This review explored the age at first presentation to orthodox clinical practice of African children with ASDs and their expressive language ability at presentation. METHODS: A literature search of case series and case reports of ASDs from Africa was done through PubMed/MEDLINE, Google Scholar, African Journals Online (AJOL), and archives of the Nigerian Journal of Psychiatry. Six articles included content relating to age of the child at first presentation to orthodox clinical practice and symptoms at presentation related to expressive language ability and therefore fulfilled the inclusion criteria. Suggestions are made to explain the observations emanating from the review. RESULTS: An excess of non-verbal over verbal cases of ASDs have been presenting to orthodox clinical practice and there is a common denominator of late presentation/diagnosis and in turn late intervention, with most cases presenting for the first time well above 8 years of age. Attempts to explain these observations included low levels of knowledge and awareness about ASDs in Africa; problems with help-seeking behaviour; and lack of mental healthcare facilities and trained personnel. CONCLUSIONS: Enhancement of processes directed at ensuring early diagnosis and interventions, especially interventions aimed at improving speech and language development well and sufficiently early, may bring about a shift in the trend of excess non-verbal cases of ASDs over verbal cases presenting to orthodox clinical practice.
2. Barber AB, Wetherby AM, Chambers NW. {{Brief Report: Repetitive Behaviors in Young Children with Autism Spectrum Disorder and Developmentally Similar Peers: A Follow Up to Watt et al. (2008)}}. {J Autism Dev Disord}. 2012 Jan 6.
The present study extended the findings of Watt et al. (J Autism Dev Disord 38:1518-1533, 2008) by investigating repetitive and stereotyped behaviors (RSB) demonstrated by children (n = 50) and typical development (TD; n = 50) matched on developmental age, gender, and parents’ education level. RSB were coded from videotaped Communication and Symbolic Behavior Scales Behavior Samples (Wetherby and Prizant 2002) using the Noldus Pro Observer(c) video software. Children with ASD demonstrated significantly higher frequencies of RSB with body objects excluding categories involving banging or tapping objects or surfaces. Behaviors demonstrated by both groups indicated overlapping RSB profiles at this age. These findings highlight the significance of RSB in the early identification and support the need for future research to further determine ASD-specific RSB.
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3. Brasic JR, Bibat G, Kumar A, Zhou Y, Hilton J, Yablonski ME, Dogan AS, Guevara MR, Stephane M, Johnston M, Wong DF, Naidu S. {{Correlation of the vesicular acetylcholine transporter densities in the striata to the clinical abilities of women with rett syndrome (RTT)}}. {Synapse (New York, NY)}. 2011 Dec 28.
Rett syndrome (RTT) is a neurodevelopmental disability characterized by mutations in the X-linked methyl-CpG-binding protein 2 (MeCP2) located at the Xq28 region. The severity is modified in part by X chromosomal inactivation resulting in wide clinical variability. We hypothesized that the ability to perform the activities of daily living (ADL) is correlated with the density of vesicular acetylcholine transporters in the striata of women with RTT. The density of the vesicular acetylcholine transporters in the living human brain can be estimated by single-photon emission-computed tomography (SPECT) after the administration of (-)-5-[(123) I]iodobenzovesamicol ([(123) I]IBVM). Twenty-four (24) hours following the intravenous injection of approximately 333 MBq (9 mCi) [(123) I]IBVM, four women with RTT and nine healthy adult volunteer control participants underwent SPECT brain scans for sixty (60) minutes. The Vesicular Acetylcholine Transporter Binding Site Index (VATBSI) (Kuhl et al., 1994), a measurement of the density of vesicular acetylcholine transporters, was estimated in the striatum and the reference structure, the cerebellum. The women with RTT were assessed for certain activities of daily living (ADL). Although striatal VATSBI was not significantly lower in RTT (5.2 +/- 0.9) than in healthy adults (5.7 +/- 1.6), RTT striatal VATSBI and ADL scores were linearly associated (ADL = 0.89*VATSBI + 4.5; R(2) =0.93; p<0.01), suggesting a correlation between the ability to perform ADL and the density of vesicular acetylcholine transporters in the striata of women with RTT. [(123) I]IBVM is a promising tool to characterize the pathophysiological mechanisms of RTT and other neurodevelopmental disabilities. Synapse, 2011. (c) 2011 Wiley-Liss, Inc.
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4. Brynska A. {{[Asperger’s syndrome: continuum or spectrum of autistic disorders?]}}. {Psychiatria polska}. 2011 Sep-Oct;45(5):749-58.
Pervasive Developmental Disorders (PPD) refers to the group of disorders characterised by delayed or inappropriate development of multiple basic functions including socialisation, communication, behaviour and cognitive functioning. The term,,autistic spectrum disorders » was established as a result of the magnitude of the intensity of symptoms and their proportions observed in all types of pervasive developmental disorders. Asperger’s Syndrome (AS) remains the most controversial diagnosis in terms of its place within autism spectrum disorders. AS if often described as an equivalent of High Functioning Autism (HFA) or as a separate spectrum-related disorder with unique diagnostic criteria. Another important issue is the relationship between AS and speech disorders. Although it is relatively easy to draw a line between children with classical autism and speech disorders, the clear cut frontiers between them still remain to be found. The main distinguishing feature is the lack of stereotypic interests and unimpaired social interaction observed in children with speech disorders, such as semantic-pragmatic disorder.
5. Deveney SL, Hoffman L, Cress CJ. {{Communication-Based Assessment of Developmental Age for Young Children with Developmental Disabilities}}. {J Speech Lang Hear Res}. 2012 Jan 5.
PURPOSE: This study compared a multiple-domain strategy for assessing developmental age of young children with developmental disabilities who were at risk for long-term reliance on AAC to a communication-based strategy composed of receptive language and communication indices that may be less affected by physically challenging tasks than traditional developmental age scores. METHOD: Participants were 42 children (9-27 months) with developmental disabilities at risk for long-term reliance on AAC. Children were assessed longitudinally in their homes at three occasions over 18 months using multiple-domain and communication-based measures. Confirmatory factor analysis examined dimensionality across the measures and age equivalency scores under each strategy were compared where possible. RESULTS: The communication-based latent factor of developmental age demonstrated good reliability and was almost perfectly correlated with the multiple-domain latent factor. However, the mean age equivalency score of the communication-based assessment significantly exceeded that of the multiple-domain assessment by 5.2 months across ages. CONCLUSIONS: Clinicians working with young children with developmental disabilities should consider a communication-based approach as an alternative developmental age assessment strategy for characterizing children’s capabilities, identifying challenges, and developing interventions. A communication-based developmental age estimation is sufficiently reliable and may result in more valid inferences about developmental age for children whose developmental or cognitive age scores may otherwise be physically limited.
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6. Farra N, Zhang WB, Pasceri P, Eubanks JH, Salter MW, Ellis J. {{Rett syndrome induced pluripotent stem cell-derived neurons reveal novel neurophysiological alterations}}. {Molecular psychiatry}. 2012 Jan 10.
Rett syndrome (RTT) is a neurodevelopmental autism spectrum disorder caused by mutations in the methyl-CpG-binding protein 2 (MECP2) gene. Here, we describe the first characterization and neuronal differentiation of induced pluripotent stem (iPS) cells derived from Mecp2-deficient mice. Fully reprogrammed wild-type (WT) and heterozygous female iPS cells express endogenous pluripotency markers, reactivate the X-chromosome and differentiate into the three germ layers. We directed iPS cells to produce glutamatergic neurons, which generated action potentials and formed functional excitatory synapses. iPS cell-derived neurons from heterozygous Mecp2(308) mice showed defects in the generation of evoked action potentials and glutamatergic synaptic transmission, as previously reported in brain slices. Further, we examined electrophysiology features not yet studied with the RTT iPS cell system and discovered that MeCP2-deficient neurons fired fewer action potentials, and displayed decreased action potential amplitude, diminished peak inward currents and higher input resistance relative to WT iPS-derived neurons. Deficiencies in action potential firing and inward currents suggest that disturbed Na(+) channel function may contribute to the dysfunctional RTT neuronal network. These phenotypes were additionally confirmed in neurons derived from independent WT and hemizygous mutant iPS cell lines, indicating that these reproducible deficits are attributable to MeCP2 deficiency. Taken together, these results demonstrate that neuronally differentiated MeCP2-deficient iPS cells recapitulate deficits observed previously in primary neurons, and these identified phenotypes further illustrate the requirement of MeCP2 in neuronal development and/or in the maintenance of normal function. By validating the use of iPS cells to delineate mechanisms underlying RTT pathogenesis, we identify deficiencies that can be targeted for in vitro translational screens.Molecular Psychiatry advance online publication, 10 January 2012; doi:10.1038/mp.2011.180.
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7. Frye RE, Sequeira JM, Quadros EV, James SJ, Rossignol DA. {{Cerebral folate receptor autoantibodies in autism spectrum disorder}}. {Molecular psychiatry}. 2012 Jan 10.
Cerebral folate deficiency (CFD) syndrome is a neurodevelopmental disorder typically caused by folate receptor autoantibodies (FRAs) that interfere with folate transport across the blood-brain barrier. Autism spectrum disorders (ASDs) and improvements in ASD symptoms with leucovorin (folinic acid) treatment have been reported in some children with CFD. In children with ASD, the prevalence of FRAs and the response to leucovorin in FRA-positive children has not been systematically investigated. In this study, serum FRA concentrations were measured in 93 children with ASD and a high prevalence (75.3%) of FRAs was found. In 16 children, the concentration of blocking FRA significantly correlated with cerebrospinal fluid 5-methyltetrahydrofolate concentrations, which were below the normative mean in every case. Children with FRAs were treated with oral leucovorin calcium (2 mg kg(-1) per day; maximum 50 mg per day). Treatment response was measured and compared with a wait-list control group. Compared with controls, significantly higher improvement ratings were observed in treated children over a mean period of 4 months in verbal communication, receptive and expressive language, attention and stereotypical behavior. Approximately one-third of treated children demonstrated moderate to much improvement. The incidence of adverse effects was low. This study suggests that FRAs may be important in ASD and that FRA-positive children with ASD may benefit from leucovorin calcium treatment. Given these results, empirical treatment with leucovorin calcium may be a reasonable and non-invasive approach in FRA-positive children with ASD. Additional studies of folate receptor autoimmunity and leucovorin calcium treatment in children with ASD are warranted.Molecular Psychiatry advance online publication, 10 January 2012; doi:10.1038/mp.2011.175.
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8. Geretsegger M, Holck U, Gold C. {{Randomised controlled Trial of Improvisational Music therapy’s Effectiveness for children with Autism spectrum disorders (TIME-A): Study protocol}}. {BMC pediatrics}. 2012 Jan 5;12(1):2.
ABSTRACT: BACKGROUND: Previous research has suggested that music therapy may facilitate skills in areas typically affected by autism spectrum disorders such as social interaction and communication. However, generalisability of previous findings has been restricted, as studies were limited in either methodological accuracy or the clinical relevance of their approach. The aim of this study is to determine effects of improvisational music therapy on social communication skills of children with autism spectrum disorders. An additional aim of the study is to examine if variation in dose of treatment (i.e., number of music therapy sessions per week) affects outcome of therapy, and to determine cost-effectiveness. METHODS: Children aged between 4;0 and 6;11 years who are diagnosed with autism spectrum disorder will be randomly assigned to one of three conditions. Parents of all participants will receive three sessions of parent counselling (at 0, 2, and 5 months). In addition, children randomised to the two intervention groups will be offered individual, improvisational music therapy over a period of five months, either one session (low-intensity) or three sessions (high-intensity) per week. Generalised effects of music therapy will be measured using standardised scales completed by blinded assessors (Autism Diagnostic Observation Schedule, ADOS) and parents (Social Responsiveness Scale, SRS) before and 2, 5, and 12 months after randomisation. Cost effectiveness will be calculated as man years. A group sequential design with first interim look at N = 235 will ensure both power and efficiency. DISCUSSION: Responding to the need for more rigorously designed trials examining the effectiveness of music therapy in autism spectrum disorders, this pragmatic trial sets out to generate findings that will be well generalisable to clinical practice. Addressing the issue of dose variation, this study’s results will also provide information on the relevance of session frequency for therapy outcome. Trial registration: Current Controlled Trials ISRCTN78923965.
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9. Godler DE, Slater HR, Bui QM, Storey E, Ono MY, Gehling F, Inaba Y, Francis D, Hopper JL, Kinsella G, Amor DJ, Hagerman RJ, Loesch DZ. {{Fragile X Mental Retardation 1 (FMR1) Intron 1 Methylation in Blood Predicts Verbal Cognitive Impairment in Female Carriers of Expanded FMR1 Alleles: Evidence from a Pilot Study}}. {Clinical chemistry}. 2012 Jan 10.
BACKGROUND:Cognitive status in females with mutations in the FMR1 (fragile X mental retardation 1) gene is highly variable. A biomarker would be of value for predicting which individuals were liable to develop cognitive impairment and could benefit from early intervention. A detailed analysis of CpG sites bridging exon 1 and intron 1 of FMR1, known as fragile X- related epigenetic element 2 (FREE2), suggests that a simple blood test could identify these individuals.METHODS:Study participants included 74 control females (<40 CGG repeats), 62 premutation (PM) females (55-200 CGG repeats), and 18 full-mutation (FM) females assessed with Wechsler intelligence quotient (IQ) tests. We used MALDI-TOF mass spectrometry to determine the methylation status of FREE2 CpG sites that best identified low-functioning (IQ <70) FM females (>200 CGG repeats), compared the results with those for Southern blot FMR1 activation ratios, and related these assessments to the level of production of the FMR1 protein product in blood.RESULTS:A methylation analysis of intron 1 CpG sites 10-12 showed the highest diagnostic sensitivity (100%) and specificity (98%) of all the molecular measures tested for detecting females with a standardized verbal IQ of <70 among the study participants. In the group consisting of only FM females, methylation of these sites was significantly correlated with full-scale IQ, verbal IQ, and performance IQ. Several verbal subtest scores showed strong correlation with the methylation of these sites (P = 1.2 x 10(-5)) after adjustment for multiple measures.CONCLUSIONS:The data suggest that hypermethylation of the FMR1 intron 1 sites in blood is predictive of cognitive impairment in FM females, with implications for improved fragile X syndrome diagnostics in young children and screening of the newborn population.
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10. Jyonouchi H, Geng L, Streck DL, Toruner GA. {{Immunological characterization and transcription profiling of peripheral blood (PB) monocytes in children with autism spectrum disorders (ASD) and specific polysaccharide antibody deficiency (SPAD): Case study}}. {J Neuroinflammation}. 2012 Jan 7;9(1):4.
ABSTRACT: INTRODUCTION: There exists a small subset of children with autism spectrum disorders (ASD) characterized by fluctuating behavioral symptoms and cognitive skills following immune insults. Some of these children also exhibit specific polysaccharide antibody deficiency (SPAD), resulting in frequent infection caused by encapsulated organisms, and they often require supplemental intravenous immunoglobulin (IVIG) (ASD/SPAD). This study assessed whether these ASD/SPAD children have distinct immunological findings in comparison with ASD/non-SPAD or non-ASD/SPAD children. Case description: We describe 8 ASD/SPAD children with worsening behavioral symptoms/cognitive skills that are triggered by immune insults. These ASD/SPAD children exhibited delayed type food allergy (5/8), treatment-resistant seizure disorders (4/8), and chronic gastrointestinal (GI) symptoms (5/8) at high frequencies. Control subjects included ASD children without SPAD (N=39), normal controls (N=37), and non-ASD children with SPAD (N=12). Discussion and Evaluation: We assessed their innate and adaptive immune responses, by measuring the production of pro-inflammatory and counter-regulatory cytokines by peripheral blood mononuclear cells (PBMCs) in responses to agonists of toll like receptors (TLR), stimuli of innate immunity, and T cell stimulants. Transcription profiling of PB monocytes was also assessed. ASD/SPAD PBMCs produced less proinflammatory cytokines with agonists of TLR7/8 (IL-6, IL-23), TLR2/6 (IL-6), TLR4 (IL-12p40), and without stimuli (IL-1beta, IL-6, and TNF-alpha) than normal controls. In addition, cytokine production of ASD/SPAD PBMCs in response to T cell mitogens (IFN-gamma, IL-17, and IL-12p40) and candida antigen (Ag) (IL-10, IL-12p40) were less than normal controls. ASD/non-SPAD PBMDs revealed similar results as normal controls, while non-ASD/SPAD PBMCs revealed lower production of IL-6, IL-10 and IL-23 with a TLR4 agonist. Only common features observed between ASD/SPAD and non-ASD/SPAD children is lower IL-10 production in the absence of stimuli. Transcription profiling of PB monocytes revealed over a 2-fold up (830 and 1250) and down (653 and 1235) regulation of genes in ASD/SPAD children, as compared to normal (N=26) and ASD/non-SPAD (N=29) controls, respectively. Enriched gene expression of TGFBR (p<0.005), Notch (p<0.01), and EGFR1 (p<0.02) pathways was found in the ASD/SPAD monocytes as compared to ASD/non-SPAD controls. CONCLUSIONS: The Immunological findings in the ASD/SPAD children who exhibit fluctuating behavioral symptoms and cognitive skills cannot be solely attributed to SPAD. Instead, these findings may be more specific for ASD/SPAD children with the above-described clinical characteristics, indicating a possible role of these immune abnormalities in their neuropsychiatric symptoms.
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11. Khanna R, Jariwala K. {{Awareness and knowledge of autism among pharmacists}}. {Research in social & administrative pharmacy : RSAP}. 2012 Jan 3.
BACKGROUND: In the past few decades, the prevalence of autism has increased tremendously in the United States. The prevalence of autism is now higher than the combined prevalence of juvenile diabetes, pediatric cancer, and pediatric AIDS. As health care professionals with a high visibility in a community, pharmacists are likely to encounter more and more families having a child affected by this disorder. OBJECTIVES: The purpose of this study was to assess pharmacists’ awareness and knowledge of autism. The study aimed to assess pharmacists’ familiarity with autism symptoms, treatment medications, and community resources devoted to this disorder. Further, pharmacists’ knowledge of common myths associated with autism, etiology, prognosis, and treatment were assessed. METHODS: Using a cross-sectional design, an online survey of pharmacists registered in the state of Mississippi (MS) was conducted, using the Qualtrics software program. Descriptive analysis of study items was conducted. RESULTS: A total of 147 usable responses (5.8%) were received. The results indicated gaps in pharmacists’ awareness and knowledge of autism. Approximately, 23% of pharmacists did not know that autism is a developmental disorder, and 32% did not believe that genetics has a major role in autism etiology. More than 18% believed that vaccines can cause autism. Most (>90%) felt that they could benefit from autism continuing education (CE). CONCLUSION: Policy makers and autism agencies should consider providing educational interventions or CE programs to increase pharmacists’ awareness and knowledge of autism.
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12. Liu ZH, Huang T, Smith CB. {{Lithium reverses increased rates of cerebral protein synthesis in a mouse model of fragile X syndrome}}. {Neurobiology of disease}. 2011 Dec 29.
Individuals with fragile X syndrome (FXS), an inherited form of cognitive disability, have a wide range of symptoms including hyperactivity, autistic behavior, seizures and learning deficits. FXS is caused by silencing of FMR1 and the consequent absence of fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein that associates with polyribosomes and negatively regulates translation. In a previous study of a mouse model of FXS (Fmr1 knockout (KO)) we demonstrated that in vivo rates of cerebral protein synthesis (rCPS) were elevated in selective brain regions suggesting that the absence of FMRP in FXS may result in dysregulation of cerebral protein synthesis. Lithium, a drug used clinically to treat bipolar disorder, has been used to improve mood dysregulation in individuals with FXS. We reported previously that in the Fmr1 KO mouse chronic dietary lithium treatment reversed or ameliorated both behavioral and morphological abnormalities. Herein we report that chronic dietary lithium treatment reversed the increased rCPS in Fmr1 KO mice with little effect on wild type mice. We also report our results of analyses of key signaling molecules involved in regulation of mRNA translation. Our analyses indicate that neither effects on the PI3K/Akt nor the MAPK/ERK 1/2 pathway fully account for the effects of lithium treatment on rCPS. Collectively our findings and those from other laboratories on the efficacy of lithium treatment in animal models support further studies in patients with FXS.
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13. Majnemer A. {{Vigilance to Behavioral Problems Needed for Children with Developmental Disability}}. {Phys Occup Ther Pediatr}. 2012 Jan 5.
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14. Marshall CR, Scherer SW. {{Detection and characterization of copy number variation in autism spectrum disorder}}. {Methods in molecular biology (Clifton, NJ)}. 2012;838:115-35.
There now exist multiple lines of evidence pointing to a significant genetic component underlying the aetiology of autism spectrum disorders (ASDs). The advent of methodologies for scanning the human genome at high resolution, coupled with the recognition of copy number variation (CNV) as a prevalent source of genomic variation, has led to new strategies in the identification of clinically relevant loci. Balanced genomic changes, such as translocations and inversions, also contribute to ASD, but current studies have shown that screening with microarrays has up to fivefold increase in diagnostic yield. Recent work by our group and others has shown unbalanced genomic alterations that are likely pathogenic in upwards of 10% of cases, highlighting an important role for CNVs in the genetic aetiology of ASD. A trend in our empirical data has shifted focus for discovery of candidate loci towards individually rare but highly penetrant CNVs instead of looking for common variants of low penetrance. This strategy has proven largely successful in identifying ASD-susceptibility candidate loci, including gains and losses at 16p11.2, SHANK2, NRXN1, and PTCHD1. Another emerging and intriguing trend is the identification of the same genes implicated by rare CNVs across neurodevelopmental disorders, including schizophrenia, attention deficit hyperactivity disorder, and intellectual disability. These observations indicate that similar pathways may be involved in phenotypically distinct outcomes. Although interrogation of the genome at high resolution has led to these novel discoveries, it has also made cataloguing, characterization, and clinical interpretation of the increasing amount of CNV data difficult. Herein, we describe the history of genomic structural variation in ASD and how CNV discovery has been used to pinpoint novel ASD-susceptibility loci. We also discuss the overlap of CNVs across neurodevelopmental disorders and comment on the current challenges of understanding the relationship between CNVs and associated phenotypes in a clinical context.
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15. Mazzone L, Vassena L, Ruta L, Mugno D, Galesi O, Fichera M. {{Brief Report: Peculiar Evolution of Autistic Behaviors in Two Unrelated Children with Brachidactyly-Mental Retardation Syndrome}}. {J Autism Dev Disord}. 2012 Jan 6.
Brachidactyly-Mental Retardation (BDMR) Syndrome (MIM 600430) is associated with terminal deletions at chromosome 2q37 and a limited number of studies also reported an association between 2q37 –> qter deletion and autism. Herein we describe two cases of autism in unrelated children with BDMR Syndrome, showing physical, cognitive, behavioral, and disease natural history homologies, with a very prominent social impairment in the first 4 years of life. At follow-up evaluations, spanning a 5-years period, both children experienced a progressive reduction of the autistic symptoms, besides retaining compromised cognitive ability. This report supports the hypothesis that genes in the 2q37 region may contribute to the etiology of autism, leading, however, to a peculiar evolution of the disease, with symptoms severity decreasing over time.
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16. Mostafa GA, Al-Ayadhi LY. {{The relationship between the increased frequency of serum antineuronal antibodies and the severity of autism in children}}. {European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society}. 2012 Jan 5.
BACKGROUND: Autism may involve an autoimmune pathogenesis. Immunotherapy may have a role in autistic children who have brain auto-antibodies. AIM: This study aimed to investigate the frequency of serum antineuronal auto-antibodies, as indicators of the presence of autoimmunity to brain, in a group of autistic children. We are the first to measure the relationship between these antibodies and the degree of the severity of autism. METHODS: Serum antineuronal antibodies were measured, by indirect immunofluorescence technique, in 80 autistic children, aged between 6 and 12 years, in comparison to 80 healthy-matched children. The severity of autism was assessed by using the Childhood Autism Rating Scale. RESULTS: Autistic children had significantly higher percent positivity of serum antineuronal antibodies (62.5%) than healthy controls (5%), P<0.001. The frequency of the positivity of serum antineuronal antibodies was significantly higher in children with severe autism (87.5%) than children with mild to moderate autism (25%), P<0.001. Similarly, the frequency of the positivity of these antibodies was significantly higher in female children with autism (90%) than male autistic children (53.3%), P=0.001. CONCLUSIONS: Serum antineuronal antibodies were found in a subgroup of autistic children and they were significantly correlated to the severity of autism. Thus, autism may be, in part, one of the pediatric autoimmune neuropsychiatric disorders. Further wide-scale studies are warranted to shed light on the etiopathogenic role of antineuronal antibodies in autism. The role of immunotherapy in autistic patients, who are seropositive for antineuronal antibodies, should also be studied.
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17. Parellada M, Moreno C, Mac-Dowell K, Leza JC, Giraldez M, Bailon C, Castro C, Miranda-Azpiazu P, Fraguas D, Arango C. {{Plasma antioxidant capacity is reduced in Asperger syndrome}}. {Journal of psychiatric research}. 2012 Jan 4.
Recent evidence suggests that children with autism have impaired detoxification capacity and may suffer from chronic oxidative stress. To our knowledge, there has been no study focusing on oxidative metabolism specifically in Asperger syndrome (a milder form of autism) or comparing this metabolism with other psychiatric disorders. In this study, total antioxidant status (TAOS), non-enzymatic (glutathione and homocysteine) and enzymatic (catalase, superoxide dismutase, and glutathione peroxidase) antioxidants, and lipid peroxidation were measured in plasma or erythrocyte lysates in a group of adolescent patients with Asperger syndrome, a group of adolescents with a first episode of psychosis, and a group of healthy controls at baseline and at 8-12 weeks. TAOS was also analyzed at 1 year. TAOS was reduced in Asperger individuals compared with healthy controls and psychosis patients, after covarying by age and antipsychotic treatment. This reduced antioxidant capacity did not depend on any of the individual antioxidant variables measured. Psychosis patients had increased homocysteine levels in plasma and decreased copper and ceruloplasmin at baseline. In conclusion, Asperger patients seem to have chronic low detoxifying capacity. No impaired detoxifying capacity was found in the first-episode psychosis group in the first year of illness.
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18. Peacock G, Lin SC. {{Enhancing early identification and coordination of intervention services for young children with autism spectrum disorders: Report from the Act Early Regional Summit Project}}. {Disability and health journal}. 2012 Jan;5(1):55-9.
BACKGROUND: Increasing prevalence of autism spectrum disorders (ASD) and the merits of early intervention support the importance of early identification and detection. The Act Early Initiative attempts to address the states’ capacity to support this process of early identification and early intervention. OBJECTIVE: The Centers for Disease Control and Prevention (CDC) Health Resources and Services Administration (HRSA) collaborated with the Association of University Centers on Disabilities (AUCD) to develop strategies that will address state capacity for responding to the increasing demand for earlier identification, earlier diagnoses, and coordination of service systems for children with ASDs and other developmental disabilities (DD). METHODS: Act Early regional summits were held to engage stakeholders from the early detection and intervention community including parents, state agencies, provider groups, autism and related disability organizations, and academia. The stakeholders then used the Logic Model to facilitate the teams’ planning process. The Logic Model enables teams to understand the strengths and gaps within their state resources and plan specific activities to achieve concrete outcomes. RESULTS: States identified opportunities and challenges in early identification of children with delay. One of the particular challenges identified were low income, rural and non-English speaking populations encountering more challenges than others in accessing diagnosis and early intervention services. CONCLUSIONS: The Summits are a unique model that demonstrates the importance of developing comprehensive state plans to advance the collaboration and coordination of early detection and intervention service systems for children with ASDs and related DDs from all racial, ethnic, geographical, and socioeconomic backgrounds.
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19. Prat CS, Stocco A. {{Information routing in the basal ganglia: Highways to abnormal connectivity in autism? Comment on « Disrupted cortical connectivity theory as an explanatory model for autism spectrum disorders » by Kana et al}}. {Physics of life reviews}. 2011 Dec 30.
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20. Rahbar MH, Samms-Vaughan M, Loveland KA, Pearson DA, Bressler J, Chen Z, Ardjomand-Hessabi M, Shakespeare-Pellington S, Grove ML, Beecher C, Bloom K, Boerwinkle E. {{Maternal and Paternal Age are Jointly Associated with Childhood Autism in Jamaica}}. {J Autism Dev Disord}. 2012 Jan 10.
Several studies have reported maternal and paternal age as risk factors for having a child with Autism Spectrum Disorder (ASD), yet the results remain inconsistent. We used data for 68 age- and sex-matched case-control pairs collected from Jamaica. Using Multivariate General Linear Models (MGLM) and controlling for parity, gestational age, and parental education, we found a significant (p < 0.0001) joint effect of parental ages on having children with ASD indicating an adjusted mean paternal age difference between cases and controls of [5.9 years; 95% CI (2.6, 9.1)] and a difference for maternal age of [6.5 years; 95% CI (4.0, 8.9)]. To avoid multicollinearity in logistic regression, we recommend joint modeling of parental ages as a vector of outcome variables using MGLM.
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21. Schieve LA, Boulet SL, Blumberg SJ, Kogan MD, Yeargin-Allsopp M, Boyle CA, Visser SN, Rice C. {{Association between parental nativity and autism spectrum disorder among US-born non-Hispanic white and Hispanic children, 2007 National Survey of Children’s Health}}. {Disability and health journal}. 2012 Jan;5(1):18-25.
BACKGROUND: Limited studies suggest the prevalence of autism spectrum disorders (ASD) varies by whether maternal and child birth country are discordant. OBJECTIVE/HYPOTHESIS: We explored associations between ASD and maternal and paternal nativity in a sample of US-born non-Hispanic white (NHW, n = 37,265) and US-born Hispanic (n = 4,690) children in the 2007 National Survey of Children’s Health (NSCH). METHODS: We assessed ASD prevalence within race-ethnicity and parental nativity subgroups. Prevalence ratios (aPR), comparing each group to NHW children with 2 US-born parents, were adjusted for child age, sex, and receipt of care in a medical home. Estimates were weighted to reflect US noninstitutionalized children. Standard errors were adjusted to account for the complex sample design. RESULTS: In NHW children with 2 US-born parents, ASD prevalence was 1.19%; estimates were similar for NHW children with a foreign-born mother or father. There was a striking heterogeneity between Hispanic children with 2 US-born versus 2 foreign-born parents (ASD prevalence 2.39% versus 0.31%, p = .05). Even after adjustment, PRs comparing ASD prevalence in Hispanic versus NHW children were vastly different for Hispanic subgroups, suggesting a substantially lower prevalence for Hispanic children with both parents foreign-born (aPR 0.2, 95% confidence interval 0.1-0.5) and a higher prevalence for Hispanic children with both parents US-born (aPR 2.0 [0.8-4.6]). CONCLUSIONS: Previous studies comparing ASD prevalence between NHW and Hispanic children based on a composite Hispanic grouping without consideration of parental nativity likely missed important differences between these racial-ethnic groups. Continuing efforts toward improving early identification in Hispanic children are needed.
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22. Sell NK, Giarelli E, Blum N, Hanlon AL, Levy SE. {{A comparison of Autism Spectrum Disorder DSM-IV criteria and associated features among African American and white children in Philadelphia County}}. {Disability and health journal}. 2012 Jan;5(1):9-17.
BACKGROUND: Racial differences are documented in the timing and type of autism spectrum disorder (ASD) diagnosis among white and African American children. Differences in clinical presentation by race may contribute to these disparities. This study explores documented differences in core ASD symptoms and associated behavioral features among African American and white children. METHODS: This project is a secondary data analysis from the Pennsylvania Autism and Developmental Disabilities Surveillance Program and utilized methodology that evaluates existing records, reviews, and codes for DSM-IV criteria for ASD and 12 associated behavioral features. The sample comprised 343 children meeting surveillance case definition for ASD, from 3 population-based cohorts of children in Philadelphia County. RESULTS: A higher frequency of white children compared to African American children with ASD have documented DSM-IV criteria of inflexible adherence to nonfunctional routines/rituals (92% vs 81%; p = .005) and persistent preoccupation with parts of objects (67% vs 50%; p = .002). A higher frequency of white children with ASD compared to African American children with ASD have documented abnormal motor development (74% vs 60%; p = .008) and odd responses to sensory stimuli (76% vs 51%; p < .001). There were no significant differences in externalizing behaviors or reciprocal social interaction. CONCLUSIONS: This study suggests differences in the types of ASD symptoms and associated behavioral features exhibited by African American as compared to white children with ASD. Further research is needed to determine if these differences contribute to disparities in the timing or type of ASD diagnosis.
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23. Shishido E. {{[Autism spectrum disorder and genes for synaptic proteins]}}. {Brain and nerve = Shinkei kenkyu no shinpo}. 2012 Jan;64(1):65-70.
Abstract Autism spectrum disorder (ASD) is characterized by impaired social interaction and communication, and restricted interests. It is generally accepted that ASD is caused by abnormalities in the structure or functions of the brain. Recent genome-wide analyses have identified copy number variations (CNVs) of neuronal genes in the genomes of ASD patients. CNV is a commonly observed phenomenon in human beings. During the first cell division of meiosis, irregular crossing over between homologous chromosomes results in loss or duplication of a segment. From 2007 to 2010, several groups performed a large-scale virtual screening of CNVs in ASD genomes. Genes affected by CNV, de novo CNVs, and rare CNVs were more prevalent in ASD. The results highlighted the CNVs of many neuronal genes associated with ASD. A fraction of these genes was previously identified in ASD but some were newly identified in each study. The CNVs implicated in ASD include neuronal genes belonging to 4 classes. These genes encode (1) neural adhesion molecules, including cadherins, neuroligin, and neurexin; (2) scaffold proteins such as SHANK3; (3) protein kinases and other intracellular signaling molecules; and (4) proteins that regulate protein syntheses. In general, these proteins play a role in synapse of glutamatergic neurons. The CNVs detected in the ASD patient genomes of imply a link between the synaptic proteins and pathological characteristics of ASD. Altered protein dosage by the CNVs may alter the functional quality of ASD patient’s synapses, and may consequently affect their development of language and communication skills. There are 2 types of ASD, one is sporadic and, the other is familial. According to some reports, de novo CNVs are more frequently observed in sporadic-type ASD. However, it is generally understood that a combination of particular CNVs and other possible mutations underlie the pathology of ASD regardless of ASD type. The major symptoms of ASD are often curable with behavioral intervention during early childhood. An early diagnosis, followed by early start of treatment is crucial for language development and communication skills. Further and broader research on genomes will eventually provide information on the biological characteristics of ASD, as well as on specific ASD genotypes, thus aiding in the establishment of optimal treatment and medication to meet the biological conditions of each patient. (Received: November 19, 2010, Accepted: July 4, 2011).
24. Szkup-Jablonska M, Karakiewicz B, Grochans E, Jurczak A, Zaremba-Pechmann L, Rotter I, Nowak-Starz G, Samochowiec J. {{[The effects of lead level in the blood on social functioning in children with developmental disabilities]}}. {Psychiatria polska}. 2011 Sep-Oct;45(5):713-22.
AIM: The aim of the study was to assess the relationship between lead levels in children’s blood and the development of social disorders. METHOD: Lead levels were measured in every child’s blood test and following on from that the influence of this toxin on children’s behaviour was assessed. Manfred Cierpka questionnaire was used as the assessment tool examining children’s family relationships and Children’s Health Questionnaire Parent Form-28 was used to assess the subjects’ health profile. RESULTS: The statistical analysis revealed a statistically significant relationship between lead concentration in the child’s blood and whether or not the child was able to meet social expectations (p = 0.018), form affective relationships (p = 0.046), its nervousness (p = 0.024) and a generally lower assessment of his/her behavior in comparison with the peer group (p = 0.024). CONCLUSIONS: Neurotoxic influence of lead on the developing child’s organism results in developmental disabilities in its behaviour. These dysfunctions can lead to disorders in the child’s social development and they can hinder its functioning. An increased concentration of metal toxins in the child’s blood can be responsible for difficulties in meeting social expectation, which in turn is connected with increased nervousness and disorders in forming relationships. Children facing these problems often receive negative marks for their behaviour in comparison with the peer group. Such difficulties can lead to the child’s social exclusion and predispose it to making antisocial or criminal decisions in the future.
25. Teo CR, Law HY, Lee CG, Chong SS. {{Fragile X Mental Retardation 1 Gene CGG Repeat Expansion Screening by Melting Curve Analysis of Combined 5′ and 3′ Direct Triplet-Primed PCRs}}. {Clinical chemistry}. 2012 Jan 5.
BACKGROUND:CGG repeat expansions in the FMR1 (fragile X mental retardation 1) gene are associated with fragile X syndrome, fragile X-associated tremor/ataxia syndrome, and fragile X-associated primary ovarian insufficiency. We evaluated the use of melting curve analysis (MCA) of triplet-primed PCR (TP-PCR) assays as a rapid screening tool for the positive identification of expanded FMR1 alleles in men and women.METHODS:Both 5′- and 3′-weighted direct TP-PCRs (dTP-PCRs) were evaluated on 29 cell line-derived DNA samples and 44 blinded clinical samples. The presence of expansions was identified by the melting curve profiles generated automatically through MCA on the LightCycler 480 Real-Time PCR System. All samples were also analyzed by capillary electrophoresis to confirm the identities of the PCR fragments that gave rise to the observed melt peak profiles.RESULTS:The presence of expanded alleles in samples from both males and females produced melt peak profiles that were distinct from those of individuals with the normal allelic form. In the blinded test, positive and negative calls for the presence of an expanded allele corroborated with previously determined genotype classifications for all samples.CONCLUSIONS:The approach of dTP-PCR plus MCA offers a single-step strategy with high diagnostic sensitivity and specificity for rapid screening detection of FMR1 CGG repeat expansions, regardless of sex. The combined use of 5′- and 3′-weighted dTP-PCR assays minimizes the incidence of false-negative results arising from repeat-flanking deletions.
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26. Wang J, Zhou X, Xia W, Sun CH, Wu LJ, Wang JL, Tomoda A. {{Parent-reported health care expenditures associated with autism spectrum disorders in Heilongjiang Province, China}}. {BMC health services research}. 2012 Jan 10;12(1):7.
ABSTRACT: BACKGROUND: The aim of this study was to determine the health expenses incurred by families with children with autism spectrum disorder (ASD) and those expenses relation to total household income and expenditures. METHODS: In this cross-sectional study, health care expenditure data were collected through face-to-face interviews. Expenses included annual costs for clinic visits, medication, behavioral therapy, transportation, and accommodations. Health care costs as a percentage of total household income and expenditures were also determined. The participants included 290 families with ASD children who were treated at the Children Development and Behavior Research Center, Harbin Medical University, China. RESULTS: Families with ASD children from urban and rural areas had higher per-capita household expenditures by 60.8% and 74.7%, respectively, compared with provincial statistics for 2007. Behavioral therapy accounted for the largest proportion of health expenses (54.3%) for ASD children. In 19.9% of urban and 38.2% of rural families, health care costs exceeded the total annual household income. Most families (89.3% of urban families; 88.1% of rural families) in that province reported a higher share of health care expenditures than the reported household average. CONCLUSION: For families with ASD children, the economic burden of health care is substantially higher than the provincial average.
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27. Williams BL, Hornig M, Parekh T, Lipkin WI. {{Application of Novel PCR-Based Methods for Detection, Quantitation, and Phylogenetic Characterization of Sutterella Species in Intestinal Biopsy Samples from Children with Autism and Gastrointestinal Disturbances}}. {mBio}. 2012;3(1).
ABSTRACT Gastrointestinal disturbances are commonly reported in children with autism and may be associated with compositional changes in intestinal bacteria. In a previous report, we surveyed intestinal microbiota in ileal and cecal biopsy samples from children with autism and gastrointestinal dysfunction (AUT-GI) and children with only gastrointestinal dysfunction (Control-GI). Our results demonstrated the presence of members of the family Alcaligenaceae in some AUT-GI children, while no Control-GI children had Alcaligenaceae sequences. Here we demonstrate that increased levels of Alcaligenaceae in intestinal biopsy samples from AUT-GI children result from the presence of high levels of members of the genus Sutterella. We also report the first Sutterella-specific PCR assays for detecting, quantitating, and genotyping Sutterella species in biological and environmental samples. Sutterella 16S rRNA gene sequences were found in 12 of 23 AUT-GI children but in none of 9 Control-GI children. Phylogenetic analysis revealed a predominance of either Sutterella wadsworthensis or Sutterella stercoricanis in 11 of the individual Sutterella-positive AUT-GI patients; in one AUT-GI patient, Sutterella sequences were obtained that could not be given a species-level classification based on the 16S rRNA gene sequences of known Sutterella isolates. Western immunoblots revealed plasma IgG or IgM antibody reactivity to Sutterella wadsworthensis antigens in 11 AUT-GI patients, 8 of whom were also PCR positive, indicating the presence of an immune response to Sutterella in some children. IMPORTANCE Autism spectrum disorders affect ~1% of the population. Many children with autism have gastrointestinal (GI) disturbances that can complicate clinical management and contribute to behavioral problems. Understanding the molecular and microbial underpinnings of these GI issues is of paramount importance for elucidating pathogenesis, rendering diagnosis, and administering informed treatment. Here we describe an association between high levels of intestinal, mucoepithelial-associated Sutterella species and GI disturbances in children with autism. These findings elevate this little-recognized bacterium to the forefront by demonstrating that Sutterella is a major component of the microbiota in over half of children with autism and gastrointestinal dysfunction (AUT-GI) and is absent in children with only gastrointestinal dysfunction (Control-GI) evaluated in this study. Furthermore, these findings bring into question the role Sutterella plays in the human microbiota in health and disease. With the Sutterella-specific molecular assays described here, some of these questions can begin to be addressed.
