1. Abadie P. {{Conduites suicidaires chez les adolescents et les jeunes adultes avec un trouble envahissant du développement}}. {Sante Ment Que};2012 (Autumn);37(2):175-191.
The Autistic Spectrum Disorders (ASD) are characterized by an atypical sociability, alterations in communication, restricted interests and stereotypies, with adding affective and adaptative disabilities. The suicidal behaviors are frequently observed in the adolescents and adults with an ASD without intellectual deficience. However, the clinical research on the topic is limited and the diagnosis not assessed in the emergency units. Among the individual risk factors of the suicidal behavior in ASD patients, mood and anxiety disorders are found as well as a familial affective disorder history. The intimidation and the lack of socio-professional integration were also reported as environnemental risk factors. Laters tudies taking into account the cognitive characteristics would permit to investigate the suicidal phenomenology in ASD patients.
2. Berry-Kravis E, Doll E, Sterling A, Kover ST, Schroeder SM, Mathur S, Abbeduto L. {{Development of an expressive language sampling procedure in fragile x syndrome: a pilot study}}. {J Dev Behav Pediatr};2013 (May);34(4):245-251.
OBJECTIVE: : There is a great need for valid outcome measures of functional improvement for impending clinical trials of targeted interventions for fragile X syndrome (FXS). Families often report conversational language improvement during clinical treatment, but no validated measures exist to quantify this outcome. This small-scale study sought to determine the feasibility, reproducibility, and clinical validity of highly structured expressive language sampling as an outcome measure reflecting language ability. METHODS: : Narrative and conversation tasks were administered to 36 verbal participants (25 males and 11 females) with FXS (aged 5-36 years, mean, 18 +/- 7 years). Alternate versions were used with randomized task order at 2- to 3-week intervals (mean, 19.6 +/- 6.4 days). Audio recordings of sessions were transcribed and analyzed. Dependent measures reflected talkativeness (total number of utterances), utterance planning (proportion of communication [C] units with mazes), articulation (proportion of unintelligible/partly unintelligible C-units), vocabulary (number of different word roots), and syntactic ability (mean length of utterance [MLU] in words). Reproducibility of measures was evaluated with intraclass correlation coefficients (ICC). RESULTS: : All participants could complete the tasks. Coded data were highly reproducible with Pearson’s correlations at p < .01 for all measures and ICC values of .911 to .966 (conversation) and .728 to .940 (narration). Some measures including MLU and different word roots were correlated with expressive language subscale scores from the Vineland Adaptive Behavior Scale. CONCLUSIONS: : These expressive language sampling tasks appear to be feasible, reproducible, and clinically valid and should be further validated in a larger cohort, as a promising means of assessing functional expressive language outcomes during clinical trials in FXS.
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3. Berube M, Hubbard C, Mallory L, Larsen E, Morrison P, Augustyn M. {{Historic condition in a modern child with autism}}. {J Dev Behav Pediatr};2013 (May);34(4):288-290.
CASE:: Haven is an 11-year-old primary care patient who you have followed since her birth. She was the 9 lb 6 oz product of a 38-week gestation complicated by maternal hypertension and seizure disorder treated with tegretol. Her delivery and neonatal course were uneventful. She was diagnosed with austistic disorder at age 2 years, at which time she used no functional language or gestures, had repetitive motor mannerisms, and limited eye contact. She had strong tactile sensory aversions. Her diet was very restricted including only banana yogurt and drinking milk and apple juice for the first several years of life.She was followed by a developmental-behavioral pediatrician approximately annually through age 8 years and then more frequently. She was healthy other than lead exposure (maximum serum level 18 at age 3 years) and multiple febrile seizures with other possible absence episodes. Her development remained very delayed with use of single words and short phrases. She developed multiple repetitive, anxious, obsessive behaviors (picking up lint, organizing, cleaning, and freezing in certain postures) that were treated with a selective serotonin reuptake inhibitors fluvoxamine. Sensory issues were ongoing, with restrictive eating (primarily peanut butter and jelly sandwiches, cereal bars, milk, and a kiwi-strawberry drink). She took a liquid multivitamin until age 8.At age 11 years, 3 weeks prior to admission, Haven developed acute loss of ambulation over the course of 1 day, initially dragging her right leg, and then refusing to walk and her parents brought her in to see you. She had fever, vomiting, and general weakness. She developed extensive bruising over her legs, especially in the popliteal fossae. She was also noted to have friability and dark discoloration of her gums. Initially, you suspected a post-viral syndrome and close monitoring.She was seen twice in the next 2 weeks in a local emergency room where her erythrocyte sedimentation rate was reported to be elevated and juvenile rheumatoid arthritis or a reaction to fluvoxamine were suspected. Antibiotics were also prescribed for gingivitis. She was seen by an orthopedist who felt it was not an orthopedic issue and leg films were unremarkable. With her second emergency room visit, she was transferred to a tertiary medical center and admitted for further evaluation. Where would you go from here?
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4. Ginsberg MR, Rubin RA, Natowicz MR. {{Patterning of regional gene expression in autism: new complexity}}. {Sci Rep};2013 (May 13);3:1831.
Autism is a common and often severe neurodevelopmental disorder for which diverse pathophysiological processes have been proposed. Recent gene expression data comparing autistic and control brains suggest that the normal differential gene expression between frontal and temporal cortex is attenuated in autistic brains. It is unknown if regional de-differentiation occurs elsewhere in autistic brain. Using high resolution, genome-wide RNA expression microarrays and brain specimens meeting stringent selection criteria we evaluated gene expression data of two other regions: Brodmann area 19 (occipital cortex) and cerebellar cortex. In contrast to frontal/temporal cortical data, our data do not indicate an attenuation of regional specialization between occipital and cerebellar cortical regions in autistic brains.
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5. Herbert MR, Buckley JA. {{Autism and Dietary Therapy: Case Report and Review of the Literature}}. {J Child Neurol};2013 (May 10)
We report the history of a child with autism and epilepsy who, after limited response to other interventions following her regression into autism, was placed on a gluten-free, casein-free diet, after which she showed marked improvement in autistic and medical symptoms. Subsequently, following pubertal onset of seizures and after failing to achieve full seizure control pharmacologically she was advanced to a ketogenic diet that was customized to continue the gluten-free, casein-free regimen. On this diet, while still continuing on anticonvulsants, she showed significant improvement in seizure activity. This gluten-free casein-free ketogenic diet used medium-chain triglycerides rather than butter and cream as its primary source of fat. Medium-chain triglycerides are known to be highly ketogenic, and this allowed the use of a lower ratio (1.5:1) leaving more calories available for consumption of vegetables with their associated health benefits. Secondary benefits included resolution of morbid obesity and improvement of cognitive and behavioral features. Over the course of several years following her initial diagnosis, the child’s Childhood Autism Rating Scale score decreased from 49 to 17, representing a change from severe autism to nonautistic, and her intelligence quotient increased 70 points. The initial electroencephalogram after seizure onset showed lengthy 3 Hz spike-wave activity; 14 months after the initiation of the diet the child was essentially seizure free and the electroencephalogram showed only occasional 1-1.5 second spike-wave activity without clinical accompaniments.
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6. Higashimori H, Morel L, Huth J, Lindemann L, Dulla C, Taylor A, Freeman M, Yang Y. {{Astroglial FMRP-dependent translational down-regulation of mGluR5 underlies glutamate transporter GLT1 dysregulation in the fragile X mouse}}. {Hum Mol Genet};2013 (May 15);22(10):2041-2054.
Fragile X syndrome (FXS) is a neurodevelopmental disorder caused by the loss-of-function of fragile X mental retardation protein (FMRP). The loss of FMRP function in neurons abolishes its suppression on mGluR1/5-dependent dendritic protein translation, enhancing mGluR1/5-dependent synaptic plasticity and other disease phenotypes in FXS. In this study, we describe a new activation function of FMRP in regulating protein expression in astroglial cells. We found that astroglial glutamate transporter subtype glutamate transporter 1 (GLT1) and glutamate uptake is significantly reduced in the cortex of fmr1(-/-) mice. Correspondingly, neuronal excitability is also enhanced in acute fmr1(-/-) (but not in fmr1(+/+) control) cortical slices treated with low doses (10 mum) of the GLT1-specific inhibitor dihydrokainate (DHK). Using mismatched astrocyte and neuron co-cultures, we demonstrate that the loss of astroglial (but not neuronal) FMRP particularly reduces neuron-dependent GLT1 expression and glutamate uptake in co-cultures. Interestingly, protein (but not mRNA) expression and the (S)-3,5-dihydroxyphenylglycine-dependent Ca(2+) responses of astroglial mGluR5 receptor are also selectively reduced in fmr1(-/-) astrocytes and brain slices, attenuating neuron-dependent GLT1 expression. Subsequent FMRP immunoprecipitation and QRT-PCR analysis showed that astroglial mGluR5 (but not GLT1) mRNA is associated with FMRP. In summary, our results provide evidence that FMRP positively regulates translational expression of mGluR5 in astroglial cells, and FMRP-dependent down-regulation of mGluR5 underlies GLT1 dysregulation in fmr1(-/-) astrocytes. The dysregulation of GLT1 and reduced glutamate uptake may potentially contribute to enhanced neuronal excitability observed in the mouse model of FXS.
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7. Krueger DD, Brose N. {{Evidence for a common endocannabinoid-related pathomechanism in autism spectrum disorders}}. {Neuron};2013 (May 8);78(3):408-410.
In this issue of Neuron, Foldy et al. (2013) report that endocannabinoid-mediated signaling at inhibitory synapses is dysregulated in mouse models of autism-associated Neuroligin-3 mutations. These findings carry implications regarding the pathophysiology of autism spectrum disorders and the development of treatment strategies.
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8. Lionel AC, Vaags AK, Sato D, Gazzellone MJ, Mitchell EB, Chen HY, Costain G, Walker S, Egger G, Thiruvahindrapuram B, Merico D, Prasad A, Anagnostou E, Fombonne E, Zwaigenbaum L, Roberts W, Szatmari P, Fernandez BA, Georgieva L, Brzustowicz LM, Roetzer K, Kaschnitz W, Vincent JB, Windpassinger C, Marshall CR, Trifiletti RR, Kirmani S, Kirov G, Petek E, Hodge JC, Bassett AS, Scherer SW. {{Rare exonic deletions implicate the synaptic organizer Gephyrin (GPHN) in risk for autism, schizophrenia and seizures}}. {Hum Mol Genet};2013 (May 15);22(10):2055-2066.
The GPHN gene codes for gephyrin, a key scaffolding protein in the neuronal postsynaptic membrane, responsible for the clustering and localization of glycine and GABA receptors at inhibitory synapses. Gephyrin has well-established functional links with several synaptic proteins that have been implicated in genetic risk for neurodevelopmental disorders such as autism spectrum disorder (ASD), schizophrenia and epilepsy including the neuroligins (NLGN2, NLGN4), the neurexins (NRXN1, NRXN2, NRXN3) and collybistin (ARHGEF9). Moreover, temporal lobe epilepsy has been linked to abnormally spliced GPHN mRNA lacking exons encoding the G-domain of the gephyrin protein, potentially arising due to cellular stress associated with epileptogenesis such as temperature and alkalosis. Here, we present clinical and genomic characterization of six unrelated subjects, with a range of neurodevelopmental diagnoses including ASD, schizophrenia or seizures, who possess rare de novo or inherited hemizygous microdeletions overlapping exons of GPHN at chromosome 14q23.3. The region of common overlap across the deletions encompasses exons 3-5, corresponding to the G-domain of the gephyrin protein. These findings, together with previous reports of homozygous GPHN mutations in connection with autosomal recessive molybdenum cofactor deficiency, will aid in clinical genetic interpretation of the GPHN mutation spectrum. Our data also add to the accumulating evidence implicating neuronal synaptic gene products as key molecular factors underlying the etiologies of a diverse range of neurodevelopmental conditions.
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9. Mattard-Labrecque C, Ben Amor L, Couture MM. {{Children with Autism and Attention Difficulties: A Pilot Study of the Association between Sensory, Motor, and Adaptive Behaviors}}. {J Can Acad Child Adolesc Psychiatry};2013 (May);22(2):139-146.
OBJECTIVES: This pilot study aimed to compare sensory processing, motor skills and adaptive behaviors in children with a double diagnosis of Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) (ASD+ADHD) with children with ADHD alone and to examine the association of sensory processing and motor skills with adaptive behaviors (self-care). METHOD: Thirty children aged 5-14 years diagnosed with ASD+ADHD (n = 13) or ADHD (n = 17) were evaluated on their sensory processing and motor skills and adaptive behaviors. Analysis of covariance compared the groups on these dimensions. Correlation analyses examined the association between sensory processing and motor skills and adaptive behaviors. RESULTS: Compared to children with ADHD alone, children with ASD+ADHD had poorer skills in sensory processing (p < 0.001), motor (p = 0.001) and adaptive behaviors (p < 0.001). For all children, increased autonomy in self-care was correlated with better sensory processing (p < 0.001) and motor skills (p = 0.002). CONCLUSION: Children with ASD+ADHD have poorer sensory processing, motor and adaptive skills than those with ADHD alone. Sensory processing and motor deficits were negatively associated with autonomy in self-care. Interventions aiming to improve sensory processing and motor skills and autonomy in self-care should become important targets for these children.
10. Oguchi-Katayama A, Monma A, Sekino Y, Moriguchi T, Sato K. {{Comparative gene expression analysis of the amygdala in autistic rat models produced by pre- and post-natal exposures to valproic acid}}. {J Toxicol Sci};2013;38(3):391-402.
Gene expression profiles in the amygdala of juvenile rats were compared between the two autistic rat models for mechanistic insights into impaired social behavior and enhanced anxiety in autism. The rats exposed to VPA by intraperitoneal administration to their dams at embryonic day (E) 12 were used as a model for autism (E2IP), and those by subcutaneous administration at postnatal day (P) 14 (P14SC) were used as a model for regressive autism; both of the models show impaired social behavior and enhanced anxiety as symptoms. Gene expression profiles in the amygdala of the rats (E12IP and P14SC) were analyzed by microarray and compared to each other. Only two genes, Neu2 and Mt2a, showed significant changes in the same direction in both of the rat models, and there were little similarities in the overall gene expression profiles between them. It was considered that gene expression changes per se in the amygdala might be an important cause for impaired social behavior and enhanced anxiety, rather than expression changes of particular genes.
11. Ponde MP, Rousseau C. {{Immigrant Children with Autism Spectrum Disorder: The Relationship between the Perspective of the Professionals and the Parents’ Point of View}}. {J Can Acad Child Adolesc Psychiatry};2013 (May);22(2):131-138.
BACKGROUND: The purpose of this study was to compare a medical diagnosis of autism spectrum disorder (ASD) with the perceptions of immigrant parents regarding their child’s difficulties. METHODS: Semistructured interviews were conducted with parents. The children were assessed using the ADOS, and a multiaxial diagnosis was reached using the DSM-IV. RESULTS: The majority of parents recognized symptoms in their child that were related to autism. Less often, however, parents believed their children had a developmental delay or communication problem rather than an ASD. There were also parents who failed to see any problem at all in their child although the child was, nonetheless, diagnosed as having an ASD. CONCLUSIONS: The failure of immigrant mothers to acknowledge a diagnosis of ASD in their younger children may represent an attempt to preserve hope for their child’s future. Mothers of older children may not, however, agree with the psychiatric diagnosis. Community services need to balance the need to convey accurate medical information with the need to protect parents’ investment in their children. This may be particularly true for immigrant parents who are living outside their cultural framework.
12. Reddy K, Pearson CE. {{RAN Translation: Fragile X in the Running}}. {Neuron};2013 (May 8);78(3):405-408.
In this issue of Neuron, Todd et al. (2013) reveal that noncanonical repeat associated non-AUG (RAN) translation occurs on nonexpanded (CGG)30-50 and premutation (CGG)59-160 repeats, associated with the FMR1 gene, suggesting that the polyglycine and polyalanine products might have natural and pathogenic roles.
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13. Riby DM, Hancock PJ, Jones N, Hanley M. {{Spontaneous and cued gaze-following in autism and Williams syndrome}}. {J Neurodev Disord};2013 (May 10);5(1):13.
BACKGROUND: From a young age the typical development of social functioning relies upon the allocation of attention to socially relevant information, which in turn allows experience at processing such information and thus enhances social cognition. As such, research has attempted to identify the developmental processes that are derailed in some neuro-developmental disorders that impact upon social functioning. Williams syndrome (WS) and autism are disorders of development that are characterized by atypical yet divergent social phenotypes and atypicalities of attention to people. METHODS: We used eye tracking to explore how individuals with WS and autism attended to, and subsequently interpreted, an actor’s eye gaze cue within a social scene. Images were presented for 3 seconds, initially with an instruction simply to look at the picture. The images were then shown again, with the participant asked to identify the object being looked at. Allocation of eye gaze in each condition was analyzed by analysis of variance and accuracy of identification was compared with t tests. RESULTS: Participants with WS allocated more gaze time to face and eyes than their matched controls, both with and without being asked to identify the item being looked at; while participants with autism spent less time on face and eyes in both conditions. When cued to follow gaze, participants with WS increased gaze to the correct targets; those with autism looked more at the face and eyes but did not increase gaze to the correct targets, while continuing to look much more than their controls at implausible targets. Both groups identified fewer objects than their controls. CONCLUSIONS: The atypicalities found are likely to be entwined with the deficits shown in interpreting social cognitive cues from the images. WS and autism are characterized by atypicalities of social attention that impact upon socio-cognitive expertise, but, importantly, the type of atypicality is syndrome specific.
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14. Taylor LJ, Maybery MT, Grayndler L, Whitehouse AJ. {{Evidence for Distinct Cognitive Profiles in Autism Spectrum Disorders and Specific Language Impairment}}. {J Autism Dev Disord};2013 (May 15)
Findings that a subgroup of children with an autism spectrum disorder (ASD) have linguistic capabilities that resemble specific language impairment (SLI) have led some authors to hypothesise that ASD and SLI have a shared aetiology. While considerable research has explored overlap in the language phenotypes of the two conditions, little research has examined possible overlap in cognitive characteristics. In this study, we explored nonword and sentence repetition performance, as well as performance on the Children’s Embedded Figures Test (CEFT) for children with ASD or SLI. As expected, ‘language impaired’ children with ASD (ALI) and children with SLI performed worse than both ‘language normal’ ASD (ALN) and typically developing (TD) children on the nonword and sentence repetition tests. Further, the SLI children performed worse than all other groups on the CEFT. This finding supports distinct cognitive profiles in ASD and SLI and may provide further evidence for distinct aetiological mechanisms in the two conditions.
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15. Wong VC, Fung CK, Wong PT. {{Use of Dysmorphology for Subgroup Classification on Autism Spectrum Disorder in Chinese Children}}. {J Autism Dev Disord};2013 (May 12)
Data from 1,261 Chinese Autistic Spectrum Disorder (ASD) patients were evaluated and categorized into dysmorphic (10.79 %) and non-dysmorphic groups (89.21 %) upon physical examination by the presence of dysmorphic features. Abnormal MRI/CT result, IQ scores and epilepsy were significantly associated with the dysmorphic group of ASD children. However, gender, EEG abnormality and family history and recurrence of ASD were not found to be significantly different between group statuses. It is suggested that results collected from the Chinese population generally resembles that found in the Caucasians with ethnical differences still present. Current study supports the result shown in Miles’ study (Miles et al. in Am J Med Genet 135A:171-180, 2005), in which heterogeneity subtypes of autism of different genetic origins which could be distinguished by presence of dysmorphic features on the patients.
