1. Ecker C, Spooren W, Murphy DG. {{Translational approaches to the biology of Autism: false dawn or a new era?}}. {Mol Psychiatry};2012 (Jul 17)
Discovering novel treatments for Autism Spectrum Disorders (ASD) is a challenge. Its etiology and pathology remain largely unknown, the condition shows wide clinical diversity, and case identification is still solely based on symptomatology. Hence clinical trials typically include samples of biologically and clinically heterogeneous individuals. ‘Core deficits’, that is, deficits common to all individuals with ASD, are thus inherently difficult to find. Nevertheless, recent reports suggest that new opportunities are emerging, which may help develop new treatments and biomarkers for the condition. Most important, several risk gene variants have now been identified that significantly contribute to ASD susceptibility, many linked to synaptic functioning, excitation-inhibition balance, and brain connectivity. Second, neuroimaging studies have advanced our understanding of the ‘wider’ neural systems underlying ASD; and significantly contributed to our knowledge of the complex neurobiology associated with the condition. Last, the recent development of powerful multivariate analytical techniques now enable us to use multi-modal information in order to develop complex ‘biomarker systems’, which may in the future be used to assist the behavioral diagnosis, aid patient stratification and predict response to treatment/intervention. The aim of this review is, therefore, to summarize some of these important new findings and highlight their potential significant translational value to the future of ASD research.Molecular Psychiatry advance online publication, 17 July 2012; doi:10.1038/mp.2012.102.
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2. Falter CM, Noreika V, Wearden JH, Bailey AJ. {{More consistent, yet less sensitive: Interval timing in autism spectrum disorders}}. {Q J Exp Psychol (Hove)};2012 (Jul 16)
Even though phenomenological observations and anecdotal reports suggest atypical time processing in individuals with an autism spectrum disorder (ASD), very few psychophysical studies have investigated interval timing, and the obtained results are contradictory. The present study aimed to clarify which timing processes function atypically in ASD and whether they are related to the ASD diagnostic profile. Visual, auditory, and cross-modal interval timing was assessed in 18 individuals with ASD using a repeated standards version of the temporal generalization task. The use of two different standard durations (600 and 1,000 ms) allowed for an assessment of the scalar property of interval timing in ASD, a fundamental characteristic of interval timing. The ASD group showed clearer adherence to the scalar property of interval timing than the control group. In addition, both groups showed the normal effect that auditory stimuli had longer subjective durations than visual ones. Yet, signal detection analysis showed that the sensitivity of temporal discrimination was reduced in the ASD group across modalities, in particular for auditory standards. Moreover, response criteria in the ASD group were related to symptom strength in the communication domain. The findings suggest that temporal intervals are fundamentally processed in the same way in ASD and TD, but with reduced sensitivity for temporal interval differences in ASD. Individuals with ASD may show a more conservative response strategy due to generally decreased sensitivity for the perception of time intervals.
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3. Grecucci A, Brambilla P, Siugzdaite R, Londero D, Fabbro F, Rumiati RI. {{Emotional Resonance Deficits in Autistic Children}}. {J Autism Dev Disord};2012 (Jul 18)
According to some theories imitation, defined as an action resonance mechanism, is deficient in autism. In contrast, other theories (e.g., the « top down control of imitation » hypothesis) state that the problem is not in imitation per se but in the way social cues modulate imitative responses. In this study, 15 high-functioning children with autism and 15 matched controls were tested for their ability to imitate finger movements preceded by neutral and emotional facial expressions (primes) in a stimulus-response compatibility task. Hand movements performed after neutral expressions did not differ between the two groups (i.e., they both showed a normal imitative tendency). However, hand movements performed after emotional expressions significantly differed between the two populations, with controls, but not autistic spectrum disorder (ASD), showing enhanced imitation in the emotional condition. This study supports the view that, in ASD, imitation abilities are spared but they are not modulated according to the emotional and social context.
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4. Hsiao EY, McBride SW, Chow J, Mazmanian SK, Patterson PH. {{Modeling an autism risk factor in mice leads to permanent immune dysregulation}}. {Proc Natl Acad Sci U S A};2012 (Jul 16)
Increasing evidence highlights a role for the immune system in the pathogenesis of autism spectrum disorder (ASD), as immune dysregulation is observed in the brain, periphery, and gastrointestinal tract of ASD individuals. Furthermore, maternal infection (maternal immune activation, MIA) is a risk factor for ASD. Modeling this risk factor in mice yields offspring with the cardinal behavioral and neuropathological symptoms of human ASD. In this study, we find that offspring of immune-activated mothers display altered immune profiles and function, characterized by a systemic deficit in CD4(+) TCRbeta(+) Foxp3(+) CD25(+) T regulatory cells, increased IL-6 and IL-17 production by CD4(+) T cells, and elevated levels of peripheral Gr-1(+) cells. In addition, hematopoietic stem cells from MIA offspring exhibit altered myeloid lineage potential and differentiation. Interestingly, repopulating irradiated control mice with bone marrow derived from MIA offspring does not confer MIA-related immunological deficits, implicating the peripheral environmental context in long-term programming of immune dysfunction. Furthermore, behaviorally abnormal MIA offspring that have been irradiated and transplanted with immunologically normal bone marrow from either MIA or control offspring no longer exhibit deficits in stereotyped/repetitive and anxiety-like behaviors, suggesting that immune abnormalities in MIA offspring can contribute to ASD-related behaviors. These studies support a link between cellular immune dysregulation and ASD-related behavioral deficits in a mouse model of an autism risk factor.
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5. Lee C, Walter G, Cleary M. {{Communicating with Children with Autism Spectrum Disorder and Their Families: A Practical Introduction}}. {J Psychosoc Nurs Ment Health Serv};2012 (Jul 15):1-5.
Impaired communication and social interaction are symptoms central to autism spectrum disorder (ASD). Children or young people with ASD have varied intellectual ability, learning difficulty, and needs. For caregivers and health care professionals providing care to children with ASD, many challenges are encountered in everyday conversations. Enhanced knowledge of the spectrum and understanding the child or young person with ASD may improve conversation and social experiences. This article provides a practical introduction for health professionals seeking to improve their interaction with young people with ASD. Fictional vignettes, in which children with ASD are seeking care and support are presented, followed by discussion on communicating with children with ASD.
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6. Siegel M, Milligan B, Robbins D, Prentice G. {{Electroconvulsive Therapy in an Adolescent With Autism and Bipolar I Disorder}}. {J ECT};2012 (Jul 13)
OBJECTIVES: We report a positive response to electroconvulsive therapy in a severely functionally impaired adolescent with autistic disorder and classic bipolar I disorder, including an episodic pattern of decreased need for sleep, hypersexuality, expansive and agitated affect, aggression, self-injury, and property destruction. METHODS: After ineffective trials of mood stabilizers and antipsychotics as well as inability to sustain a positive response to lithium due to medication noncompliance, a course of acute and maintenance electroconvulsive therapy was attempted. RESULTS: A marked and sustained improvement across all symptom categories, as measured by directly observed frequency counts of target behaviors in an inpatient setting, was obtained. CONCLUSIONS: Electroconvulsive therapy should be considered a potentially useful intervention in cases of children with autistic disorder and a severe comorbid affective disorder.
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7. Silverman JL, Oliver CF, Karras MN, Gastrell PT, Crawley JN. {{AMPAKINE enhancement of social interaction in the BTBR mouse model of autism}}. {Neuropharmacology};2012 (Jul 16)
Autism is a neurodevelopmental disorder in which the first diagnostic symptom is unusual reciprocal social interactions. Approximately half of the children diagnosed with an autism spectrum disorder also have intellectual impairments. General cognitive abilities may be fundamental to many aspects of social cognition. Cognitive enhancers could conceivably be of significant benefit to children and adults with autism. AMPAKINE compounds are a novel class of pharmacological agents that act as positive modulators of AMPA receptors to enhance excitatory glutamatergic neurotransmission. This class of compounds was reported to improve learning and memory in several rodent and non-human primate tasks, and to normalize respiratory abnormalities in a mouse model of Rett syndrome. Here we evaluate the actions of AMPA compounds in adult male and female BTBR mice, a well characterized mouse model of autism. Acute treatment with CX1837 and CX1739 reversed the deficit in sociability in BTBR mice on the most sensitive parameter, time spent sniffing a novel mouse as compared to time spent sniffing a novel object. The less sensitive parameter, time in the chamber containing the novel mouse versus time in the chamber containing the novel object, was not rescued by CX1837 or CX1739 treatment. Preliminary data with CX546, in which beta-cyclodextrin was the vehicle, revealed behavioral effects of the acute intraperitoneal and oral administration of vehicle alone. To circumvent the artifacts introduced by the vehicle administration, we employed a novel treatment regimen using pellets of peanut butter for drug delivery. Absence of vehicle treatment effects when CX1837 and CX1739 were given in the peanut butter pellets, to multiple cohorts of BTBR and B6 control mice, confirmed that the pharmacologically-induced improvements in sociability in BTBR were not confounded by the administration procedures. The highest dose of CX1837 improved the cognitive deficit in novel object recognition in BTBR. No drug effects were detected on the high levels of repetitive self-grooming in BTBR. In open field tests, CX1837 and CX1739 did not induce hyperactivity or sedation in either strain. It is interesting to speculate that the ability of CX1837 and CX1739 to restore aspects of sociability in BTBR mice could utilize synaptic mechanisms regulating social cognition, suggesting a potential pharmacological target for interventions to treat symptoms of autism. This article is part of a Special Issue entitled ‘Cognitive Enhancers’.
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8. Tsuchiya KJ, Matsumoto K, Yagi A, Inada N, Kuroda M, Inokuchi E, Koyama T, Kamio Y, Tsujii M, Sakai S, Mohri I, Taniike M, Iwanaga R, Ogasahara K, Miyachi T, Nakajima S, Tani I, Ohnishi M, Inoue M, Nomura K, Hagiwara T, Uchiyama T, Ichikawa H, Kobayashi S, Miyamoto K, Nakamura K, Suzuki K, Mori N, Takei N. {{Reliability and Validity of Autism Diagnostic Interview-Revised, Japanese Version}}. {J Autism Dev Disord};2012 (Jul 18)
To examine the inter-rater reliability of Autism Diagnostic Interview-Revised, Japanese Version (ADI-R-JV), the authors recruited 51 individuals aged 3-19 years, interviewed by two independent raters. Subsequently, to assess the discriminant and diagnostic validity of ADI-R-JV, the authors investigated 317 individuals aged 2-19 years, who were divided into three diagnostic groups as follows: autistic disorder (AD), pervasive developmental disorder not otherwise specified, and other psychiatric diagnosis or no diagnosis, according to the consensus clinical diagnosis. As regards inter-rater reliability, intraclass correlation coefficients of greater than 0.80 were obtained for all three domains of ADI-R-JV. As regards discriminant validity, the mean scores of the three domains was significantly higher in individuals with AD than in those of other diagnostic groups. As regards diagnostic validity, sensitivity and specificity for correctly diagnosing AD were 0.92 and 0.89, respectively, but sensitivity was 0.55 for individuals younger than 5 years. Specificity was consistently high regardless of age and intelligence. ADI-R-JV was shown to be a reliable tool, and has sufficient discriminant validity and satisfactory diagnostic validity for correctly diagnosing AD, although the diagnostic validity appeared to be compromised with respect to the diagnosis of younger individuals.
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9. Welberg L. {{Neurodevelopmental disorders: TSCerebellar autism in mice}}. {Nat Rev Neurosci};2012 (Jul 18)
