1. Auyeung B, Ahluwalia J, Thomson L, Taylor K, Hackett G, KJ OD, Baron-Cohen S. {{Prenatal versus postnatal sex steroid hormone effects on autistic traits in children at 18 to 24 months of age}}. {Mol Autism};2012 (Dec 11);3(1):17.
ABSTRACT: BACKGROUND: Studies of prenatal exposure to sex steroid hormones predict autistic traits in children at 18 to 24 and at 96 months of age. However, it is not known whether postnatal exposure to these hormones has a similar effect. This study compares prenatal and postnatal sex steroid hormone levels in relation to autistic traits in 18 to 24-month-old children.Fetal testosterone (fT) and fetal estradiol (fE) levels were measured in amniotic fluid from pregnant women (n = 35) following routine second-trimester amniocentesis. Saliva samples were collected from these children when they reached three to four months of age and were analyzed for postnatal testosterone (pT) levels. Mothers were asked to complete the Quantitative Checklist for Autism in Toddlers (Q-CHAT), a measure of autistic traits in children 18 to 24 months old.Finding: fT (but not pT) levels were positively associated with scores on the Q-CHAT. fE and pT levels showed no sex differences and no relationships with fT levels. fT levels were the only variable that predicted Q-CHAT scores. CONCLUSIONS: These preliminary findings are consistent with the hypothesis that prenatal (but not postnatal) androgen exposure, coinciding with the critical period for sexual differentiation of the brain, is associated with the development of autistic traits in 18 to 24 month old toddlers. However, it is recognized that further work with a larger sample population is needed before the effects of postnatal androgen exposure on autistic traits can be ruled out. These results are also in line with the fetal androgen theory of autism, which suggests that prenatal, organizational effects of androgen hormones influence the development of autistic traits in later life.
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2. Banerjee A, Garcia-Oscos F, Roychowdhury S, Galindo LC, Hall S, Kilgard MP, Atzori M. {{Impairment of cortical GABAergic synaptic transmission in an environmental rat model of autism}}. {Int J Neuropsychopharmacol};2012 (Dec 11):1-10.
The biological mechanisms of autism spectrum disorders (ASDs) are largely unknown in spite of extensive research. ASD is characterized by altered function of multiple brain areas including the temporal cortex and by an increased synaptic excitation:inhibition ratio. While numerous studies searched for evidence of increased excitation in ASD, fewer have investigated the possibility of reduced inhibition. We characterized the cortical gamma-amino butyric acid (GABA)ergic system in the rat temporal cortex of an ASD model [offspring of mothers prenatally injected with valproic acid (VPA)], by monitoring inhibitory post-synaptic currents (IPSCs) with patch-clamp. We found that numerous features of inhibition were severely altered in VPA animals compared to controls. Among them were the frequency of miniature IPSCs, the rise time and decay time of electrically-evoked IPSCs, the slope and saturation of their input/output curves, as well as their modulation by adrenergic and muscarinic agonists and by the synaptic GABAA receptor allosteric modulator zolpidem (but not by the extra-synaptic modulator gaboxadol). Our data suggest that both pre- and post-synaptic, but not extra-synaptic, inhibitory transmission is impaired in the offspring of VPA-injected mothers. We speculate that impairment in the GABAergic system critically contributes to an increase in the ratio between synaptic excitation and inhibition, which in genetically predisposed individuals may alter cortical circuits responsible for emotional, communication and social impairments at the core of ASD.
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3. El-Ansary A, Al-Ayadhi L. {{Neuroinflammation in autism spectrum disorders}}. {J Neuroinflammation};2012 (Dec 11);9(1):265.
ABSTRACT: Objectives: The neurobiological basis for autism remains poorly understood. However, research suggests that environmentalfactors and neuroinflammation, as well as genetic factors, are contributors. This study aims to test the role that might be played by heat shock protein (HSP)70, transforming growth factor (TGF)-beta2, Caspase 7 and interferon-gamma (IFN-gamma)in the pathophysiology of autism.Materials and methods: HSP70, TGF-beta2, Caspase 7 and INF-gamma as biochemical parameters related to inflammation were determined in plasma of 20 Saudi autistic male patients and compared to 19 age- and gender-matched control samples. RESULTS: The obtained data recorded that Saudi autistic patients have remarkably higher plasma HSP70, TGF-beta2, Caspase 7 and INF-gamma compared to age and gender-matched controls. INF-gamma recorded the highest (67.8%) while TGF-beta recorded the lowest increase (49.04%). Receiver Operating Characteristics (ROC) analysis together with predictiveness diagrams proved that the measured parameters recorded satisfactory levels of specificity and sensitivity and all could be used as predictive biomarkers. CONCLUSION: Alteration of the selected parameters confirm the role of neuroinflammation and apoptosis mechanisms in the etiology of autism together with the possibility of the use of HSP70, TGF-beta2, Caspase 7 and INF-gamma as predictive biomarkers that could be used to predict safety, efficacy of a specific suggested therapy or natural supplements, thereby providing guidance in selecting it for patients or tailoring its dose.
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4. Lemonnier E, Degrez C, Phelep M, Tyzio R, Josse F, Grandgeorge M, Hadjikhani N, Ben-Ari Y. {{A randomised controlled trial of bumetanide in the treatment of autism in children}}. {Transl Psychiatry};2012;2:e202.
Gamma aminobutyric acid (GABA)-mediated synapses and the oscillations they orchestrate are altered in autism. GABA-acting benzodiazepines exert in some patients with autism paradoxical effects, raising the possibility that like in epilepsies, GABA excites neurons because of elevated intracellular concentrations of chloride. Following a successful pilot study,(1) we have now performed a double-blind clinical trial using the diuretic, chloride-importer antagonist bumetanide that reduces intracellular chloride reinforcing GABAergic inhibition. Sixty children with autism or Asperger syndrome (3-11 years old) received for 3 months placebo or bumetanide (1 mg daily), followed by 1-month wash out. Determination of the severity of autism was made with video films at day 0 (D0) and D90 by blind, independent evaluators. Bumetanide reduced significantly the Childhood Autism Rating Scale (CARS) (D90-D0; P<0.004 treated vs placebo), Clinical Global Impressions (P<0.017 treated vs placebo) and Autism Diagnostic Observation Schedule values when the most severe cases (CARS values above the mean+/-s.d.; n=9) were removed (Wilcoxon test: P-value=0.031; Student’s t-test: P-value=0.017). Side effects were restricted to an occasional mild hypokalaemia (3.0-3.5 mM l(-1) K(+)) that was treated with supplemental potassium. In a companion study, chronic bumetanide treatment significantly improved accuracy in facial emotional labelling, and increased brain activation in areas involved in social and emotional perception (Hadjikhani et al., submitted). Therefore, bumetanide is a promising novel therapeutic agent to treat autism. Larger trials are warranted to better determine the population best suited for this treatment.
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5. Maras KL, Memon A, Lambrechts A, Bowler DM. {{Recall of a live and personally experienced eyewitness event by adults with autism spectrum disorder}}. {J Autism Dev Disord};2012 (Dec 11)
The aim of the present study was to (a) extend previous eyewitness research in autism spectrum disorder (ASD) using a live and personally experienced event; (b) examine whether witnesses with ASD demonstrate a facilitative effect in memory for self- over other-performed actions; (c) explore source monitoring abilities by witnesses with ASD in discriminating who performed which actions within the event. Eighteen high-functioning adults with ASD and 18 age- and IQ-matched typical counterparts participated in a live first aid scenario in which they and the experimenter each performed a number of actions. Participants were subsequently interviewed for their memory of the event using a standard interview procedure with free recall followed by questioning. The ASD group recalled just as many correct details as the comparison group from the event overall, however they made more errors. This was the case across both free recall and questioning phases. Both groups showed a self-enactment effect across both interview phases, recalling more actions that they had performed themselves than actions that the experimenter had performed. However, the ASD group were more likely than their typical comparisons to confuse the source of self-performed actions in free recall, but not in questioning, which may indicate executive functioning difficulties with unsupported test procedures. Findings are discussed in terms of their theoretical and practical implications.
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6. Milne E, Scope A, Griffiths H, Codina C, Buckley D. {{Brief Report: Preliminary Evidence of Reduced Sensitivity in the Peripheral Visual Field of Adolescents with Autistic Spectrum Disorder}}. {J Autism Dev Disord};2012 (Dec 11)
A number of studies have demonstrated atypical perception in individuals with ASD. However, the majority of these studies have presented stimuli to central vision. The aim of the study presented here was to test the sensitivity of peripheral vision in ASD. This was achieved by asking participants to detect brief flashes of light presented between 30 and 85 degrees away from fixation. We found that participants with ASD detected fewer ligh-flashes than the control participants. This deficit was more pronounced in the nasal hemifield than the temporal hemifield. We suggest that the imbalance between nasal and temporal hemifield sensitivity may contribute to the peripheral-field stimulation and lateral glances that are observed in ASD.
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7. Milton D, Mills R, Pellicano E. {{Ethics and Autism: Where is the Autistic Voice? Commentary on Post et al}}. {J Autism Dev Disord};2012 (Dec 11)
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8. Parmanto B, Pulantara IW, Schutte JL, Saptono A, McCue MP. {{An Integrated Telehealth System for Remote Administration of an Adult Autism Assessment}}. {Telemed J E Health};2012 (Dec 11)
Abstract We developed a telehealth system to administer an autism assessment remotely. The remote assessment system integrates videoconferencing, stimuli presentation, recording, image and video presentation, and electronic assessment scoring into an intuitive software platform. This is an advancement over existing technologies used in telemental health, which currently require several devices. The number of children, adolescents, and adults with autism spectrum disorders (ASDs) has increased dramatically over the past 20 years and is expected to continue to increase in coming years. In general, there are not many clinicians trained in either the diagnosis or treatment of adults with ASD. Given the number of adults with autism in need, a remote assessment system can potentially provide a solution to the lack of trained clinicians. The goal is to make the remote assessment system as close to face-to-face assessment as possible, yet versatile enough to support deployment in underserved areas. The primary challenge to achieving this goal is that the assessment requires social interaction that appears natural and fluid, so the remote system needs to be able to support fluid natural interaction. For this study we developed components to support this type of interaction and integrated these components into a system capable of supporting the entire autistic assessment protocol. We then implemented the system and evaluated the system on real patients. The results suggest that we have achieved our goal in developing a system with high-quality interaction that is easy to use.
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9. Wan MW, Green J, Elsabbagh M, Johnson M, Charman T, Plummer F. {{Quality of interaction between at-risk infants and caregiver at 12-15 months is associated with 3-year autism outcome}}. {J Child Psychol Psychiatry};2012 (Dec 11)
Background: Recent models of the early emergence of autism spectrum disorder (ASD) propose that infant intrinsic risk susceptibilities in behaviour may be amplified by interaction within the early social environment into an increasingly atypical developmental trajectory. This study examines whether 6- and 12-month parent-infant interactions in at-risk siblings differ from those with low-risk and whether – in at-risk siblings – such interactions predict later 3-year classification of ASD or no ASD. Method: Within the British Autism Study of Infant Siblings (BASIS), 6-min videotaped episodes of parent-infant free play in infants at 6-10 months (45 at-risk siblings and 47 low-risk siblings) and 12-15 months (43 at-risk siblings and 48 low-risk siblings) in a laboratory setting were rated on the Manchester Assessment of Caregiver-Infant Interaction (MACI), blind to participant information. Standard tests were administered for concurrent behavioural signs of ASD features and developmental level. Systematic consensus diagnostic classification of ASD was made at 3 years for the at-risk siblings. Results: Parent nondirectiveness and sensitive responsiveness differed in relation to ASD/risk status (at-risk ASD, at-risk no-ASD and low-risk) at both 6 and 12 months. At 6 months, infant liveliness was lower in the at-risk groups; at 12 months, infant attentiveness to parent and positive affect were lower in the at-risk group later diagnosed with ASD. Dyadic mutuality and intensity of engagement showed a group effect at 12 months. Dyadic mutuality, infant positive affect and infant attentiveness to parent at 12 months (but not 6 months) predicted 3-year ASD outcome, whereas infant ASD-related behavioural atypicality did not. Conclusions: This is the first prospective evidence that early dyadic interaction between at-risk infants and their parents is associated with later diagnostic outcome in ASD. Possible explanations for these findings and their theoretical implications are considered.
