1. Zhu H, Li J, Fan Y, Li X, Huang D, He S. {{Atypical prefrontal cortical responses to joint/non-joint attention in children with autism spectrum disorder (ASD): A functional near-infrared spectroscopy study}}. {Biomed Opt Express};2015 (Mar 1);6(3):690-701.
Autism spectrum disorder (ASD) is a neuro-developmental disorder, characterized by impairments in one’s capacity for joint attention. In this study, functional near-infrared spectroscopy (fNIRS) was applied to study the differences in activation and functional connectivity in the prefrontal cortex between children with autism spectrum disorder (ASD) and typically developing (TD) children. 21 ASD and 20 TD children were recruited to perform joint and non-joint attention tasks. Compared with TD children, children with ASD showed reduced activation and atypical functional connectivity pattern in the prefrontal cortex during joint attention. The atypical development of left prefrontal cortex might play an important role in social cognition defects of children with ASD.
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2. Rodakis J. {{An n=1 case report of a child with autism improving on antibiotics and a father’s quest to understand what it may mean}}. {Microb Ecol Health Dis};2015;26:26382.
The author, a parent of a child with autism, describes an n=1 case in which his child’s autism symptoms dramatically and rapidly improved following administration of a common antibiotic. The author asserts that this finding is not unusual in the autism population and that, when combined with prior recent medical research, suggests that a link between autism and the microbiome in some children is not just plausible, but in fact likely for some meaningful percentage of cases. The author argues for increased funding for a more thorough examination of links between autism and the microbiome and poses a series of questions to be further examined in future research.
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3. Nakamura T, Matsumoto J, Takamura Y, Ishii Y, Sasahara M, Ono T, Nishijo H. {{Relationships among Parvalbumin-Immunoreactive Neuron Density, Phase-Locked Gamma Oscillations, and Autistic/Schizophrenic Symptoms in PDGFR-beta Knock-Out and Control Mice}}. {PLoS One};2015;10(3):e0119258.
Cognitive deficits and negative symptoms are important therapeutic targets for schizophrenia and autism disorders. Although reduction of phase-locked gamma oscillation has been suggested to be a result of reduced parvalbumin-immunoreactive (putatively, GABAergic) neurons, no direct correlations between these have been established in these disorders. In the present study, we investigated such relationships during pharmacological treatment with a newly synthesized drug, T-817MA, which displays neuroprotective and neurotrophic effects. In this study, we used platelet-derived growth factor receptor-beta gene knockout (PDGFR-beta KO) mice as an animal model of schizophrenia and autism. These mutant mice display a reduction in social behaviors; deficits in prepulse inhibition (PPI); reduced levels of parvalbumin-immunoreactive neurons in the medical prefrontal cortex, hippocampus, amygdala, and superior colliculus; and a deficit in of auditory phase-locked gamma oscillations. We found that oral administration of T-817MA ameliorated all these symptoms in the PDGFR-beta KO mice. Furthermore, phase-locked gamma oscillations were significantly correlated with the density of parvalbumin-immunoreactive neurons, which was, in turn, correlated with PPI and behavioral parameters. These findings suggest that recovery of parvalbumin-immunoreactive neurons by pharmacological intervention relieved the reduction of phase-locked gamma oscillations and, consequently, ameliorated PPI and social behavioral deficits. Thus, our findings suggest that phase-locked gamma oscillations could be a useful physiological biomarker for abnormality of parvalbumin-immunoreactive neurons that may induce cognitive deficits and negative symptoms of schizophrenia and autism, as well as of effective pharmacological interventions in both humans and experimental animals.
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4. Mankad D, Dupuis A, Smile S, Roberts W, Brian J, Lui T, Genore L, Zaghloul D, Iaboni A, Marcon PM, Anagnostou E. {{A randomized, placebo controlled trial of omega-3 fatty acids in the treatment of young children with autism}}. {Mol Autism};2015;6:18.
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting more than 1% of children. It is characterized by social communication deficits and repetitive behaviors/restricted interests. In the absence of any medications known to improve core symptom domains, parents often use complementary alternative treatments, including omega-3 fatty acid supplements. METHODS: We conducted a 6-month, randomized, placebo controlled trial of omega-3 fatty acid supplements (1.5 g) vs placebo in children 2 to 5 years of age with ASD. Primary outcome measures included the autism composite score of the Pervasive Developmental Disorders Behavioral Inventory (PDDBI) and the externalizing problems score of the Behavior Assessment System for Children (BASC-2). Secondary outcome measures included clinical global improvement (Clinical Global Impression-Improvement (CGI-I)), adaptive function (Vineland Adaptive Behavior Scale (VABS-II)), and language gains (Preschool Language Scale (PLS-4)), as well as safety. Exploratory analysis investigated potential correlations between changes in cytokine profiles and treatment response. RESULTS: Thirty-eight participants were randomized in a 1:1 fashion. There was no significant difference between groups on the 0- to 24-week change in PDDBI autism composite scores (p = 0.5). There was a significant group by week interaction on the BASC-2 externalizing problem score, with participants randomized to the treatment group demonstrating worsening scores (p = 0.02). There was no statistically significant week by group effect on either adaptive function (p = 0.09) or language (p = 0.6). Omega-3s were relatively well tolerated. Changes in cytokines during the study did not significantly correlate with treatment response. CONCLUSIONS: This study does not support high dose supplementation of omega-3 fatty acids in young children with ASD. TRIAL REGISTRATION: Clinicaltrials.gov NCT01248728. Registered 22 November 2010.
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5. Libero LE, DeRamus TP, Lahti AC, Deshpande G, Kana RK. {{Multimodal neuroimaging based classification of autism spectrum disorder using anatomical, neurochemical, and white matter correlates}}. {Cortex};2015 (Mar 3);66:46-59.
Neuroimaging techniques, such as fMRI, structural MRI, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (1H-MRS) have uncovered evidence for widespread functional and anatomical brain abnormalities in autism spectrum disorder (ASD) suggesting it to be a system-wide neural systems disorder. Nevertheless, most previous studies have focused on examining one index of neuropathology through a single neuroimaging modality, and seldom using multiple modalities to examine the same cohort of individuals. The current study aims to bring together multiple brain imaging modalities (structural MRI, DTI, and 1H-MRS) to investigate the neural architecture in the same set of individuals (19 high-functioning adults with ASD and 18 typically developing (TD) peers). Morphometry analysis revealed increased cortical thickness in ASD participants, relative to typical controls, across the left cingulate, left pars opercularis of the inferior frontal gyrus, left inferior temporal cortex, and right precuneus, and reduced cortical thickness in right cuneus and right precentral gyrus. ASD adults also had reduced fractional anisotropy (FA) and increased radial diffusivity (RD) for two clusters on the forceps minor of the corpus callosum, revealed by DTI analyses. 1H-MRS results showed a reduction in the N-acetylaspartate/Creatine ratio in dorsal anterior cingulate cortex (dACC) in ASD participants. A decision tree classification analysis across the three modalities resulted in classification accuracy of 91.9% with FA, RD, and cortical thickness as key predictors. Examining the same cohort of adults with ASD and their TD peers, this study found alterations in cortical thickness, white matter (WM) connectivity, and neurochemical concentration in ASD. These findings underscore the potential for multimodal imaging to better inform on the neural characteristics most relevant to the disorder.
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6. Lake JK, Vogan V, Sawyer A, Weiss JA, Lunsky Y. {{Psychotropic Medication Use Among Adolescents and Young Adults with an Autism Spectrum Disorder: Parent Views About Medication Use and Healthcare Services}}. {J Child Adolesc Psychopharmacol};2015 (Mar 24)
OBJECTIVE: Psychotropic medications are frequently used to treat mental health and behavioral issues in adolescents and adults with an autism spectrum disorder (ASD). Although parents of individuals with ASD frequently take on medication management for their child, there is limited literature on parent perspectives of their child’s medication use or their views about the healthcare services they receive, particularly in adulthood. The current study examined and compared parents of adolescents and of young adults with ASD regarding their child’s psychotropic medication use and their views about healthcare services. METHODS: One hundred parents of adolescents and young adults with ASD (ages 12-30 years) completed an online survey about their experience with their child’s healthcare services and medication use. RESULTS: Parents of young adults were less likely to use nonpharmacological services before using a psychotropic medication than were parents of adolescents. Parents of young adults were also less likely to believe that their prescribing healthcare provider had adequate expertise in ASD, and were less satisfied with how their prescriber monitored their child’s medication use. CONCLUSION: Findings highlight the need to build capacity among healthcare providers supporting individuals with ASD as they transition into adulthood. There is also a need for improved medication monitoring and increased awareness of the different mental health challenges that individuals with ASD encounter as they age.
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7. Lai WW, Goh TJ, Oei TP, Sung M. {{Coping and Well-Being in Parents of Children with Autism Spectrum Disorders (ASD)}}. {J Autism Dev Disord};2015 (Mar 24)
This study examined psychological well-being and coping in parents of children with ASD and parents of typically developing children. 73 parents of children with ASD and 63 parents of typically developing children completed a survey. Parents of children with ASD reported significantly more parenting stress symptoms (i.e., negative parental self-views, lower satisfaction with parent-child bond, and experiences of difficult child behaviors), more depression symptoms, and more frequent use of Active Avoidance coping, than parents of typically developing children. Parents of children with ASD did not differ significantly in psychological well-being and coping when compared as according to child’s diagnosis. Study results reinforced the importance of addressing well-being and coping needs of parents of children with ASD.
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8. Kabatas EU, Ozer PA, Ertugrul GT, Kurtul BE, Bodur S, Alan BE. {{Initial Ophthalmic Findings in Turkish Children with Autism Spectrum Disorder}}. {J Autism Dev Disord};2015 (Mar 24)
Children with autism spectrum disorders (ASD) frequently have ophthalmologic disorders. Due to poor cooperation with ophthalmological examination, ocular abnormalities in such children may be overlooked. We retrospectively studied the records of 324 patients diagnosed as ASD that underwent ophthalmological examination between January 2011 and November 2014 at Dr. Sami Ulus Maternity and Children Research and Training Hospital, Ankara, Turkey. Ophthalmic pathology was noted in 26.9 % of patients with ASD, of which 22 % had significant refractive errors and 8.6 % had strabismus. Comprehensive eye examination by a pediatric ophthalmologist is recommended for all children diagnosed as ASD.
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9. Jarvinen A, Ng R, Crivelli D, Neumann D, Grichanik M, Arnold AJ, Lai P, Trauner D, Bellugi U. {{Patterns of Sensitivity to Emotion in Children with Williams Syndrome and Autism: Relations Between Autonomic Nervous System Reactivity and Social Functioning}}. {J Autism Dev Disord};2015 (Mar 24)
Williams syndrome (WS) and autism spectrum disorder (ASD) are associated with atypical social-emotional functioning. Affective visual stimuli were used to assess autonomic reactivity and emotion identification, and the social responsiveness scale was used to determine the level social functioning in children with WS and ASD contrasted with typical development (TD), to examine syndrome-specific and syndrome-general features. Children with ASD exhibited the highest arousal in response to faces, with a lack of difference in autonomic sensitivity across different emotional expressions, unlike in WS and TD. The WS group demonstrated unique deficits in identifying neutral stimuli. While autonomic responsivity to neutral faces was associated with social functioning in all children, converging profiles characterized children with WS contrasted with TD and ASD.
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10. Hu Y, Chen Z, Fu Y, He Q, Jiang L, Zheng J, Gao Y, Mei P, Ren X. {{The amino-terminal structure of human fragile X mental retardation protein obtained using precipitant-immobilized imprinted polymers}}. {Nat Commun};2015;6:6634.
Flexibility is an intrinsic property of proteins and essential for their biological functions. However, because of structural flexibility, obtaining high-quality crystals of proteins with heterogeneous conformations remain challenging. Here, we show a novel approach to immobilize traditional precipitants onto molecularly imprinted polymers (MIPs) to facilitate protein crystallization, especially for flexible proteins. By applying this method, high-quality crystals of the flexible N-terminus of human fragile X mental retardation protein are obtained, whose absence causes the most common inherited mental retardation. A novel KH domain and an intermolecular disulfide bond are discovered, and several types of dimers are found in solution, thus providing insights into the function of this protein. Furthermore, the precipitant-immobilized MIPs (piMIPs) successfully facilitate flexible protein crystal formation for five model proteins with increased diffraction resolution. This highlights the potential of piMIPs for the crystallization of flexible proteins.
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11. D’Urso G, Bruzzese D, Ferrucci R, Priori A, Pascotto A, Galderisi S, Altamura AC, Bravaccio C. {{Transcranial direct current stimulation for hyperactivity and noncompliance in autistic disorder}}. {World J Biol Psychiatry};2015 (Mar 24):1-6.
OBJECTIVES: To evaluate the safety, efficacy, and feasibility of inhibitory transcranial direct current stimulation (tDCS) for the treatment of behavioural abnormalities of autistic patients. METHODS: Twelve young adult patients with autistic disorder were enrolled. All subjects presented intellectual disability and most of them had speech impairment. The Aberrant Behavior Checklist (ABC) was administered as the primary outcome measure before and after a 2-week tDCS course. All subjects received 10 daily applications of 20 min/1.5 mA/cathodal (inhibitory) tDCS over the left dorso-lateral pre-frontal cortex. RESULTS: Eight out of 10 study completers improved in their abnormal behaviours, reaching an average reduction of 26.7% of the total ABC score. The remaining two patients showed no changes. In the whole group of completers, among the five subscales contributing to the significant reduction of the total score, the most remarkable and statistically significant change was seen in the subscale assessing hyperactivity and non-compliance (-35.9%, P = 0.002). No adverse effects were reported. CONCLUSIONS: Inhibitory tDCS improved the ABC rating scores for autistic behaviours. Owing to its ease of use, cost-effectiveness and the limited availability of specific treatment strategies, tDCS might be a valid therapeutic option to be tested in autistic patients.
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12. Delaveau P, Arzounian D, Rotge JY, Nadel J, Fossati P. {{Does imitation act as an oxytocin nebulizer in autism spectrum disorder?}}. {Brain};2015 (Mar 21)
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13. De Felice A, Scattoni ML, Ricceri L, Calamandrei G. {{Prenatal exposure to a common organophosphate insecticide delays motor development in a mouse model of idiopathic autism}}. {PLoS One};2015;10(3):e0121663.
Autism spectrum disorders are characterized by impaired social and communicative skills and repetitive behaviors. Emerging evidence supported the hypothesis that these neurodevelopmental disorders may result from a combination of genetic susceptibility and exposure to environmental toxins in early developmental phases. This study assessed the effects of prenatal exposure to chlorpyrifos (CPF), a widely diffused organophosphate insecticide endowed with developmental neurotoxicity at sub-toxic doses, in the BTBR T+tf/J mouse strain, a validated model of idiopathic autism that displays several behavioral traits relevant to the autism spectrum. To this aim, pregnant BTBR mice were administered from gestational day 14 to 17 with either vehicle or CPF at a dose of 6 mg/kg/bw by oral gavages. Offspring of both sexes underwent assessment of early developmental milestones, including somatic growth, motor behavior and ultrasound vocalization. To evaluate the potential long-term effects of CPF, two different social behavior patterns typically altered in the BTBR strain (free social interaction with a same-sex companion in females, or interaction with a sexually receptive female in males) were also examined in the two sexes at adulthood. Our findings indicate significant effects of CPF on somatic growth and neonatal motor patterns. CPF treated pups showed reduced weight gain, delayed motor maturation (i.e., persistency of immature patterns such as pivoting at the expenses of coordinated locomotion) and a trend to enhanced ultrasound vocalization. At adulthood, CPF associated alterations were found in males only: the altered pattern of investigation of a sexual partner, previously described in BTBR mice, was enhanced in CPF males, and associated to increased ultrasonic vocalization rate. These findings strengthen the need of future studies to evaluate the role of environmental chemicals in the etiology of neurodevelopment disorders.
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14. Caria A, de Falco S. {{Anterior insular cortex regulation in autism spectrum disorders}}. {Front Behav Neurosci};2015;9:38.
Autism spectrum disorders (ASDs) comprise a heterogeneous set of neurodevelopmental disorders characterized by dramatic impairments of interpersonal behavior, communication, and empathy. Recent neuroimaging studies suggested that ASD are disorders characterized by widespread abnormalities involving distributed brain network, though clear evidence of differences in large-scale brain network interactions underlying the cognitive and behavioral symptoms of ASD are still lacking. Consistent findings of anterior insula cortex hypoactivation and dysconnectivity during tasks related to emotional and social processing indicates its dysfunctional role in ASD. In parallel, increasing evidence showed that successful control of anterior insula activity can be attained using real-time fMRI paradigms. More importantly, successful regulation of this region was associated with changes in behavior and brain connectivity in both healthy individuals and psychiatric patients. Building on these results we here propose and discuss the use of real-time fMRI neurofeedback in ASD aiming at improving emotional and social behavior.
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15. Brisson J, Martel K, Serres J, Sirois S, Adrien JL. {{Acoustic analysis of oral productions of infants later diagnosed with autism and their mother}}. {Infant Ment Health J};2014 (May);35(3):285-295.
Research on early signs of autism in social interactions often focuses on infants’ motor behaviors; few studies have focused on speech characteristics. This study examines infant-directed speech of mothers of infants later diagnosed with autism (LDA; n = 12) or of typically developing infants (TD; n = 11) as well as infants’ productions (13 LDA, 13 TD). Since LDA infants appear to behave differently in the first months of life, it can affect the functioning of dyadic interactions, especially the first vocal productions, sensitive to expressiveness and emotions sharing. We assumed that in the first 6 months of life, prosodic characteristics (mean duration, mean pitch, and intonative contour types) will be different in dyads with autism. We extracted infants’ and mothers’ vocal productions from family home movies and analyzed the mean duration and pitch as well as the pitch contours in interactive episodes. Results show that mothers of LDA infants use relatively shorter productions as compared to mothers talking to TD infants. LDA infants’ productions are not different in duration or pitch, but they use less complex modulated productions (i.e., those with more than two melodic modulations) than do TD. Further studies should focus on developmental profiles in the first year, analyzing prosody monthly.
