Pubmed du 13/07/19

samedi 13 juillet 2019

1. Ahmad SF, Ansari MA, Nadeem A, Bakheet SA, Alanazi AZ, Alsanea S, As Sobeai HM, Almutairi MM, Mahmood HM, Attia SM. The Stat3 inhibitor, S3I-201, downregulates lymphocyte activation markers, chemokine receptors, and inflammatory cytokines in the BTBR T(+) Itpr3(tf)/J mouse model of autism. Brain Res Bull ;2019 (Jul 9) ;152:27-34.

Autism is a complex neurodevelopmental disorder with a high incidence rate. It is characterized by deficits in communication, a lack of social skills, cognitive inflexibility, and stereotypical behaviors. Autism has been gradually increasing in children over the past several years, without the existence of an effective treatment. BTBR T(+) Itpr3(tf)/J (BTBR) mice serve as an accepted model to evaluate autistic-like behaviors as they display core behavioral symptoms displayed in autism. Previous findings showed that S3I-201, a selective Stat3 inhibitor, can be used to treat neuroinflammation disorders. Previously, we showed that S3I-201 treatment has therapeutic effects on autism-like behaviors, and Th1/Th17 and regulatory T cells in BTBR mice. The objective of the present study was to further explore the role of S3I-201 in BTBR mice, and this was performed by investigating the effects of S3I-201 treatment on lymphocyte activation markers (CD4(+)CD25(+) and CD4(+)CD69(+)), chemokine receptors (CD4(+)CCR6(+), CD4(+)CCR7(+), CD4(+)CXCR4(+), and CD4(+)CXCR5(+)), and proinflammatory cytokines (CD4(+)IL-6(+) and CD4(+)TNF-alpha(+)) in the spleen cells of BTBR and C57BL/6 (C57) mice. The mRNA and protein expression levels of CD69, CCR6, CCR7, CXCR4, CXCR5, IL-1beta, IL-6, and TNF-alpha were examined in the brain tissues, and in BTBR mice, a significant decrease in CD25, CD69, CCR6, CCR7, CXCR4, CXCR5, IL-6, and TNF-alpha producing CD4(+) T cells was observed. The present findings suggest that treatment with S3I-201 may be a therapeutic approach to improve immune abnormalities in a subgroup of autistic subjects.

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2. Al-Mazroua HA, Alomar HA, Ahmad SF, Attia MSA, Nadeem A, Bakheet SA, Alsaad AMS, Alotaibi MR, Attia SM. Assessment of DNA repair efficiency in the inbred BTBR T(+)tf/J autism spectrum disorder mouse model exposed to gamma rays and treated with JNJ7777120. Prog Neuropsychopharmacol Biol Psychiatry ;2019 (Jul 13) ;93:189-196.

Information regarding DNA repair in autism is limited to a few studies, which have reported inconsistent results. Therefore, we designed a study to determine whether DNA repair efficiency is altered in autism and to investigate whether the H4 ligand JNJ7777120 can enhance DNA repair efficiency in BTBR T(+)tf/J (BTBR) mice ; we also attempted to elucidate the mechanism(s) underlying this amelioration. Evaluation of DNA damage using the comet assay on bone marrow cells showed increased levels of DNA damage in BTBR mice compared with age-matched control C57BL/6J mice. Conversely, BTBR animals pretreated with 20mg/kg JNJ7777120 for five days exhibited significant decreases in DNA damage compared with that of control BTBR mice. Our results also indicated higher sensitivity of BTBR mice exposed to gamma rays to DNA damage generation. A marked difference was observed between BTBR and C57BL/6J mice at different sampling times after irradiation, with BTBR mice showing a higher percentage of DNA damage and slower repair rate than that of C57BL/6J mice. JNJ7777120 led to enhanced repair of the DNA damage induced by radiation when administered to BTBR mice five days prior to radiation. Additionally, oxidative stress in BTBR mice was significantly elevated with a reduced GSH/GSSG ratio ; significant amelioration was subsequently observed in JNJ7777120-pretreated BTBR mice. Furthermore, repetitive behaviors were also attenuated in BTBR mice by JNJ7777120 treatment without altering locomotor activity. Our results suggest that JNJ7777120 can be developed for use as a therapeutic agent to enhance DNA repair efficiency in autism spectrum disorder.

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3. Asgarihafshejani A, Nashmi R, Delaney KR. Cell-Genotype Specific Effects of Mecp2 Mutation on Spontaneous and Nicotinic Acetylcholine Receptor-Evoked Currents in Medial Prefrontal Cortical Pyramidal Neurons in Female Rett Model Mice. Neuroscience ;2019 (Jul 9)

Rett syndrome (RTT) is a neurodevelopmental disorder caused by mutation in the X-linked MECP2 gene. Random X-inactivation produces a mosaic of mutant (MT) and wild-type (WT) neurons in female Mecp2+/- (het) mice. Many RTT symptoms are alleviated by increasing activity in medial prefrontal cortex (mPFC) in RTT model mice (Howell et al., 2017). Using a GFP-MeCP2 fusion protein to distinguish WT from MT pyramidal neurons in mPFC we found cell autonomous (cell genotype specific) and non-autonomous effects of MeCP2 deficiency on spontaneous excitatory/inhibitory balance, nicotinic acetylcholine receptor (nAChR) currents and evoked activity. MT Layer 5 and 6 (L5, L6) neurons of male nulls, and MT L6 of het mice had reduced spontaneous excitatory synaptic input compared to WT in wild-type male (WTm), female (WTf) and het mice. Inhibitory synaptic charge in MT L6 equaled WT in 2-4-month hets. At 6-7months inhibitory charge in WT in het slices was increased compared to both MT in het and WT in WTf ; however, in hets the excitatory/inhibitory charge ratio was still greater in WT compared to MT. nAChR currents were reduced in L6 of nulls and MT L6 in het slices compared to WT neurons of het, WTm and WTf. At 2-4months, ACh perfusion increased frequency of inhibitory currents to L6 neurons equally in all genotypes but increased excitatory inputs to MT and WT in hets less than WT in WTfs. Unexpectedly ACh perfusion evoked greater sustained IPSC and EPSC input to L5 neurons of nulls compared to WTm.

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4. Crucitti J, Hyde C, Stokes MA. Hammering that Nail : Varied Praxis Motor Skills in Younger Autistic Children. J Autism Dev Disord ;2019 (Jul 11)

Previous studies measuring praxis abilities in young autistic children have only used praxis measures that were not optimised for autistic individuals. Hence, we used the FAB-R to measure praxis skills in autistic (n = 38) and typically developing (TD) children (n = 38) aged between four and 10 years. Praxis abilities were generally not different between autistic and TD children. However, total dyspraxia and errors during verbal command and tool use were impaired in autistic children from a specialist autistic school (SAS). In contrast, autistic participants from the GC typically did not differ in praxis performance compared to controls. Hence, praxis abilities significantly vary between autistic younger children. Exploring mediating influences of such variability is imperative.

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5. Giserman-Kiss I, Carter AS. Stability of Autism Spectrum Disorder in Young Children with Diverse Backgrounds. J Autism Dev Disord ;2019 (Jul 11)

Determining diagnostic stability of ASD, as well stability of functioning in early childhood, is relevant to prevalence, best practices for communicating early ASD diagnoses to caregivers, families’ experiences, and developmental trajectories. Generalizability of findings from prior research has been limited by small and homogenous samples, short follow-up time intervals, and inconsistent diagnostic procedures. This report presents follow-up evaluations of 60 children (86.7% male, mean age : 51.3 months) with diverse backgrounds (79.7% racial/ethnic minorities) who received initial ASD diagnoses before 36 months of age (mean age : 27 months). Fifty-three children (88.3%) met diagnostic criteria for ASD at follow-up, a proportion consistent with previous studies. On average, children demonstrated significant cognitive gains and ASD symptom improvement. Clinical implications of findings are discussed.

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6. Grossi E, Buscema M, Della Torre F, Swatzyna RJ. The "MS-ROM/IFAST" Model, a Novel Parallel Nonlinear EEG Analysis Technique, Distinguishes ASD Subjects From Children Affected With Other Neuropsychiatric Disorders With High Degree of Accuracy. Clin EEG Neurosci ;2019 (Jul 11):1550059419861007.

Background and Objective. In a previous study, we showed a new EEG processing methodology called Multi-Scale Ranked Organizing Map/Implicit Function As Squashing Time (MS-ROM/IFAST) performing an almost perfect distinction between computerized EEG of Italian children with autism spectrum disorder (ASD) and typically developing children. In this study, we assessed this system in distinguishing ASD subjects from children affected with other neuropsychiatric disorders (NPD). Methods. At a psychiatric practice in Texas, 20 children diagnosed with ASD and 20 children diagnosed with NPD were entered into the study. Continuous segments of artifact-free EEG data lasting 10 minutes were entered in MS-ROM/IFAST. From the new variables created by MS-ROM/IFAST, only 12 has been selected according to a correlation criterion. The selected features represent the input on which supervised machine learning systems (MLS) acted as blind classifiers. Results. The overall predictive capability in distinguishing ASD from other NPD cases ranged from 93% to 97.5%. The results were confirmed in further experiments in which Italian and US data have been combined. In this analysis, the best MLS reached 95.0% global accuracy in 1 out of 3 classes distinction (ASD, NPD, controls). This study demonstrates the value of EEG processing with advanced MLS in the differential diagnosis between ASD and NPD cases. The results were not affected by age, ethnicity and technicalities of EEG acquisition, confirming the existence of a specific EEG signature in ASD cases. To further support these findings, it was decided to test the behavior of already trained neural networks on 10 Italian very young ASD children (25-37 months). In this test, 9 out of 10 cases have been correctly recognized as ASD subjects in the best case. Conclusions. These results confirm the possibility of an early automatic autism detection based on standard EEG.

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7. Harrop C, Jones D, Zheng S, Nowell S, Schultz R, Parish-Morris J. Visual attention to faces in children with autism spectrum disorder : are there sex differences ?. Mol Autism ;2019 ;10:28.

Background : The male bias in autism spectrum disorder (ASD) diagnoses is well documented. As a result, less is known about the female ASD phenotype. Recent research suggests that conclusions drawn from predominantly male samples may not accurately capture female behavior. In this study, we explore potential sex differences in attention to social stimuli, which is generally reported to be diminished in ASD. Population-based sex differences in attention to faces have been reported, such that typically developing (TD) females attend more to social stimuli (including faces) from infancy through adulthood than TD males. It is yet unknown whether population-based sex differences in the face domain are preserved in ASD. Methods : A dynamic, naturalistic infrared eye-tracking paradigm measured attention to social stimuli (faces) in 74 school-aged males and females with ASD (male N = 23 ; female N = 19) and without ASD (male N = 16 ; female N = 16). Two kinds of video stimuli were presented that varied in social content : rich social scenes (dyadic play between two children) and lean social scenes (parallel play by two children). Results : Results revealed a significant 3-way interaction between sex, diagnosis, and condition after controlling for chronological and mental age. ASD females attended more to faces than ASD males in the socially lean condition. This effect was not found in the typically developing (TD) group. ASD males attended less to faces regardless of social context ; however, ASD females only attended significantly less to faces compared to TD females in the socially rich condition. TD males and ASD females did not differ in their attention to faces in either condition. Conclusions : This study has implications for how the field understands core social deficits in children with ASD, which should ideally be benchmarked against same-sex peers (male and female). Social attention in ASD females fell on a continuum-greater than their ASD male peers, but not as great as TD females. Overall, their social attention mirrored that of TD males. Improved understanding of the female social phenotype in ASD will enhance early screening and diagnostic efforts and will guide the development of sex-sensitive experimental paradigms and social interventions.

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8. Kay JC, Kisamore AN, Vladescu JC, Sidener TM, Reeve KF, Taylor-Santa C, Pantano NA. Effects of exposure to prompts on the acquisition of intraverbals in children with autism spectrum disorder. J Appl Behav Anal ;2019 (Jul 12)

The current experiment is a systematic replication of previous studies that evaluated the efficiency of echoic and tact prompts on the acquisition of intraverbals (i.e., French-to-English translations) following exposure to each prompt type. We extended these studies by (a) evaluating participants’ language skills on standardized assessments, (b) incorporating descriptive praise for correct responding, (c) presenting trials via voice recording, and (d) evaluating teacher preference for each prompt type as a social validity measure. All participants learned at least one set of intraverbals faster with the procedure that was most recently used during teaching. These findings suggest that results from previous prompt comparison studies might be a function of previous exposure to prompt types and that it might be possible to manipulate learning histories such that a particular prompt type becomes more efficient.

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9. Kuo SS, Wojtalik JA, Mesholam-Gately RI, Keshavan MS, Eack SM. Transdiagnostic validity of the MATRICS Consensus Cognitive Battery across the autism-schizophrenia spectrum. Psychol Med ;2019 (Jul 12):1-10.

BACKGROUND : Autism Spectrum Disorder (ASD) and schizophrenia are neurodevelopmental disorders which share substantial overlap in cognitive deficits during adulthood. However, treatment evaluation in ASD and treatment comparisons across ASD and schizophrenia are limited by a dearth of empirical work establishing the validity of a standard cognitive battery across ASD and schizophrenia. Promisingly, the MATRICS Consensus Cognitive Battery (MCCB) has been validated in schizophrenia and encompasses cognitive domains that are impacted in ASD. Thus, this study aimed to establish MCCB’s generalizability from schizophrenia to ASD. METHODS : Community-residing adults with schizophrenia (N = 100) and ASD (N = 113) underwent MCCB assessment. Using multigroup confirmatory factor analysis, MCCB’s transdiagnostic validity was evaluated by examining whether schizophrenia and ASD demonstrate the same configuration, magnitude, and directionality of relationships within and among measures and their underlying cognitive domains. RESULTS : Across schizophrenia and ASD, the same subsets of MCCB measures inform three cognitive domains : processing speed, attention/working memory, and learning. Except for group means in category fluency, continuous performance, and spatial span, both groups show vastly comparable factor structures and characteristics. CONCLUSIONS : To our knowledge, this study is the first to establish the validity of a standard cognitive battery in adults with ASD and furthermore the first to establish a cognitive battery’s comparability across ASD and schizophrenia. Cognitive domain scores can be compared across new samples using weighted sums of MCCB scores resulting from this study. These findings highlight MCCB’s applicability to ASD and support its utility for standardizing treatment evaluation of cognitive outcomes across the autism-schizophrenia spectrum.

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10. Stickel S, Weismann P, Kellermann T, Regenbogen C, Habel U, Freiherr J, Chechko N. Audio-visual and olfactory-visual integration in healthy participants and subjects with autism spectrum disorder. Hum Brain Mapp ;2019 (Jul 13)

The human capacity to integrate sensory signals has been investigated with respect to different sensory modalities. A common denominator of the neural network underlying the integration of sensory clues has yet to be identified. Additionally, brain imaging data from patients with autism spectrum disorder (ASD) do not cover disparities in neuronal sensory processing. In this fMRI study, we compared the underlying neural networks of both olfactory-visual and auditory-visual integration in patients with ASD and a group of matched healthy participants. The aim was to disentangle sensory-specific networks so as to derive a potential (amodal) common source of multisensory integration (MSI) and to investigate differences in brain networks with sensory processing in individuals with ASD. In both groups, similar neural networks were found to be involved in the olfactory-visual and auditory-visual integration processes, including the primary visual cortex, the inferior parietal sulcus (IPS), and the medial and inferior frontal cortices. Amygdala activation was observed specifically during olfactory-visual integration, with superior temporal activation having been seen during auditory-visual integration. A dynamic causal modeling analysis revealed a nonlinear top-down IPS modulation of the connection between the respective primary sensory regions in both experimental conditions and in both groups. Thus, we demonstrate that MSI has shared neural sources across olfactory-visual and audio-visual stimulation in patients and controls. The enhanced recruitment of the IPS to modulate changes between areas is relevant to sensory perception. Our results also indicate that, with respect to MSI processing, adults with ASD do not significantly differ from their healthy counterparts.

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11. Uratani M, Ota T, Iida J, Okazaki K, Yamamuro K, Nakanishi Y, Kishimoto N, Kishimoto T. Reduced prefrontal hemodynamic response in pediatric autism spectrum disorder measured with near-infrared spectroscopy. Child Adolesc Psychiatry Ment Health ;2019 ;13:29.

Background : Functional neuroimaging studies suggest that prefrontal cortex dysfunction is present in people with autism spectrum disorder (ASD). Near-infrared spectroscopy is a noninvasive optical tool for examining oxygenation and hemodynamic changes in the cerebral cortex by measuring changes in oxygenated hemoglobin. Methods : Twelve drug-naive male participants, aged 7-15 years and diagnosed with ASD according to DSM-5 criteria, and 12 age- and intelligence quotient (IQ)-matched healthy control males participated in the present study after giving informed consent. Relative concentrations of oxyhemoglobin were measured with frontal probes every 0.1 s during the Stroop color-word task, using 24-channel near-infrared spectroscopy. Results : Oxyhemoglobin changes during the Stroop color-word task in the ASD group were significantly smaller than those in the control group at channels 12 and 13, located over the dorsolateral prefrontal cortex (FDR-corrected P : 0.0021-0.0063). Conclusion : The results suggest that male children with ASD have reduced prefrontal hemodynamic responses, measured with near-infrared spectroscopy.

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