1. Bishop-Fitzpatrick L, Minshew NJ, Mazefsky CA, Eack SM. {{Perception of Life as Stressful, Not Biological Response to Stress, is Associated with Greater Social Disability in Adults with Autism Spectrum Disorder}}. {J Autism Dev Disord};2016 (Sep 30)
This study examined differences between adults with autism spectrum disorder (ASD; N = 40) and typical community volunteers (N = 25) on measures of stressful life events, perceived stress, and biological stress response (cardiovascular and cortisol reactivity) during a novel social stress task. Additional analyses examined the relationship between stress and social functioning as measured by the Social Adjustment Scale-II and the Waisman Activities of Daily Living scale. Results indicated that adults with ASD experienced significantly more stressful life events and perceived stress, and greater systolic blood pressure reactivity than typical community volunteers. Results also indicated that perceived stress and stressful life events were significantly associated with social disability. Interventions targeting stress management might improve social function in adults with ASD.
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2. Cage E, Bird G, Pellicano E. {{Reputation Management in Children on the Autism Spectrum}}. {J Autism Dev Disord};2016 (Sep 30)
Being able to manage reputation is an important social skill, but it is unclear whether autistic children can manage reputation. This study investigated whether 33 autistic children matched to 33 typical children could implicitly or explicitly manage reputation. Further, we examined whether cognitive processes-theory of mind, social motivation, inhibitory control and reciprocity-contribute to reputation management. Results showed that neither group implicitly managed reputation, and there was no group difference in explicit reputation management. Results suggested different mechanisms contribute to reputation management in these groups-social motivation in typical children and reciprocity in autistic children. Explicit reputation management is achievable for autistic children, and there are individual differences in its relationship to underlying cognitive processes.
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3. Drenthen GS, Barendse EM, Aldenkamp AP, van Veenendaal TM, Puts NA, Edden RA, Zinger S, Thoonen G, Hendriks MP, Kessels RP, Jansen JF. {{Altered neurotransmitter metabolism in adolescents with high-functioning autism}}. {Psychiatry Res};2016 (Sep 20);256:44-49.
Previous studies have suggested that alterations in excitatory/inhibitory neurotransmitters might play a crucial role in autism spectrum disorder (ASD). Proton magnetic resonance spectroscopy (1H-MRS) can provide valuable information about abnormal brain metabolism and neurotransmitter concentrations. However, few 1H-MRS studies have been published on the imbalance of the two most abundant neurotransmitters in ASD: glutamate (Glu) and gamma-aminobutyric acid (GABA). Moreover, to our knowledge none of these published studies is performed with a study population consisting purely of high-functioning autism (HFA) adolescents. Selecting only individuals with HFA eliminates factors possibly related to intellectual impairment instead of ASD. This study aims to assess Glu and GABA neurotransmitter concentrations in HFA. Occipital concentrations of Glu and GABA plus macromolecules (GABA+) were obtained using 1H-MRS relative to creatine (Cr) in adolescents with HFA (n=15 and n=13 respectively) and a healthy control group (n=17). Multiple linear regression revealed significantly higher Glu/Cr and lower GABA+/Glu concentrations in the HFA group compared to the controls. These results imply that imbalanced neurotransmitter levels of excitation and inhibition are associated with HFA in adolescents.
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4. Forbes PA, Pan X, de CHAF. {{Reduced Mimicry to Virtual Reality Avatars in Autism Spectrum Disorder}}. {J Autism Dev Disord};2016 (Sep 30)
Mimicry involves unconsciously copying the actions of others. Increasing evidence suggests that autistic people can copy the goal of an observed action but show differences in their mimicry. We investigated mimicry in autism spectrum disorder (ASD) within a two-dimensional virtual reality environment. Participants played an imitation game with a socially engaged avatar and socially disengaged avatar. Despite being told only to copy the goal of the observed action, autistic participants and matched neurotypical participants mimicked the kinematics of the avatars’ movements. However, autistic participants mimicked less. Social engagement did not modulate mimicry in either group. The results demonstrate the feasibility of using virtual reality to induce mimicry and suggest mimicry differences in ASD may also occur when interacting with avatars.
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5. Groom MJ, Young Z, Hall CL, Gillott A, Hollis C. {{The incremental validity of a computerised assessment added to clinical rating scales to differentiate adult ADHD from autism spectrum disorder}}. {Psychiatry Res};2016 (Sep 30);243:168-173.
There is a clinical need for objective evidence-based measures that are sensitive and specific to ADHD when compared with other neurodevelopmental disorders. This study evaluated the incremental validity of adding an objective measure of activity and computerised cognitive assessment to clinical rating scales to differentiate adult ADHD from Autism spectrum disorders (ASD). Adults with ADHD (n=33) or ASD (n=25) performed the QbTest, comprising a Continuous Performance Test with motion-tracker to record physical activity. QbTest parameters measuring inattention, impulsivity and hyperactivity were combined to provide a summary score (‘QbTotal’). Binary stepwise logistic regression measured the probability of assignment to the ADHD or ASD group based on scores on the Conners Adult ADHD Rating Scale-subscale E (CAARS-E) and Autism Quotient (AQ10) in the first step and then QbTotal added in the second step. The model fit was significant at step 1 (CAARS-E, AQ10) with good group classification accuracy. These predictors were retained and QbTotal was added, resulting in a significant improvement in model fit and group classification accuracy. All predictors were significant. ROC curves indicated superior specificity of QbTotal. The findings present preliminary evidence that adding QbTest to clinical rating scales may improve the differentiation of ADHD and ASD in adults.
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6. Gross L. {{In Search of Autism’s Roots}}. {PLoS Biol};2016 (Sep);14(9):e2000958.
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7. Hahn LJ, Brady NC, Fleming KK, Warren SF. {{Joint Engagement and Early Language in Young Children With Fragile X Syndrome}}. {J Speech Lang Hear Res};2016 (Sep 28):1-12.
Purpose: In this study, we examine joint engagement (JE) in young children with fragile X syndrome (FXS) and its relationship to language abilities and autism spectrum disorder symptomatology at 24 to 36 months (toddler period) and 59 to 68 months (child period). Method: Participants were 28 children with FXS (24 boys, four girls) and their mothers. Videotaped home observations were conducted during the toddler period and coded for JE. Language abilities were measured at both ages from a developmental assessment, a functional measure, and from a language sample. The Childhood Autism Rating Scale (Schopler, Reichler, & Renner, 1988) was completed at both ages. Results: Children with FXS spent more time in supported JE than in coordinated JE. Using a weighted JE variable, we found that children with FXS who had higher weighted JE scores also had more advanced expressive language skills at both the toddler and child periods. Weighted JE was negatively related to autism symptomatology in the toddler period. Conclusion: This study provides evidence that children with FXS who use more JE also have more advanced expressive language skills in early development. Therefore, existing early interventions that target JE behaviors may be effective for promoting language, social communication, and social interaction in this population.
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8. Ibrahim GM, Morgan BR, Vogan VM, Leung RC, Anagnostou E, Taylor MJ. {{Mapping the Network of Neuropsychological Impairment in Children with Autism Spectrum Disorder: A Graph Theoretical Analysis}}. {J Autism Dev Disord};2016 (Sep 30)
Children with autism spectrum disorder (ASD) exhibit social-communicative impairments. Less is known about the neuropsychological profile of ASD, although cognitive and neuropsychological deficits are evident. We modelled neuropsychological function in 20 children with ASD and 20 sex, age and IQ matched typically-developing controls (ages 7-14) as a network of interacting parameters. Graph theoretical analysis was applied to identify critical topographic regions within this network. Two areas were significantly stronger hubs in typically-developing children, the ability to shift attention (p < 0.001) and overall executive function (p < 0.001). Planning/organization was a stronger hub in the cognitive networks of children with ASD (p = 0.001). We show that ASD is not only characterized by impairments in various neurocognitive domains, but also alterations in their interaction. Lien vers le texte intégral (Open Access ou abonnement)
9. Lee CY, Chen MH, Jeng MJ, Hsu JW, Tsai SJ, Bai YM, Hung GY, Yen HJ, Chen TJ, Su TP. {{Longitudinal association between early atopic dermatitis and subsequent attention-deficit or autistic disorder: A population-based case-control study}}. {Medicine (Baltimore)};2016 (Sep);95(39):e5005.
Atopic dermatitis (AD) is one of the common allergic diseases in children. The presence of allergic diseases was found to have association with the risk of developing attention-deficit hyperactivity disorder (ADHD) or autistic spectrum disorder (ASD) in children, but it is still inconclusive. This study was to investigate the longitudinal relationship between AD developed during toddlerhood and subsequent development of ADHD or ASD in later childhood. Toddlers born between 1998 and 2008 and diagnosed with AD at the age younger than 3 years and older than 1 month were retrieved from Taiwan’s National Health Insurance Research Database. Age- and gender-matched toddlers with no lifetime AD were enrolled as the control group. All enrolled toddlers were followed until 2011 to identify the development of ADHD or ASD. Multivariate Cox regression analysis was performed to analyze the hazard ratios (HRs). The risks associated with allergic comorbidities were analyzed. A total of 18,473 toddlers were enrolled into the AD group. The presence of AD significantly increased the risk of developing ADHD (HR = 2.92, 95% confidence interval [CI] = 2.48-3.45) or ASD (HR = 8.90, 95% CI = 4.98-15.92) when aged 3 years or older. Children from the AD group with 3 comorbidities together, namely, allergic rhinitis, allergic conjunctivitis, and asthma, had the greatest risk of developing ADHD and ASD (ADHD: HR = 4.67, 95% CI = 3.81-5.43; ASD: HR = 16.65, 95% CI = 8.63-30.60). In conclusion, toddlers who suffer from AD at the age younger than 3 years are at a higher risk of developing ADHD and ASD during later childhood. Pediatricians taking care of toddlers with AD should have knowledge of this increased risk of developing ADHD and ASD later in life, especially when children have certain comorbidities such as allergic rhinitis, allergic conjunctivitis, and asthma.
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10. Libero LE, Burge WK, Deshpande HD, Pestilli F, Kana RK. {{White Matter Diffusion of Major Fiber Tracts Implicated in Autism Spectrum Disorder}}. {Brain Connect};2016 (Sep 30)
Autism spectrum disorder (ASD) is a neurodevelopmental disorder found to have widespread alterations in the function and synchrony of brain regions. These differences may underlie alterations in microstructural organization, such as in white matter pathways. To investigate the diffusion of major white matter tracts, the current study examined multiple indices of white matter diffusion in 42 children and adults with ASD and 44 typically developing (TD) age- and IQ-matched peers using diffusion tensor imaging. Diffusivity measures were compared between groups for the following tracts: bilateral cingulum bundle, corpus callosum, inferior longitudinal fasciculus, superior longitudinal fasciculus, and uncinate fasciculus. Results indicate a significant reduction in fractional anisotropy (FA) for the left superior longitudinal fasciculus (LSLF) in ASD children and adults compared with TD peers. A significant increase in radial diffusivity for ASD participants was also found in the same cluster along the LSLF. In addition, a significant positive correlation emerged for all subjects between FA for the LSLF and age, with FA increasing with age. These findings point to a significant alteration in long-distance white matter connectivity in children and adults with ASD, potentially underscoring the relationship between alterations in white matter diffusion and the ASD phenotype. These results also suggest that the white matter alterations in autism may be subtle and related to the developmental trajectory.
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11. Liu X, Han D, Somel M, Jiang X, Hu H, Guijarro P, Zhang N, Mitchell A, Halene T, Ely JJ, Sherwood CC, Hof PR, Qiu Z, Paabo S, Akbarian S, Khaitovich P. {{Disruption of an Evolutionarily Novel Synaptic Expression Pattern in Autism}}. {PLoS Biol};2016 (Sep);14(9):e1002558.
Cognitive defects in autism spectrum disorder (ASD) include socialization and communication: key behavioral capacities that separate humans from other species. Here, we analyze gene expression in the prefrontal cortex of 63 autism patients and control individuals, as well as 62 chimpanzees and macaques, from natal to adult age. We show that among all aberrant expression changes seen in ASD brains, a single aberrant expression pattern overrepresented in genes involved synaptic-related pathways is enriched in nucleotide variants linked to autism. Furthermore, only this pattern contains an excess of developmental expression features unique to humans, thus resulting in the disruption of human-specific developmental programs in autism. Several members of the early growth response (EGR) transcription factor family can be implicated in regulation of this aberrant developmental change. Our study draws a connection between the genetic risk architecture of autism and molecular features of cortical development unique to humans.
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12. Lo YC, Chen YJ, Hsu YC, Tseng WI, Gau SS. {{Reduced tract integrity of the model for social communication is a neural substrate of social communication deficits in autism spectrum disorder}}. {J Child Psychol Psychiatry};2016 (Sep 28)
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder with social communication deficits as one of the core symptoms. Recently, a five-level model for the social communication has been proposed in which white matter tracts corresponding to each level of the model are identified. Given that the model for social communication subserves social language functions, we hypothesized that the tract integrity of the model for social communication may be reduced in ASD, and the reduction may be related to social communication deficits. METHODS: Sixty-two right-handed boys with ASD and 55 typically developing (TD) boys received clinical evaluations, intelligence tests, the Social Communication Questionnaire (SCQ), and MRI scans. Generalized fractional anisotropy (GFA) was measured by diffusion spectrum imaging to indicate the microstructural integrity of the tracts for each level of the social communication model. Group difference in the tract integrity and its relationship with the SCQ subscales of social communication and social interaction were investigated. RESULTS: We found that the GFA values of the superior longitudinal fasciculus III (SLF III, level 1) and the frontal aslant tracts (FAT, level 2) were decreased in ASD compared to TD. Moreover, the GFA values of the SLF III and the FAT were associated with the social interaction subscale in ASD. CONCLUSIONS: The tract integrity of the model for social communication is reduced in ASD, and the reduction is associated with impaired social interaction. Our results support that reduced tract integrity of the model for social communication might be a neural substrate of social communication deficits in ASD.
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13. Luciano K. {{Autism spectrum disorder}}. {JAAPA};2016 (Oct);29(10):14-15.
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14. Pini G, Bigoni S, Congiu L, Romanelli AM, Scusa MF, Di Marco P, Benincasa A, Morescalchi P, Ferlini A, Bianchi F, Tropea D, Zappella M. {{Rett syndrome: a wide clinical and autonomic picture}}. {Orphanet J Rare Dis};2016;11(1):132.
BACKGROUND: Rett Syndrome is a neurodevelopmental disorder almost exclusively affecting females, characterized by a broad clinical spectrum of signs and symptoms and a peculiar course. The disease affects different body systems: nervous, muscolo-skeletal, gastro-enteric. Moreover, part of the symptoms are related to the involvement of the autonomic nervous system. In the Tuscany Rett Center at Versilia Hospital, we collected data from 151 subjects with a clinical diagnosis of classical or variant RTT syndrome. For each subject, we assessed the severity of the condition with clinical-rating scales (ISS, PBZ), we quantified the performance of the autonomic nervous system, and we performed genetic analysis. We used multivariate statistical analysis of the data to evaluate the relation between the different clinical RTT forms, the cardiorespiratory phenotype, the different genetic mutations and the severity of the clinical picture. Individuals were classified according to existing forms: Classical RTT and three atypical RTT: Z-RTT, Hanefeld, Congenital. A correlation between C-Terminal deletions and lower severity of the clinical manifestations was evident, in the previous literature, but, considering the analysis of autonomic behaviour, the original classification can be enriched with a more accurate subdivision of Rett subgroups, which may be useful for early diagnosis. RESULTS: Present data emphasize some differences, not entirely described in the literature, among RTT variants. In our cohort the Z-RTT variant cases show clinical features (communication, growth, epilepsy and development), well documented by specific ISS items, less severe, if compared to classical RTT and show autonomic disorders, previously not reported in the literature. In this form epilepsy is rarely present. In contrast, Hanefeld variant shows the constant presence of epilepsy which has an earlier onset In Hanefeld variant the frequency of apneas was rare and, among the cardiorespiratory phenotypes, the feeble type is lacking. CONCLUSION: A quantitative analysis of the different autonomic components reveals differences across typical and atypical forms of RTT that leads to a more accurate classification of the groups. In our cohort of RTT individuals, the inclusion of autonomic parameter in the classification leads to an improved diagnosis at earlier stages of development.
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15. Ryan C, Stafford M, King RJ. {{Brief Report: Seeing the Man in the Moon: Do Children with Autism Perceive Pareidolic Faces? A Pilot Study}}. {J Autism Dev Disord};2016 (Sep 30)
Faces are one of the most socially significant visual stimuli encountered in the environment, whereas pareidolias are illusions of faces arising from ambiguous stimuli in the environment. Autism spectrum disorder (ASD) is characterised by deficits in response to social stimuli. We found that children with ASD (n = 60) identify significantly fewer pareidolic faces in a sequence of ambiguous stimuli than typically developing peers. The two groups did not differ in the number of objects identified, indicating that the children with ASD had a specific lack of attention to faces. Pareidolia have considerable potential as naturalistic and easy-to-create materials for the investigation of spontaneous attention to social stimuli in children with ASD.
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16. Samson AC, Dougherty RF, Lee IA, Phillips JM, Gross JJ, Hardan AY. {{White matter structure in the uncinate fasciculus: Implications for socio-affective deficits in Autism Spectrum Disorder}}. {Psychiatry Res};2016 (Sep 30);255:66-74.
Individuals with Autism Spectrum Disorder (ASD) have social and communication deficits and difficulties regulating emotions. The brain bases of these socio-affective deficits are not yet clear, but one candidate is structural connectivity in the left uncinate fasciculus, which connects limbic temporal and frontal areas thought to be involved in socio-affective processing. In this study, we assessed white matter structure in the left and right uncinate fasciculus in 18 high-functioning individuals with ASD and 18 group-matched typically developing (TD) controls using Diffusion Tensor Imaging. To test specificity of the associations, we also examined the association between both uncinate fasciculi and restricted and repetitive behaviors. Compared to TD individuals, individuals with ASD had significantly lower fractional anisotropy (FA) in the left and right uncinate. Group status significantly moderated the association between left uncinate and socio-affective deficits, indicating that within the ASD group, FA was associated with socio-affective deficits: Individuals with ASD with lower FA in the left uncinate had significantly more social and emotion regulation deficits. There was no association with restricted and repetitive behaviors. This study provides evidence that the left uncinate may play a critical role in socio-affective skills in individuals with ASD.
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17. Sicca F, Ambrosini E, Marchese M, Sforna L, Servettini I, Valvo G, Brignone MS, Lanciotti A, Moro F, Grottesi A, Catacuzzeno L, Baldini S, Hasan S, D’Adamo MC, Franciolini F, Molinari P, Santorelli FM, Pessia M. {{Gain-of-function defects of astrocytic Kir4.1 channels in children with autism spectrum disorders and epilepsy}}. {Sci Rep};2016;6:34325.
Dysfunction of the inwardly-rectifying potassium channels Kir4.1 (KCNJ10) represents a pathogenic mechanism contributing to Autism-Epilepsy comorbidity. To define the role of Kir4.1 variants in the disorder, we sequenced KCNJ10 in a sample of affected individuals, and performed genotype-phenotype correlations. The effects of mutations on channel activity, protein trafficking, and astrocyte function were investigated in Xenopus laevis oocytes, and in human astrocytoma cell lines. An in vivo model of the disorder was also explored through generation of kcnj10a morphant zebrafish overexpressing the mutated human KCNJ10. We detected germline heterozygous KCNJ10 variants in 19/175 affected children. Epileptic spasms with dysregulated sensory processing represented the main disease phenotype. When investigated on astrocyte-like cells, the p.R18Q mutation exerted a gain-of-function effect by enhancing Kir4.1 membrane expression and current density. Similarly, the p.R348H variant led to gain of channel function through hindrance of pH-dependent current inhibition. The frequent polymorphism p.R271C seemed, instead, to have no obvious functional effects. Our results confirm that variants in KCNJ10 deserve attention in autism-epilepsy, and provide insight into the molecular mechanisms of autism and seizures. Similar to neurons, astrocyte dysfunction may result in abnormal synaptic transmission and electrical discharge, and should be regarded as a possible pharmacological target in autism-epilepsy.
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18. Tchanturia K, Larsson E, Adamson J. {{How anorexia nervosa patients with high and low autistic traits respond to group Cognitive Remediation Therapy}}. {BMC Psychiatry};2016;16(1):334.
BACKGROUND: The current study aimed to evaluate group Cognitive remediation therapy (CRT) inpatients with Anorexia Nervosa (AN). We aimed to examine the treatment response of group CRT in AN patients with high or low levels of autistic traits. METHODS: Thirty-five in patients with an AN diagnosis received group CRT intervention for 6 sessions in a national eating disorder unit. All participants completed self-report questionnaires on thinking styles and motivation before and after the intervention. RESULTS: Patients with low autistic traits had statistically significant medium size effect improvements in self-reported thinking style scales as well as confidence (ability) to change. Patients with high autistic traits showed no statistically significant improvements in any outcome measure. CONCLUSIONS: The brief group format CRT intervention improves self-reported cognitive and motivational aspects in people with AN without autistic traits. For patients with higher autistic traits brief group CRT does not improve self-reported cognitive style or motivation. This finding suggests that brief group format CRT might not be the best suited format for individuals with elevated autistic traits and individual or more tailored CRT should be explored.
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19. Thiemann-Bourque K, Brady N, McGuff S, Stump K, Naylor A. {{Picture Exchange Communication System and Pals: A Peer-Mediated Augmentative and Alternative Communication Intervention for Minimally Verbal Preschoolers With Autism}}. {J Speech Lang Hear Res};2016 (Sep 27):1-13.
Purpose: This study was conducted to investigate the effectiveness of a social intervention that integrates peer-mediated approaches and the Picture Exchange Communication System (PECS). Method: Effects were evaluated using a series of A-B designs replicated across 4 children with severe autism and limited verbal skills. Seven peers without disabilities were trained to use PECS and facilitative social skills. Measures of changes included rates of communication behaviors, modes, functions, and engagement. Results: Outcomes revealed an intervention effect for 1 child with autism, and this effect was replicated across 3 other children. All children improved in peer-directed communication, with greater increases for 2 children during snack time. For each child with autism, the primary communication behavior was to initiate with picture symbols to request; the peer’s primary communication was to respond. Two children increased communicative functions to comment and to share, and all 4 children showed improved social engagement. All peers increased their communication with the children with autism. Conclusions: These findings add to the limited research on the benefits of teaching typically developing peers to be responsive listeners to preschoolers with autism by learning to use PECS. These results invite further investigation of teaching peers other augmentative and alternative communication approaches and how to increase children’s communication with peers for different purposes.
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20. Wang Y, Tang S, Xu S, Weng S, Liu Z. {{Maternal Body Mass Index and Risk of Autism Spectrum Disorders in Offspring: A Meta-analysis}}. {Sci Rep};2016;6:34248.
Controversial results of the association between maternal body mass index (BMI) and risk of autism spectrum disorder (ASD) in offspring were reported among several studies. This meta-analysis was conducted to estimate the overall association between maternal BMI and risk of ASD in offspring. PubMed, EMBASE, Web of Science, and the Cochrane Library were searched until January 2016. Cohort and case-control studies addressing the association between maternal BMI and risk of ASD in offspring were included. We used random-effect models to estimate the summary relative risks (RRs), we also performed a dose-response meta-analysis to estimate the trend from the correlated log RR estimates across levels of BMI quantitatively. Totally, 6 cohort studies and 1 case-control study involving 8,403 cases and 509,167 participants were included for analysis. The summary RR (95% confidence interval) for ASD in offspring in relation to maternal underweight, overweight, and obesity vs. normal weight during pre-pregnancy or pregnancy, was 1.07 (0.93, 1.23), 1.28 (1.19, 1.36) and 1.36 (1.03, 1.78), respectively. A linear dose-response relationship was found, with a pooled RR of 1.16 (1.01, 1.33) for each 5 kg/m2. increment in maternal BMI. The present study suggests that excessive maternal BMI is associated with increased ASD risk in offspring.
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21. Xing Z, Zeng M, Hu H, Zhang H, Hao Z, Long Y, Chen S, Su H, Yuan Z, Xu M, Chen J. {{Fragile X mental retardation protein promotes astrocytoma proliferation via the MEK/ERK signaling pathway}}. {Oncotarget};2016 (Sep 23)
OBJECTIVE: To examine the association between fragile X mental retardation protein (FMRP) expression and astrocytoma characteristics. METHODS: Pathologic grade and expressions of glial fibrillary acidic protein (GFAP), Ki67 (proliferation marker), and FMRP were determined in astrocytoma specimens from 74 patients. Kaplan-Meier survival analysis was undertaken. Pathologic grade and protein levels of FMRP were determined in 24 additional patients with astrocytoma and 6 controls (cerebral trauma). In cultured U251 and U87 cell lines, the effects of FMRP knock-down on cell proliferation, AKT/mTOR/GSK-3beta and MEK/ERK signaling were studied. The effects of FMRP knock-down on the volumes and weights of U251 cell-derived orthotopic tumors in mice were investigated. RESULTS: In patients, FMRP expression was increased in grade IV (5.1-fold, P<0.01) and grade III (3.2-fold, P<0.05) astrocytoma, compared with controls. FMRP and Ki67 expressions were positively correlated (R2=0.877, P<0.001). Up-regulation of FMRP was associated with poorer survival among patients with FMRP integrated optical density >30 (P<0.01). In astrocytoma cell lines, FMRP knock-down slowed proliferation (P<0.05), inhibited total MEK levels P<0.05, and reduced phosphorylation of MEK (Ser217/221) and ERK (Thr202/Tyr204) (P<0.05). In mice with orthotopic tumors, FMRP knock-down decreased FMRP and Ki67 expressions, and reduced tumor volume and weight (36.3% or 61.5% on day 15, both P<0.01). Also, phosphorylation of MEK (Ser217/221) and ERK (Thr202/Tyr204), and total MEK in xenografts were decreased in sh-FMRP xenografts compared with non-transfected ones (all P<0.05). CONCLUSION: Enhanced FMRP expression in astrocytoma may promote proliferation through activation of MEK/ERK signaling. Lien vers le texte intégral (Open Access ou abonnement)
22. Yoshida K, Go Y, Kushima I, Toyoda A, Fujiyama A, Imai H, Saito N, Iriki A, Ozaki N, Isoda M. {{Single-neuron and genetic correlates of autistic behavior in macaque}}. {Sci Adv};2016 (Sep);2(9):e1600558.
Atypical neurodevelopment in autism spectrum disorder is a mystery, defying explanation despite increasing attention. We report on a Japanese macaque that spontaneously exhibited autistic traits, namely, impaired social ability as well as restricted and repetitive behaviors, along with our single-neuron and genomic analyses. Its social ability was measured in a turn-taking task, where two monkeys monitor each other’s actions for adaptive behavioral planning. In its brain, the medial frontal neurons responding to others’ actions, abundant in the controls, were almost nonexistent. In its genes, whole-exome sequencing and copy number variation analyses identified rare coding variants linked to human neuropsychiatric disorders in 5-hydroxytryptamine (serotonin) receptor 2C (HTR2C) and adenosine triphosphate (ATP)-binding cassette subfamily A13 (ABCA13). This combination of systems neuroscience and cognitive genomics in macaques suggests a new, phenotype-to-genotype approach to studying mental disorders.
