1. Abu-Akel A, Testa RR, Jones HP, Ross N, Skafidas E, Tonge B, Pantelis C. {{Attentional set-shifting and social abilities in children with schizotypal and comorbid autism spectrum disorders}}. {Aust N Z J Psychiatry};2017 (May 01):4867417708610.
OBJECTIVE: While diagnostically independent, autism and schizotypal disorders can co-occur. Their concurrent impact on outcomes and phenotypes has not been investigated. We investigated the impact of comorbid autism and schizotypal disorders in children on executive functioning and socio-pragmatic skills – core features of both disorders. METHOD: Executive functioning (assessed with the Cambridge Neuropsychological Test Automated Battery) and socio-pragmatic skills (assessed using the Melbourne Assessment of Schizotypy in Kids) were investigated in a total of 67 (6-12 year old) children with autism ( n = 15; M/F = 10/5), schizotypal disorder ( n = 8; M/F = 5/3) and comorbid autism and schizotypal disorder ( n = 12; M/F = 5/7) and typically developing children ( n = 32; M/F = 17/15). RESULTS: Both the autism and schizotypal disorder groups performed more poorly than the typically developing group on socio-pragmatic skills and overall performance (i.e. number of stages completed) of the intra-/extra-dimensional set-shifting task (all ps < 0.001). Clear distinctions between the autism and schizotypal groups were present in the intra-/extra-dimensional task relative to the typically developing group - the autism group had difficulties with extra-dimensional shifts ( p < 0.001), and the schizotypal disorder group with intra-dimensional shifts ( p = 0.08). Interestingly, the overall performance of the comorbid group on the intra-/extra-dimensional task was not significantly different from the typically developing group, and they were superior to both the autism ( p = 0.019) and schizotypal disorder ( p = 0.042) groups on socio-pragmatic skills. CONCLUSION: The phenotypical overlap between autism and schizotypal disorders may be precipitated by different cognitive styles and/or mechanisms associated with attention and information processing. We propose that sustaining and switching attention represent two poles of irregularities across the autism and schizotypal spectra, which appear to converge in a compensatory manner in the comorbid group. Our findings highlight the importance of investigating children with a dual diagnosis of autism and schizotypal disorders, and raise intriguing questions about possible mechanisms to explain the attenuated impairment observed in the group of children with comorbid autism and schizotpyal disorders. Lien vers le texte intégral (Open Access ou abonnement)
2. Baron-Cohen S. {{Editorial Perspective: Neurodiversity – a revolutionary concept for autism and psychiatry}}. {J Child Psychol Psychiatry};2017 (Jun);58(6):744-747.
Should we continue to refer to autism as a ‘disease’ or ‘disorder’, or is the framework of ‘neurodiversity’ a more humane and accurate lens through which to view people with autism? Evidence at the genetic, neural, behavioural and cognitive levels reveals people with autism show both differences, and signs of disability, but not disorder. Disability requires societal support, acceptance of difference and diversity, and societal « reasonable adjustment », whilst disorder is usually taken to require cure or treatment. These are very different frameworks. It will be important to see how the concept of neurodiversity is applied to the 300 diagnoses in DSM-5, and if it revolutionizes both the science and the practice of psychiatry.
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3. Brewer R, Biotti F, Bird G, Cook R. {{Typical integration of emotion cues from bodies and faces in Autism Spectrum Disorder}}. {Cognition};2017 (May 16);165:82-87.
Contextual cues derived from body postures bias how typical observers categorize facial emotion; the same facial expression may be perceived as anger or disgust when aligned with angry and disgusted body postures. Individuals with Autism Spectrum Disorder (ASD) are thought to have difficulties integrating information from disparate visual regions to form unitary percepts, and may be less susceptible to visual illusions induced by context. The current study investigated whether individuals with ASD exhibit diminished integration of emotion cues extracted from faces and bodies. Individuals with and without ASD completed a binary expression classification task, categorizing facial emotion as ‘Disgust’ or ‘Anger’. Facial stimuli were drawn from a morph continuum blending facial disgust and anger, and presented in isolation, or accompanied by an angry or disgusted body posture. Participants were explicitly instructed to disregard the body context. Contextual modulation was inferred from a shift in the resulting psychometric functions.Contrary to prediction, observers with ASD showed typical integration of emotion cues from the face and body. Correlation analyses suggested a relationship between the ability to categorize emotion from isolated faces, and susceptibility to contextual influence within the ASD sample; individuals with imprecise facial emotion classification were influenced more by body posture cues.
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4. Chen Y, Yu J, Niu Y, Qin D, Liu H, Li G, Hu Y, Wang J, Lu Y, Kang Y, Jiang Y, Wu K, Li S, Wei J, He J, Wang J, Liu X, Luo Y, Si C, Bai R, Zhang K, Liu J, Huang S, Chen Z, Wang S, Chen X, Bao X, Zhang Q, Li F, Geng R, Liang A, Shen D, Jiang T, Hu X, Ma Y, Ji W, Sun YE. {{Modeling Rett Syndrome Using TALEN-Edited MECP2 Mutant Cynomolgus Monkeys}}. {Cell};2017 (May 18);169(5):945-955.e910.
Gene-editing technologies have made it feasible to create nonhuman primate models for human genetic disorders. Here, we report detailed genotypes and phenotypes of TALEN-edited MECP2 mutant cynomolgus monkeys serving as a model for a neurodevelopmental disorder, Rett syndrome (RTT), which is caused by loss-of-function mutations in the human MECP2 gene. Male mutant monkeys were embryonic lethal, reiterating that RTT is a disease of females. Through a battery of behavioral analyses, including primate-unique eye-tracking tests, in combination with brain imaging via MRI, we found a series of physiological, behavioral, and structural abnormalities resembling clinical manifestations of RTT. Moreover, blood transcriptome profiling revealed that mutant monkeys resembled RTT patients in immune gene dysregulation. Taken together, the stark similarity in phenotype and/or endophenotype between monkeys and patients suggested that gene-edited RTT founder monkeys would be of value for disease mechanistic studies as well as development of potential therapeutic interventions for RTT.
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5. de Zeeuw EL, van Beijsterveldt CEM, Hoekstra RA, Bartels M, Boomsma DI. {{The etiology of autistic traits in preschoolers: a population-based twin study}}. {J Child Psychol Psychiatry};2017 (May 19)
BACKGROUND: Autism Spectrum Disorders (ASD) are highly heritable, but the exact etiological mechanisms underlying the condition are still unclear. METHODS: Using a multiple rater twin design in a large sample of general population preschool twins, this study aimed to (a) estimate the contribution of genetic and environmental factors to autistic traits, controlling for the possible effects of rater bias, (b) to explore possible sex differences in etiology and (c) to investigate the discordance in autistic traits in monozygotic and same-sex dizygotic twin pairs. The Netherlands Twin Register collected maternal and paternal ratings on autistic traits from a general population of 38,798 three-year-old twins. Autistic traits were assessed with the DSM-oriented Pervasive Developmental Problems scale of the Child Behavior Check List for preschoolers (1(1/2)-5 years). RESULTS: Mother and fathers showed high agreement in their assessment of autistic traits (r = .60-.66). Differences between children in autistic traits were largely accounted for by genetic effects (boys: 78% and girls: 83%). Environmental effects that are unique to a child also played a modest role. Environmental effects shared by children growing up in the same family were negligible, once rater bias was controlled for. While the prevalence for clinical ASD is higher in boys than in girls, this study did not find evidence for striking differences in the etiology of autistic traits across the sexes. Even though the heritability was high, 29% of MZ twin pairs were discordant for high autistic traits (clinical range vs. normal development), suggesting that despite high genetic risk, environmental factors might lead to resilience, unaffected status in the context of genetic risk, in some children. CONCLUSIONS: It is important to focus future research on risk factors that might interplay with a genetic disposition for ASD, but also on protective factors that make a difference in the lives of children at genetic risk.
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6. Hoffman K, Weisskopf MG, Roberts AL, Raz R, Hart JE, Lyall K, Hoffman EM, Laden F, Vieira VM. {{Geographic patterns of autism spectrum disorder among children of Nurses’ Health Study II women}}. {Am J Epidemiol};2017 (May 19)
Data indicate that autism spectrum disorder (ASD) prevalence may be increasing and varies geographically. We investigated associations between residential location and ASD in the children of Nurses’ Health Study II women in order to generate hypotheses about social and environmental factors related to etiology or diagnosis. Analyses included 13,507 children born from 1989-1999 (486 with ASD). We explored relationships between ASD and residential location at both birth and age 6 years (i.e. closer to average diagnosis age). Generalized additive models were used to predict ASD odds across the US. Children born in New England were 50% more likely to be diagnosed with ASD compared to children born elsewhere in the US. Patterns were not explained by geographic variation in maternal age, birth year, child’s sex, community income or prenatal exposure to hazardous air pollutants, indicating that spatial variation is not attributable to these factors. Using the residential address at age 6 produced similar results; however, areas of significantly decreased ASD odds were observed in the Southeast, where children were half as likely to have ASD. These results may indicate that diagnostic factors are driving spatial patterns; however, we cannot rule out the possibility that other environmental factors are influencing distributions.
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7. Johannessen J, Naerland T, Hope S, Torske T, Hoyland AL, Strohmaier J, Heiberg A, Rietschel M, Djurovic S, Andreassen OA. {{Parents’ Attitudes toward Clinical Genetic Testing for Autism Spectrum Disorder-Data from a Norwegian Sample}}. {Int J Mol Sci};2017 (May 18);18(5)
Clinical genetic testing (CGT) of children with autism spectrum disorder (ASD) may have positive and negative effects. Knowledge about parents’ attitudes is needed to ensure good involvement of caregivers, which is crucial for accurate diagnosis and effective clinical management. This study aimed to assess parents’ attitudes toward CGT for ASD. Parent members of the Norwegian Autism Society were given a previously untested questionnaire and 1455 answered. Linear regression analyses were conducted to evaluate contribution of parent and child characteristics to attitude statements. Provided it could contribute to a casual explanation of their child’s ASD, 76% would undergo CGT. If it would improve the possibilities for early interventions, 74% were positive to CGT. Between 49-67% agreed that CGT could have a negative impact on health insurance, increase their concern for the child’s future and cause family conflicts. Parents against CGT (9%) were less optimistic regarding positive effects, but not more concerned with negative impacts. The severity of the children’s ASD diagnosis had a weak positive association with parent’s positive attitudes to CGT (p-values range from <0.001 to 0.975). Parents prefer that CGT is offered to those having a child with ASD (65%), when the child's development deviates from normal (48%), or before pregnancy (36%). A majority of the parents of children with ASD are positive to CGT due to possibilities for an etiological explanation. Lien vers le texte intégral (Open Access ou abonnement)
8. Kalb LG, Hagopian LP, Gross AL, Vasa RA. {{Psychometric characteristics of the mental health crisis assessment scale in youth with autism spectrum disorder}}. {J Child Psychol Psychiatry};2017 (May 19)
BACKGROUND: Youth with autism spectrum disorder (ASD) exhibit high rates of psychopathology. These symptoms can pose a risk of injury to self or others when the child is in crisis. Despite this danger, there are no instruments available to identify those with ASD who are at risk or actively in crisis. This study examined the psychometric properties of the Mental Health Crisis Assessment Scale (MCAS), a 28 item parent report measure. METHODS: The MCAS was administered to the parents of 606 children and young adults (aged 3-25 years, M age = 13 years, SD = 5 years) enrolled in the Interactive Autism Network, an online registry of families raising a child with ASD. The MCAS asks parents to rate the severity of various emotional and behavioral symptoms exhibited by their child. The parent then selects the behavior they perceive as the most dangerous behavior and rates the acuity of as well as their efficacy in managing this behavior. The MCAS was tested for internal consistency, construct validity, criterion validity, and convergent validity. RESULTS: The MCAS demonstrated strong internal consistency (Total Scale Cronbach’s alpha = .88). The exploratory and confirmatory factor analyses suggested that a two factor (acuity and behavioral efficacy) model fit the data well, providing evidence of construct validity. Criterion validity, which was assessed by comparing the MCAS to clinician determination of crisis, indicated high levels of agreement (ROC = .85). Strong positive relationships emerged between the MCAS and measures of family distress (r = .56), parental stress, and frustration (r = .48), and use of emergency psychiatric services (OR = 24.2, 95% CI: 8.6-68.2), indicating convergent validity of the measure (all p < .05). CONCLUSIONS: Results of the psychometric analyses suggest the MCAS appears to be a promising tool that can measure mental health crises in youth with ASD. Lien vers le texte intégral (Open Access ou abonnement)
9. Lamont RF, Jorgensen JS. {{Oxytocin-receptor antagonists in the aetiology of autism spectrum disorder}}. {Early Hum Dev};2017 (May 15)
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10. Maras KL, Crane L, Mulcahy S, Hawken T, Cooper P, Wurtzel D, Memon A. {{Brief Report: Autism in the Courtroom: Experiences of Legal Professionals and the Autism Community}}. {J Autism Dev Disord};2017 (May 18)
Online surveys were used to sample the views of judges, barristers and solicitors (n = 33) about their engagement with autistic individuals in criminal courts in England and Wales. Despite an understanding of some of the difficulties experienced by individuals with autism, and the adjustments suitable for supporting them, legal professionals reported constraints arising from a lack of understanding by others within the criminal justice system. These results are considered alongside the views and perspectives of autistic adults (n = 9) and parents of children on the autism spectrum (n = 19), who had encountered the criminal courts as witnesses or defendants and were largely dissatisfied with their experiences. Training, understanding and the provision of appropriate adjustments were identified as key issues by all respondent groups.
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11. Martinez de Paz A, Ausio J. {{MeCP2, A Modulator of Neuronal Chromatin Organization Involved in Rett Syndrome}}. {Adv Exp Med Biol};2017;978:3-21.
From an epigenetic perspective, the genomic chromatin organization of neurons exhibits unique features when compared to somatic cells. Methyl CpG binding protein 2 (MeCP2), through its ability to bind to methylated DNA, seems to be a major player in regulating such unusual organization. An important contribution to this uniqueness stems from the intrinsically disordered nature of this highly abundant chromosomal protein in neurons. Upon its binding to methylated/hydroxymethylated DNA, MeCP2 is able to recruit a plethora of interacting protein and RNA partners. The final outcome is a highly specialized chromatin organization wherein linker histones (histones of the H1 family) and MeCP2 share an organizational role that dynamically changes during neuronal development and that it is still poorly understood. MeCP2 mutations alter its chromatin-binding dynamics and/or impair the ability of the protein to interact with some of its partners, resulting in Rett syndrome (RTT). Therefore, deciphering the molecular details involved in the MeCP2 neuronal chromatin arrangement is critical for our understanding of the proper and altered functionality of these cells.
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12. Obiols-Guardia A, Guil S. {{The Role of Noncoding RNAs in Neurodevelopmental Disorders: The Case of Rett Syndrome}}. {Adv Exp Med Biol};2017;978:23-37.
Current technologies have demonstrated that only a small fraction of our genes encode for protein products. The vast majority of the human transcriptome corresponds to noncoding RNA (ncRNA) of different size, localization, and expression profile. Despite the fact that a biological function remains yet to be determined for most ncRNAs, growing evidence points to their crucial regulatory roles at all stages in gene expression regulation, including transcriptional and posttranscriptional control, so that proper cell homeostasis seems to depend largely on a variety of ncRNA-mediated regulatory networks. This is particularly relevant in the human brain, which displays the richest repertoire of ncRNA species, and where several different ncRNA molecules are known to be involved in crucial steps for brain development and maturation. Rett syndrome is a neurodevelopmental disorder characterized by loss of function mutations in the X-linked gene encoding for methyl-CpG-binding protein 2 (MeCP2). MECP2 deficiency impacts globally on gene expression programs, mainly through its role as a transcriptional repressor, and growing data also points to an important dysregulation of the noncoding transcriptome in the disease. Here, we review the current knowledge on ncRNA alterations in Rett and explore links with other pathologies that might indicate the potential use of particular noncoding transcripts as therapeutical targets, tools, or disease biomarkers.
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13. Ousley O, Evans AN, Fernandez-Carriba S, Smearman EL, Rockers K, Morrier MJ, Evans DW, Coleman K, Cubells J. {{Examining the Overlap between Autism Spectrum Disorder and 22q11.2 Deletion Syndrome}}. {Int J Mol Sci};2017 (May 18);18(5)
22q11.2 deletion syndrome (22q11.2DS) is a genomic disorder reported to associate with autism spectrum disorders (ASDs) in 15-50% of cases; however, others suggest that individuals with 22q11.2DS present psychiatric or behavioral features associated with ASDs, but do not meet full criteria for ASD diagnoses. Such wide variability in findings may arise in part due to methodological differences across studies. Our study sought to determine whether individuals with 22q11.2DS meet strict ASD diagnostic criteria using research-based guidelines from the Collaborative Programs of Excellence in Autism (CPEA), which required a gathering of information from three sources: the Autism Diagnostic Interview-Revised (ADI-R), the Autism Diagnostic Observational Schedule (ADOS), and a clinician’s best-estimate diagnosis. Our study examined a cohort of children, adolescents, and young adults (n = 56) with 22q11.2DS, who were ascertained irrespective of parents’ behavioral or developmental concerns, and found that 17.9% (n = 10) of the participants met CPEA criteria for an ASD diagnosis, and that a majority showed some level of social-communication impairment or the presence of repetitive behaviors. We conclude that strictly defined ASDs occur in a substantial proportion of individuals with 22q11.2DS, and recommend that all individuals with 22q11.2DS be screened for ASDs during early childhood.
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14. Pagan C, Goubran-Botros H, Delorme R, Benabou M, Lemiere N, Murray K, Amsellem F, Callebert J, Chaste P, Jamain S, Fauchereau F, Huguet G, Maronde E, Leboyer M, Launay JM, Bourgeron T. {{Disruption of melatonin synthesis is associated with impaired 14-3-3 and miR-451 levels in patients with autism spectrum disorders}}. {Sci Rep};2017 (May 18);7(1):2096.
Autism spectrum disorders (ASD) are characterized by a wide genetic and clinical heterogeneity. However, some biochemical impairments, including decreased melatonin (crucial for circadian regulation) and elevated platelet N-acetylserotonin (the precursor of melatonin) have been reported as very frequent features in individuals with ASD. To address the mechanisms of these dysfunctions, we investigated melatonin synthesis in post-mortem pineal glands – the main source of melatonin (9 patients and 22 controls) – and gut samples – the main source of serotonin (11 patients and 13 controls), and in blood platelets from 239 individuals with ASD, their first-degree relatives and 278 controls. Our results elucidate the enzymatic mechanism for melatonin deficit in ASD, involving a reduction of both enzyme activities contributing to melatonin synthesis (AANAT and ASMT), observed in the pineal gland as well as in gut and platelets of patients. Further investigations suggest new, post-translational (reduced levels of 14-3-3 proteins which regulate AANAT and ASMT activities) and post-transcriptional (increased levels of miR-451, targeting 14-3-3zeta) mechanisms to these impairments. This study thus gives insights into the pathophysiological pathways involved in ASD.
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15. Siu MT, Weksberg R. {{Epigenetics of Autism Spectrum Disorder}}. {Adv Exp Med Biol};2017;978:63-90.
Autism spectrum disorder (ASD), one of the most common childhood neurodevelopmental disorders (NDDs), is diagnosed in 1 of every 68 children. ASD is incredibly heterogeneous both clinically and aetiologically. The etiopathogenesis of ASD is known to be complex, including genetic, environmental and epigenetic factors. Normal epigenetic marks modifiable by both genetics and environmental exposures can result in epigenetic alterations that disrupt the regulation of gene expression, negatively impacting biological pathways important for brain development. In this chapter we aim to summarize some of the important literature that supports a role for epigenetics in the underlying molecular mechanism of ASD. We provide evidence from work in genetics, from environmental exposures and finally from more recent studies aimed at directly determining ASD-specific epigenetic patterns, focusing mainly on DNA methylation (DNAm). Finally, we briefly discuss some of the implications of current research on potential epigenetic targets for therapeutics and novel avenues for future work.
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16. Zander E, Willfors C, Berggren S, Coco C, Holm A, Jifalt I, Kosieradzki R, Linder J, Nordin V, Olafsdottir K, Bolte S. {{The Interrater Reliability of the Autism Diagnostic Interview-Revised (ADI-R) in Clinical Settings}}. {Psychopathology};2017 (May 20)
BACKGROUND: The Autism Diagnostic Interview-Revised (ADI-R) is considered a first choice assessment tool in autism spectrum disorder. Nevertheless, despite its wide use in psychiatric practice and recommendations by various clinical guidelines, its interrater reliability has predominantly been confirmed in research settings by specially trained, research reliability interviewers. The reliability of ADI-R assessments among clinicians has not yet been established. Therefore, this study examined the spontaneous interrater reliability of the ADI-R in a naturalistic clinical multicenter setting. SAMPLING AND METHODS: Ten video-recorded ADI-R administrations were rated by 5 different raters each from a pool of 11 raters affiliated to 8 different clinical sites. RESULTS: The interrater reliability for the 12 diagnostic criteria operationalizing autism spectrum disorders according to DSM-IV/ICD-10 in the ADI-R algorithms ranged between G(q,k) (analogous to intraclass correlations) = 0.96 and 0.99 for reciprocal social interaction, 0.96 and 1.00 for communication, and 0.91 and 0.97 for repetitive and restricted behavior. Reliability of diagnostic classification was kCohen 0.83. CONCLUSIONS: The findings endorse the psychometric properties of ADI-R in terms of interrater reliability previously reported from research settings and support their generalization to common clinical settings. Limitations of this study include an unbalanced sample composition.
