1. Cauda F, Costa T, Nani A, Fava L, Palermo S, Bianco F, Duca S, Tatu K, Keller R. {{Are schizophrenia, autistic, and obsessive spectrum disorders dissociable on the basis of neuroimaging morphological findings?: A voxel-based meta-analysis}}. {Autism Res};2017 (Mar 24)
Schizophrenia spectrum disorder (SCZD), autism spectrum disorder (ASD), and obsessive-compulsive spectrum disorder (OCSD) are considered as three separate psychiatric conditions with, supposedly, different brain alterations patterns. From a neuroimaging perspective, this meta-analytic study aimed to address whether this nosographical differentiation is actually supported by different brain patterns of gray matter (GM) or white matter (WM) morphological alterations. We explored two possibilities: (a) to find out whether GM alterations are specific for SCZD, ASD, and OCSD; and (b) to associate the identified brain alteration patterns with cognitive dysfunctions by means of an analysis of lesion decoding. Our analysis reveals that these psychiatric spectra do not present clear distinctive patterns of alterations; rather, they all tend to be distributed in two alteration clusters. Cluster 1, which is more specific for SCZD, includes the anterior insular, anterior cingulate cortex, ventromedial prefrontal cortex, and frontopolar areas, which are parts of the cognitive control system. Cluster 2, which is more specific for OCSD, presents occipital, temporal, and parietal alteration patterns with the involvement of sensorimotor, premotor, visual, and lingual areas, thus forming a network that is more associated with the auditory-visual, auditory, premotor visual somatic functions. In turn, ASD appears to be uniformly distributed in the two clusters. The three spectra share a significant set of alterations. Our new approach promises to provide insight into the understanding of psychiatric conditions under the aspect of a common neurobiological substrate, possibly related to neuroinflammation during brain development. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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2. Chenausky K, Tager-Flusberg H. {{Acquisition of voice onset time in toddlers at high and low risk for autism spectrum disorder}}. {Autism Res};2017 (Mar 24)
Although language delay is common in autism spectrum disorder (ASD), research is equivocal on whether speech development is affected. We used acoustic methods to investigate the existence of sub-perceptual differences in the speech of toddlers who developed ASD. Development of the distinction between b and p was prospectively tracked in 22 toddlers at low risk for ASD (LRC), 22 at high risk for ASD without ASD (HRA-), and 11 at high risk for ASD who were diagnosed with ASD at 36 months (HRA+). Voice onset time (VOT), the main acoustic difference between b and p, was measured from spontaneously produced words at 18, 24, and 36 months. Number of words, number of tokens (instances) of syllable-initial b and p produced, error rates, language scores, and motor ability were also assessed. All groups’ mean language scores were within the average range or slightly higher. No between-group differences were found in number of words, b’s, p’s, or errors produced; or in mean or standard deviation of VOT. Binary logistic regression showed that only diagnostic status, not language score, motor ability, number of words, number of b’s and p’s, or number of errors significantly predicted whether a toddler produced acoustically distinct b and p populations at 36 months. HRA+ toddlers were significantly less likely to produce acoustically distinct b’s and p’s at 36 months, which may indicate that the HRA+ group may be using different strategies to produce this distinction. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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3. Constantino JN. {{Measurement of Autism Symptomatology in Children With Neurodevelopmental Impairment}}. {J Am Acad Child Adolesc Psychiatry};2017 (Apr);56(4):354-355.
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4. Hellings JA, Arnold LE, Han J. {{Dopamine antagonists for treatment resistance in autism spectrum disorders: review and focus on BDNF stimulators loxapine and amitriptyline}}. {Expert Opin Pharmacother};2017 (Mar 24)
INTRODUCTION: Drug development is urgently needed for individuals with autism spectrum disorders (ASD) and psychiatric comorbidity, which often presents as aggression and self-injury. At the same time, most psychiatric medications are drugs that have been repurposed following clinical observations of efficacy for a new treatment purpose. Areas Covered: This review aims to provide an overview of dopamine antagonists, including classical and atypical, as well as unconventional antipsychotics in ASD, since they are a mainstay of treatment for such problems. In the event of only partial treatment response practitioners urgently need other prescribing options. The older antipsychotic loxapine is discussed in terms of preliminary albeit limited evidence for efficacy and safety, as well as possible neurotrophic effects in the brain. Emerging promise of the unconventional weak dopamine blocking/tricyclic antidepressant amitriptyline in ASD is discussed more briefly. Promising BDNF effects of loxapine and amitriptyline are included. The need for any antipsychotic tapering plan to be extremely gradual, unless neuroleptic malignant syndrome is present, is also emphasized. Expert Opinion: While behavioral treatments can improve core symptoms in ASD, pharmacotherapy and specifically dopamine antagonists are often prescribed for serious challenging behaviors including aggression. The classical antipsychotics received some study and are still often used in antipsychotic polypharmacy however individuals with ASD are more susceptible to the neuromotor side effects which may further impair already compromised mobility as well as cause tardive dyskinesia and neuroleptic malignant syndrome. The novel antipsychotics risperidone and aripiprazole have received most study in ASD and are FDA-approved for irritability in children over age 5 years. However individuals with ASD are more prone to weight gain, Type II diabetes and associated side effects, for which most novel antipsychotics carry a black box warning. The common practice of prescribing SSRIs that inhibit metabolism of many psychoactive drugs together with antipsychotics compounds the side effects. Low dose loxapine has properties of classical as well as novel antipsychotics but importantly appears more weight neutral, and with promising use in adolescents and adults with ASD. Amitriptyline appears effective in ASD for irritability, impulsive aggression, gastrointestinal problems, and insomnia, in children, adolescents and adults however our adult data on amitriptyline in ASD is still in preparation for publication. Both loxapine and amitriptyline may have positive BDNF effects. Further studies are warranted of both medications in ASD.
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5. Krsicka D, Geryk J, Vlckova M, Havlovicova M, Macek M, Jr., Pourova R. {{Identification of likely associations between cerebral folate deficiency and complex genetic- and metabolic pathogenesis of autism spectrum disorders by utilization of a pilot interaction modeling approach}}. {Autism Res};2017 (Mar 24)
Recently, cerebral folate deficiency (CFD) was suggested to be involved in the pathogenesis of autism spectrum disorders (ASD). However, the exact role of folate metabolism in the pathogenesis of ASD, identification of underlying pathogenic mechanisms and impaired metabolic pathways remain unexplained. The aim of our study was to develop and test a novel, unbiased, bioinformatics approach in order to identify links between ASD and disturbed cerebral metabolism by focusing on abnormal folate metabolism, which could foster patient stratification and novel therapeutic interventions. An unbiased, automatable, computational workflow interaction model was developed using available data from public databases. The interaction network model of ASD-associated genes with known cerebral expression and function (SFARI) and metabolic networks (MetScape), including connections to known metabolic substrates, metabolites and cofactors involving folates, was established. Intersection of bioinformatically created networks resulted in a limited amount of interaction modules pointing to common disturbed metabolic pathways, linking ASD to CFD. Two independent interaction modules (comprising three pathways) covering enzymes encoded by ASD-related genes and folate cofactors utilizing enzymes were generated. Module 1 suggested possible interference of CFD with serine and lysine metabolism, while module 2 identified correlations with purine metabolism and inosine monophosphate production. Since our approach was primarily conceived as a proof of principle, further amendments of the presented initial model are necessary to obtain additional actionable outcomes. Our modelling strategy identified not only previously known interactions supported by evidence-based analyses, but also novel plausible interactions, which could be validated in subsequent functional and/or clinical studies. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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6. Langley E, Totsika V, Hastings RP. {{Parental relationship satisfaction in families of children with autism spectrum disorder (ASD): A multilevel analysis}}. {Autism Res};2017 (Mar 24)
Caring for a child with Autism Spectrum Disorder (ASD) has been linked to a range of negative outcomes for parents but less is known about the putative impact upon the parental couple relationship. The relationship satisfaction of parents of children with ASD was investigated using multilevel modeling. Mothers and fathers (146 couples) reported on their relationship satisfaction, their own well-being, and the behavior problems of the child with ASD and a sibling. Results indicated that mothers and fathers reported similar levels of relationship satisfaction and it was significantly and negatively associated with parental depression and the behavior problems of the child with ASD. Relationship satisfaction was unrelated to the behavior problems of a sibling, the number of children in the household, and family socioeconomic position (SEP). Further longitudinal research that captures a broader range of variables is required to build a theoretical understanding of relationship satisfaction in families of children with ASD. Current evidence suggests that early intervention routes targeting either child behavior problems, parental mental health, or the couple relationship have the potential to benefit inter-connected subsystems within the broader family system. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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7. Liu G, Pearl AM, Kong L, Leslie DL, Murray MJ. {{Erratum to: A Profile on Emergency Department Utilization in Adolescents and Young Adults with Autism Spectrum Disorders}}. {J Autism Dev Disord};2017 (Mar 23)
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8. Magdalon J, Sanchez-Sanchez SM, Griesi-Oliveira K, Sertie AL. {{Dysfunctional mTORC1 Signaling: A Convergent Mechanism between Syndromic and Nonsyndromic Forms of Autism Spectrum Disorder?}}. {Int J Mol Sci};2017 (Mar 18);18(3)
Whereas autism spectrum disorder (ASD) exhibits striking heterogeneity in genetics and clinical presentation, dysfunction of mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway has been identified as a molecular feature common to several well-characterized syndromes with high prevalence of ASD. Additionally, recent findings have also implicated mTORC1 signaling abnormalities in a subset of nonsyndromic ASD, suggesting that defective mTORC1 pathway may be a potential converging mechanism in ASD pathology across different etiologies. However, the mechanistic evidence for a causal link between aberrant mTORC1 pathway activity and ASD neurobehavioral features varies depending on the ASD form involved. In this review, we first discuss six monogenic ASD-related syndromes, including both classical and potentially novel mTORopathies, highlighting their contribution to our understanding of the neurobiological mechanisms underlying ASD, and then we discuss existing evidence suggesting that aberrant mTORC1 signaling may also play a role in nonsyndromic ASD.
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9. Peled-Avron L, Shamay-Tsoory SG. {{Don’t touch me! autistic traits modulate early and late ERP components during visual perception of social touch}}. {Autism Res};2017 (Mar 24)
Although individuals with autism spectrum disorder (ASD) have impaired responses to interpersonal touch, the underlying neural correlates remain largely unknown. Here, we examined the neural correlates that underlie interpersonal touch perception in individuals with either high or low autistic traits. Fifty-three participants were classified as having either high or low autistic traits based on their performance on the autism quotient (AQ) questionnaire. We hypothesized that individuals with high AQ scores would have relatively high touch hypervigilance, reflected as earlier P1 and stronger late positive potential (LPP) responses, two components of event-related potentials that serve as electrophysiological markers of anxiety bias. We recorded each participant’s electroencephalography activity during presentation of images depicting human touch, object touch, and non-touch control images. Consistent with our hypothesis, AQ scores were positively correlated with social touch aversion. Moreover, participants with high AQ scores had earlier P1 and stronger LPP responses when presented with human touch compared to the control images. Importantly, a regression model revealed that earlier P1 and larger LPP amplitude measured during social touch observation can accurately predict higher autistic trait levels. Taken together, these findings indicate that individuals with high levels of autistic traits may have a hypervigilant response to observed social touch. Autism Res 2017, 0: 000-000. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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10. Reiersen AM. {{Early Identification of Autism Spectrum Disorder: Is Diagnosis by Age 3 a Reasonable Goal?}}. {J Am Acad Child Adolesc Psychiatry};2017 (Apr);56(4):284-285.
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11. Samaritter R, Payne H. {{Through the Kinesthetic Lens: Observation of Social Attunement in Autism Spectrum Disorders}}. {Behav Sci (Basel)};2017 (Mar 18);7(1)
This paper will present a movement-informed perspective to social attunement in Autism Spectrum Disorders (ASD). BACKGROUND: Dance movement therapy (DMT) is a psychotherapeutic intervention that is used with participants with ASD in various settings. Regular clinical outcome monitoring in an outpatient setting in the Netherlands had shown positive effects on social attunement capacities in young people with ASD. However, a systematic study of the development of social attunement movement behaviors of participants with ASD throughout a DMT intervention was not yet available. METHODS: A series of individual cases of DMT with young people with ASD (mean age 12.2 years.) were analyzed for changes in interpersonal movement behaviors employing video-based retrospective observation. RESULTS: The findings were summarized in an observation scale for interpersonal movement behaviors. This scale was then tested for its applicability for the monitoring of social attunement behaviors throughout therapy. DISCUSSION: A movement-informed perspective may be helpful to inventory changes in social attunement behaviors in participants with ASD. The relevance of a movement-informed perspective for the concept of social attunement in ASD will be discussed.
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12. Sheldrick RC, Maye MP, Carter AS. {{Age at First Identification of Autism Spectrum Disorder: An Analysis of Two US Surveys}}. {J Am Acad Child Adolesc Psychiatry};2017 (Apr);56(4):313-320.
OBJECTIVE: Evidence regarding the age at which autism spectrum disorder (ASD) is identified is essential for improving early detection, yet many extant studies have not applied time-to-event analyses, which account for statistical biases that arise from sampling in cross-sectional surveys by adjusting for child age at time of parental report. Our objective was to estimate age distributions for first identification of ASD in national parent surveys using time-to-event analyses. METHOD: We conducted time-to-event analyses of responses to identical questions in the 2011 to 2012 National Survey of Children’s Health (n = 95,677) and the 2009 to 2010 National Survey of Children with Special Health Care Needs (n = 371,617). RESULTS: Parents in both surveys reported that a minority of ASD cases were identified before age 3 years, and that one-third to one-half of cases were identified after 6 years. In both surveys, a majority of parents described their child’s ASD severity as mild, and these parents reported the oldest age at identification (mean, 5.6 and 8.6 years). In contrast, parents who described their child’s ASD as severe reported earlier age at identification (mean, 3.7 and 4.5 years). Time-to-event analyses yielded older estimates of age at identification than analyses based on raw distributions. CONCLUSION: In two national surveys, a majority of parents of children with ASD reported identification after 3 years, when eligibility for early intervention services expires, and many reported identification of ASD after school age. Later identification of children with milder symptoms highlights the need for early screening that is sensitive to all forms of ASD, regardless of severity.
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13. Stevenson RA, Baum SH, Segers M, Ferber S, Barense MD, Wallace MT. {{Multisensory speech perception in autism spectrum disorder: From phoneme to whole-word perception}}. {Autism Res};2017 (Mar 24)
Speech perception in noisy environments is boosted when a listener can see the speaker’s mouth and integrate the auditory and visual speech information. Autistic children have a diminished capacity to integrate sensory information across modalities, which contributes to core symptoms of autism, such as impairments in social communication. We investigated the abilities of autistic and typically-developing (TD) children to integrate auditory and visual speech stimuli in various signal-to-noise ratios (SNR). Measurements of both whole-word and phoneme recognition were recorded. At the level of whole-word recognition, autistic children exhibited reduced performance in both the auditory and audiovisual modalities. Importantly, autistic children showed reduced behavioral benefit from multisensory integration with whole-word recognition, specifically at low SNRs. At the level of phoneme recognition, autistic children exhibited reduced performance relative to their TD peers in auditory, visual, and audiovisual modalities. However, and in contrast to their performance at the level of whole-word recognition, both autistic and TD children showed benefits from multisensory integration for phoneme recognition. In accordance with the principle of inverse effectiveness, both groups exhibited greater benefit at low SNRs relative to high SNRs. Thus, while autistic children showed typical multisensory benefits during phoneme recognition, these benefits did not translate to typical multisensory benefit of whole-word recognition in noisy environments. We hypothesize that sensory impairments in autistic children raise the SNR threshold needed to extract meaningful information from a given sensory input, resulting in subsequent failure to exhibit behavioral benefits from additional sensory information at the level of whole-word recognition. Autism Res 2017. (c) 2017 International Society for Autism Research, Wiley Periodicals, Inc.
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14. Vogelgesang S, Niebert S, Renner U, Mobius W, Hulsmann S, Manzke T, Niebert M. {{Analysis of the Serotonergic System in a Mouse Model of Rett Syndrome Reveals Unusual Upregulation of Serotonin Receptor 5b}}. {Front Mol Neurosci};2017;10:61.
Mutations in the transcription factor methyl-CpG-binding-protein 2 (MeCP2) cause a delayed-onset neurodevelopmental disorder known as Rett syndrome (RTT). Although alteration in serotonin levels have been reported in RTT patients, the molecular mechanisms underlying these defects are not well understood. Therefore, we chose to investigate the serotonergic system in hippocampus and brainstem of male Mecp2-/y knock-out mice in the B6.129P2(C)-Mecp2(tm1.1Bird) mouse model of RTT. The serotonergic system in mouse is comprised of 16 genes, whose mRNA expression profile was analyzed by quantitative RT-PCR. Mecp2-/y mice are an established animal model for RTT displaying most of the cognitive and physical impairments of human patients and the selected areas receive significant modulation through serotonin. Using anatomically and functional characterized areas, we found region-specific differential expression between wild type and Mecp2-/y mice at post-natal day 40. In brainstem, we found five genes to be dysregulated, while in hippocampus, two genes were dysregulated. The one gene dysregulated in both brain regions was dopamine decarboxylase, but of special interest is the serotonin receptor 5b (5-ht5b), which showed 75-fold dysregulation in brainstem of Mecp2-/y mice. This dysregulation was not due to upregulation, but due to failure of down-regulation in Mecp2-/y mice during development. Detailed analysis of 5-ht5b revealed a receptor that localizes to endosomes and interacts with Galphai proteins.
