Autisme Information Science

20 mai 2017

Concentration urinaire des métabolites des insecticides organophosphorés pendant la grossesse et comportement interpersonnel, communication, répétitif et stéréotypé des enfants à l'âge de 8 ans: l'étude à domicile

Aperçu: G.M.

L'exposition prénatale aux insecticides organophosphorés peut être associée à des troubles du spectre de l'autisme et à des comportements connexes. Cette association peut être modifiée par des polymorphismes nucléotidiques simples dans l'enzyme de la paraoxonase (PON1).

Parmi 224 femmes enceintes, les chercheurs ont quantifié les concentrations de six métabolites non spécifiques du phosphate de dialkyle (DAP) des insecticides organophosphorés dans deux échantillons d'urine recueillis à ~ 16 et ~ 26 semaines de gestation.

Lorsque les enfants avaient huit ans, les chercheurs leur ont fait passé l'échelle de réceptivité sociale (SRS), une mesure continue de diverses dimensions du comportement interpersonnel, de la communication et des comportements répétitifs / stéréotypés. Ils ont ensuite estimé l'association entre une augmentation de 10 fois de la somme de six concentrations de DAP (ΣDAP) et les scores de SRS. ILs ont enfin examiné si les génotypes enfants PON1192 et PON1-108 ont modifié cette association.

Après l'ajustement covariable, les concentrations de ΣDAP n'ont pas été associées aux scores SRS

2017 May 10;157:9-16. doi: 10.1016/j.envres.2017.05.008.

Urinary organophosphate insecticide metabolite concentrations during pregnancy and children's interpersonal, communication, repetitive, and stereotypic behaviors at 8 years of age: The home study

Millenson ME¹, Braun JM², Calafat AM³, Barr DB⁴, Huang YT⁵, Chen A⁶, Lanphear BP⁷, Yolton K⁸.

Author information

1: Department of Epidemiology, Brown University, Providence, RI 02912, USA.
2: Department of Epidemiology, Brown University, Providence, RI 02912, USA. Electronic address: joseph_braun_1@brown.edu.
3: Division of Laboratory Sciences, National Center for Environmental Health, Centers for Disease Control and Prevention, Atlanta, GA, USA.
4: Department of Environmental Health, Emory University, Atlanta, GA, USA.
5: Institute of Statistical Science, Academia Sinica, Taipei, Taiwan.
6: Department of Environmental Health, University of Cincinnati, Cincinnati, OH, USA.
7: Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada.
8: Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.

Abstract

BACKGROUND:

Prenatal exposure to organophosphate insecticides may be associated with autism spectrum disorders and related behaviors. This association may be modified by single nucleotide polymorphisms in the paraoxonase (PON1) enzyme.

OBJECTIVE:

We examined the relationship of prenatal organophosphate insecticide biomarkers with reciprocal social, repetitive, and stereotypic behaviors in 8-year old children, and modification of this relationship by child PON1 polymorphisms.

METHODS:

Among 224 pregnant women, we quantified concentrations of six nonspecific dialkyl phosphate (DAP) metabolites of organophosphate insecticides in two urine samples collected at ~16 and ~26 weeks gestation. When children were eight years old, we administered the Social Responsiveness Scale (SRS), a continuous measure of various dimensions of interpersonal behavior, communication, and repetitive/stereotypic behaviors. We estimated the association between a 10-fold increase in the sum of six DAP concentrations (ΣDAP) and SRS scores. We examined whether child PON1₁₉₂ and PON1_-108 genotypes modified this association.

RESULTS:

After covariate adjustment, ΣDAP concentrations were not associated with SRS scores [β=-1.2; 95% confidence interval (CI): -4.0, 1.6]. Among children with the PON1_-108TT genotype, ΣDAP concentrations were associated with 2.5-point higher (95% CI: -4.9, 9.8) SRS scores; however, the association was not different from the 1.8-point decrease (95% CI: -5.8, 2.2) among children with PON1_-108CT/CC genotypes (ΣDAP × PON1_-108 p-value =0.54). The association between ΣDAP concentrations and SRS scores was not modified by PON1₁₉₂ (ΣDAP × PON1₁₉₂ p-value =0.89).

CONCLUSIONS:

In this cohort, prenatal urinary DAP concentrations were not associated with children's social behaviors; these associations were not modified by child PON1 genotype.

PMID: 28501654
DOI: 10.1016/j.envres.2017.05.008

Phénotypes cognitifs aberrants et expression de BDNF altérée par l'hippocampe liées à des modifications épigénétiques chez la souris dépourvue de protéine d'échafaudage post-synaptique SHANK1: Implications pour le trouble du spectre de l'autisme

Aperçu: G.M.

L'ensemble des résultats indique que les deletions de Shank1 conduisent à un phénotype cognitif aberrant caractérisé par des déficiences graves dans la mémoire de reconnaissance d'objet et l'augmentation des taux de BDNF hippocampiques, éventuellement à cause de modifications épigénétiques.

Ce résultat confirme le lien entre TSA et handicap intellectuel, et suggère une régulation épigénétique comme cible thérapeutique potentielle.

2017 May 12. doi: 10.1002/hipo.22741.

Aberrant cognitive phenotypes and altered hippocampal BDNF expression related to epigenetic modifications in mice lacking the post-synaptic scaffolding protein SHANK1: Implications for autism spectrum disorder

Sungur AÖ¹, Jochner MCE¹, Harb H², Kılıç A², Garn H², Schwarting RKW¹, Wöhr M¹.

Author information

1: Behavioral Neuroscience, Experimental and Biological Psychology, Philipps-University of Marburg, Marburg, Germany.
2: Institute of Laboratory Medicine and Pathobiochemistry-Molecular Diagnostics, Philipps-University of Marburg, Marburg, Germany.

Abstract

Autism spectrum disorder (ASD) is a class of neurodevelopmental disorders characterized by persistent deficits in social communication/interaction, together with restricted/repetitive patterns of behavior. ASD is among the most heritable neuropsychiatric conditions, and while available evidence points to a complex set of genetic factors, the SHANK gene family has emerged as one of the most promising candidates. Here, we assessed ASD-related phenotypes with particular emphasis on social behavior and cognition in Shank1 mouse mutants in comparison to heterozygous and wildtype littermate controls across development in both sexes. While social approach behavior was evident in all experimental conditions and social recognition was only mildly affected by genotype, Shank1^-/- null mutant mice were severely impaired in object recognition memory. This effect was particularly prominent in juveniles, not due to impairments in object discrimination, and replicated in independent mouse cohorts. At the neurobiological level, object recognition deficits were paralleled by increased brain-derived neurotrophic factor (BDNF) protein expression in the hippocampus of Shank1^-/- mice; yet BDNF levels did not differ under baseline conditions. We therefore investigated changes in the epigenetic regulation of hippocampal BDNF expression and detected an enrichment of histone H3 acetylation at the Bdnf promoter1 in Shank1^-/- mice, consistent with increased learning-associated BDNF. Together, our findings indicate that Shank1 deletions lead to an aberrant cognitive phenotype characterized by severe impairments in object recognition memory and increased hippocampal BDNF levels, possibly due to epigenetic modifications. This result supports the link between ASD and intellectual disability, and suggests epigenetic regulation as a potential therapeutic target. This article is protected by copyright. All rights reserved.

PMID: 28500650
DOI: 10.1002/hipo.22741

Vers des résultats significatifs dans l'enseignement de la conversation et des compétences de salutation avec les personnes avec un diagnostic de trouble du spectre de l'autisme

Aperçu: G.M.

Les chercheurs ont identifié des déficits de salutation et de conversation basés sur une entrevue parentale et une évaluation directe semi-structurée pour un enfant et deux adolescents avec un diagnostic de trouble du spectre de l'autisme. Les intervenants ont enseigné les compétences de salut et de conversation en utilisant la formation sur les comportements et les commentaires correctifs au sein de la session.

L'enseignement a produit une acquisition, une généralisation, une maintenance et une extension du traitement robustes pour 15 des 16 compétences ciblées pour les participants. Les rapports des participants et des parents indiquaient des niveaux élevés de validité sociale pour l'intervention et les résultats.

Les résultats valident l'évaluation et l'intervention individualisées dans le but d'améliorer les compétences de salut et la conversation pendant les interactions sans scénarios, qui sont nécessaires pour des interactions sociales plus étendues et plus complexes.

2017 May 13. doi: 10.1002/jaba.388.

Toward meaningful outcomes in teaching conversation and greeting skills with individuals with autism spectrum disorder

Hood SA¹, Luczynski KC², Mitteer DR².

Author information

1: Briar Cliff University.
2: University of Nebraska Medical Center's Munroe-Meyer Institute.

Abstract

We identified greeting and conversation deficits based on a parent interview and semistructured direct assessment for one child and two adolescents with autism spectrum disorder. We taught the greeting and conversation skills using behavioral skills training and within-session corrective feedback. A multiple baseline across conversation and greeting skills demonstrated experimental control over the effects of the teaching on acquisition and generalization to novel adults. We also conducted embedded reversals to assess maintenance of the acquired skills. Teaching produced robust acquisition, generalization, maintenance, and treatment extension for 15 of the 16 targeted skills across participants. Participant and parent reports indicated high levels of social validity for the intervention and outcomes. The results support individualized assessment and intervention for improving greeting and conversation skills during unscripted interactions, which are requisite for more extended and complex social interactions.

KEYWORDS:

autism spectrum disorder; behavioral skills training; conversation skills; generality; generalization; greeting skills; social skills; social validity; treatment extension

PMID: 28500642
DOI: 10.1002/jaba.388

Les progrès dans la compréhension de la physiopathologie des troubles du spectre de l'autisme

Aperçu: G.M.

Les troubles du spectre de l'autisme (TSA) sont des troubles du développement neurologique hétérogènes communs avec la triade typique de symptômes: troubles de l'interaction sociale, anomalies du langage et de la communication et comportement stéréotypé. Malgré une recherche approfondie, l'étiologie et la pathogenèse des TSA demeurent largement incertaines. Le manque de connaissances solides sur les mécanismes de ces troubles diminue les possibilités de traitement pathogénétique de l'autisme. Différentes théories sont proposées pour expliquer la pathophysiologie sous-jacente aux TSA. Malgré le fait qu'aucun d'entre eux n'est en mesure d'expliquer complètement les altérations du système nerveux des patients avec un diagnostic de TSA, ces hypothèses ont contribué à mettre en évidence les mécanismes les plus importants dans le développement de ce trouble complexe. Certaines théories nouvelles sont basées sur des études de neurovisualisation, d'autres sur les données provenant d'études génomiques, qui sont de plus en plus disponibles dans le monde entier. Comme la recherche dans ce domaine dépend en grande partie des modèles animaux, il y a une discussion en cours et la recherche de la reproduction la plus appropriée de la pathologie. Ici, l'étude fournit un aperçu des théories actuelles de l'origine et du développement des TSA discutées dans le contexte des modèles existants et propose des modèle murins du TSA.

2017 May 9. pii: S0166-4328(17)30431-X. doi: 10.1016/j.bbr.2017.04.038.

Advances in Understanding the Pathophysiology of Autism Spectrum Disorders

Yenkoyan K¹, Grigoryan A², Fereshetyan K³, Yepremyan D³.

Author information

1: Yerevan State Medical University, Biochemistry Department, Yerevan, Armenia. Electronic address: konstantin.yenkoyan@meduni.am
2: Yerevan State Medical University, Pathophysiology Department, Yerevan, Armenia.
3: Yerevan State Medical University, Biochemistry Department, Yerevan, Armenia.

Abstract

Autism spectrum disorders (ASD) are common heterogeneous neurodevelopmental disorders with typical triad of symptoms: impaired social interaction, language and communication abnormalities, and stereotypical behavior. Despite extensive research, the etiology and pathogenesis of ASD remain largely unclear. The lack of solid knowledge on the mechanisms of these disorders decreases the opportunities for pathogenetic treatment of autism. Various theories where proposed in order to explain the pathophysiology underlying ASD. Despite the fact that none of them is able to completely explain the impairments in the nervous system of ASD patients, these hypotheses were instrumental in highlighting the most important mechanisms in the development of this complex disorder. Some new theories are based on neurovisualization studies, others on the data from genomic studies, which become increasingly available worldwide. As the research in this field is largely dependent on the animal models, there is an ongoing discussion and search for the most appropriate one adequately reproducing the pathology. Here we provide an overview of current theories of the origin and development of ASD discussed in the context of existing and proposed rodent models of ASD.

PMID: 28499914
DOI: 10.1016/j.bbr.2017.04.038

Intervention pour la formation à la pensée positive pour les aidants naturels des personnes avec un diagnostic d'autisme: instaurer la fidélité

Aperçu: G.M.

Plus de 3,5 millions aux États-Unis sont diagnostiqués avec un trouble du spectre de l'autisme (TSA) et les soignants éprouvent un stress qui affecte négativement leur bien-être. L'intervention de la formation à la pensée positive (PTT) peut minimiser ce stress. Cependant, avant de tester l'efficacité de PTT, sa fidélité doit être établie. Cet essai d'intervention pilote a examiné la fidélité d'une intervention PTT en ligne pour les aidants naturels TSA avec une assignation aléatoire de 73 soignants à l'intervention PTT en ligne et au groupe témoin.

Les résultats fournissent des preuves de la fidélité à la mise en œuvre de l'intervention PTT et appuient l'évolution de l'efficacité PTT dans la promotion du bien-être des soignants.

2017 Jun;31(3):306-310. doi: 10.1016/j.apnu.2017.02.006. Epub 2017 Feb 16.

Positive Thinking Training Intervention for Caregivers of Persons with Autism: Establishing Fidelity

Bekhet AK¹.

Author information

1: Marquette University College of Nursing, Clark Hall 530 N. 16th Street, Milwaukee, WI 53233, United States. Electronic address: abir.bekhet@marquette.edu

Abstract

More than 3.5 million in the US are diagnosed with autism spectrum disorder (ASD) and caregivers experience stress that adversely affects their well-being. Positive thinking training (PTT) intervention can minimize that stress. However, before testing the effectiveness of PTT, its fidelity must be established. This pilot intervention trial examined fidelity of an online PTT intervention for ASD caregivers with a random assignment of 73 caregivers to either the online PTT intervention or to the control group. Quantitative data [Positive Thinking Skills Scale (PTSS)] and qualitative data (online weekly homework) were collected. The mean scores for the PTSS improved for the intervention group and decreased for the control group post intervention. Evidence for use of PTT was found in caregivers' online weekly homework. The findings provide evidence of the implementation fidelity of PTT intervention and support moving forward to test PTT effectiveness in promoting caregivers' well-being.

KEYWORDS:

Autism spectrum disorders; Caregivers; Fidelity; Online intervention; Positive thinking

PMID: 28499573
DOI: 10.1016/j.apnu.2017.02.006

Suppressions et duplications du syndrome de Williams: fenêtres génétiques pour comprendre l'anxiété, la socialité, l'autisme et la schizophrénie

Aperçu: G.M.

Les chercheurs décrivent et évaluent une hypothèse intégrative pour aider à expliquer les principales caractéristiques neurocognitives des individus atteints de délétions et de doublons de la région du syndrome de Williams.

2017 May 10;79:14-26. doi: 10.1016/j.neubiorev.2017.05.004.

Williams syndrome deletions and duplications: Genetic windows to understanding anxiety, sociality, autism, and schizophrenia

Crespi BJ¹, Procyshyn TL².

Author information

1: Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada. Electronic address: crespi@sfu.ca
2: Department of Biological Sciences, Simon Fraser University, Burnaby, British Columbia, V5A 1S6, Canada.

Abstract

We describe and evaluate an integrative hypothesis for helping to explain the major neurocognitive features of individuals with Williams syndrome region deletions and duplications. First, we demonstrate how the cognitive differences between Williams syndrome individuals, individuals with duplications of this region, and healthy individuals parallel the differences between individuals subject to effects of increased or decreased oxytocin. Second, we synthesize evidence showing that variation in expression of the gene GTF2I (General Transcription Factor II-I) underlies the primary social phenotypes of Williams syndrome and that common genetic variation in GTF2I mediates oxytocin reactivity, and its correlates, in healthy populations. Third, we describe findings relevant to the hypothesis that the GTF2I gene is subject to parent of origin effects whose behavioral expression fits with predictions from the kinship theory of genomic imprinting. Fourth, we describe how Williams syndrome can be considered, in part, as an autistic syndrome of Lorna Wing's 'active-but-odd' autism subtype, in contrast to associations of duplications with both schizophrenia and autism.

PMID: 28499504
DOI: 10.1016/j.neubiorev.2017.05.004

Les mastocytes dans la neuroinflammation et les troubles du cerveau

Aperçu: G.M.

Il est bien reconnu que la neuroinflammation est impliquée dans la pathogenèse de diverses maladies neurodégénératives. La microglie et les astrocytes sont des composants pathogènes majeurs dans ce processus et sont connus pour répondre aux médiateurs pro-inflammatoires libérés des cellules immunitaires telles que les mastocytes. Les mastocytes résident dans le cerveau et constituent une source importante de molécules inflammatoires.

Les mastocytes sont considérés comme des premiers intervenants et peuvent initier et amplifier les réponses immunitaires dans le cerveau. Leur rôle possible dans les troubles neurodégénératifs tels que la sclérose en plaques, la maladie d'Alzheimer et l'autisme a suscité un intérêt croissant.

2017 May 9. pii: S0149-7634(17)30029-5. doi: 10.1016/j.neubiorev.2017.05.001.

Mast cells in neuroinflammation and brain disorders

Hendriksen E¹, van Bergeijk D¹, Oosting RS¹, Redegeld FA².

Author information

1: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, The Netherlands.
2: Division of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, The Netherlands. Electronic address: f.a.m.redegeld@uu.nl.

Abstract

It is well recognized that neuroinflammation is involved in the pathogenesis of various neurodegenerative diseases. Microglia and astrocytes are major pathogenic components within this process and known to respond to proinflammatory mediators released from immune cells such as mast cells. Mast cells reside in the brain and are an important source of inflammatory molecules. Mast cell interactions with glial cells and neurons result in the release of mediators such as cytokines, proteases and reactive oxygen species. During neuroinflammation, excessive levels of these mediators can influence neurogenesis, neurodegeneration and blood-brain barrier (BBB) permeability. Mast cells are considered first responders and are able to initiate and magnify immune responses in the brain. Their possible role in neurodegenerative disorders such as multiple sclerosis, Alzheimer's disease and autism has gained increasing interest. We discuss the possible involvement of mast cells and their mediators in neurogenesis, neurodegeneration and BBB permeability and their role in neuronal disorders such as cerebral ischemia, traumatic brain injury, neuropathic pain, multiple sclerosis, Alzheimer's disease, migraine, autism, and depression.

PMID: 28499503
DOI: 10.1016/j.neubiorev.2017.05.001

Les protéines 1 et 3 du domaine PAS neuronal sont les régulateurs maîtres des gènes de risque neuropsychiatrique

Aperçu: G.M.

Ensemble, ces données fournissent une vision claire et impartiale de l'ensemble des gènes régulés par NPAS1 et NPAS3 et montrent que ces facteurs de transcription sont des régulateurs maîtres de la fonction neuropsychiatrique. Ces résultats exposent la pathophysiologie moléculaire des mutations NPAS1 / 3 et fournissent un exemple frappant de la nature combinatoire des voies moléculaires qui sous-tendent des états neuropsychiatriques diagnostiqués distinctement.

2017 Apr 6. pii: S0006-3223(17)31460-9. doi: 10.1016/j.biopsych.2017.03.021.

Neuronal PAS Domain Proteins 1 and 3 Are Master Regulators of Neuropsychiatric Risk Genes

Michaelson JJ¹, Shin MK², Koh JY², Brueggeman L², Zhang A², Katzman A², McDaniel L², Fang M³, Pufall M³, Pieper AA⁴.

Author information

1: Department of Psychiatry, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, Iowa; Department of Biomedical Engineering, University of Iowa College of Engineering, University of Iowa, Iowa City, Iowa; Department of Communication Sciences and Disorders, University of Iowa College of Liberal Arts and Sciences, University of Iowa, Iowa City, Iowa; Iowa Institute of Human Genetics, University of Iowa, Iowa City, Iowa; Genetics Cluster Initiative, University of Iowa, Iowa City, Iowa; The DeLTA Center, University of Iowa, Iowa City, Iowa; University of Iowa Informatics Initiative, University of Iowa, Iowa City, Iowa. Electronic address: Jacob-Michaelson@uiowa.edu.
2: Department of Psychiatry, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, Iowa.
3: Department of Biochemistry, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, Iowa.
4: Department of Psychiatry, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, Iowa; Department of Neurology, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, Iowa; Free Radical and Radiation Biology Program, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, Iowa; Department of Veterans Affairs, University of Iowa Carver College of Medicine, University of Iowa, Iowa City, Iowa; Pappajohn Biomedical Institute, University of Iowa, Iowa City, Iowa; Weill Cornell Autism Research Program, Weill Cornell Medicine, Cornell University, New York, New York.

Abstract

BACKGROUND:

NPAS3 has been established as a robust genetic risk factor in major mental illness. In mice, loss of neuronal PAS domain protein 3 (NPAS3) impairs postnatal hippocampal neurogenesis, while loss of the related protein NPAS1 promotes it. These and other findings suggest a critical role for NPAS proteins in neuropsychiatric functioning, prompting interest in the molecular pathways under their control.

METHODS:

We used RNA sequencing coupled with chromatin immunoprecipitation sequencing to identify genes directly regulated by NPAS1 and NPAS3 in the hippocampus of wild-type, Npas1^-/-, and Npas3^-/- mice. Computational integration with human genetic and expression data revealed the disease relevance of NPAS-regulated genes and pathways. Specific findings were confirmed at the protein level by Western blot.

RESULTS:

This is the first in vivo, transcriptome-scale investigation of genes regulated by NPAS1 and NPAS3. These transcription factors control an ensemble of genes that are themselves also major regulators of neuropsychiatric function. Specifically, Fmr1 (fragile X syndrome) and Ube3a (Angelman syndrome) are transcriptionally regulated by NPAS3, as is the neurogenesis regulator Notch. Dysregulation of these pathways was confirmed at the protein level. Furthermore, NPAS1/3 targets show increased human genetic burden for schizophrenia and intellectual disability.

CONCLUSIONS:

Together, these data provide a clear, unbiased view of the full spectrum of genes regulated by NPAS1 and NPAS3 and show that these transcription factors are master regulators of neuropsychiatric function. These findings expose the molecular pathophysiology of NPAS1/3 mutations and provide a striking example of the shared, combinatorial nature of molecular pathways that underlie diagnostically distinct neuropsychiatric conditions.

PMID: 28499489
DOI: 10.1016/j.biopsych.2017.03.021

Etiologie en psychiatrie: embrasser la réalité de la causalité poly-génétique-environnementale de la maladie mentale

Aperçu: G.M.

Les résultats intrigants sur la causalité génétique et environnementale suggèrent un besoin de recadrer l'étiologie des troubles mentaux.

La génétique moléculaire montre que des milliers de variantes génétiques communes et rares contribuent à la maladie mentale. Des études épidémiologiques ont identifié des dizaines d'expositions environnementales associées à la psychopathologie.

Les analyses intégratives de la co-causalité, y compris l'interaction génique-environnement et les interactions environnement-environnement, permettent de découvrir des types et mécanismes de causalité susceptibles de générer de nouveaux outils préventifs et thérapeutiques.

Cliquez ICI pour télécharger l'intégralité de l'article en anglais

2017 Jun;16(2):121-129. doi: 10.1002/wps.20436.

Etiology in psychiatry: embracing the reality of poly-gene-environmental causation of mental illness

Uher R¹, Zwicker A¹.

Author information

1: Departments of Psychiatry and Pathology, Dalhousie University, Halifax, B3H 2E2, Nova Scotia, Canada.

Abstract

Intriguing findings on genetic and environmental causation suggest a need to reframe the etiology of mental disorders. Molecular genetics shows that thousands of common and rare genetic variants contribute to mental illness. Epidemiological studies have identified dozens of environmental exposures that are associated with psychopathology. The effect of environment is likely conditional on genetic factors, resulting in gene-environment interactions. The impact of environmental factors also depends on previous exposures, resulting in environment-environment interactions. Most known genetic and environmental factors are shared across multiple mental disorders. Schizophrenia, bipolar disorder and major depressive disorder, in particular, are closely causally linked. Synthesis of findings from twin studies, molecular genetics and epidemiological research suggests that joint consideration of multiple genetic and environmental factors has much greater explanatory power than separate studies of genetic or environmental causation. Multi-factorial gene-environment interactions are likely to be a generic mechanism involved in the majority of cases of mental illness, which is only partially tapped by existing gene-environment studies. Future research may cut across psychiatric disorders and address poly-causation by considering multiple genetic and environmental measures across the life course with a specific focus on the first two decades of life. Integrative analyses of poly-causation including gene-environment and environment-environment interactions can realize the potential for discovering causal types and mechanisms that are likely to generate new preventive and therapeutic tools.

PMID:28498595
PMCID:PMC5428165 [Available on 2017-06-01]
DOI:10.1002/wps.20436

L'influence des pragmatiques maternelles sur les compétences linguistiques des enfants avec un diagnostic d'autisme

Aperçu: G.M.

Cette étude a examiné la relation entre le langage pragmatique des mères et de l'enfant dans les troubles du spectre de l'autisme (TSA) et le retard de langage (LD) dans les dyades mère-enfant sans TSA.Les participants se composaient de 20 dyades de mères et de leurs enfants de 24 à 48 mois, avec TSA (n = 10) ou LD sans TSA (n = 10).

Ces résultats indiquent que les pragmatiques parentaux contribuent probablement à l'apprentissage précoce des langues et que les effets de la pragmatique maternelle sur la langue précoce dans la TSA peuvent être indirects (par exemple, par l'utilisation par les parents de stratégies de facilitation).

Les interventions linguistiques menées par les parents pour la TSA devraient donc considérer les pragmatiques parentaux, en particulier étant donné que des différences pragmatiques ont été identifiées dans des membres de la famille non affectés de personnes avec un diagnostic de TSA

2017 May 15. doi: 10.1097/DBP.0000000000000445.

The Influence of Maternal Pragmatics on the Language Skills of Children with Autism

Stern YS¹, Maltman N, Roberts MY.

Author information

1: Roxelyn and Richard Pepper Department of Communication Sciences and Disorders, Northwestern University, Evanston, IL.

Abstract

OBJECTIVE:

This study examined the relationship between mothers' pragmatics and child language in autism spectrum disorder (ASD) and non-ASD language delay (LD) mother-child dyads.

METHODS:

Participants consisted of 20 dyads of mothers and their toddlers aged 24 to 48 months, with ASD (n = 10) or non-ASD LD (n = 10). Groups were matched on child chronological age, language, and cognition. Maternal pragmatic language was qualified based on the degree of pragmatic violations during a semistructured interview, and was examined in relation to both child language, as measured by the Preschool Language Scale-4 and maternal use of language facilitation strategies during play.

RESULTS:

Lower rates of maternal pragmatic violations were associated with higher expressive language scores in children with ASD, and with higher receptive language scores for children with non-ASD LD. Within ASD dyads, maternal pragmatic violations were negatively related to mothers' use of linguistic expansions.

CONCLUSION:

These findings indicate that parental pragmatics likely contribute to early language learning, and that the effects of maternal pragmatics on early language in ASD may be indirect (e.g., through parents' use of facilitative strategies). Parent-mediated language interventions for ASD should therefore consider parent pragmatics, especially given that pragmatic differences have been identified in unaffected family members of individuals with ASD.

PMID: 28514238
DOI: 10.1097/DBP.0000000000000445

19 mai 2017

La télémédecine aide les parents d'enfants atteints de troubles du développement neurologique vivant dans des régions éloignées et défavorisées

Traduction: G.M.

2017 May 12:1-3. doi: 10.1080/20469047.2017.1315914.

Telemedicine is helping the parents of children with neurodevelopmental disorders living in remote and deprived areas

Stuckey R¹, Domingues-Montanari S^1,².

Author information

1: a Longdom Publishing , Barcelona , Spain.
2: b Qustodio Technologies , Barcelona , Spain.

Abstract

Les technologies de télécommunication progressent rapidement avec d'énormes investissements pour améliorer l'infrastructure dans les zones rurales. La télémédecine apporte les avantages des télécommunications aux soins de santé, en particulier dans les communautés à ressources limitées et éloignées. La littérature récente sur la télémédecine en pédiatrie sera examinée, en mettant particulièrement l'accent sur son application pour aider les enfants avec des troubles du développement neurologique et leurs familles vivant dans des régions éloignées et / ou des pays à faible revenu et les lacunes identifiées pour les recherches futures. Des études montrent que la télémédecine peut permettre l'accès d'une famille à une aide qualifiée qui, physiquement, ne peut être disponible qu'à des centaines de kilomètres, ce qui contribue à surmonter les obstacles géographiques. La télémédecine peut également former les parents et les doter des connaissances et des compétences nécessaires pour mieux s'occuper de leurs enfants. Malgré certains obstacles technologiques à la mise en œuvre, la télémédecine peut aider à transformer toutes les étapes du traitement de l'autisme. Cependant, d'autres études sont nécessaires dans les pays à revenu faible et intermédiaire pour élucider pleinement les avantages offerts par la télémédecine aux enfants autistes et à leurs familles.

Telecommunication technologies are advancing rapidly with huge investment to improve infrastructure in rural areas. Telemedicine brings the benefits of telecommunication to healthcare, especially in resource-limited and remote communities. The recent literature on telemedicine in paediatrics will be reviewed, with particular focus on its application to help children with neurodevelopmental disorders and their families living in remote regions and/or low-income countries, and gaps identified for future research. Studies show that telemedicine can enable a family's access to appropriately qualified help that physically may only be available hundreds of miles away, helping to overcome geographic barriers. Telemedicine can also train parents and equip them with the knowledge and skills to better care for their children. Despite some technological barriers to implementation, telemedicine can help transform all stages of autism treatment. However, more studies are required in low- and middle-income countries to fully elucidate the benefits offered by telemedicine to autistic children and their families.

PMID: 28498062
DOI: 10.1080/20469047.2017.1315914

Inventaire du comportement de l'autisme: un nouvel outil pour évaluer le noyau et les symptômes associés au trouble du spectre de l'autisme

Aperçu: G.M.

L'Inventaire du comportement autistique (ABI) est une nouvelle mesure pour évaluer les changements dans le noyau et les symptômes associés du trouble du spectre de l'autisme (TSA) chez les participants (âges: 3 ans-âge adulte) diagnostiqués avec TSA. Il s'agit d'un outil basé sur le Web avec cinq domaines (deux domaines principaux TSA: communication sociale, comportements restrictifs et répétitifs, trois domaines associés: santé mentale, autorégulation et comportement difficile). Cette étude décrit la conception, le développement et les propriétés psychométriques initiales de l'ABI.

Dans l'ensemble, ABI se révèle prometteur en tant qu'outil de mesure des changements dans les symptômes essentiels de l'autisme dans les études cliniques sur le TSA, avec une validation supplémentaire requise.

2017 May 12. doi: 10.1089/cap.2017.0018. ]

Autism Behavior Inventory: A Novel Tool for Assessing Core and Associated Symptoms of Autism Spectrum Disorder

Bangerter A¹, Ness S¹, Aman MG², Esbensen AJ³, Goodwin MS⁴, Dawson G⁵, Hendren R⁶, Leventhal B⁷, Khan A⁸, Opler M⁹, Harris A⁵, Pandina G¹.

Author information

1: 1 Janssen Research & Development, LLC , Titusville, New Jersey.
2: 2 The Nisonger Center University Center for Excellence in Developmental Disabilities (UCEDD), Ohio State University , Columbus, Ohio.
3: 3 Division of Developmental and Behavioral Pediatrics, Cincinnati Children's Hospital Medical Center , Cincinnati, Ohio.
4: 4 312E Robinson Hall, Department of Health Sciences, Bouvé College of Health Sciences, Northeastern University , Boston, Massachusetts.
5: 5 Duke Center for Autism and Brain Development, Duke University , Durham, North Carolina.
6: 6 Department of Psychiatry, University of California , San Francisco, California.
7: 7 UCSF Benioff Children's Hospital , San Francisco, California.
8: 8 Nathan Kline Institute , Orangeburg, New York.
9: 9 ProPhase, LLC, NYU School of Medicine, Columbia University Medical Center , New York, New York.

Abstract

OBJECTIVE:

Autism Behavior Inventory (ABI) is a new measure for assessing changes in core and associated symptoms of autism spectrum disorder (ASD) in participants (ages: 3 years-adulthood) diagnosed with ASD. It is a web-based tool with five domains (two ASD core domains: social communication, restrictive and repetitive behaviors; three associated domains: mental health, self-regulation, and challenging behavior). This study describes design, development, and initial psychometric properties of the ABI.

METHODS:

ABI items were generated following review of existing measures and inputs from expert clinicians. Initial ABI scale contained 161 items that were reduced to fit a factor analytic model, retaining items of adequate reliability. Two versions of the scale, ABI-full (ABI-F; 93 items) and ABI-short version (ABI-S; 36 items), were developed and evaluated for psychometric properties, including validity comparisons with commonly used measures. Both scales were administered to parents and healthcare professionals (HCPs) involved with study participants.

RESULTS:

Test-retest reliability (intraclass correlation coefficient [ICC] = 0.79) for parent ratings on ABI was robust and compared favorably to existing scales. Test-retest correlations for HCP ratings were generally lower versus parent ratings. ABI core domains and comparison measures strongly correlated (r ≥ 0.70), demonstrating good concurrent validity.

CONCLUSIONS:

Overall, ABI demonstrates promise as a tool for measuring change in core symptoms of autism in ASD clinical studies, with further validation required.

PMID: 28498053
DOI: 10.1089/cap.2017.0018

Du gène au comportement: les mécanismes du canal calcium du type L sous jacent aux symptômes neuropsychiatriques

Aperçu: G.M.

Les canaux de calcium de type L (CTRL) Cav1.2 et Cav1.3, codés par les gènes CACNA1C et CACNA1D, respectivement, sont des régulateurs importants de l'afflux de calcium dans les cellules et sont essentiels au développement normal du cerveau et à la plasticité. Chez les humains, CACNA1C est apparu comme l'un des gènes de risque candidats les plus avancés et les plus avancés pour une gamme de troubles neuropsychiatriques, y compris le trouble bipolaire (BD), la schizophrénie (SCZ), le trouble dépressif majeur, le trouble du spectre de l'autisme et le trouble déficitaire de l'attention et hyperactivité .

2017 May 11. doi: 10.1007/s13311-017-0532-0.

From Gene to Behavior: L-Type Calcium Channel Mechanisms Underlying Neuropsychiatric Symptoms

Kabir ZD^1,², Martínez-Rivera A^1,², Rajadhyaksha AM^3,^4,⁵.

Author information

1: Pediatric Neurology, Pediatrics, Weill Cornell Medicine, New York, NY, USA.
2: Weill Cornell Autism Research Program, Weill Cornell Medicine, New York, NY, USA.
3: Pediatric Neurology, Pediatrics, Weill Cornell Medicine, New York, NY, USA. amr2011@med.cornell.edu
4: Weill Cornell Autism Research Program, Weill Cornell Medicine, New York, NY, USA. amr2011@med.cornell.edu.
5: Feil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA. amr2011@med.cornell.edu.

Abstract

The L-type calcium channels (LTCCs) Ca_v1.2 and Ca_v1.3, encoded by the CACNA1C and CACNA1D genes, respectively, are important regulators of calcium influx into cells and are critical for normal brain development and plasticity. In humans, CACNA1C has emerged as one of the most widely reproduced and prominent candidate risk genes for a range of neuropsychiatric disorders, including bipolar disorder (BD), schizophrenia (SCZ), major depressive disorder, autism spectrum disorder, and attention deficit hyperactivity disorder. Separately, CACNA1D has been found to be associated with BD and autism spectrum disorder, as well as cocaine dependence, a comorbid feature associated with psychiatric disorders. Despite growing evidence of a significant link between CACNA1C and CACNA1D and psychiatric disorders, our understanding of the biological mechanisms by which these LTCCs mediate neuropsychiatric-associated endophenotypes, many of which are shared across the different disorders, remains rudimentary. Clinical studies with LTCC blockers testing their efficacy to alleviate symptoms associated with BD, SCZ, and drug dependence have provided mixed results, underscoring the importance of further exploring the neurobiological consequences of dysregulated Ca_v1.2 and Ca_v1.3. Here, we provide a review of clinical studies that have evaluated LTCC blockers for BD, SCZ, and drug dependence-associated symptoms, as well as rodent studies that have identified Ca_v1.2- and Ca_v1.3-specific molecular and cellular cascades that underlie mood (anxiety, depression), social behavior, cognition, and addiction.

PMID: 28497380
DOI: 10.1007/s13311-017-0532-0