Autisme Information Science

30 mars 2017

La variabilité accrue de la force est associée à une modification de la modulation de l'activité de l'activité d'ensemble de motoneurones dans le trouble du spectre de l'autisme

Aperçu: G.M.

Les déficits de contrôle de la force ont été documentés à plusieurs reprises dans le trouble du spectre de l'autisme (TSA). Ils sont associés à une plus grande détérioration des habiletés sociales et de la vie quotidienne chez les personnes, ce qui suggère que développer une compréhension plus mécanique des processus centraux et périphériques qui les causent peut aider à guider le développement de traitements qui améliorent les résultats multiples dans le TSA.

Les personnes avec un diagnostic de TSA présentaient une plus grande variabilité de force que les témoins lorsqu'ils essayaient de maintenir une force constante. Ces résultats suggèrent que des altérations des mécanismes centraux qui contrôlent le déclenchement d'ensembles de motoneurones peuvent sous-tendre les symptômes communs et souvent invalidants des TSA.

Cliquer ICI pour accéder à l'intégralité de l'article en anglais

2017 Mar 25;18(4). pii: E698. doi: 10.3390/ijms18040698.

Increased Force Variability Is Associated with Altered Modulation of the Motorneuron Pool Activity in Autism Spectrum Disorder (ASD)

Wang Z^1,^2,³, Kwon M^4,^5,⁶, Mohanty S⁷, Schmitt LM^8,^9,¹⁰, White SP¹¹, Christou EA¹², Mosconi MW^13,^14,¹⁵.

Author information

1: Schiefelbusch Institute for Life Span Studies, University of Kansas, 1000 Sunnyside Ave., Lawrence, KS 66045, USA. zhengwang@ku.edu
2: Clinical Child Psychology Program, University of Kansas, 1000 Sunnyside Ave., Lawrence, KS 66045, USA. zhengwang@ku.edu.
3: Kansas Center for Autism Research and Training (K-CART), University of Kansas Medical School, Overland Park, KS 66213, USA. zhengwang@ku.edu.
4: Schiefelbusch Institute for Life Span Studies, University of Kansas, 1000 Sunnyside Ave., Lawrence, KS 66045, USA. minhyuk.kwon@marquette.edu.
5: Clinical Child Psychology Program, University of Kansas, 1000 Sunnyside Ave., Lawrence, KS 66045, USA. minhyuk.kwon@marquette.edu.
6: Kansas Center for Autism Research and Training (K-CART), University of Kansas Medical School, Overland Park, KS 66213, USA. minhyuk.kwon@marquette.edu.
7: Center for Autism and Developmental Disabilities, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. smohanty3@humana.com.
8: Schiefelbusch Institute for Life Span Studies, University of Kansas, 1000 Sunnyside Ave., Lawrence, KS 66045, USA. lmschmitt@ku.edu.
9: Clinical Child Psychology Program, University of Kansas, 1000 Sunnyside Ave., Lawrence, KS 66045, USA. lmschmitt@ku.edu.
10: Kansas Center for Autism Research and Training (K-CART), University of Kansas Medical School, Overland Park, KS 66213, USA. lmschmitt@ku.edu.
11: Center for Autism and Developmental Disabilities, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA. Stormi.White@UTsouthwestern.edu.
12: Department of Applied Physiology and Kinesiology, University of Florida, Gainesville, FL 32611, USA. eachristou@hhp.ufl.edu.
13: Schiefelbusch Institute for Life Span Studies, University of Kansas, 1000 Sunnyside Ave., Lawrence, KS 66045, USA. mosconi@ku.edu.
14: Clinical Child Psychology Program, University of Kansas, 1000 Sunnyside Ave., Lawrence, KS 66045, USA. mosconi@ku.edu.
15: Kansas Center for Autism Research and Training (K-CART), University of Kansas Medical School, Overland Park, KS 66213, USA. mosconi@ku.edu.

Abstract

Force control deficits have been repeatedly documented in autism spectrum disorder (ASD). They are associated with worse social and daily living skill impairments in patients suggesting that developing a more mechanistic understanding of the central and peripheral processes that cause them may help guide the development of treatments that improve multiple outcomes in ASD. The neuromuscular mechanisms underlying force control deficits are not yet understood. Seventeen individuals with ASD and 14 matched healthy controls completed an isometric index finger abduction test at 60% of their maximum voluntary contraction (MVC) during recording of the first dorsal interosseous (FDI) muscle to determine the neuromuscular processes associated with sustained force variability. Central modulation of the motorneuron pool activation of the FDI muscle was evaluated at delta (0-4 Hz), alpha (4-10 Hz), beta (10-35 Hz) and gamma (35-60 Hz) frequency bands. ASD patients showed greater force variability than controls when attempting to maintain a constant force. Relative to controls, patients also showed increased central modulation of the motorneuron pool at beta and gamma bands. For controls, reduced force variability was associated with reduced delta frequency modulation of the motorneuron pool activity of the FDI muscle and increased modulation at beta and gamma bands. In contrast, delta, beta, and gamma frequency oscillations were not associated with force variability in ASD. These findings suggest that alterations of central mechanisms that control motorneuron pool firing may underlie the common and often impairing symptoms of ASD.

PMID: 28346344
DOI: 10.3390/ijms18040698

Stimulation magnétique transcrânienne répétitive pour le traitement des déficits des fonctions exécutives dans le trouble du spectre de l'autisme: approche par essai clinique

Aperçu: G.M.

Les déficits de la fonction exécutive (EF) chez les personnes avec un diagnostic de trouble du spectre de l'autisme (TSA) sont omniprésents et peu étudiés. En outre, il n'existe pas de traitements efficaces basés sur la neuroscience pour traiter cette caractéristique invalidante des TSA.
La stimulation magnétique transcrânienne répétitive (SMTr) a démontré la promesse de s'attaquer aux déficits de l'EF dans les troubles neuropsychiatriques chez l'adulte. L'article décrit la conception d'un essai randomisé et contrôlé, actuellement en cours, de rTMS bilatéral de 20MHz, , appliquée au cortex préfrontal dorsolatéral (DLPFC) pour le traitement des déficits de l'EF dans les TSA .

2017 Mar 27. doi: 10.1089/cap.2016.0146.

Repetitive Transcranial Magnetic Stimulation for the Treatment of Executive Function Deficits in Autism Spectrum Disorder: Clinical Trial Approach

Ameis SH^1,^2,³, Daskalakis ZJ^3,⁴, Blumberger DM^3,⁴, Desarkar P^3,⁴, Drmic I⁵, Mabbott DJ^6,⁷, Lai MC^1,^2,³, Croarkin PE⁸, Szatmari P^1,^2,³.

Author information

1: 1 Centre for Brain and Mental Health, The Hospital for Sick Children , Toronto, Canada .
2: 2 The Margaret and Wallace McCain Centre for Child, Youth and Family Mental Health, Campbell Family Mental Health Research Institute, The Centre for Addiction and Mental Health, University of Toronto , Toronto, Canada .
3: 3 Department of Psychiatry, Faculty of Medicine, University of Toronto , Toronto, Canada .
4: 4 Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute , Centre for Addiction and Mental Health, Toronto, Ontario, Canada .
5: 5 Genetics and Genome Biology and Autism Research Unit, The Centre for Applied Genomics, The Hospital for Sick Children , Toronto, Canada .
6: 6 Program in Neurosciences and Mental Health, Research Institute , The Hospital for Sick Children, Toronto, Canada .
7: 7 Department of Psychology, Faculty of Graduate Studies, University of Toronto , Toronto, Canada .
8: 8 Division of Child and Adolescent Psychiatry, Department of Psychiatry and Psychology, Mayo Clinic , Rochester, Minnesota.

Abstract

OBJECTIVE:

Executive function (EF) deficits in patients with autism spectrum disorder (ASD) are ubiquitous and understudied. Further, there are no effective, neuroscience-based treatments to address this impairing feature of ASD. Repetitive transcranial magnetic stimulation (rTMS) has demonstrated promise in addressing EF deficits in adult neuropsychiatric disorders. This article will outline the design of a novel randomized-controlled trial of bilateral, 20 Hz, rTMS applied to the dorsolateral prefrontal cortex (DLPFC) for treatment of EF deficits in ASD that is currently ongoing. We describe prior therapeutic rTMS research for ASD and prior rTMS trials targeting EFs in adult neuropsychiatric disorders. A neurophysiological rationale for rTMS treatment of EF deficits in ASD is presented.

METHODS:

An ongoing protocol will enroll participants aged 16-35 with ASD and no intellectual disability. Psychotropic medications will be continued during the 4-week trial of active 20 Hz versus sham rTMS applied to the DLPFC. Twenty, active treatment sessions consisting of 25 stimulation trains at a 90% motor threshold will be administered. The primary outcome measure is the Cambridge Neuropsychological Test Automated Battery (CANTAB) spatial working memory task. At present, recruitment, enrollment, and treatment within the described clinical trial are ongoing.

CONCLUSIONS:

EF deficits are common and impairing symptoms of ASD. There are no evidence-based treatments for EF deficits in ASD. The protocol described here will provide important preliminary data on the feasibility and efficacy of 20 Hz rTMS to DLPFC for EF deficits in ASD.

PMID: 28346865
DOI: 10.1089/cap.2016.0146

Stimulation magnétique transcrânienne répétitive pour le traitement des déficits des fonctions exécutives dans le trouble du spectre de l'autisme: approche par essai clinique

Aperçu: G.M.

2017 Mar 27. doi: 10.1089/cap.2016.0146.

Repetitive Transcranial Magnetic Stimulation for the Treatment of Executive Function Deficits in Autism Spectrum Disorder: Clinical Trial Approach

Ameis SH^1,^2,³, Daskalakis ZJ^3,⁴, Blumberger DM^3,⁴, Desarkar P^3,⁴, Drmic I⁵, Mabbott DJ^6,⁷, Lai MC^1,^2,³, Croarkin PE⁸, Szatmari P^1,^2,³.

Author information

1: 1 Centre for Brain and Mental Health, The Hospital for Sick Children , Toronto, Canada .
2: 2 The Margaret and Wallace McCain Centre for Child, Youth and Family Mental Health, Campbell Family Mental Health Research Institute, The Centre for Addiction and Mental Health, University of Toronto , Toronto, Canada .
3: 3 Department of Psychiatry, Faculty of Medicine, University of Toronto , Toronto, Canada .
4: 4 Temerty Centre for Therapeutic Brain Intervention, Campbell Family Mental Health Research Institute , Centre for Addiction and Mental Health, Toronto, Ontario, Canada .
5: 5 Genetics and Genome Biology and Autism Research Unit, The Centre for Applied Genomics, The Hospital for Sick Children , Toronto, Canada .
6: 6 Program in Neurosciences and Mental Health, Research Institute , The Hospital for Sick Children, Toronto, Canada .
7: 7 Department of Psychology, Faculty of Graduate Studies, University of Toronto , Toronto, Canada .
8: 8 Division of Child and Adolescent Psychiatry, Department of Psychiatry and Psychology, Mayo Clinic , Rochester, Minnesota.

Abstract

OBJECTIVE:

METHODS:

CONCLUSIONS:

PMID: 28346865
DOI: 10.1089/cap.2016.0146

Axe Cerveau-intestin et comportement

Aperçu: G.M.

Au cours des 5 dernières années, l'intérêt pour les interactions entre le microbiome intestinal, le cerveau et le comportement a explosé. Des preuves cliniques prouvent le rôle du microbiome intestinal dans les réponses comportementales associées à la douleur, aux émotions, aux interactions sociales et à l'apport alimentaire.Alors que les études réalisées chez des patients souffrant de dépression et de modèles de rongeurs générés par le transfert microbien fécal de ces patients suggèrent une causalité, il n'existe pas d'évidence d'une influence des altérations microbiennes aiguës sur les paramètres comportementaux et cliniques humains. Il y a peu de temps encore, une thérapie de transfert microbien ouverte chez des enfants avec un diagnostic de TSA a validé provisoirement le microbiote intestinal comme cible thérapeutique.

2017;88:45-53. doi: 10.1159/000461732. Epub 2017 Mar 27.

Gut-Brain Axis and Behavior

Martin CR, Mayer EA.

Abstract

In the last 5 years, interest in the interactions among the gut microbiome, brain, and behavior has exploded. Preclinical evidence supports a role of the gut microbiome in behavioral responses associated with pain, emotion, social interactions, and food intake. Limited, but growing, clinical evidence comes primarily from associations of gut microbial composition and function to behavioral and clinical features and brain structure and function. Converging evidence suggests that the brain and the gut microbiota are in bidirectional communication. Observed dysbiotic states in depression, chronic stress, and autism may reflect altered brain signaling to the gut, while altered gut microbial signaling to the brain may play a role in reinforcing brain alterations. On the other hand, primary dysbiotic states due to Western diets may signal to the brain, altering ingestive behavior. While studies performed in patients with depression and rodent models generated by fecal microbial transfer from such patients suggest causation, evidence for an influence of acute gut microbial alterations on human behavioral and clinical parameters is lacking. Only recently has an open-label microbial transfer therapy in children with autism tentatively validated the gut microbiota as a therapeutic target. The translational potential of preclinical findings remains unclear without further clinical investigation.

© 2017 Nestec Ltd., Vevey/S. Karger AG, Basel.

PMID: 28346923
DOI: 10.1159/000461732

Atténuation de la fonction sociale chez les jeunes femmes ayant une Anorexie nerveuse récente et des personnes rétablies

Aperçu: G.M.

Un sous-groupe de personnes souffrant d'anorexie mentale (AN) présente des difficultés sociales; Cependant, il n'est pas clair si les personnes avec un une comorbidite de TSA expliquent ces difficultés.

L'étude a porté sur 43 jeunes femmes ayant eu un premier épisode anorexique sans TSA, 23 personnes ayant récupéré à l'adolescente d'une anorexie et 41 sans troubles.

Les participants ayant un premier épisode AN et ceux ayant récupéré d'une AN ont présenté des difficultés dans la fonction sociale, qui n'étaient pas associées à l'indice de masse corporelle ou à d'autres facteurs liés à un trouble chez les patients ayant un premier épisode AN. Les troubles de l'humeur et l'anxiété n'étaient pas associés à ces difficultés.

Finalement, seuls les participants se sont remis de l'AN ont démontré des déficits dans des domaines spécifiques de la cognition sociale: perception de gestes corporels non verbaux et prosodie vocale.

2017 Jan;60(1):23-32. doi: 10.1016/j.jadohealth.2016.08.011. Epub 2016 Oct 27.

Impairment of Social Function in Young Females With Recent-Onset Anorexia Nervosa and Recovered Individuals

Bentz M¹, Jepsen JR², Pedersen T³, Bulik CM⁴, Pedersen L⁵, Pagsberg AK⁶, Plessen KJ⁶.

Author information

1: Child and Adolescent Mental Health Centre, Mental Health Services in the Capital Region of Denmark, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: mette.bentz@regionh.dk
2: Child and Adolescent Mental Health Centre, Mental Health Services in the Capital Region of Denmark, Copenhagen, Denmark; Lundbeck Foundation Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), Psychiatric Center, Glostrup, Denmark; Center for Neuropsychiatric Schizophrenia Research (CNSR), Psychiatric Center, Glostrup, Denmark.
3: Child and Adolescent Mental Health Centre, Mental Health Services in the Capital Region of Denmark, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Danish Research Centre for Magnetic Resonance, Centre for Functional and Diagnostic Imaging and Research, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
4: Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
5: Center for Autisme, Herlev, Denmark.
6: Child and Adolescent Mental Health Centre, Mental Health Services in the Capital Region of Denmark, Copenhagen, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Abstract

PURPOSE:

A subgroup of individuals with anorexia nervosa (AN) displays social difficulties; however, it is not clear if individuals with comorbid autism spectrum disorders account for these difficulties.

METHODS:

We compared social function using the Autism Diagnostic Observation Schedule in 43 young females with first-episode AN who did not have comorbid autism spectrum disorder, 28 individuals recovered from adolescent-onset AN, and 41 healthy comparison individuals (age range 14-22 years). We measured adaptive behavior with the Vineland-II parent questionnaire, and aspects of social cognition with psychological tests, such as the Reading-the-Mind-in-the-Eyes test, Profile of Nonverbal Sensitivity short version, The Awareness of Social Inference Test, Animated Triangles, and the CANTAB Affective Go/No-go task.

RESULTS:

Participants with first-episode AN and those recovered from AN displayed difficulties in social function, which were not associated with body mass index or other state factors of the disorder in those with first-episode AN. Mood problems and anxiety were not associated with these difficulties. Parents rated participants with first-episode AN lower than recovered and control participants on the Socialization Domain of Vineland-II. Finally, only participants recovered from AN demonstrated deficits in specific domains of social cognition: perceiving nonverbal bodily gesture and vocal prosody.

CONCLUSIONS:

Young females with first-episode AN and those recovered from AN displayed impairments in social function, which may represent more stable traits of the disorder. Only participants recovered from AN demonstrated deficits in social cognition.

29 mars 2017

Auto-immunité, autoanticorps et trouble du spectre de l'autisme

Aperçu: G.M.

De façon alarmante, dans la majorité des cas, les causes des TSA sont largement inconnues.
Bien que les recherches aient porté sur l'identification des anomalies génétiques, les études émergentes suggèrent de plus en plus que le dysfonctionnement immunitaire est un facteur de risque viable contribuant aux déficits neurodéveloppementaux observés dans le TSA.

2017 Mar 1;81(5):383-390. doi: 10.1016/j.biopsych.2016.08.031. Epub 2016 Sep 1.

Autoimmunity, Autoantibodies, and Autism Spectrum Disorder

Edmiston E¹, Ashwood P², Van de Water J³.

Author information

1: Division of Rheumatology/Allergy and Clinical Immunology, University of California, Davis, Davis, California; The M.I.N.D. Institute, University of California, Davis, Davis, California.
2: The M.I.N.D. Institute, University of California, Davis, Davis, California; NIEHS Center for Children's Environmental Health, University of California, Davis, Davis, California; Department of Medical Microbiology and Immunology, University of California, Davis, Davis, California.
3: Division of Rheumatology/Allergy and Clinical Immunology, University of California, Davis, Davis, California; The M.I.N.D. Institute, University of California, Davis, Davis, California; NIEHS Center for Children's Environmental Health, University of California, Davis, Davis, California. Electronic address: javandewater@ucdavis.edu

Abstract

Auism spectrum disorder (ASD) now affects one in 68 births in the United States and is the fastest growing neurodevelopmental disability worldwide. Alarmingly, for the majority of cases, the causes of ASD are largely unknown, but it is becoming increasingly accepted that ASD is no longer defined simply as a behavioral disorder, but rather as a highly complex and heterogeneous biological disorder. Although research has focused on the identification of genetic abnormalities, emerging studies increasingly suggest that immune dysfunction is a viable risk factor contributing to the neurodevelopmental deficits observed in ASD. This review summarizes the investigations implicating autoimmunity and autoantibodies in ASD.

PMID: 28340985
DOI: 10.1016/j.biopsych.2016.08.031

A travers l'optique kinesthésique: Observation de l'inadéquation sociale dans les troubles du spectre de l'autisme

Aperçu: G.M.
La thérapie de mouvement de danse (DMT) est une intervention psychothérapeutique qui est utilisée avec les participants avec ASD dans divers environnements. une étude systématique du développement des comportements de syntonie sociale des participants avec un diagnostic de TSA tout au long d'une intervention DMT n'était pas encore disponible.
Une perspective axée sur le mouvement peut être utile pour inventorier les changements dans les comportements d'harmonisation sociale chez les participants.
Cliquer ici pour accéder à l'intégralité de l'article en anglais

2017 Mar 18;7(1). pii: E14. doi: 10.3390/bs7010014.

Through the Kinesthetic Lens: Observation of Social Attunement in Autism Spectrum Disorders

Samaritter R^1,², Payne H³.

Author information

1: Codarts University of the Arts, MA Arts Therapies, Kruisplein 26, 3012 CC Rotterdam, The Netherlands. rasamaritter@codarts.nl
: KenVaK Research Centre for the Arts Therapies, PO Box 550, 6400 AN Heerlen, The Netherlands. rasamaritter@codarts.nl
3: School of Education, University of Hertfordshire, Hatfield AL10 9EU, UK. h.l.payne@herts.ac.uk

Abstract

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.

PMID: 28335467
DOI: 10.3390/bs7010014

28 mars 2017

Antagonistes de la dopamine pour la résistance au traitement dans les troubles du spectre de l'autisme: examiner et se concentrer sur les stimulateurs du BDNF, la loxapine et l'amitriptyline

Aperçu: G.M.

Le développement de médicaments est urgent pour les personnes avec un diagnostic de trouble du spectre de l'autisme (TSA) et des comorbidités psychiatriques, qui se présentent souvent comme l'agression et l'automutilation.

L'ancien antipsychotique loxapine est discuté en termes de preuves préliminaires, bien que limitées pour l'efficacité et la sécurité, ainsi que les possibles effets neurotrophiques dans le cerveau.

Les antipsychotiques classiques sont encore souvent utilisés dans la poly pharmacologie antipsychotique cependant les personnes avec TSA sont plus sensibles aux effets secondaires neuromoteurs qui peuvent tard compromettre la mobilité aussi bien que provoquer une dyskinésie tardive et un syndrome malin neuroleptique.

Les nouveaux antipsychotiques risperidone et aripiprazole sont approuvés par la FDA pour l'irritabilité chez les enfants plus de 5 ans. Cependant, les personnes avec un diagnostic de TSA sont plus sujettes au gain de poids, au diabète de type II et aux effets secondaires associés.

La pratique courante de prescrire des ISRS qui inhibent le métabolisme de nombreux médicaments psychoactifs avec des antipsychotiques aggrave les effets secondaires.

Une faible dose de loxapine possède des propriétés des antipsychotiques classiques et nouveaux mais elle semble surtout plus neutre en poids, et avec une utilisation prometteuse chez les adolescents et les adultes avec TSA.

L'amitriptyline semble efficace dans les TSA pour l'irritabilité, l'agressivité impulsive, les problèmes gastro-intestinaux et l'insomnie, chez les enfants, les adolescents et les adultes.

2017 Mar 24. doi: 10.1080/14656566.2017.1308483.

Dopamine antagonists for treatment resistance in autism spectrum disorders: review and focus on BDNF stimulators loxapine and amitriptyline

Hellings JA¹, Arnold LE², Han J³.

Author information

1: a University of Missouri-Kansas City , Kansas City Regional Center of Missouri Department of Mental Health , Kansas City Missouri , USA.
2: b The Ohio State University Nisonger Center , Columbus , Ohio , USA.
3: c University of Tennessee , 454R Le Bonheur Children's Foundation Research Center , Memphis , Tennessee , USA.

Abstract

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.

PMID: 28335658

DOI: 10.1080/14656566.2017.1308483

Anomalies de l'épaisseur corticale dans les troubles du spectre autistique au cours de l'enfance, l'adolescence et l'âge adulte: une étude IRM à grande échelle

Aperçu: G.M.

Les études de neuroimagerie dans les troubles du spectre de l'autisme (TSA) ont fourni des preuves incohérentes d'anomalies corticales. Cela s'explique probablement par la faible taille des échantillons utilisés dans la plupart des études et par les différences importantes dans les caractéristiques de l'échantillon, notamment l'âge, ainsi que l'hétérogénéité du trouble.

Les résultats montrent une augmentation de l'épaisseur corticale dans le TSA, principalement latéralisé à gauche, à partir de 6 ans, avec des différences diminuant au cours de l'âge adulte. La gravité des symptômes liés à l'affect social et la communication est corrélée avec ces anomalies corticales.

2017 Feb 18:1-11. doi: 10.1093/cercor/bhx038.

Cortical Thickness Abnormalities in Autism Spectrum Disorders Through Late Childhood, Adolescence, and Adulthood: A Large-Scale MRI Study

Khundrakpam BS¹, Lewis JD¹, Kostopoulos P¹, Carbonell F¹, Evans AC¹.

Author information

1: Montreal Neurological Institute, McGill University, Montreal, QC, CanadaH3H2P1.

Abstract

Neuroimaging studies in autism spectrum disorders (ASDs) have provided inconsistent evidence of cortical abnormality. This is probably due to the small sample sizes used in most studies, and important differences in sample characteristics, particularly age, as well as to the heterogeneity of the disorder. To address these issues, we assessed abnormalities in ASD within the Autism Brain Imaging Data Exchange data set, which comprises data from approximately 1100 individuals (~6-55 years). A subset of these data that met stringent quality control and inclusion criteria (560 male subjects; 266 ASD; age = 6-35 years) were used to compute age-specific differences in cortical thickness in ASD and the relationship of any such differences to symptom severity of ASD. Our results show widespread increased cortical thickness in ASD, primarily left lateralized, from 6 years onwards, with differences diminishing during adulthood. The severity of symptoms related to social affect and communication correlated with these cortical abnormalities. These results are consistent with the conjecture that developmental patterns of cortical thickness abnormalities reflect delayed cortical maturation and highlight the dynamic nature of morphological abnormalities in ASD.

PMID: 28334080
DOI: 10.1093/cercor/bhx038

Âge de la première identification du trouble du spectre de l'autisme: une analyse de deux enquêtes américaines

Aperçu: G.M.

Des données probantes concernant l'âge auquel le trouble du spectre autistique est identifié sont essentielles pour améliorer le dépistage précoce. L'objectif de la recherche était d'estimer la répartition par âge pour la première identification des TSA dans les enquêtes nationales auprès des parents.

Dans deux enquêtes nationales, la majorité des parents d'enfants avec un diagnostic de TSA ont déclaré avoir eu une identification après 3 ans, lorsque l'admissibilité aux services d'intervention précoce a expiré et beaucoup ont déclaré avoir eu une identification de TSA après l'âge scolaire. L'identification tardive des enfants présentant des symptômes plus légers met en évidence la nécessité d'un dépistage précoce qui est sensible à toutes les formes de TSA, quelle que soit la gravité.

2017 Apr;56(4):313-320. doi: 10.1016/j.jaac.2017.01.012. Epub 2017 Feb 3.

Age at First Identification of Autism Spectrum Disorder: An Analysis of Two US Surveys

Sheldrick RC¹, Maye MP², Carter AS².

Author information

1: Tufts Medical Center, Boston. Electronic address: rsheldrick@tuftsmedicalcenter.org
2: University of Massachusetts, Boston.

Abstract

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.

PMID: 28335875
DOI: 10.1016/j.jaac.2017.01.012

Les difficultés sociales et de communication sont-elles un facteur de risque pour le développement de l'anxiété sociale?

Aperçu: G.M.

L'anxiété sociale (AS) est une condition courante associée aux difficultés sociales et de communication (SC) chez les jeunes en développement, ainsi qu'avec les troubles du spectre de l'autisme. L'étude vise à démêler la relation entre les symptômes de SA et les difficultés de SC à l'aide d'un échantillon basé sur une population de 9 491 enfant.

Plus de difficultés SC ont été associés à de plus grands symptômes AS à tous les âges. Des difficultés précoces de SC difficultés prédisaient une petite quantité, mais significative de la variance dans les symptômes AS plus tard. On n'a pas observé la relation inverse entre les difficultés de AS et SC. La relation entre les difficultés de SC et l'AS était plus forte de 7 à 10 ans. Aucune différence de sexe n'a été observée.

2017 Apr;56(4):344-351.e3. doi: 10.1016/j.jaac.2017.01.007. Epub 2017 Feb 1.

Are Social and Communication Difficulties a Risk Factor for the Development of Social Anxiety?

Pickard H¹, Rijsdijk F², Happé F², Mandy W³.

Author information

1: Medical Research Council (MRC) Social, Genetic, and Developmental Psychiatry (SGDP) Centre, King's College London, UK. Electronic address: hannah.pickard@kcl.ac.uk
2: Medical Research Council (MRC) Social, Genetic, and Developmental Psychiatry (SGDP) Centre, King's College London, UK.
3: University College London, UK.

Abstract

OBJECTIVE:

Social anxiety (SA) is a common condition associated with social and communication (SC) difficulties in typically developing young people, as well as those with autism spectrum disorder (ASD). Whether SC difficulties place children at risk for developing SA is unclear. Using a longitudinal design, the present study aimed to disentangle the relationship between SA symptoms and SC difficulties using a population-based sample of 9,491 children from the Avon Longitudinal Study of Parents and Children (ALSPAC).

METHOD:

Parent-reported data on SC difficulties and SA symptoms were collected at ages 7, 10, and 13 years. A cross-lagged panel model was used to investigate the longitudinal stability and directional relationship between latent SC difficulties and SA constructs over time.

RESULTS:

More SC difficulties were associated with greater SA symptoms at all ages. Earlier SC difficulties predicted a small but significant amount of variance in later SA symptoms. The reverse relationship from SA to SC difficulties was not observed. The relationship from SC difficulties to SA was strongest from age 7 to 10 years. No sex differences were observed.

CONCLUSION:

The evidence suggests that SC difficulties may be an important risk factor for the development of SA. These findings suggest the potential usefulness of incorporating social skills training alongside effective interventions to prevent or alleviate symptoms of SA in childhood.

PMID: 28335879
DOI: 10.1016/j.jaac.2017.01.007

Acquisition du temps d'apparition de la voix chez les tout-petits à faible et fort un risque de développer un trouble du spectre de l'autisme

Aperçu: G.M.

Bien que le retard de langage soit fréquent dans le trouble du spectre de l'autisme (TSA), la recherche est équivoque sur la question de savoir si le développement de la parole est affecté.

Le temps d'apparition de la parole (VOT), la principale différence acoustique entre b et p, a été mesuré à partir des mots spontanément produits à 18, 24 et 36 mois.

Le développement de la distinction entre b et p a été suivi prospectivement chez 22 enfants avec faible risque de TSA (LRC), 22 à risque élevé de TSA sans TSA (HRA-) et 11 à risque élevé de TSA qui ont reçu un diagnostic de TSA à 36 Mois (HRA +).

Les enfants HRA + étaient significativement moins susceptibles de produire des b et p p acoustiquement distincts à 36 mois,

2017 Mar 24. doi: 10.1002/aur.1775.

Acquisition of voice onset time in toddlers at high and low risk for autism spectrum disorder

Chenausky K¹, Tager-Flusberg H².

Author information

1: Music and Neuroimaging Lab, Neurology Department, Beth Israel Deaconess Medical Center, 330 Brookline Avenue, Boston, Massachusetts.
2: Department of Psychological and Brain Sciences, Center for Autism Research Excellence at Boston University, 100 Cummington Mall, Boston, Massachusetts.

Abstract

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. © 2017 International Society for Autism Research, Wiley Periodicals, Inc.

PMID: 28339140
DOI: 10.1002/aur.1775