Protocole d'étude du ASD-Net, le consortium de recherche allemand pour l'étude du trouble du spectre autistique tout au long de la vie: d'une meilleure compréhension étiologique, par un diagnostic valide, à des soins de santé plus efficaces

Aperçu: G.M.

Le "trouble du spectre de l'autisme" (TSA) est un trouble neurologique sévère et durable qui a un début précoce qui constitue un lourd fardeau pour les personnes touchées et leurs familles. En raison de la nécessité de services de santé, d'éducation et de formation professionnelle hautement spécialisés, la TSA est un trouble à forte intensité de coût et la tension sur les systèmes de soins de santé augmente avec l'âge de l'individu touché.

Le TSA-Net étudiera la plus grande cohorte de patients atteints de TSA en Allemagne pendant la durée de vie. En combinant l'expertise méthodologique de tous les niveaux de recherche clinique, l'ASD-Net suivra une approche translationnelle nécessaire pour identifier les voies neurobiologiques de différents phénotypes et leur identification et traitement appropriés.

 

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BMC Psychiatry. 2017 Jun 2;17(1):206. doi: 10.1186/s12888-017-1362-7.

Study protocol of the ASD-Net, the German research consortium for the study of Autism Spectrum Disorder across the lifespan: from a better etiological understanding, through valid diagnosis, to more effective health care

Kamp-Becker I¹, Poustka L^2,3,4, Bachmann C⁵, Ehrlich S^6,7, Hoffmann F⁸, Kanske P⁹, Kirsch P¹⁰, Krach S¹¹, Paulus FM¹¹, Rietschel M¹², Roepke S¹³, Roessner V⁶, Schad-Hansjosten T², Singer T⁹, Stroth S¹⁴, Witt S¹², Wermter AK¹⁴.

Author information

1

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Medical Clinic, Philipps-University Marburg, Marburg, Germany. kampbeck@med.uni-marburg.de

2

Department of Child and Adolescent Psychiatry and Psychotherapy, Medical Faculty Mannheim, Central Institute of Mental Health, Heidelberg University, Mannheim, Germany.

3

Department of Child and Adolescent Psychiatry, Medical University of Vienna, Vienna, Austria.

4

Department of Child and Adolescent Psychiatry/Psychotherapy, University Medical Center Göttingen, Göttingen, Germany.

5

Faculty of Medicine, Philipps University Marburg, Marburg, Germany.

6

Department of Child & Adolescent Psychiatry, Medical Faculty of the Technical University Dresden, Dresden, Germany.

7

Division of Psychological and Social Medicine and Developmental Neurosciences, Faculty of Medicine, TU Dresden, Dresden, Germany.

8

Department of Health Services Research, Carl von Ossietzky University Oldenburg, Oldenburg, Germany.

9

Department of Social Neuroscience, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.

10

Department of Clinical Psychology Central Institute of Mental Health, Mannheim, Germany.

11

Department for Psychiatry and Psychotherapy, University Schleswig-Holstein Campus Lübeck, Lübeck, Germany.

12

Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Mannheim, Germany.

13

Department of Psychiatry, Campus Benjamin Franklin, Charité - Medical Faculty Berlin, Berlin, Germany.

14

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, Medical Clinic, Philipps-University Marburg, Marburg, Germany.

Abstract

BACKGROUND:

Autism Spectrum Disorder (ASD) is a severe, lifelong neurodevelopmental disorder with early onset that places a heavy burden on affected individuals and their families. Due to the need for highly specialized health, educational and vocational services, ASD is a cost-intensive disorder, and strain on health care systems increases with increasing age of the affected individual.

METHODS:

The ASD-Net will study Germany's largest cohort of patients with ASD over the lifespan. By combining methodological expertise from all levels of clinical research, the ASD-Net will follow a translational approach necessary to identify neurobiological pathways of different phenotypes and their appropriate identification and treatment. The work of the ASD-Net will be organized into three clusters concentrating on diagnostics, therapy and health economics. In the diagnostic cluster, data from a large, well-characterized sample (N = 2568) will be analyzed to improve the efficiency of diagnostic procedures. Pattern classification methods (machine learning) will be used to identify algorithms for screening purposes. In a second step, the developed algorithm will be tested in an independent sample. In the therapy cluster, we will unravel how an ASD-specific social skills training with concomitant oxytocin administration can modulate behavior through neurobiological pathways. For the first time, we will characterize long-term effects of a social skills training combined with oxytocin treatment on behavioral and neurobiological phenotypes. Also acute effects of oxytocin will be investigated to delineate general and specific effects of additional oxytocin treatment in order to develop biologically plausible models for symptoms and successful therapeutic interventions in ASD. Finally, in the health economics cluster, we will assess service utilization and ASD-related costs in order to identify potential needs and cost savings specifically tailored to Germany. The ASD-Net has been established as part of the German Research Network for Mental Disorders, funded by the BMBF (German Federal Ministry of Education and Research).

DISCUSSION:

The highly integrated structure of the ASD-Net guarantees sustained collaboration of clinicians and researchers to alleviate individual distress, harm, and social disability of patients with ASD and reduce costs to the German health care system.

TRIAL REGISTRATION:

Both clinical trials of the ASD-Net are registered in the German Clinical Trials Register: DRKS00008952 (registered on August 4, 2015) and DRKS00010053 (registered on April 8, 2016).

KEYWORDS:

ASD-net; Autism spectrum disorder; Diagnosis; Genetic; German research network for mental disorders; Health economics; Oxytocin; Screening; Social competence training; Therapy

PMID:28577550

PMCID:PMC5455122

DOI:10.1186/s12888-017-1362-7

Le rôle du système vasopressine antioxydine / arginine dans les modèles animaux du "trouble du spectre de l'autisme"

Aperçu: G.M.

L'ocytocine non peptide (OXT) et l'arginine vasopressine (AVP) sont deux médiateurs clés dans la régulation de divers aspects des comportements sociaux des mammifères. Il existe des preuves selon lesquelles des variantes génétiques du système OXT / AVP existent dans le "trouble du spectre de l'autisme" (TSA) et que ce système est dysfonctionnel au moins dans certaines entités TSA.  Ces résultats ont stimulé l'intérêt d'effectuer des études testant l'application thérapeutique potentielle d'OXT / AVP dans les TSA. D'après les résultats des modèles animaux qui montrent des altérations du système OXT / AVP, on a laissé entendre que l'administration à dose unique ou multiple ou la stimulation de la libération endogène peuvent améliorer plusieurs déficits sociaux. Les chercheurs examinent de manière exhaustive le rôle du système OXT / AVP dans la reconnaissance sociale, l'interaction sociale et le comportement maternel à la lumière des différents modèles animaux ASD et des études sur les patients. Leur étude porte davantage sur les implications pour les interventions pharmacologiques liées à l'OXT / AVP pour atténuer les déficits sociaux dans les TSA dans le futur.

 

Adv Anat Embryol Cell Biol. 2017;224:135-158. doi: 10.1007/978-3-319-52498-6_8.

The Role of the Oxytocin/Arginine Vasopressin System in Animal Models of Autism Spectrum Disorder

Zhang R^1,2,3, Xu XJ^4,5,6,7, Zhang HF^4,5,6,8, Han SP⁹, Han JS^4,5,6.

Author information

1

Neuroscience Research Institute, Peking University, Beijing, China. zhangrong@bjmu.edu.cn

2

Department of Neurobiology, Health Science Center, School of Basic Medical Sciences, Peking University, Beijing, China. zhangrong@bjmu.edu.cn

3

Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China. zhangrong@bjmu.edu.cn.

4

Neuroscience Research Institute, Peking University, Beijing, China.

5

Department of Neurobiology, Health Science Center, School of Basic Medical Sciences, Peking University, Beijing, China.

6

Key Laboratory for Neuroscience, Ministry of Education/National Health and Family Planning Commission, Peking University, Beijing, China.

7

Department of Scientific Research, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China.

8

Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, College of Medicine, Collaborative Innovation Center for Brain Science, Xiamen University, Xiamen, China.

9

Wuxi shenpingxintai Medical Technology Co., Ltd., Wuxi, China.

Abstract

The nonapeptides oxytocin (OXT) and arginine vasopressin (AVP) are two key mediators in regulating various aspects of mammalian social behaviours. There are several lines of evidence that genetic variants of the OXT/AVP system exist in autism spectrum disorder (ASD) and that this system is dysfunctional at least in some ASD entities. These findings have stimulated the interest to perform studies testing the potential therapeutic application of OXT/AVP in ASD. In this respect animal models are critical for investigating the pathophysiology and for compound screening leading to new therapeutic approaches. Based on findings in animal models that show alterations of the OXT/AVP system, it has been hypothesised that single- or multiple-dose administration or the stimulation of endogenous release can improve several social deficits. Here we comprehensively review the role of the OXT/AVP system in social recognition, social interaction and maternal behaviour in the light of different ASD animal models and patient studies. We further discuss implications for OXT/AVP-related pharmacological interventions to alleviate social deficits in ASD in the future.

PMID:28551755

DOI:10.1007/978-3-319-52498-6_8

Déficience de la communication dans le répertoire vocal ultrasonique pendant la période de chagrin chez des souris Cd157 Knockout: amélioration transitoire par l'oxytocine

Aperçu: G.M.

La communication consiste en une interaction sociale, une reconnaissance et une transmission de l'information. La capacité de communication est la composante la plus touchée chez les enfants avec un diagnostic de "troubles du spectre  de l'autisme"(TSA). 

Récemment, cette équipe a signalé que le gène CD157 / BST1 est associé au TSA et que les souris C5157 (Cd157 - / -) montrent des déficiences sévères du comportement social améliorées par le traitement par l'ocytocine (OXT). Ici, les chercheurs ont essayé de déterminer si les souris Cd157 - / - peuvent être utilisées comme un modèle approprié pour les déficits de communication en mesurant les vocalisations ultrasonores (VSM), en particulier au début de la phase de développement.

Le nombre d'appels produits chez les souriceaux en raison de l'isolement  était plus élevé au 3ème jour après la naissance (PND) 3 chez les souriceaux knock-out que les souris de type sauvage, mais était plus faible chez les PND 7 et 10. Les souriceaux des deux génotypes avaient des répertoires vocaux de taille similaire au PND 3. Plus tard, aux PND 7 et 10, alors que les souriceaux de type sauvage émettent des USV composés de six types de syllabes différents, les souriceaux knock-out sont vocalisés avec seulement deux types. Cette altération du développement dans les émissions des VSM a été récupérée dans les 30 minutes par traitement OXT par voie intrapéritonéale, mais est rapidement revenue aux niveaux de contrôle après 120 min, ce qui montre un effet transitoire d'OXT.  

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Front Neurosci. 2017 May 17;11:266. doi: 10.3389/fnins.2017.00266. eCollection 2017.

Communication Impairment in Ultrasonic Vocal Repertoire during the Suckling Period of Cd157 Knockout Mice: Transient Improvement by Oxytocin

Lopatina OL^1,2, Furuhara K¹, Ishihara K³, Salmina AB², Higashida H¹.

Author information

1

Department of Basic Research on Social Recognition and Memory, Research Center for Child Mental Development, Kanazawa UniversityKanazawa, Japan.

2

Department of Biochemistry, Medical, Pharmaceutical, and Toxicological Chemistry, Krasnoyarsk State Medical University Named after Prof. V.F. Voino-YasenetskyKrasnoyarsk, Russia.

3

Department of Immunology and Molecular Genetics, Kawasaki Medical SchoolKurashiki, Japan.

Abstract

Communication consists of social interaction, recognition, and information transmission. Communication ability is the most affected component in children with autism spectrum disorder (ASD). Recently, we reported that the CD157/BST1 gene is associated with ASD, and that CD157 knockout (Cd157^-/-) mice display severe impairments in social behavior that are improved by oxytocin (OXT) treatment. Here, we sought to determine whether Cd157^-/- mice can be used as a suitable model for communication deficits by measuring ultrasonic vocalizations (USVs), especially in the early developmental stage. Call number produced in pups due to isolation from dams was higher at postnatal day (PND) 3 in knockout pups than wild-type mice, but was lower at PNDs 7 and 10. Pups of both genotypes had similarly limited voice repertoires at PND 3. Later on, at PNDs 7 and 10, while wild-type pups emitted USVs consisting of six different syllable types, knockout pups vocalized with only two types. This developmental impairment in USV emission was rescued within 30 min by intraperitoneal OXT treatment, but quickly returned to control levels after 120 min, showing a transient effect of OXT. USV impairment was partially observed in Cd157^+/- heterozygous mice, but not in Cd157^-/- adult male mice examined while under courtship. These results demonstrate that CD157 gene deletion results in social communication insufficiencies, and suggests that CD157 is likely involved in acoustic communication. This unique OXT-sensitive developmental delay in Cd157^-/- pups may be a useful model of communicative interaction impairment in ASD.

PMID: 28566999

PMCID: PMC5434149

DOI: 10.3389/fnins.2017.00266

Effets socio-cognitifs dépendants de la dose d'ocytocine intranasale délivrés avec un nouveau dispositif Propulsé par souffle chez les adultes avec un diagnostic de "trouble du spectre de l'autisme" : un essai randomisé en double aveugle et contrôlé par placebo

Aperçu: G.M.

Le neuropeptide oxytocine s'est avéré prometteur en tant que traitement des symptômes des troubles du spectre autistique (ASD). Cependant, les progrès de la recherche clinique ont été entravés par une mauvaise compréhension de la dose-réponse de l'ocytocine et des méthodes de transmission intranasales sous-optimales. 

Dans une séquence aléatoire de séances à dose unique, 17 hommes adultes avec un diagnostic de TSA ont reçu 8 unités internationales (UI) d'ocytocine, 24 UI d'ocytocine ou de placebo suivies de quatre tâches cognitivo-cognitives. Les chercheurs ont observé un effet principal du traitement sur la mesure de résultat primaire de la sensibilité d'émotion ouverte telle que mesurée par les cotes émotionnelles des visages (η2 = 0,18).  

Par rapport au placebo, le traitement de 8IU a augmenté la salivité globale (P = 0,02, d = 0,63). Il n'y a eu aucune augmentation statistiquement significative après 24 IU de traitement (P = 0,12, d = 0,4). Les effets après 8IU d'ocytocine ont été observés malgré aucune augmentation significative des concentrations d'ocytocine dans le sang périphérique. Nous n'avons trouvé aucun effet significatif pour la performance de la tâche de lecture de l'esprit dans les yeux,ou les tâches socio-cognitives secondaires.

Il s'agit du premier essai pour évaluer les effets dépendant de la dose d'une seule administration d'ocytocine dans l'autisme, les résultats indiquant qu'une faible dose d'ocytocine peut moduler de manière significative la sensibilité émotionnelle malgré une exposition systémique minimale.

Transl Psychiatry. 2017 May 23;7(5):e1136. doi: 10.1038/tp.2017.103.

Dose-dependent social-cognitive effects of intranasal oxytocin delivered with novel Breath Powered device in adults with autism spectrum disorder: a randomized placebo-controlled double-blind crossover trial

Quintana DS^1,2, Westlye LT^1,2,3, Hope S^1,2,4, Nærland T^1,2,5, Elvsåshagen T^1,2,6,7, Dørum E^1,2, Rustan Ø^1,2, Valstad M^1,2,3, Rezvaya L^1,2,3, Lishaugen H^1,2,3, Stensønes E^1,2,3, Yaqub S^1,2,3, Smerud KT⁸, Mahmoud RA⁹, Djupesland PG¹⁰, Andreassen OA^1,2.

Author information

1

NORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

2

Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.

3

Department of Psychology, University of Oslo, Oslo, Norway.

4

Department of Neuro Habilitation, Oslo University Hospital, Oslo, Norway.

5

NevSom, Department of Rare Disorders and Disabilities, Oslo University Hospital, Oslo, Norway.

6

Department of Neurology, Oslo University Hospital, Oslo, Norway.

7

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

8

Smerud Medical Research International AS, Oslo, Norway.

9

OptiNose US Inc, Yardley, PA, USA.

10

OptiNose AS, Oslo, Norway.

Abstract

The neuropeptide oxytocin has shown promise as a treatment for symptoms of autism spectrum disorders (ASD). However, clinical research progress has been hampered by a poor understanding of oxytocin's dose-response and sub-optimal intranasal delivery methods. We examined two doses of oxytocin delivered using a novel Breath Powered intranasal delivery device designed to improve direct nose-to-brain activity in a double-blind, crossover, randomized, placebo-controlled trial. In a randomized sequence of single-dose sessions, 17 male adults with ASD received 8 international units (IU) oxytocin, 24IU oxytocin or placebo followed by four social-cognitive tasks. We observed an omnibus main effect of treatment on the primary outcome measure of overt emotion salience as measured by emotional ratings of faces (η²=0.18). Compared to placebo, 8IU treatment increased overt emotion salience (P=0.02, d=0.63). There was no statistically significant increase after 24IU treatment (P=0.12, d=0.4). The effects after 8IU oxytocin were observed despite no significant increase in peripheral blood plasma oxytocin concentrations. We found no significant effects for reading the mind in the eyes task performance or secondary outcome social-cognitive tasks (emotional dot probe and face-morphing). To our knowledge, this is the first trial to assess the dose-dependent effects of a single oxytocin administration in autism, with results indicating that a low dose of oxytocin can significantly modulate overt emotion salience despite minimal systemic exposure.

PMID: 28534875

DOI: 10.1038/tp.2017.103

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.  

Neurosci Biobehav Rev. 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.

Copyright © 2017 Elsevier Ltd. All rights reserved.

PMID: 28499504

DOI: 10.1016/j.neubiorev.2017.05.004

Les niveaux d'oxytocine sérique et un polymorphisme génétique des récepteurs d'oxytocine (rs2254298) révèlent les déficits sociaux chez les enfants et les adolescents avec un diagnostic de troubles du spectre de l'autisme

Aperçu: G.M.

Les résultats de l'étude indiquent que les personnes avec un diagnostic de TSA peuvent présenter une dysrégulation dans la neuropeptide ocytocine en fonction des changements dans l'expression du gène OXTR ainsi que des altérations induites par l'environnement du système oxytocinergique pour déterminer leurs déficits sociaux

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Front Neurosci. 2017 Apr 21;11:221. doi: 10.3389/fnins.2017.00221. eCollection 2017.

Serum Oxytocin Levels and an Oxytocin Receptor Gene Polymorphism (rs2254298) Indicate Social Deficits in Children and Adolescents with Autism Spectrum Disorders

Yang S¹, Dong X¹, Guo X¹, Han Y¹, Song H², Gao L¹, Dai W¹, Su Y¹, Zhang X¹.

Author information

1

Department of Maternal, Child and Adolescent Health, School of Public Health, Tianjin Medical UniversityTianjin, China.

2

Department of Applied Science, The College of William and MaryWilliamsburg, VA, USA.

Abstract

The neuropeptide oxytocin (OT) and its receptor (OXTR) have been predicted to be involved in the regulation of social functioning in autism spectrum disorders (ASD). Objective of the study was to investigate serum OT levels and the OXTR rs2254298 polymorphism in Chinese Han children and adolescents with ASD as well as to identify their social deficits relevant to the oxytocinergic system. We tested serum OT levels using ELISA in 55 ASD subjects and 110 typically developing (TD) controls as well as genotyped the OXTR rs2254298 polymorphism using PCR-RFLP in 100 ASD subjects and 232 TD controls. Autistic symptoms were assessed by the Autism Behavior Checklist (ABC) and the Childhood Autism Rating Scale (CARS). There were no significant associations between OXTR rs2254298 polymorphism and ASD, serum OT levels and age, as well as serum OT levels and intelligent quotient (IQ) in both ASD and TD groups. However, ASD subjects exhibited elevated serum OT levels compared to TD controls and positive correlations between serum OT levels and "adaptation to change score" in the CARS and CARS total scores. Moreover, in the ASD group, significant relationships were revealed between the single-nucleotide polymorphism (SNP) rs2254298 and serum OT levels, the category "stereotypes and object use" in the ABC and the category "adaptation to change" in the CARS. These findings indicated that individuals with ASD may exhibit a dysregulation in OT on the basis of changes in OXTR gene expression as well as environmentally induced alterations of the oxytocinergic system to determine their social deficits.

PMID:28484366

PMCID:PMC5399030

DOI:10.3389/fnins.2017.00221

L'administration d'oxytocine pendant le travail spontané: lignes directrices pour la pratique clinique. Chapitre 6: Risques fœtaux, néonatals et pédiatriques et effets néfastes de l'utilisation de l'augmentation de l'ocytocine pendant le travail spontané

Aperçu: G.M.

Il existe globalement 5 types de risques potentiels et d'effets néfastes auxquels l'utilisation d'ocytocine pendant le travail spontané peut exposer le foetus ou l'enfant: 1) difficultés d'adaptation à la vie extra-utérine, 2) l'ictère néonatale, 3) l'hyponatrémie néonatale, 4) la perturbation des réflexes de succion pendant la période néonatale, et 5) troubles du développement généralisé (troubles du spectre de l'autisme) chez les enfants.

La démonstration dans les enquêtes de population générale sur les effets indésirables suggérant que l'ocytocine est administrée dans des conditions non nécessairement recommandées ou optimales (indication, dosage, préparation).  

Néanmoins, compte tenu de la fréquence actuelle de l'utilisation d'oxytocine pendant le travail spontané en France, notre groupe consultatif d'experts recommande aux médecins de faire preuve de prudence dans son utilisation et, en particulier, les équipes d'obstétrique rédigent des protocoles pour l'administration d'oxytocine pendant le travail spontané dans chaque maternité, analysent L'administration d'ocytocine lors des audits ou des examens de morbidité et de mortalité parmi les nouveau-nés avec une mauvaise adaptation à la vie extra-utérine et surveillent les taux d'administration d'ocytocine pendant le travail spontané dans chaque maternité.

J Gynecol Obstet Hum Reprod. 2017 May 2. pii: S2468-7847(17)30110-1. doi: 10.1016/j.jogoh.2017.04.012. [Epub ahead of print]

Oxytocin administration during spontaneous labor: Guidelines for clinical practice. Chapter 6: Fetal, neonatal and pediatric risks and adverse effects of using oxytocin augmentation during spontaneous labor

Burguet A¹, Rousseau A².

Author information

1

Pédiatrie 2, CHU Dijon, 21030 Dijon Cedex, France; Réseau Périnatal Franche-Comté, CHU Besançon, 25030 Besançon Cedex, France. Electronic address: antoine.burguet@chu-dijon.fr.

2

Département de Maïeutique, EA 7285 RISCQ, UFR des Sciences de la Santé Simone Veil, Université Versailles Saint Quentin, 2, avenue de la Source-de-la-Bièvre, 78180 Montigny-le-Bretonneux, France.

Abstract

There are globally 5 types of potential risks and adverse effects to which oxytocin use during spontaneous labor might expose the fetus or child: 1) difficulties in adaptation to extrauterine life, 2) neonatal jaundice, 3) neonatal hyponatremia, 4) disruption of the sucking reflex and thus beastfeeding in the neonatal period, and 5) pervasive developmental disorders (autism spectrum disorders) in children. Numerous methodological difficulties make it impossible to establish a causal association between oxytocin exposure and these five adverse effects: lack of power of the randomized trials, selection of women in the randomized trials who are not representative of those observed in general population surveys, and inversely, the demonstration in general population surveys of adverse effects suggesting that oxytocin is administered in not necessarily recommended or optimum conditions (indication, dosage, preparation). Nonetheless, in view of the currently high frequency of oxytocin use during spontaneous labor in France, our expert advisory group recommends that physicians exercise caution in its use, and specifically that obstetrics teams draft protocols for oxytocin administration during spontaneous labor in each maternity ward, analyze oxytocin administration during audits or reviews of morbidity and mortality among newborns with a poor adaptation to extrauterine life, and monitor the rates of oxytocin administration during spontaneous labor in each maternity ward.

Copyright © 2017. Published by Elsevier Masson SAS.

PMID:28476693

DOI:10.1016/j.jogoh.2017.04.012

Méta-analyse des effets de l'ocytocine intranasale sur l'interprétation et l'expression des émotions

Aperçu: G.M.

Une interprétation précise et une expression appropriée des émotions sont des aspects clés de la connaissance sociale. Plusieurs troubles mentaux sont caractérisés par des difficultés transdiagnostiques dans ces domaines et, récemment, il y a eu un intérêt croissant à explorer les effets de l'ocytocine sur le fonctionnement socio-émotionnel. Cette revue comprend 33 études. Quinze des études comprenaient des personnes avec un diagnostic de trouble du spectre de l'autisme, de schizophrénie, de trouble de la personnalité limite, de démence frontotemporelle, d'anorexie mentale, de boulimie mentale, du syndrome de stress post-traumatique, de dépression et de dépendance aux opioïdes et à l'alcool.

Une seule dose d'oxytocine intranasale a considérablement amélioré la reconnaissance des émotions de base, en particulier la peur, et a augmenté l'expression d'émotions positives chez les personnes en bonne santé. 

L'ocytocine n'a pas influencé de manière significative la théorie de l'esprit ni l'expression d'émotions négatives chez les personnes en bonne santé.

Enfin, l'ocytocine intranasale n'a pas eu d'influence significative sur l'interprétation ou l'expression d'émotions chez les populations cliniques. 

Neurosci Biobehav Rev. 2017 Apr 30. pii: S0149-7634(16)30744-8. doi: 10.1016/j.neubiorev.2017.04.010.

Meta-analysis of the effects of intranasal oxytocin on interpretation and expression of emotions

Leppanen J¹, Ng KW², Tchanturia K³, Treasure J⁴.

Author information

1

King's College London, Institute of Psychiatry, Psychology, and Neuroscience, Department of Psychological Medicine, London, United Kingdom. Electronic address: jenni.leppanen@kcl.ac.uk

2

Singapore General Hospital,20 College Road, Academia, 169865, Singapore.

3

King's College London, Institute of Psychiatry, Psychology, and Neuroscience, Department of Psychological Medicine, London, United Kingdom; Department of Psychology, Illia State University, Tbilisi, Georgia.

4

King's College London, Institute of Psychiatry, Psychology, and Neuroscience, Department of Psychological Medicine, London, United Kingdom.

Abstract

Accurate interpretation and appropriate expression of emotions are key aspects of social-cognition. Several mental disorders are characterised by transdiagnostic difficulties in these areas and, recently, there has been increasing interest in exploring the effects of oxytocin on social-emotional functioning. This review consists of 33 studies. Fifteen of the studies included people with autism spectrum disorder, schizophrenia, borderline personality disorder, frontotemporal dementia, anorexia nervosa, bulimia nervosa, post-traumatic stress disorder, depression, and opioid and alcohol dependence. We conducted ten meta-analyses examining the effects of intranasal oxytocin on expression of emotions, emotional theory of mind, sensitivity to recognise basic emotions, and recognition of basic emotions. A single dose of intranasal oxytocin significantly improved the recognition of basic emotions, particularly fear, and increased the expression of positive emotions among the healthy individuals. Oxytocin did not significantly influence theory of mind or the expression of negative emotions among the healthy individuals. Finally, intranasal oxytocin did not significantly influence interpretation or expression of emotions among the clinical populations.

Copyright © 2017. Published by Elsevier Ltd.

PMID:28467893

DOI: 10.1016/j.neubiorev.2017.04.010

La corrélation entre les concentrations d'ocytocine centrale et périphérique: un examen systématique et une méta-analyse

Aperçu: G.M.

Les résultats indiquent une coordination de la libération d'oxytocine centrale et périphérique après le stress et après administration intranasale. Bien que populaire, l'approche consistant à utiliser des niveaux d'ocytocine périphériques pour se rapprocher des niveaux centraux dans des conditions basales n'est pas justifiée par les résultats actuels.

Neurosci Biobehav Rev. 2017 Apr 22. pii: S0149-7634(17)30144-6. doi: 10.1016/j.neubiorev.2017.04.017.

The correlation between central and peripheral oxytocin concentrations: a systematic review and meta-analysis

Valstad M¹, Alvares GA², Egknud M³, Matziorinis AM¹, Andreassen OA³, Westlye LT¹, Quintana DS⁴.

Author information

1

NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, University of Oslo, Oslo University Hospital, Oslo, Norway; Department of Psychology, University of Oslo, Oslo, Norway.

2

Telethon Kids Institute, University of Western Australia, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Long Pocket, Brisbane, Australia.

3

NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, University of Oslo, Oslo University Hospital, Oslo, Norway.

4

NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, University of Oslo, Oslo University Hospital, Oslo, Norway. Electronic address: daniel.quintana@medisin.uio.no

Abstract

There is growing interest in the role of the oxytocin system in social cognition and behavior. Peripheral oxytocin concentrations are regularly used to approximate central concentrations in psychiatric research, however, the validity of this approach is unclear. Here we conducted a pre-registered systematic search and meta-analysis of correlations between central and peripheral oxytocin concentrations. A search of databases yielded 17 eligible studies, resulting in a total sample size of 516 participants and subjects. Overall, a positive association between central and peripheral oxytocin concentrations was revealed [r=0.29, 95% CI (0.14, 0.42), p<0.0001]. This association was moderated by experimental context [Q_b(4), p=0.003]. While no association was observed under basal conditions (r=0.08, p=0.31), significant associations were observed after intranasal oxytocin administration (r=0.66, p<.0001), and after experimentally induced stress (r=0.49, p=0.0011). These results indicate a coordination of central and peripheral oxytocin release after stress and after intranasal administration. Although popular, the approach of using peripheral oxytocin levels to approximate central levels under basal conditions is not supported by the present results.

Copyright © 2017 Elsevier Ltd. All rights reserved.

PMID: 28442403

DOI: 10.1016/j.neubiorev.2017.04.017

La concentration d'oxytocine salivaire associe le sentiment subjectif de la propriété du corps pendant l'illusion de la main en caoutchouc

Aperçu: G.M.

L'oxytocine est une hormone de l'hypophyse postérieure qui favorise la lactation, le lien maternel et la naissance. Des études récentes ont montré que l'ocytocine peut moduler la reconnaissance sociale chez les deux sexes, et donc elle peut être liée à l'empathie. Les régions cérébrales qui sont associées à la reconnaissance sociale et à l'empathie (p. Ex. Le cortex insulaire) sont activées dans l'illusion de main en caoutchouc (RHI), qui implique une propriété illusoire d'une main en caoutchouc causée par des mouvements de pinceaux appliqués de manière synchrone à la fois sur une main en caoutchouc et sur l'une des mains du participant, cachée de sa vue.  

Dans la présente étude, les chercheurs ont étudié la relation entre la concentration d'oxytocine salivaire et le sentiment de possession de main en caoutchouc.  

L'oxytocine salivaire a été mesurée avant et après les tâches comportementales. Il a été constaté que les participants qui avaient des concentrations élevées d'ocytocine salivaire avaient tendance à se sentir fortement propriétaires de la main en caoutchouc. 

Nous avons également constaté que les participants ayant un score de quotient du spectre autistique élevé (AQ) qui ont particulièrement ressenti des difficultés dans les compétences sociales et les communications ont tendance à se sentir faussement la propriété de la main en caoutchouc. Nous avons observé que la propriété illusoire du corps était étroitement liée aux communications sociales et à une base neuroendocrine connexe. Les résultats de la présente étude suggèrent que la concentration d'oxytocine salivaire d'un individu peut prédire dans quelle mesure l'individu est sensible au RHI; De plus, l'ocytocine pourrait moduler la sensation de propriété du corps.

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Front Hum Neurosci. 2017 Apr 7;11:166. doi: 10.3389/fnhum.2017.00166. eCollection 2017.

Salivary Oxytocin Concentration Associates with the Subjective Feeling of Body Ownership during the Rubber Hand Illusion

Ide M^1,2, Wada M¹.

Author information

1

Developmental Disorders Section, Department of Rehabilitation for Brain Functions, Research Institute of National Rehabilitation Center for Persons with DisabilitiesTokorozawa, Japan.

2

Japan Society for the Promotion of ScienceTokyo, Japan.

Abstract

Oxytocin is a hormone of the posterior pituitary that promotes lactation, maternal bonding, and birth. Recent studies have shown that oxytocin may modulate social recognition in both sexes, and thus it may be related to empathy. Brain regions that are associated with social recognition and empathy (e.g., the insular cortex) are activated in the rubber hand illusion (RHI), which involves illusory ownership of a rubber hand caused by brush strokes applied synchronously to both a rubber hand and one of the participant's hand, which is hidden from view. It is intriguing to examine whether oxytocin modulates plastic changes in body representation, such as the changes occurring in the RHI. In the present study, we investigated the relationship between salivary oxytocin concentration and the feeling of rubber hand ownership. Brush strokes were applied synchronously or asynchronously to the participant's hand and a rubber hand on different days. Salivary oxytocin was measured before and after the behavioral tasks. We found that participants who had high concentrations of salivary oxytocin tended to feel strong ownership of the rubber hand. We also found that the participants with a high autism spectrum quotient (AQ) score who particularly felt difficulties in social skills and communications tended to feel weak rubber hand ownership. We observed that illusory body ownership was closely linked to social communications and a related neuroendocrine basis. The results of the present study suggest that an individual's salivary oxytocin concentration can predict the extent to which the individual experiences the RHI; furthermore, oxytocin might modulate the sensation of body ownership.

KEYWORDS:

autistic traits; body ownership; neuroendocrine; rubber hand illusion; salivary oxytocin; visuotactile integration

PMID: 28439234  
PMCID: PMC5383663  
DOI: 10.3389/fnhum.2017.00166