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      Advances in the Research of Melatonin in Autism Spectrum Disorders: Literature Review and New Perspectives

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          Abstract

          Abnormalities in melatonin physiology may be involved or closely linked to the pathophysiology and behavioral expression of autistic disorder, given its role in neurodevelopment and reports of sleep-wake rhythm disturbances, decreased nocturnal melatonin production, and beneficial therapeutic effects of melatonin in individuals with autism. In addition, melatonin, as a pineal gland hormone produced from serotonin, is of special interest in autistic disorder given reported alterations in central and peripheral serotonin neurobiology. More specifically, the role of melatonin in the ontogenetic establishment of circadian rhythms and the synchronization of peripheral oscillators opens interesting perspectives to ascertain better the mechanisms underlying the significant relationship found between lower nocturnal melatonin excretion and increased severity of autistic social communication impairments, especially for verbal communication and social imitative play. In this article, first we review the studies on melatonin levels and the treatment studies of melatonin in autistic disorder. Then, we discuss the relationships between melatonin and autistic behavioral impairments with regard to social communication (verbal and non-verbal communication, social interaction), and repetitive behaviors or interests with difficulties adapting to change. In conclusion, we emphasize that randomized clinical trials in autism spectrum disorders are warranted to establish potential therapeutic efficacy of melatonin for social communication impairments and stereotyped behaviors or interests.

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          Most cited references157

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          Parent-infant synchrony and the construction of shared timing; physiological precursors, developmental outcomes, and risk conditions.

          Synchrony, a construct used across multiple fields to denote the temporal relationship between events, is applied to the study of parent-infant interactions and suggested as a model for intersubjectivity. Three types of timed relationships between the parent and child's affective behavior are assessed: concurrent, sequential, and organized in an ongoing patterned format, and the development of each is charted across the first year. Viewed as a formative experience for the maturation of the social brain, synchrony impacts the development of self-regulation, symbol use, and empathy across childhood and adolescence. Different patterns of synchrony with mother, father, and the family and across cultures describe relationship-specific modes of coordination. The capacity to engage in temporally-matched interactions is based on physiological mechanisms, in particular oscillator systems, such as the biological clock and cardiac pacemaker, and attachment-related hormones, such as oxytocin. Specific patterns of synchrony are described in a range of child-, parent- and context-related risk conditions, pointing to its ecological relevance and usefulness for the study of developmental psychopathology. A perspective that underscores the organization of discrete relational behaviors into emergent patterns and considers time a central parameter of emotion and communication systems may be useful to the study of interpersonal intimacy and its potential for personal transformation across the lifespan.
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            Inter-Brain Synchronization during Social Interaction

            During social interaction, both participants are continuously active, each modifying their own actions in response to the continuously changing actions of the partner. This continuous mutual adaptation results in interactional synchrony to which both members contribute. Freely exchanging the role of imitator and model is a well-framed example of interactional synchrony resulting from a mutual behavioral negotiation. How the participants' brain activity underlies this process is currently a question that hyperscanning recordings allow us to explore. In particular, it remains largely unknown to what extent oscillatory synchronization could emerge between two brains during social interaction. To explore this issue, 18 participants paired as 9 dyads were recorded with dual-video and dual-EEG setups while they were engaged in spontaneous imitation of hand movements. We measured interactional synchrony and the turn-taking between model and imitator. We discovered by the use of nonlinear techniques that states of interactional synchrony correlate with the emergence of an interbrain synchronizing network in the alpha-mu band between the right centroparietal regions. These regions have been suggested to play a pivotal role in social interaction. Here, they acted symmetrically as key functional hubs in the interindividual brainweb. Additionally, neural synchronization became asymmetrical in the higher frequency bands possibly reflecting a top-down modulation of the roles of model and imitator in the ongoing interaction.
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              Autistic disturbances of affective contact.

              L Kanner (1968)
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                Molecular Diversity Preservation International (MDPI)
                1422-0067
                October 2013
                14 October 2013
                : 14
                : 10
                : 20508-20542
                Affiliations
                [1 ]Hospital-University Department of Child and Adolescent Psychiatry, Guillaume Régnier Hospital, Rennes 1 University, Rennes 35000, France; E-Mails: imen.najjar@ 123456gmail.com (I.N.); inas-lagdas@ 123456hotmail.com (E.L.); solennkermarrec@ 123456yahoo.fr (S.K.); sophie.ribardiere@ 123456yahoo.fr (S.R.); julie9175@ 123456hotmail.fr (J.V.-L.)
                [2 ]Laboratory of Psychology of Perception, CNRS UMR 8158, Paris 75270, France; E-Mail: marianne.barburoth@ 123456parisdescartes.fr
                [3 ]Inserm CIC 0203 Clinical Investigation Centre, University Hospital, Rennes 1 University, Rennes 35033, France; E-Mails: eric.bellissant@ 123456chu-rennes.fr (E.B.); claire.fougerou@ 123456chu-rennes.fr (C.F.)
                [4 ]Department of Clinical Pharmacology, University Hospital, Rennes 1 University, Rennes 35033, France
                [5 ]Laboratory of Developmental Neurochemistry, Yale Child Study Center, New Haven, CT 06519, USA; E-Mail: george.anderson@ 123456yale.edu
                [6 ]Department of Laboratory Medicine, Yale University School of Medicine, New Haven, CT 06519, USA
                [7 ]Hospital-University Department of Child and Adolescent Psychiatry, Pitié-SalpétrièreHospital, Paris 6 University, Paris 75013, France; E-Mail: david.cohen@ 123456psl.aphp.fr
                [8 ]CIC INSERM U 802, CHU de Poitiers, Unité de recherche clinique intersectorielle en psychiatrie du Centre Hospitalier Henri Laborit, Poitiers 86022, France; E-Mail: nemat.jaafari@ 123456ch-poitiers.fr
                [9 ]INSERM UMR U978, University of Paris 13, Bobigny 93009, France; E-Mails: olivier.schischmanoff@ 123456avc.aphp.fr (O.S.); remi.fagard@ 123456avc.aphp.fr (R.F.)
                [10 ]Laboratoire de Biochimie et Biologie Moléculaire, Hôpital Avicenne, APHP, Bobigny 93009, France
                [11 ]Service Hospitalo-Universitaire de Psychiatrie de l’Enfant et de l’Adolescent de Brest, UBO, Brest 29238, France; E-Mail: michel.botbol@ 123456orange.fr
                [12 ]Maison Départementale de l’Adolescent et Centre Médico-Psycho-Pédagogique, Conseil Général des Bouches-du-Rhône; Laboratoire de Santé Publique EA3279, Faculté de Médecine de la Timone, Marseille 13256, France; E-Mail: guillaume.bronsard@ 123456free.fr
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: s.tordjman@ 123456yahoo.fr ; Tel.: +33-6-15-38-07-48; Fax: +33-2-99-64-18-07.
                Article
                ijms-14-20508
                10.3390/ijms141020508
                3821628
                24129182
                596a5d8c-d436-49ff-94c7-19f0beb40963
                © 2013 by the authors; licensee MDPI, Basel, Switzerland

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 06 August 2013
                : 03 September 2013
                : 13 September 2013
                Categories
                Review

                Molecular biology
                melatonin,biological clocks,circadian rhythm,synchrony,autism spectrum disorders,social communication,stereotyped behaviors

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