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      Perspectives of Pitocin administration on behavioral outcomes in the pediatric population: recent insights and future implications

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          Abstract

          Oxytocin plays an important role in the regulation of parturition as this peptide hormone promotes uterine smooth muscle contractility in gravid women undergoing labor. Here, we review the impact of Pitocin administration on behavioral outcomes in the pediatric population. Pitocin is a synthetic preparation of oxytocin widely used in the obstetric practice for the management of labor and postpartum hemorrhage. We begin by tracing the neuroanatomy of oxytocin-containing cells from an evolutionary perspective and then summarize key findings on behavioral and neural activity reported from offspring dosed with Pitocin during vaginal delivery. Finally, we discuss future directions that are experimentally tractable for understanding the developmental consequences of Pitocin administration on a small but growing subset of children worldwide. Given that fetal past experiences can shape the future behavior of the adult, further work on oxytocin signaling pathways will provide valuable references and insights for early-brain development and state-dependent regulation of behavioral outcome.

          Abstract

          Neuroscience; Behavioral neuroscience; Cellular neuroscience; Systems neuroscience; Evolutionary biology; Women's health; Health profession; Oxytocin signaling; Epigenetic phenomena; Breathing behavior; Misfolded proteins; Cardiovascular function

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          Oxytocin pathways and the evolution of human behavior.

          C Carter (2014)
          This review examines the hypothesis that oxytocin pathways--which include the neuropeptide oxytocin, the related peptide vasopressin, and their receptors--are at the center of physiological and genetic systems that permitted the evolution of the human nervous system and allowed the expression of contemporary human sociality. Unique actions of oxytocin, including the facilitation of birth, lactation, maternal behavior, genetic regulation of the growth of the neocortex, and the maintenance of the blood supply to the cortex, may have been necessary for encephalization. Peptide-facilitated attachment also allows the extended periods of nurture necessary for the emergence of human intellectual development. In general, oxytocin acts to allow the high levels of social sensitivity and attunement necessary for human sociality and for rearing a human child. Under optimal conditions oxytocin may create an emotional sense of safety. Oxytocin dynamically moderates the autonomic nervous system, and effects of oxytocin on vagal pathways, as well as the antioxidant and anti-inflammatory effects of this peptide, help to explain the pervasive adaptive consequences of social behavior for emotional and physical health.
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            The timing of eukaryotic evolution: does a relaxed molecular clock reconcile proteins and fossils?

            E. Douzery, E. A. Snell, E Bapteste … (2004)
            The use of nucleotide and amino acid sequences allows improved understanding of the timing of evolutionary events of life on earth. Molecular estimates of divergence times are, however, controversial and are generally much more ancient than suggested by the fossil record. The limited number of genes and species explored and pervasive variations in evolutionary rates are the most likely sources of such discrepancies. Here we compared concatenated amino acid sequences of 129 proteins from 36 eukaryotes to determine the divergence times of several major clades, including animals, fungi, plants, and various protists. Due to significant variations in their evolutionary rates, and to handle the uncertainty of the fossil record, we used a Bayesian relaxed molecular clock simultaneously calibrated by six paleontological constraints. We show that, according to 95% credibility intervals, the eukaryotic kingdoms diversified 950-1,259 million years ago (Mya), animals diverged from choanoflagellates 761-957 Mya, and the debated age of the split between protostomes and deuterostomes occurred 642-761 Mya. The divergence times appeared to be robust with respect to prior assumptions and paleontological calibrations. Interestingly, these relaxed clock time estimates are much more recent than those obtained under the assumption of a global molecular clock, yet bilaterian diversification appears to be approximately 100 million years more ancient than the Cambrian boundary.
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              Oxytocin Pathway Genes: Evolutionary Ancient System Impacting on Human Affiliation, Sociality, and Psychopathology.

              Ruth Feldman, Mikhail Monakhov, Maayan Pratt … (2016)
              Oxytocin (OT), a nonapeptide signaling molecule originating from an ancestral peptide, appears in different variants across all vertebrate and several invertebrate species. Throughout animal evolution, neuropeptidergic signaling has been adapted by organisms for regulating response to rapidly changing environments. The family of OT-like molecules affects both peripheral tissues implicated in reproduction, homeostasis, and energy balance, as well as neuromodulation of social behavior, stress regulation, and associative learning in species ranging from nematodes to humans. After describing the OT-signaling pathway, we review research on the three genes most extensively studied in humans: the OT receptor (OXTR), the structural gene for OT (OXT/neurophysin-I), and CD38. Consistent with the notion that sociality should be studied from the perspective of social life at the species level, we address human social functions in relation to OT-pathway genes, including parenting, empathy, and using social relationships to manage stress. We then describe associations between OT-pathway genes with psychopathologies involving social dysfunctions such as autism, depression, or schizophrenia. Human research particularly underscored the involvement of two OXTR single nucleotide polymorphisms (rs53576, rs2254298) with fewer studies focusing on other OXTR (rs7632287, rs1042778, rs2268494, rs2268490), OXT (rs2740210, rs4813627, rs4813625), and CD38 (rs3796863, rs6449197) single nucleotide polymorphisms. Overall, studies provide evidence for the involvement of OT-pathway genes in human social functions but also suggest that factors such as gender, culture, and early environment often confound attempts to replicate first findings. We conclude by discussing epigenetics, conceptual implications within an evolutionary perspective, and future directions, especially the need to refine phenotypes, carefully characterize early environments, and integrate observations of social behavior across ecological contexts.
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                Author and article information

                Contributors
                German Torres
                Journal
                Journal ID (nlm-ta): Heliyon
                Journal ID (iso-abbrev): Heliyon
                Title: Heliyon
                Publisher: Elsevier
                ISSN (Electronic): 2405-8440
                Publication date PMC-release: 29 May 2020
                Publication date Collection: May 2020
                Publication date (Electronic): 29 May 2020
                Volume: 6
                Issue: 5
                Electronic Location Identifier: e04047
                Affiliations
                [a ]Department of Counseling and Clinical Psychology, Medaille College, Buffalo, New York USA
                [b ]Department of Clinical Specialties, New York College of Osteopathic Medicine, Old Westbury, New York USA
                [c ]Department of Biology, Anoka-Ramsey Community College, Coon Rapids, Minnesota USA
                Author notes
                [∗ ]Corresponding author. gthominid5@ 123456gmail.com
                Article
                Publisher ID: S2405-8440(20)30891-4 Publisher ID: e04047
                DOI: 10.1016/j.heliyon.2020.e04047
                PMC ID: 7264063
                SO-VID: 3f4cd656-5de9-4a34-b629-8e39d0e7d58a
                Copyright © © 2020 The Author(s)
                License:

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                Date received : 6 November 2019
                Date revision received : 18 January 2020
                Date accepted : 19 May 2020
                Categories
                Subject: Article

                Keywords: neuroscience,behavioral neuroscience,cellular neuroscience,systems neuroscience,evolutionary biology,women's health,health profession,oxytocin signaling,epigenetic phenomena,breathing behavior,misfolded proteins,cardiovascular function
                Data availability:
                Keywords: neuroscience, behavioral neuroscience, cellular neuroscience, systems neuroscience, evolutionary biology, women's health, health profession, oxytocin signaling, epigenetic phenomena, breathing behavior, misfolded proteins, cardiovascular function

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