Recommendations for the standardisation of oxytocin nasal administration and guidelines for its reporting in human research.

doi:10.1016/J.PSYNEUEN.2012.11.019

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Recommendations for the standardisation of oxytocin nasal administration and guidelines for its reporting in human research.

Journal Article•DOI•

Recommendations for the standardisation of oxytocin nasal administration and guidelines for its reporting in human research.

Adam J. Guastella¹, Ian B. Hickie¹, Margaret M. McGuinness¹, Margaret M. McGuinness², Melissa Otis², Melissa Otis¹, Elizabeth A. Woods³, Elizabeth A. Woods¹, Hannah M. Disinger¹, Hannah M. Disinger⁴, Hak-Kim Chan¹, Timothy F. Chen¹, Richard B. Banati⁵, Richard B. Banati¹ - Show less +10 more•Institutions (5)

University of Sydney¹, Boston University², University of Kentucky³, University of Minnesota⁴, Australian Nuclear Science and Technology Organisation⁵

01 May 2013-Psychoneuroendocrinology (Elsevier)-Vol. 38, Iss: 5, pp 612-625

TL;DR: A summary of factors that influence transmucosal nasal drug delivery, deposition, and their impact on bioavailability is provided, including variations in anatomy and resultant airflow dynamic, vascularisation, status of blood vessels, mode of spray application, gallenic formulation, and amount and method of administration.

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About: This article is published in Psychoneuroendocrinology.The article was published on 2013-05-01. It has received 313 citations till now. The article focuses on the topics: Nasal spray & Nasal administration.

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Journal Article•DOI•

Elevated cerebrospinal fluid and blood concentrations of oxytocin following its intranasal administration in humans

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Nadine Striepens¹, Keith M. Kendrick², Vanessa Hanking¹, Rainer Landgraf³, Ullrich Wüllner¹, Wolfgang Maier⁴, Wolfgang Maier¹, René Hurlemann¹ - Show less +4 more•Institutions (4)

University of Bonn¹, University of Electronic Science and Technology of China², Max Planck Society³, German Center for Neurodegenerative Diseases⁴

06 Dec 2013-Scientific Reports

TL;DR: Combined blood and cerebrospinal fluid sampling in subjects receiving either 24 IU of oxytocin or placebo is shown to show that oxytocIn levels significantly increased in both plasma and CSF, however, whereas Oxytocin plasma concentrations peaked at 15 min after intranasal administration and decreased after 75’�min, CSF concentrations took up to 75”min to reach a significant level.

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Abstract: There has been an unprecedented interest in the modulatory effects of intranasal oxytocin on human social cognition and behaviour, however as yet no study has actually demonstrated that this modality of administration increases concentrations of the peptide in the brain as well as blood in humans. Here using combined blood and cerebrospinal fluid (CSF) sampling in subjects receiving either 24 IU of oxytocin (n = 11) or placebo (n = 4) we have shown that oxytocin levels significantly increased in both plasma and CSF. However, whereas oxytocin plasma concentrations peaked at 15 min after intranasal administration and decreased after 75 min, CSF concentrations took up to 75 min to reach a significant level. Moreover, there was no correlation (r = <0.10) between oxytocin plasma and CSF concentrations. Together, these data provide crucial insights into the plasma and CSF kinetics of intranasally administered oxytocin.

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413 citations

Journal Article•DOI•

Sniffing around oxytocin : Review and meta-analyses of trials in healthy and clinical groups with implications for pharmacotherapy

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Marian J. Bakermans-Kranenburg¹, M.H. van IJzendoorn¹•Institutions (1)

Leiden University¹

21 May 2013-Translational Psychiatry

TL;DR: It is hypothesize that for some of the other disorders, etiological factors rooted in negative childhood experiences may also have a role in the diminished effectiveness of treatment with OT.

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Abstract: The popularity of oxytocin (OT) has grown exponentially during the past decade, and so has the number of OT trials in healthy and clinical groups We take stock of the evidence from these studies to explore potentials and limitations of pharmacotherapeutic applications In healthy participants, intranasally administered OT leads to better emotion recognition and more trust in conspecifics, but the effects appear to be moderated by context (perceived threat of the ‘out-group’), personality and childhood experiences In individuals with untoward childhood experiences, positive behavioral or neurobiological effects seem lowered or absent In 19 clinical trials, covering autism, social anxiety, postnatal depression, obsessive-compulsive problems, schizophrenia, borderline personality disorder and post-traumatic stress, the effects of OT administration were tested, with doses ranging from 15 IU to more than 7000 IU The combined effect size was d=032 (N=304; 95% confidence interval (CI): 018–047; P<001) However, of all disorders, only studies on autism spectrum disorder showed a significant combined effect size (d=057; N=68; 95% CI: 015–099; P<001) We hypothesize that for some of the other disorders, etiological factors rooted in negative childhood experiences may also have a role in the diminished effectiveness of treatment with OT

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365 citations

Cites background or methods from "Recommendations for the standardisa..."

...These include the transfer of OT through the olfactory epithelium into the systemic circulation, through oral mucosa (after swallowing), through the olfactory bulb pathways directly into the cerebrospinal fluid and brain, through the trigeminal nerve that innervates the respiratory and olfactory epithelium and enters the brain stem and the pons, and through the paravascular spaces that connect into the interstitial spaces of the brain parenchyma.(29)...
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...Intranasal administration of OT is simple to use, but does it reach the receptors in the brain? The nasal mucosa provides a direct connection with the central nervous system, and five absorption routes from the nasal cavity to the central nervous system have been suggested.(29) These include the transfer of OT through the olfactory epithelium into the systemic circulation, through oral mucosa (after swallowing), through the olfactory bulb pathways directly into the cerebrospinal fluid and brain, through the trigeminal nerve that innervates the respiratory and olfactory epithelium and enters the brain stem and the pons, and through the paravascular spaces that connect into the interstitial spaces of the brain parenchyma....
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...If the pathway causing the behavioral effects of OT treatment is initially peripheral followed by increased central OT levels rather than initially central, then nasal administration is a suboptimal method for increasing central OT levels.(29) Acknowledging these unsolved puzzles, we conclude that there is sufficient experimental evidence to support the neural and behavioral changes caused by OT sniffs....
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Journal Article•DOI•

Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies

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Hasse Walum, Irwin D. Waldman¹, Larry J. Young²•Institutions (2)

Emory University¹, Yerkes National Primate Research Center²

01 Feb 2016-Biological Psychiatry

TL;DR: It is concluded that intranasal OT studies are generally underpowered and that there is a high probability that most of the published intran asal OT findings do not represent true effects.

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273 citations

Journal Article•DOI•

The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial

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Chathuri Yatawara¹, Stewart L. Einfeld¹, Ian B. Hickie¹, Tracey A Davenport¹, Adam J. Guastella¹ - Show less +1 more•Institutions (1)

University of Sydney¹

01 Sep 2016-Molecular Psychiatry

TL;DR: This study is the first clinical trial to support the potential of oxytocin as an early intervention for young children with autism to help improve social interaction deficits and nasal spray was well tolerated.

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Abstract: Interventions for autism are limited. The synthetic hormone oxytocin may provide a potential treatment to improve core social and behavioral difficulties in autism, but its efficacy has yet to be evaluated in young children who potentially may benefit to a greater extent. We investigated the efficacy, tolerability and safety of oxytocin treatment in young children with autism using a double-blind, randomized, placebo-controlled, crossover, clinical trial. Thirty-one children with autism received 12 International Units (IU) of oxytocin and placebo nasal spray morning and night (24 IU per day) for 5 weeks, with a 4-week washout period between each treatment. Compared with placebo, oxytocin led to significant improvements on the primary outcome of caregiver-rated social responsiveness. Overall, nasal spray was well tolerated, and the most common reported adverse events were thirst, urination and constipation. This study is the first clinical trial to support the potential of oxytocin as an early intervention for young children with autism to help improve social interaction deficits.

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271 citations

Journal Article•DOI•

Carrageenan Based Hydrogels for Drug Delivery, Tissue Engineering and Wound Healing

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Ramanathan Yegappan¹, Vignesh Selvaprithiviraj¹, Sivashanmugam Amirthalingam¹, Rangasamy Jayakumar¹•Institutions (1)

Amrita Institute of Medical Sciences and Research Centre¹

15 Oct 2018-Carbohydrate Polymers

TL;DR: An overview of developing various forms of carrageenan based hydrogels is provided, focusing on how these fabrication processes has an effect on physiochemical properties of the hydrogel.

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258 citations

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References

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Open Access

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Journal Article•DOI•

A paravascular pathway facilitates CSF flow through the brain parenchyma and the clearance of interstitial solutes, including amyloid β.

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Jeffrey J. Iliff¹, Minghuan Wang¹, Minghuan Wang², Yonghong Liao¹, Benjamin A. Plogg¹, Weiguo Peng¹, Georg Andreas Gundersen³, Helene Benveniste⁴, G. Edward Vates¹, Rashid Deane¹, Steven A. Goldman¹, Erlend A. Nagelhus³ - Show less +8 more•Institutions (4)

University of Rochester Medical Center¹, Huazhong University of Science and Technology², University of Oslo³, Stony Brook University⁴

15 Aug 2012-Science Translational Medicine

TL;DR: An anatomically distinct clearing system in the brain that serves a lymphatic-like function is described and may have relevance for understanding or treating neurodegenerative diseases that involve the mis-accumulation of soluble proteins, such as amyloid β in Alzheimer's disease.

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Abstract: Because it lacks a lymphatic circulation, the brain must clear extracellular proteins by an alternative mechanism. The cerebrospinal fluid (CSF) functions as a sink for brain extracellular solutes, but it is not clear how solutes from the brain interstitium move from the parenchyma to the CSF. We demonstrate that a substantial portion of subarachnoid CSF cycles through the brain interstitial space. On the basis of in vivo two-photon imaging of small fluorescent tracers, we showed that CSF enters the parenchyma along paravascular spaces that surround penetrating arteries and that brain interstitial fluid is cleared along paravenous drainage pathways. Animals lacking the water channel aquaporin-4 (AQP4) in astrocytes exhibit slowed CSF influx through this system and a ~70% reduction in interstitial solute clearance, suggesting that the bulk fluid flow between these anatomical influx and efflux routes is supported by astrocytic water transport. Fluorescent-tagged amyloid β, a peptide thought to be pathogenic in Alzheimer's disease, was transported along this route, and deletion of the Aqp4 gene suppressed the clearance of soluble amyloid β, suggesting that this pathway may remove amyloid β from the central nervous system. Clearance through paravenous flow may also regulate extracellular levels of proteins involved with neurodegenerative conditions, its impairment perhaps contributing to the mis-accumulation of soluble proteins.

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3,368 citations

"Recommendations for the standardisa..." refers background in this paper

...Psychoneuroendocrinol stem (Thorne et al., 2004; Qingfeng et al., 2012) and (5) the paravascular spaces that connect into the interstitial spaces of the brain parenchyma (Iliff et al., 2012)....
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...Efficient fluid transport appears to occur along paravascular spaces (Iliff et al., 2012)....
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Journal Article•DOI•

Oxytocin increases trust in humans

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Michael Kosfeld¹, Markus Heinrichs¹, Paul J. Zak², Urs Fischbacher¹, Ernst Fehr³, Ernst Fehr¹ - Show less +2 more•Institutions (3)

University of Zurich¹, Claremont Graduate University², ETH Zurich³

02 Jun 2005-Nature

TL;DR: It is shown that intranasal administration of oxytocin, a neuropeptide that plays a key role in social attachment and affiliation in non-human mammals, causes a substantial increase in trust among humans, thereby greatly increasing the benefits from social interactions.

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Abstract: Trust pervades human societies. Trust is indispensable in friendship, love, families and organizations, and plays a key role in economic exchange and politics. In the absence of trust among trading partners, market transactions break down. In the absence of trust in a country's institutions and leaders, political legitimacy breaks down. Much recent evidence indicates that trust contributes to economic, political and social success. Little is known, however, about the biological basis of trust among humans. Here we show that intranasal administration of oxytocin, a neuropeptide that plays a key role in social attachment and affiliation in non-human mammals, causes a substantial increase in trust among humans, thereby greatly increasing the benefits from social interactions. We also show that the effect of oxytocin on trust is not due to a general increase in the readiness to bear risks. On the contrary, oxytocin specifically affects an individual's willingness to accept social risks arising through interpersonal interactions. These results concur with animal research suggesting an essential role for oxytocin as a biological basis of prosocial approach behaviour.

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3,202 citations

"Recommendations for the standardisa..." refers background in this paper

...The role of demand characteristics in experiments, such as the Hawthorne Effect (Roethlisberger and Dickson, 2003), is particularly concerning for a drug that is believed to heighten suggestibility (Bryant et al., 2012) and trust (Kosfeld et al., 2005)....
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Journal Article•DOI•

The Oxytocin Receptor System: Structure, Function, and Regulation

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Gerald Gimpl¹, Falk Fahrenholz¹•Institutions (1)

University of Mainz¹

01 Apr 2001-Physiological Reviews

TL;DR: The regulation by gonadal and adrenal steroids is one of the most remarkable features of the OT system and is, unfortunately, the least understood.

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Abstract: The neurohypophysial peptide oxytocin (OT) and OT-like hormones facilitate reproduction in all vertebrates at several levels. The major site of OT gene expression is the magnocellular neurons of the hypothalamic paraventricular and supraoptic nuclei. In response to a variety of stimuli such as suckling, parturition, or certain kinds of stress, the processed OT peptide is released from the posterior pituitary into the systemic circulation. Such stimuli also lead to an intranuclear release of OT. Moreover, oxytocinergic neurons display widespread projections throughout the central nervous system. However, OT is also synthesized in peripheral tissues, e.g., uterus, placenta, amnion, corpus luteum, testis, and heart. The OT receptor is a typical class I G protein-coupled receptor that is primarily coupled via Gq proteins to phospholipase C-β. The high-affinity receptor state requires both Mg2+ and cholesterol, which probably function as allosteric modulators. The agonist-binding region of the receptor has bee...

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2,691 citations

"Recommendations for the standardisa..." refers background in this paper

..., 2007), OT is a nonapeptide which consists of nine amino acid subunit peptides with a molecular mass of 1007 Daltons (Gimpl and Fahrenholz, 2001)....
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...Oxytocin is primarily synthesized by, and secreted from, magnocellular cells in the supraoptic and paraventricular nuclei, with receptors spread across the central nervous system, and released into circulation by the posterior pituitary (Gimpl and Fahrenholz, 2001)....
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...Born and colleagues administered AVP (which is similar to OT in structure and has a molecular mass of 1042 Daltons) intranasally and found AVP Please cite this article in press as: Guastella, A.J., et al., Recommend guidelines for its reporting in human research....
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...Its roles in key regulatory systems have been well documented elsewhere, particularly in labor, parturition, milk ejection, and sexual behavior (Gimpl and Fahrenholz, 2001)....
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...While low molecular weight molecules, therapeutic peptides, and proteins are capable of crossing the blood brain barrier (Costantino et al., 2007), OT is a nonapeptide which consists of nine amino acid subunit peptides with a molecular mass of 1007 Daltons (Gimpl and Fahrenholz, 2001)....
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Journal Article•DOI•

Social effects of oxytocin in humans: context and person matter.

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Jennifer A. Bartz¹, Jamil Zaki², Niall Bolger³, Kevin N. Ochsner³•Institutions (3)

Icahn School of Medicine at Mount Sinai¹, Harvard University², Columbia University³

01 Jul 2011-Trends in Cognitive Sciences

TL;DR: It is proposed that this literature can be informed by an interactionist approach in which the effects of oxytocin are constrained by features of situations and/or individuals.

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1,311 citations

"Recommendations for the standardisa..." refers background or methods in this paper

...This work provided the foundation for a heated research field administering and studying OT nasal sprays effects on humans (Bartz et al., 2011)....
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...…the encoding of social memories, the retrieval of social cues, and the accurate and positive appraisal of social information at various levels of processing (see Bartz et al., 2011; Guastella and MacLeod, 2012 for thorough reviews of the psychological effects of OT nasal spray in humans)....
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...Bartz and colleagues (Bartz et al., 2011) presented a compelling argument for consideration of context and individual difference factors to account for this variation....
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Journal Article•DOI•

The neurobiology of pair bonding

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Larry J. Young¹, Zuoxin Wang²•Institutions (2)

Yerkes National Primate Research Center¹, Florida State University²

01 Oct 2004-Nature Neuroscience

TL;DR: Differential regulation of neuropeptide receptor expression may explain species differences in the ability to form pair bonds and have intriguing implications for the neurobiology of social attachment in the authors' own species.

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Abstract: A neurobiological model for pair-bond formation has emerged from studies in monogamous rodents. The neuropeptides oxytocin and vasopressin contribute to the processing of social cues necessary for individual recognition. Mesolimbic dopamine is involved in reinforcement and reward learning. Concurrent activation of neuropeptide and dopamine receptors in the reward centers of the brain during mating results in a conditioned partner preference, observed as a pair bond. Differential regulation of neuropeptide receptor expression may explain species differences in the ability to form pair bonds. These and other studies discussed here have intriguing implications for the neurobiology of social attachment in our own species.

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1,287 citations

"Recommendations for the standardisa..." refers background in this paper

...In non-human mammals, research shows that central administration of OT agonists enhances social recognition, memory for peers, the development of partner preference, and partner bonding (for a review see (Young and Wang, 2004))....
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...The nonhuman animal research has shown that direct injection of OT to specific brain targets enhances social behavior (Young and Wang, 2004), leading to assumptions that OT administration in humans also causes effects through direct central action....
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