Problems with measuring peripheral oxytocin: can the data on oxytocin and human behavior be trusted?

doi:10.1016/J.NEUBIOREV.2013.04.018

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Problems with measuring peripheral oxytocin: can the data on oxytocin and human behavior be trusted?

Journal Article•DOI•

Problems with measuring peripheral oxytocin: can the data on oxytocin and human behavior be trusted?

Michael E. McCullough¹, Patricia Smith Churchland², Armando J. Mendez¹•Institutions (2)

University of Miami¹, University of California, San Diego²

01 Sep 2013-Neuroscience & Biobehavioral Reviews (Neurosci Biobehav Rev)-Vol. 37, Iss: 8, pp 1485-1492

TL;DR: Evaluation of commercially available methods for measuring OT reveals that they lack reliability when used on unextracted samples of human fluids, and that they tag molecules in addition to OT, yielding estimates that are wildly discrepant with an extensive body of earlier findings.

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About: This article is published in Neuroscience & Biobehavioral Reviews.The article was published on 2013-09-01 and is currently open access. It has received 365 citations till now.

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Journal Article•DOI•

The Social Salience Hypothesis of Oxytocin

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Simone G. Shamay-Tsoory¹, Ahmad Abu-Akel²•Institutions (2)

University of Haifa¹, University of Birmingham²

01 Feb 2016-Biological Psychiatry

TL;DR: A theoretical framework is suggested that focuses on the overarching role of oxytocin in regulating the salience of social cues through its interaction with the dopaminergic system and is dependent on baseline individual differences such as gender, personality traits, and degree of psychopathology.

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626 citations

Cites background from "Problems with measuring peripheral ..."

...It should be noted that the data reported in inOT studies and those examining plasma OT levels (25), are correlational in nature and therefore the implications for central OT activity are controversial (for details see Yang et al; Leng and Ludwig (26) this issue)....
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Journal Article•DOI•

The Oxytocin Receptor: From Intracellular Signaling to Behavior

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Benjamin Jurek¹, Inga D. Neumann¹•Institutions (1)

University of Regensburg¹

01 Jul 2018-Physiological Reviews

TL;DR: The mechanisms of OXT expression and release, expression and binding of the OXTR in brain and periphery, OX TR-coupled signaling cascades, and their involvement in behavioral outcomes are discussed to assemble a comprehensive picture of the central and peripheral OXT system.

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Abstract: The many facets of the oxytocin (OXT) system of the brain and periphery elicited nearly 25,000 publications since 1930 (see FIGURE 1, as listed in PubMed), which revealed central roles for OXT and ...

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510 citations

Journal Article•DOI•

Intranasal Oxytocin: Myths and Delusions

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Gareth Leng¹, Mike Ludwig¹•Institutions (1)

University of Edinburgh¹

01 Feb 2016-Biological Psychiatry

TL;DR: Effects of intranasal oxytocin also need proper dose-response studies, and such studies need to include control subjects for peripheral effects, by administering Oxytocin peripherally and by blocking peripheral actions with antagonists.

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492 citations

Cites background from "Problems with measuring peripheral ..."

...In response to caustic criticism (66), the manufacturers “strongly 285 recommended” that plasma samples should be extracted to avoid matrix interference (67), a 286 recommendation reinforced by Christensen et al....
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Journal Article•DOI•

The oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: a meta-analysis.

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Devon LoParo¹, Irwin D. Waldman¹•Institutions (1)

Emory University¹

01 May 2015-Molecular Psychiatry

TL;DR: The current meta-analysis is the largest and most comprehensive investigation of the association of OXTR with ASD and the findings suggest directions for future studies of the etiology of ASD.

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Abstract: The oxytocin receptor gene (OXTR) has been studied as a risk factor for autism spectrum disorder (ASD) owing to converging evidence from multiple levels of analysis that oxytocin (OXT) has an important role in the regulation of affiliative behavior and social bonding in both nonhuman mammals and humans. Inconsistency in the effect sizes of the OXTR variants included in association studies render it unclear whether OXTR is truly associated with ASD, and, if so, which OXTR single-nucleotide polymorphisms (SNPs) are associated. Thus, a meta-analytic review of extant studies is needed to determine whether OXTR shows association with ASD, and to elucidate which specific SNPs have a significant effect on ASD. The current meta-analysis of 16 OXTR SNPs included 3941 individuals with ASD from 11 independent samples, although analyses of each individual SNP included a subset of this total. We found significant associations between ASD and the SNPs rs7632287, rs237887, rs2268491 and rs2254298. OXTR was also significantly associated with ASD in a gene-based test. The current meta-analysis is the largest and most comprehensive investigation of the association of OXTR with ASD and the findings suggest directions for future studies of the etiology of ASD.

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268 citations

Journal Article•DOI•

Oxytocin enhances brain reward system responses in men viewing the face of their female partner

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Dirk Scheele¹, Andrea Wille, Keith M. Kendrick², Birgit Stoffel-Wagner¹, Benjamin Becker, Onur Güntürkün³, Wolfgang Maier⁴, René Hurlemann - Show less +4 more•Institutions (4)

University of Bonn¹, University of Electronic Science and Technology of China², Ruhr University Bochum³, German Center for Neurodegenerative Diseases⁴

10 Dec 2013-Proceedings of the National Academy of Sciences of the United States of America

TL;DR: Evidence is provided for a mechanism by which OXT may contribute to romantic bonds in men by enhancing their partner's attractiveness and reward value compared with other women and for a finding that this finding is partner-bond specific rather than due to familiarity.

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Abstract: The biological mechanisms underlying long-term partner bonds in humans are unclear. The evolutionarily conserved neuropeptide oxytocin (OXT) is associated with the formation of partner bonds in some species via interactions with brain dopamine reward systems. However, whether it plays a similar role in humans has as yet not been established. Here, we report the results of a discovery and a replication study, each involving a double-blind, placebo-controlled, within-subject, pharmaco-functional MRI experiment with 20 heterosexual pair-bonded male volunteers. In both experiments, intranasal OXT treatment (24 IU) made subjects perceive their female partner's face as more attractive compared with unfamiliar women but had no effect on the attractiveness of other familiar women. This enhanced positive partner bias was paralleled by an increased response to partner stimuli compared with unfamiliar women in brain reward regions including the ventral tegmental area and the nucleus accumbens (NAcc). In the left NAcc, OXT even augmented the neural response to the partner compared with a familiar woman, indicating that this finding is partner-bond specific rather than due to familiarity. Taken together, our results suggest that OXT could contribute to romantic bonds in men by enhancing their partner's attractiveness and reward value compared with other women.

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262 citations

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References

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Journal Article•DOI•

Bioanalytical method validation--a revisit with a decade of progress.

[...]

Vinod P. Shah¹, Kamal K. Midha², John W. A. Findlay³, Howard Hill⁴, James D. Hulse, Iain J. McGilveray, Gordon McKay², Krys J. Miller⁵, Rabindra Patnaik¹, Mark L. Powell⁶, Alfred P. Tonelli⁷, C. T. Viswanathan¹, Avraham Yacobi - Show less +9 more•Institutions (7)

Center for Drug Evaluation and Research¹, University of Saskatchewan², Pharmacia³, Huntingdon Life Sciences⁴, Amgen⁵, Bristol-Myers Squibb⁶, Purdue Pharma⁷

01 Dec 2000-Pharmaceutical Research

TL;DR: The purpose of this report is to represent the progress in analytical methodologies over the last decade and assessment of the major agreements and issues discussed with regard to small molecules at both the conference and the workshop.

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Abstract: This report is a synthesis of (1) the earlier conference on Analytical Methods Validation−Bioavailability, Bioequivalence and Pharmacokinetic Studies (Conference held in Arlington, VA, December 3–5, 1990 and the report published in Pharmaceutical Research, 9: 588-592, 1992) and (2) the workshop on “Bioanalytical Methods Validation—A Revisit with a Decade of Progress,” (Workshop held in Arlington, VA, January 12–14, 2000), sponsored by the American Association of Pharmaceutical Scientists and the U. S. Food and Drug Administration. The bioanalytical method validation workshop of January 12–14, 2000 was directed towards small molecules. A separate workshop was held in March 1–3, 2000 to discuss validation principles for macromolecules. The purpose of this report is to represent the progress in analytical methodologies over the last decade and assessment of the major agreements and issues discussed with regard to small molecules at both the conference and the workshop. The report is also intended to provide guiding principles for validation of bioanalytical methods employed in support of bioavailability, bioequivalence, and pharmacokinetic studies in man and in animals.

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1,588 citations

Journal Article•DOI•

Oxytocin, vasopressin, and the neurogenetics of sociality.

[...]

Zoe R. Donaldson¹, Larry J. Young¹•Institutions (1)

Emory University¹

07 Nov 2008-Science

TL;DR: There is growing evidence that the neuropeptides oxytocin and vasopressin modulate complex social behavior and social cognition and suggest that variation in the genes encoding their receptors may contribute to variation in human social behavior by altering brain function.

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Abstract: There is growing evidence that the neuropeptides oxytocin and vasopressin modulate complex social behavior and social cognition. These ancient neuropeptides display a marked conservation in gene structure and expression, yet diversity in the genetic regulation of their receptors seems to underlie natural variation in social behavior, both between and within species. Human studies are beginning to explore the roles of these neuropeptides in social cognition and behavior and suggest that variation in the genes encoding their receptors may contribute to variation in human social behavior by altering brain function. Understanding the neurobiology and neurogenetics of social cognition and behavior has important implications, both clinically and for society.

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1,445 citations

"Problems with measuring peripheral ..." refers background in this paper

...…al h om epage: www.elsev ier .com/ locate /neubiorev eview roblems with measuring peripheral oxytocin: Can the data on oxytocin and uman behavior be trusted? ichael E. McCullougha, Patricia Smith Churchlandb, Armando J. Mendezc,∗ Department of Psychology, University of Miami, P.O. Box 248185,…...
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...Introduction The roles of the neurohypophyseal peptide oxytocin (OT) in schizophrenia (Beckmann et al., 1985; Donaldson and Young, 2008; Hammock and Young, 2006; Meyer-Lindenberg et al., 2011; Modahl et al., 1998)....
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Journal Article•DOI•

Oxytocin and vasopressin in the human brain: social neuropeptides for translational medicine

[...]

Andreas Meyer-Lindenberg¹, Gregor Domes², Peter Kirsch¹, Markus Heinrichs²•Institutions (2)

Heidelberg University¹, University of Freiburg²

01 Sep 2011-Nature Reviews Neuroscience

TL;DR: OXT and AVP are emerging as targets for novel treatment approaches — particularly in synergistic combination with psychotherapy — for mental disorders characterized by social dysfunction, such as autism, social anxiety disorder, borderline personality disorder and schizophrenia.

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Abstract: The neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) are evolutionarily highly conserved mediators in the regulation of complex social cognition and behaviour. Recent studies have investigated the effects of OXT and AVP on human social interaction, the genetic mechanisms of inter-individual variation in social neuropeptide signalling and the actions of OXT and AVP in the human brain as revealed by neuroimaging. These data have advanced our understanding of the mechanisms by which these neuropeptides contribute to human social behaviour. OXT and AVP are emerging as targets for novel treatment approaches — particularly in synergistic combination with psychotherapy — for mental disorders characterized by social dysfunction, such as autism, social anxiety disorder, borderline personality disorder and schizophrenia.

...read moreread less

1,436 citations

"Problems with measuring peripheral ..." refers background in this paper

...Introduction The roles of the neurohypophyseal peptide oxytocin (OT) in schizophrenia (Beckmann et al., 1985; Donaldson and Young, 2008; Hammock and Young, 2006; Meyer-Lindenberg et al., 2011; Modahl et al., 1998)....
[...]
...R P h M a b c 1 a A R R A K O P R E ( E B C 1 h i s c p ( 0 h Neuroscience and Biobehavioral Reviews 37 (2013) 1485–1492 Contents lists available at ScienceDirect Neuroscience and Biobehavioral Reviews jou rn al h om epage: www.elsev ier .com/ locate /neubiorev eview roblems with measuring peripheral oxytocin: Can the data on oxytocin and uman behavior be trusted? ichael E. McCullougha, Patricia Smith Churchlandb, Armando J. Mendezc,∗ Department of Psychology, University of Miami, P.O. Box 248185, Coral Gables, FL 33124-0751, USA Department of Philosophy, University of California, San Diego, La Jolla, CA 92093-0119, USA Diabetes Research Institute, Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, University of Miami Miller School of Medicine, 450 NW 10th Avenue, Miami, FL 33136, USA r t i c l e i n f o rticle history: eceived 18 June 2012 eceived in revised form 26 April 2013 ccepted 30 April 2013 eywords: a b s t r a c t Research on the neurobiological and behavioral effects of oxytocin (OT), as well as on its possible therapeutic applications, has intensified in the past decade....
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...…with measuring peripheral oxytocin: Can the data on oxytocin and uman behavior be trusted? ichael E. McCullougha, Patricia Smith Churchlandb, Armando J. Mendezc,∗ Department of Psychology, University of Miami, P.O. Box 248185, Coral Gables, FL 33124-0751, USA Department of…...
[...]

Journal Article•DOI•

The Diagnostic Applications of Saliva— A Review:

[...]

Eliaz Kaufman¹, Ira B. Lamster¹•Institutions (1)

Columbia University¹

01 Mar 2002-Critical Reviews in Oral Biology & Medicine

TL;DR: Analysis of saliva may be useful for the diagnosis of hereditary disorders, autoimmune diseases, malignant and infectious diseases, and endocrine disorders, as well as in the assessment of therapeutic levels of drugs and the monitoring of illicit drug use.

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Abstract: This review examines the diagnostic application of saliva for systemic diseases. As a diagnostic fluid, saliva offers distinctive advantages over serum because it can be collected non-invasively by individuals with modest training. Furthermore, saliva may provide a cost-effective approach for the screening of large populations. Gland-specific saliva can be used for diagnosis of pathology specific to one of the major salivary glands. Whole saliva, however, is most frequently used for diagnosis of systemic diseases, since it is readily collected and contains serum constituents. These constituents are derived from the local vasculature of the salivary glands and also reach the oral cavity via the flow of gingival fluid. Analysis of saliva may be useful for the diagnosis of hereditary disorders, autoimmune diseases, malignant and infectious diseases, and endocrine disorders, as well as in the assessment of therapeutic levels of drugs and the monitoring of illicit drug use.

...read moreread less

843 citations

Journal Article•DOI•

Balance of brain oxytocin and vasopressin: implications for anxiety, depression, and social behaviors

[...]

Inga D. Neumann¹, Rainer Landgraf²•Institutions (2)

University of Regensburg¹, Max Planck Society²

01 Nov 2012-Trends in Neurosciences

TL;DR: Shifting the balance between the neuropeptide systems towards oxytocin, by positive social stimuli and/or psychopharmacotherapy, may help to improve emotional behaviors and reinstate mental health.

...read moreread less

764 citations

"Problems with measuring peripheral ..." refers background in this paper

...Issues in the measurement of peripheral oxytocin in humans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1486 2.1....
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...Second, and related, it remains unknown whether xogenously administered OT interacts with endogenous levels f OT or other hormones (Churchland and Winkielman, 2012; acDonald et al., 2011; Neumann and Landgraf, 2012)....
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...…when used on unextracted sam- xytocin eptides adioimmunoassay (RIA) nzyme-linked immunoabsorbent assay ELISA) nzyme immunoassay (EIA) ples of human fluids, and that they tag molecules in addition to OT, yielding estimates that are wildly discrepant with an extensive body of earlier…...
[...]