"Animal spirits" and hormones: understanding trust in interpersonal interactions

Lead Research Organisation: King's College London
Department Name: Neuroimaging

Abstract

Prosperity in all aspects of social life, from interpersonal relationships to economic or political relationships, depends on human cooperation and trust. The concept of trust is particularly relevant these days, as some economists have attributed the ebbs and flows of the economy to irrational fluctuations in our confidence in others. Trust will be defined as the subjective expectation that others will not harm or disadvantage us in instances when they have an opportunity to do so. Accordingly, trust decisions will be defined as the decisions that give others such an opportunity. Why do people differ in the ways and degrees in which they trust familiar or unfamiliar others in given interpersonal situations? What dynamic interplay of parameters determines trust decisions in interpersonal interactions? Can such decisions be facilitated or inhibited by some intervention and how? These questions are at the heart of this project. To answer these questions we will design experiments that entail 'on-line' interpersonal exchanges and will model the complexity of human behaviour in these interactions using advanced methods. We will measure the dynamic influence of various individual traits and social signals (e.g. 'trustworthy' behaviour by others) on people's decisions to trust others. In this endeavour, we will use the oxytocin system as a tool.

The oxytocin system in the brain may be one of the main mechanisms driving individual differences in the expression of interpersonal trust. In animal studies, scientists have discovered that this neural system, which uses the hormone oxytocin to communicate with other brain areas, plays a key role in inter-species differences in social behaviour, as well as in differences between members of the same species. For example, the oxytocin system has been shown to influence the formation of lasting attachments with one's offspring or peers, the display of caring behaviour towards offspring or partners, social play, the recognition of one's partner's or offspring's by their odour, or the display of distress by offspring when abandoned. While there is also accumulating evidence that the function of the oxytocin system also influences social behaviour in humans, almost nothing is known regarding how the oxytocin system is organised in the human brain. We also know next to nothing about the possible existence of gender differences (as is the case with other species), about how this system is linked with differences in human social preferences, including decisions to trust, and about how this system can exert a dynamic influence on the processes underlying judgements of trustworthiness and decisions to trust.

In this project, we will use state-of-the-art neuroimaging techniques and innovative data modelling and analysis methods to try and shed some light on these questions. We hope to generate new findings that will make a significant contribution to understanding the processes driving trust behaviour, as well as to generate new evidence about the oxytocin system in the human brain, which will be of direct interest across a range of disciplines.

Planned Impact

The successful completion of this project will generate urgently needed findings that will be directly relevant and translatable not only to several research domains, but also to any domains of social life based on interpersonal relationships and trust.

Some of the potential benefits of this project for non-academic beneficiaries are:

(1) Intranasal oxytocin has started to emerge as a potential adjunct treatment for disorders with deficits in the processing of social information (e.g. autism), social skills (e.g. borderline personality disorder) or with anxiety and depression symptoms. While the proposed work does not directly assess the efficacy of oxytocin as a treatment for these conditions, we hope it will provide some important new findings that may guide psychiatric applications and benefit patient groups. Specifically:

- The information on the pharmacokinetics and pharmacodynamics of oxytocin in the human brain will provide the necessary basic science information for the optimal design of clinical trials using intranasal oxytocin.
- We will try to link, for the first time, differences in the geography of oxytocin receptors with differences in social behaviour. Animal research suggests that this, and not the increase in the volume of released oxytocin in the brain, is the critical factor underpinning social behaviour. This is an important issue to take into consideration when examining the use of intranasal sprays as an adjunct therapy, e.g. in autism.
- We will generate information regarding gender differences in (a) the oxytocin system in the human brain, (b) the effects of intranasal oxytocin on human behaviour and (c) the link between brain and behaviour. These findings could inform decisions regarding the potential use of oxytocin in the case of disorders with marked gender differences. Examples include the treatment of social deficits in autistic spectrum disorders, or in the treatment of anxiety and depression symptoms in mood disorders.

(2) Drug companies and neuropsychopharmacologists developing new compounds to act on the central nervous system may benefit from our research, as it will contribute to the development of a new non-invasive methodological approach to investigate the effects of compounds in the central nervous system, and estimate information about their pharmacokinetics and pharmacodynamics.

(3) We expect that the findings we will generate will be of great interest to the general public. Findings from the nascent field of oxytocin research often make the news headlines, indicating that they have a wider societal appeal. This is because oxytocin is believed to be involved in all quintessential aspects of human social life - love, sex, trust, morality to name a few. The effects of oxytocin sprays may be exaggerated by the news media when they talk about the "hormone of love", the "moral molecule" or the "trust hormone", or when concerns are raised about potential abuse, e.g. by political propaganda. But trust is the implicit fabric of our societies, the basis of our interpersonal as well as social and political relations, of which we understand so little in experimental psychology and neuroscience. We expect that the wider audience will be interested in our findings, and we will undertake an ambitious public dissemination program to this effect (see Pathways to impact).

Therefore, the outcomes of this project are expected to have both health care and societal impact.

Publications

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Hurter S (2014) Partners' empathy increases pain ratings: effects of perceived empathy and attachment style on pain report and display. in The journal of pain : official journal of the American Pain Society

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Krahé C (2015) Attachment style moderates partner presence effects on pain: a laser-evoked potentials study. in Social cognitive and affective neuroscience

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Krahé C (2016) Affective touch and attachment style modulate pain: a laser-evoked potentials study. in Philosophical transactions of the Royal Society of London. Series B, Biological sciences

 
Description Robust evidence from animals demonstrates the importance of the oxytocin system in the brain in the regulation of social behaviour and cognition. Animal research, as well as genetic studies from humans further link abnormalities in the oxytocin system with a range of neuropsychiatric disorders. This work highlights the administration of synthetic oxytocin as a promising pharmacological agent to target key brain regions that regulate social behaviour and address social impairment in psychiatric disorders.
Human studies have almost exclusively relied on the administration of synthetic oxytocin with nasal sprays. It has been assumed that synthetic oxytocin reaches the brain through direct nose to brain pathways, bypassing the blood-brain barrier (an obstacle in the delivery of large peptides like oxytocin, which do not cross the blood-brain barrier, to the brain in sufficient amounts). Yet it is argued intranasal oxytocin may not be reaching the brain directly, and its effects may be mediated by increasing the concentration of oxytocin in the blood and acting on peripheral oxytocin receptors. Furthermore, intranasal sprays provide poor control over the administered dose and an inefficient way of targeting the areas of the nasal cavity underlying direct nose to brain transportation. An additional obstacle in human research is that the time course of the effects of intranasal oxytocin in the human brain has not yet been directly established. Finally, we do not yet know how the oxytocin system is organised in the living, typically developing, human brain.
In this project we have completed important groundwork addressing these questions, which have been having and will be having an impact on a wide range of experimental studies and clinical trials in the field (as demonstrated in the wide range of collaborations linked with this grant). Specifically:
(A) We mapped the brain areas responding to synthetic oxytocin and we obtained a functional signature of the response to oxytocin using pattern recognition. Additionally, we generated a roadmap regarding the optimal timing of experimental and clinical interventions using intranasal oxytocin (Paloyelis et al., 2016).
(B) We provided new evidence supporting the hypothesis of a direct nose-to-brain pathway underlying the effects of synthetic intranasal oxytocin in the human brain, as well as evidence suggesting that some of the effects of intranasal synthetic oxytocin may be due to peripheral signalling (https://go.nature.com/2XG5P8Z; https://www.biorxiv.org/content/10.1101/563056v1). The different patterns of increases in regional cerebral blood flow between the two intranasal methods suggest that they may differ in the achieved bioavailability of oxytocin in the brain. Higher oxytocin deposition in the olfactory region might have resulted in an increased amount of oxytocin reaching the brain. Our findings help illuminate the mechanisms of absorption of intranasal oxytocin in humans and the identification of potentially more efficient intranasal administration methods compared to nasal sprays. (Abstracts presented at multiple international conferences; manuscript in submission.)
(C) We found that, despite their common use in the literature as such, baseline levels of oxytocin in blood plasma or saliva are not a reliable and hence valid biomarker of the function of an individual's oxytocin system. Additionally, saliva measurements of oxytocin do not accurately index its plasma levels and should be interpreted with caution (manuscript in submission).
(D) We clarified the impact of oxytocin on pain perception, showing that it has analgesic properties in humans (Paloyelis et al., 2016). Understanding the effects of oxytocin on pain perception was of key importance in this project as it intended to use pain units as a negative currency in neuroeconomic games aimed to understand the effect of oxytocin on decisions to trust others. We further found that the effects of intranasal oxytocin on insula activity in response to painful stimulation depend on social context (manuscript in submission).
(E) We will be producing evidence regarding the dose-response effects of oxytocin on social learning, specifically examining the effects of intranasal oxytocin on the weight we give to social and non-social information when deciding between different options, as a function of our perception of the personality of the person advising us (under analysis).
Exploitation Route In this project we have completed important groundwork addressing key questions, which have been having and will be having an impact on a wide range of experimental studies and clinical trials in the field (as demonstrated in the wide range of collaborations linked with this grant). This work has also initiated a collaboration with an industrial partner to develop a more efficient method for delivering intranasal oxytocin.
Sectors Healthcare,Pharmaceuticals and Medical Biotechnology,Other

URL https://go.nature.com/2XG5P8Z
 
Description Our work has led to a collaboration with an industrial partner (Pharmaceutical company) to develop a more efficient method for delivering intranasal oxytocin.
First Year Of Impact 2017
Sector Healthcare,Pharmaceuticals and Medical Biotechnology
Impact Types Societal,Economic

 
Description Industrial funding
Amount € 25,000 (EUR)
Funding ID PNSVUBR 
Organisation PARI GmbH 
Sector Private
Country Germany
Start  
End 12/2016
 
Description NIHR Mental Health Biomedical Research Centre, Neuroimaging Theme
Amount £32,000 (GBP)
Organisation King's College London 
Department NIHR Biomedical Research Centre
Sector Academic/University
Country United Kingdom
Start 10/2014 
End 10/2016
 
Title Use of multivariate pattern analysis to estimate the pharmacodynamics of a neurochemical agent (oxytocin) in the living human brain. 
Description We successfully applied multivariate pattern analysis on cerebral blood perfusion data which allowed us to estimate the pharmacodynamic effects of the intranasal delivery of oxytocin in the living human brain. 
Type Of Material Physiological assessment or outcome measure 
Provided To Others? No  
Impact We describe the oxytocinergic network in the living human brain for the first time and provide a roadmap for other studies using oxytocin regarding the optimal timing of experimental and clinical interventions. 
URL http://dx.doi.org/10.1016/j.biopsych.2014.10.005
 
Description A systematic examination of the influence of oxytocin on social and interoceptive processing in anorexia nervosa, Fotopoulou 
Organisation University College London
Department Division of Psychology & Language Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Expert advice on a project focusing on the systematic examination of the influence of oxytocin on social and interoceptive processing in anorexia nervosa.
Collaborator Contribution Co-development of project, project management.
Impact A research project focusing on the systematic examination of the influence of oxytocin on social and interoceptive processing in anorexia nervosa. Co-authorship on resulting research papers.
Start Year 2015
 
Description Influence of oxytocin in social cognition in patients at increased risk for psychosis, Fusar-Poli 
Organisation University of Sao Paulo
Department Institute of Psychiatry
Country Brazil 
Sector Academic/University 
PI Contribution Expert advice on a research project investigating the effect of oxytocin as a therapeutic agent to enhance social cognition in patients at increased risk for psychosis. Establishing protocol for the development of a neuroimaging oxytocin biomarker across neuropsychiatric disorders.
Collaborator Contribution Obtaining funding, project co-development, day-to-day project management.
Impact An active research project investigating the effect of oxytocin as a therapeutic agent to enhance social cognition in patients at increased risk for psychosis and contributing data to a multi-department collaboration within the Institute of Psychiatry, Psychology and Neuroscience for the purpose of developing a neuroimaging oxytocin biomarker across neuropsychiatric disorders. Co-authorhip in future papers. Two published meta-analyses (listed in research outputs). Interdisciplinary: psychiatry, social neuroscience, genetics, neuroimaging.
Start Year 2015
 
Description Influence of oxytocin on eating behaviours and stress in eating disorders, Treasure 
Organisation University of Sao Paulo
Department Institute of Psychiatry
Country Brazil 
Sector Academic/University 
PI Contribution Expert advice and development of the neuroimaging component of a project focusing on understanding the influence of oxytocin on eating behaviours and stress in eating disorders. Establishing protocol for the development of a neuroimaging oxytocin biomarker across neuropsychiatric disorders.
Collaborator Contribution Development of behavioural aspects of the project and project day-to-day running of project.
Impact A new research project focusing on understanding the influence of oxytocin on eating behaviours and stress in eating disorders. A new PhD studentship. Contributing data to a multi-department collaboration within the Institute of Psychiatry, Psychology and Neuroscience for the purpose of developing a neuroimaging oxytocin biomarker across neuropsychiatric disorders. Multi-disciplinary: Psychiatry, social neuroscience, cognitive neuroscience, behavioural neuroscience, psychopharmacology, neuroimaging, genetics.
Start Year 2015
 
Description Manipulating the 5-HT system to increase oxytocin function in the brain, Tricklebank 
Organisation University of Sao Paulo
Department Institute of Psychiatry
Country Brazil 
Sector Academic/University 
PI Contribution My work on understanding, visualising and quantifying the pharmacodynamics of oxytocin in the human brain and developing a biomarker for the human oxytocin system impacts directly and informs the aspects of this project focusing on stimulating the endogenous oxytocin system via stimulation of 5-HT receptors.
Collaborator Contribution Success in gaining a Wellcome Trust Senior Researcher Fellowship (to Dr. Mark Tricklebank) and commencement of a new research project.
Impact A successful Wellcome Trust Senior Researcher Fellowship (to Dr. Mark Tricklebank). Interdisciplinary: preclinical, psychopharmacology, neuroimaging.
Start Year 2015
 
Description Marie-Curie, Prata 
Organisation Marie Sklodowska-Curie Actions
Country Global 
Sector Academic/University 
PI Contribution Expert advice on a successful Marie Curie Career Integration Grant (CIG) to Dr. Diana Prata, and ongoing collaboration in the development and execution of research project titled: Oxytocin and Dopamine Interplay in Humans - on the Biology of Social Cognition.
Collaborator Contribution Collaboration on research program targeting the interactions between the oxytocin and the dopamine systems and their impact on social cognition.
Impact Initiation of a research program targeting the interactions between the oxytocin and the dopamine systems and their impact on social cognition. Co-authorship on papers. This is an interdisciplinary collaboration, combining social neuroscience, genetics, psychopharmacology, neuroimaging.
Start Year 2015
 
Description Marie-Curie, Prata 
Organisation University of Lisbon
Country Portugal 
Sector Academic/University 
PI Contribution Expert advice on a successful Marie Curie Career Integration Grant (CIG) to Dr. Diana Prata, and ongoing collaboration in the development and execution of research project titled: Oxytocin and Dopamine Interplay in Humans - on the Biology of Social Cognition.
Collaborator Contribution Collaboration on research program targeting the interactions between the oxytocin and the dopamine systems and their impact on social cognition.
Impact Initiation of a research program targeting the interactions between the oxytocin and the dopamine systems and their impact on social cognition. Co-authorship on papers. This is an interdisciplinary collaboration, combining social neuroscience, genetics, psychopharmacology, neuroimaging.
Start Year 2015
 
Description Optimising oxytocin nose to brain delivery 
Organisation PARI GmbH
Country Germany 
Sector Private 
PI Contribution We will be incorporating a novel device for the intranasal delivery of oxytocin in our studies which, assuming a direct nose-to-brain transfer, will optimise the delivery of oxytocin to the brain and afford better dosage control compared to extant nasal sprays. We will investigate the pharmacodynamics on oxytocin when delivered with this device in the living human brain.
Collaborator Contribution PARI GmbH will provide us with the equipment and further required analytic work to assess the amount of OT delivered by the device.
Impact Data collection has been completed and data-analysis is ongoing.
Start Year 2014
 
Description Oxytocin effects on interception, alexithymia and alcohol misuse, Critchley. 
Organisation University of Sussex
Country United Kingdom 
Sector Academic/University 
PI Contribution Expert advice on a research project focusing on oxytocin effects on interception, alexithymia and alcohol misuse.
Collaborator Contribution Co-development and execution of a research project focusing on oxytocin effects on interception, alexithymia and alcohol misuse.
Impact Collaboration on a research project focusing on oxytocin effects on interception, alexithymia and alcohol misuse. Co-authorship on resulting papers.
Start Year 2015
 
Description Oxytocin system in psychopathy, Tully 
Organisation University of Sao Paulo
Department Institute of Psychiatry
Country Brazil 
Sector Academic/University 
PI Contribution My work on understanding, visualising and quantifying the pharmacodynamics of oxytocin in the human brain and optimising oxytocin administration in humans impacted directly and informed the success of this application for a Wellcome Trust clinical research fellowship to Dr. John Tully and will inform the development of the ensuing research project.
Collaborator Contribution Successful funding application and development, in collaboration, of a research project focusing on understanding the involvement of the oxytocin system in psychopathy.
Impact A new research project focusing on understanding the involvement of the oxytocin system in psychopathy. Co-authorship on resulting future papers. Interdisciplinary: Psychiatry, behavioural/cognitive neuroscience, psychopharmacology, neuroimaging.
Start Year 2015
 
Description Lecture on the The Oxytocin System at the Biomedical Research Centre Ph.D. Program, IoPPN, KCL, May 2015. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact A talk introducing the oxytocin system, its importance for the regulation of human social behaviour and its involvement in psychiatric disorders to PhD students within the NIHR Biomedical Research Centre at the Institute of Psychiatry, Psychology and Neuroscience at King's College, London. Attended by about 30 students. The talk introduced and generated interest in this fundamental neurobiological system and its role as a possible mechanisms for the transduction of the effects of social stimuli on physiology and behaviour (e.g. pain perception) in an audience composed of a new generation of researchers in psychiatric disorders, some of whom may be working in this area.
Year(s) Of Engagement Activity 2015
 
Description Lecture on the The Oxytocin System at the Biomedical Research Centre Ph.D. Program, IoPPN, KCL, May 2016. 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Postgraduate students
Results and Impact A talk introducing the oxytocin system, its importance for the regulation of human social behaviour and its involvement in psychiatric disorders to PhD students within the NIHR Biomedical Research Centre at the Institute of Psychiatry, Psychology and Neuroscience at King's College, London. Attended by about 30 students. The talk introduced and generated interest in this fundamental neurobiological system and its role as a possible mechanisms for the transduction of the effects of social stimuli on physiology and behaviour (e.g. pain perception) in an audience composed of a new generation of researchers in psychiatric disorders, some of whom may be working in this area. 
Year(s) Of Engagement Activity 2016
 
Description Oxytocin in eating disorders: a potential new target for treatment 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact A workshop presented at the Eating Disorder International Conference, London, UK, aimed to educate professional practitioners and researchers on the following three aims:
(1) the oxytocin system in the human brain
(2) how to conduct research using oxytocin
(3) potential therapeutic applications in the treatment of eating disorders
Year(s) Of Engagement Activity 2016
 
Description Oxytocin: the molecule that binds us together 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact This was a talk to a non-specialist audience of artists, as part of the Queering Love, Queering Hormones, collaborative project between BFI, KCL, Society for Endocrinology, (Wellcome Trust Funded). The aim was to introduce them to the neurobiology of love/bonding and facilitate their development of collaborative projects between arts and science.
Year(s) Of Engagement Activity 2016
 
Description Talk and participation at the AHRC NeuroLaw Research Network on Law, Regulation and Human Enhancement Technologies, St. Anne's College, Oxford University, August 2014. 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk and participation at the AHRC NeuroLaw Research Network on Law, Regulation and Human Enhancement Technologies, St. Anne's College, Oxford University, August 2014. The aim of the meeting was to discuss current status and societal, philosophical, legal and policy making implications of using drugs targeting the central nervous system to enhance function.
Year(s) Of Engagement Activity 2014
 
Description Web article 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Sparkled conversations and interest in oxytocin research in people outside this field.

None known other than what reported above.
Year(s) Of Engagement Activity 2014
URL http://www.bap.org.uk/publicinformationitem.php?publicinfoID=29
 
Description workshop participation 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact This activity involved a presentation '(Myths and Reality Regarding) the Use of Oxytocin to Affect Human Behaviour during Social Interactions' and participation in discussions as part of the August 2014 meeting of the AHRC NeuroLaw Research Network on Law, Regulation and Human Enhancement Technologies at St. Anne's College, Oxford University. This workshop was attended by academics from different disciplines (law, science and philosophy) whith an interest in the field of regulation of human enhancement technologies. My talk and ensuing discussions informed them on the role of oxytocin in regulating human social behaviour and stimulated discussions regarding the potential use of neurochemical agents to modulate human social and moral behaviour.

Invitation to become a member of a new initiative on the theme of neurochemical enhancement/regulation of human behaviour.
Year(s) Of Engagement Activity 2014