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Bhatt B, Franco LM. Endogenous glucocorticoids and human immunity: Time to revisit old dogmas. Semin Immunol 2025; 78:101949. [PMID: 40203674 DOI: 10.1016/j.smim.2025.101949] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/15/2024] [Revised: 02/24/2025] [Accepted: 03/22/2025] [Indexed: 04/11/2025]
Abstract
Glucocorticoids (GCs) are steroid hormones with diverse and important roles in the physiologic response to stress. These include permissive and suppressive effects on immunity, which help prepare the organism for future infectious stressors and control the immunological response to a recent stressor, preventing autoimmune damage. The ability of GCs to rapidly suppress an overactive immune system has been harnessed pharmacologically and synthetic GCs have played a central role in the treatment of inflammatory and autoimmune diseases for the past eight decades. Given their importance in clinical medicine, an emphasis on the anti-inflammatory and immunosuppressive effects of synthetic GCs has overshadowed the study of the physiologic roles of endogenous GCs in human immunity. The rising interest in the intersection between neurobiology and immunity, and the development of technologies that facilitate direct experimentation with human cells and tissues, make this an ideal time to critically review existing knowledge on this subject. In this review of the past 100 years of biomedical literature on the effects of endogenous glucocorticoids on human immunity, we summarize existing experimental evidence, reveal key knowledge gaps and misconceptions, and highlight specific areas of opportunity for new research.
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Affiliation(s)
- Brinda Bhatt
- Functional Immunogenomics Section. National Institute of Arthritis and Musculoskeletal and Skin Diseases. National Institutes of Health, Bethesda, MD 20902, USA
| | - Luis M Franco
- Functional Immunogenomics Section. National Institute of Arthritis and Musculoskeletal and Skin Diseases. National Institutes of Health, Bethesda, MD 20902, USA.
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Hohl CH, Zilcha-Mano S, Delgadillo J. Is the "social hormone" oxytocin relevant to psychotherapy treatment outcomes? A systematic review of observational and experimental studies. Neurosci Biobehav Rev 2024; 167:105935. [PMID: 39481670 DOI: 10.1016/j.neubiorev.2024.105935] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2024] [Revised: 10/27/2024] [Accepted: 10/29/2024] [Indexed: 11/02/2024]
Abstract
BACKGROUND Oxytocin, popularly known as the "social hormone", has wide implications for the regulation of socially relevant cognitions, emotions and behaviors. Individual differences in oxytocin may be relevant to mental health treatment outcomes, given the centrality of the therapeutic relationship in psychotherapy. METHODS This systematic review aimed to synthesize findings from psychotherapy studies that examined oxytocin measurement and augmentation methods and their association with treatment outcomes. The methodology was preregistered in the Open Science Framework (https://osf.io/xtyvc/?view_only=2bc37dc0b2cd41f8939e2964bd8b884f). Five databases were searched on 30th of March 2023 (PubMed, SCOPUS, Web of Science, Medline, PsycINFO). Eligible studies were assessed for risk of bias and findings were summarized using narrative synthesis and vote counting methods. RESULTS Overall, 24 studies (n=881 participants) including experimental and observational designs and covering various diagnostic groups were reviewed. Findings from 9 studies (n=406) indicate that oxytocin measures were associated with psychotherapy treatment outcomes for depression, and oxytocin-augmentation improved depression outcomes. Results regarding other mental disorders were mixed and inconclusive. DISCUSSION Current evidence indicates that oxytocin-augmented psychotherapy for depression warrants further research. Currently there is not sufficient evidence to draw firm conclusions regarding the clinical relevance of oxytocin in the context of other disorders. Key limitations are the lack of meta-analytic synthesis and small sample sizes for primary studies.
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Affiliation(s)
- Caio Hummel Hohl
- Department of Psychology, University of Sheffield, United Kingdom
| | | | - Jaime Delgadillo
- Department of Psychology, University of Sheffield, United Kingdom.
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Petersson M, Uvnäs-Moberg K. Interactions of Oxytocin and Dopamine-Effects on Behavior in Health and Disease. Biomedicines 2024; 12:2440. [PMID: 39595007 PMCID: PMC11591571 DOI: 10.3390/biomedicines12112440] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2024] [Revised: 10/14/2024] [Accepted: 10/19/2024] [Indexed: 11/28/2024] Open
Abstract
The hypothalamic neuropeptide and hormone oxytocin are of fundamental importance for maternal, social, and sexual behavior. Deviations in oxytocin levels have also been associated with anxiety, autism spectrum disorders (ASD), depression, ADHD (attention deficit hyperactivity disorder), and schizophrenia. Both oxytocin and dopamine are often considered reward- and feel-good hormones, and dopamine is associated with the above-mentioned behaviors and, and dopamine is also associated with the above-mentioned behaviors and disorders. Although being structurally totally different, oxytocin, a peptide, and dopamine, a monoamine, they have a number of similar effects. They are synthesized both in the brain and in the periphery, and they affect each other's release and receptors. In addition, oxytocin and dopamine are released in response to, for example, social interaction, sex, feeding, and massage. This review discusses interactions between oxytocin and dopamine with a specific focus on behavioral effects and possible roles of oxytocin and dopamine in various mental disorders and functional diversities.
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Affiliation(s)
- Maria Petersson
- Department of Endocrinology, Karolinska University Hospital, 171 76 Stockholm, Sweden
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 77 Stockholm, Sweden
| | - Kerstin Uvnäs-Moberg
- Department of Applied Animal Science and Welfare, Swedish University of Agricultural Sciences, 532 31 Skara, Sweden
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Gnanadesikan GE, Bray EE, Cook EN, Levy KM, Douglas LELC, Kennedy BS, Tecot SR, MacLean EL. Basal plasma oxytocin & fecal cortisol concentrations are highly heritable and associated with individual differences in behavior & cognition in dog puppies. Horm Behav 2024; 165:105612. [PMID: 39116461 DOI: 10.1016/j.yhbeh.2024.105612] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 07/15/2024] [Accepted: 07/25/2024] [Indexed: 08/10/2024]
Abstract
Oxytocin and cortisol are hormones that can influence cognition and behavior, but the relationships between endogenous concentrations and individual differences in cognitive and behavioral phenotypes remain poorly understood. Across mammals, oxytocin has important roles in diverse social behaviors, and in dogs, it has been implicated in human-oriented behaviors such as social gaze and point-following. Cortisol, an end-product of the hypothalamic-pituitary-adrenal (HPA) axis, is often studied in relation to temperament and emotional reactivity, but it is also known to modulate executive functions. In this study, we measured basal fecal cortisol (n = 247) and plasma oxytocin (n = 249) in dog puppies from a pedigreed population (Canine Companions ®). We collected cognitive and behavioral data from these subjects (n = 247), including measures of human-oriented social cognition, memory, inhibitory control, perceptual discriminations, and temperament. Oxytocin concentrations were estimated to be very highly heritable (h2 = 0.90-0.99) and cortisol concentrations were estimated to be moderately-highly heritable (h2 = 0.43-0.47). Bayesian mixed models controlling for relatedness revealed that oxytocin concentrations were positively associated with spatial working memory and displayed a negative quadratic relationship with behavioral laterality, but no credible associations were seen for social measures. Cortisol concentrations exhibited a negative linear relationship with performance on an inhibitory control task and a negative quadratic relationship with bold behavioral reactions to a novel object. Collectively, our results suggest that individual differences in oxytocin and cortisol concentrations are under strong genetic control in dogs and are associated with phenotypic variation in aspects of temperament, behavioral laterality, and executive function.
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Affiliation(s)
- Gitanjali E Gnanadesikan
- School of Anthropology, University of Arizona, Tucson, AZ 85721, USA; Laboratory for the Evolutionary Endocrinology of Primates, University of Arizona, Tucson, AZ 85721, USA; Cognitive Science Program, University of Arizona, Tucson, AZ 85721, USA; Department of Anthropology, Emory University, Atlanta, GA 30322, USA.
| | - Emily E Bray
- School of Anthropology, University of Arizona, Tucson, AZ 85721, USA; Canine Companions for Independence, Santa Rosa, CA 95402, USA; College of Veterinary Medicine, University of Arizona, Tucson, AZ 85721, USA; Psychology Department, University of Arizona, Tucson, AZ 85721, USA
| | - Erica N Cook
- School of Anthropology, University of Arizona, Tucson, AZ 85721, USA; Laboratory for the Evolutionary Endocrinology of Primates, University of Arizona, Tucson, AZ 85721, USA
| | - Kerinne M Levy
- Canine Companions for Independence, Santa Rosa, CA 95402, USA
| | | | | | - Stacey R Tecot
- School of Anthropology, University of Arizona, Tucson, AZ 85721, USA; Laboratory for the Evolutionary Endocrinology of Primates, University of Arizona, Tucson, AZ 85721, USA
| | - Evan L MacLean
- School of Anthropology, University of Arizona, Tucson, AZ 85721, USA; Cognitive Science Program, University of Arizona, Tucson, AZ 85721, USA; College of Veterinary Medicine, University of Arizona, Tucson, AZ 85721, USA; Psychology Department, University of Arizona, Tucson, AZ 85721, USA
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Petersson M, Höybye C. Is Oxytocin a Contributor to Behavioral and Metabolic Features in Prader-Willi Syndrome? Curr Issues Mol Biol 2024; 46:8767-8779. [PMID: 39194735 DOI: 10.3390/cimb46080518] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2024] [Revised: 08/05/2024] [Accepted: 08/10/2024] [Indexed: 08/29/2024] Open
Abstract
Prader-Willi Syndrome (PWS) is a rare genetic disorder typically characterized by decreased social interaction, hyperphagia, poor behavioral control and temper tantrums, together with a high risk of morbid obesity unless food intake is controlled. The genetic defects that cause PWS include paternal 15q deletion (estimated in 60% of cases), chromosome 15 maternal uniparental disomy (UPD) (estimated in 35% of cases) and imprinting defects and translocations. Several studies indicate an oxytocin deficiency in PWS. Oxytocin is a hypothalamic nonapeptide with receptors located in the brain and in various other tissues in the body. It acts as a neuropeptide in several brain areas of great importance for behavioral and metabolic effects, as well as a neurohypophyseal hormone released into the circulation. Oxytocin in both rats and humans has strong and long-lasting behavioral and metabolic effects. Thus, an oxytocin deficiency might be involved in several of the behavioral and metabolic symptoms characterizing PWS. Treatment with oxytocin has, in some studies, shown improvement in psycho-social behavior and hyperphagia in individuals with PWS. This review focus on the behavioral and metabolic effects of oxytocin, the symptoms of a potential oxytocin deficiency in PWS and the effects of oxytocin treatment.
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Affiliation(s)
- Maria Petersson
- Department of Endocrinology, Karolinska University Hospital, 171 76 Stockholm, Sweden
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden
| | - Charlotte Höybye
- Department of Endocrinology, Karolinska University Hospital, 171 76 Stockholm, Sweden
- Department of Molecular Medicine and Surgery, Karolinska Institutet, 171 76 Stockholm, Sweden
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Flechsenhar A, Levine SM, Müller LE, Herpertz SC, Bertsch K. Oxytocin and social learning in socially anxious men and women. Neuropharmacology 2024; 251:109930. [PMID: 38537867 DOI: 10.1016/j.neuropharm.2024.109930] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 03/19/2024] [Accepted: 03/20/2024] [Indexed: 04/05/2024]
Abstract
OBJECTIVE This study extended a classic self-referential learning paradigm by investigating the effects of intranasally-administered oxytocin in high and low socially anxious participants during social learning, as a function of social anxiety levels and sex. METHODS In a randomized double-blinded design, 160 participants were either given intranasal oxytocin (24 I.U.) or placebo. Subsequently, while lying in an MR scanner, participants were shown neutral faces that were paired with positively, neutrally, or negatively valenced self-referential sentences, during which we measured self-reported arousal and sympathy of the facial stimuli, pupil dilation, and changes in the brain-oxygen-level dependent signal. Four-factor mixed analyses of variance with the between-subjects factors group (high socially anxious vs. low socially anxious), substance (oxytocin vs. placebo), and sex (male vs. female) and the within-subjects factor sentence valence (positive vs. neutral vs. negative) were conducted for each measure, respectively. RESULTS Administration of intranasal oxytocin yielded an increase in sympathy ratings in high socially anxious compared to low socially anxious individuals and decreased arousal ratings for positively-conditioned faces in low socially anxious participants. As an objective physiological measure of arousal, pupil dilation mirrored the behavioral results. Oxytocin effects on neural activation in the insula interacted with anxiety levels and sex: low socially anxious individuals yielded lower activation under oxytocin than placebo; the converse was observed in high socially anxious individuals. This interaction also differed between sexes, as men yielded higher activation levels than women. These findings were more prominent for positively- and negatively-conditioned faces. Within the amygdala, high socially anxious men yielded higher activation than high socially anxious women in the left hemisphere, and low socially anxious men yielded higher activation than low socially anxious women from positively- and negatively-conditioned faces, though no influence of oxytocin was detected. CONCLUSION These results suggest oxytocin-induced behavioral, physiological, and neural changes as a function of social learning in socially low and high anxious individuals. These findings challenge the amygdalocentric view of the role of emotions in social learning, instead contributing to the growing body of findings implicating the insula therein, revealing an interaction between oxytocin, sex, and emotional valence. Such discoveries raise an interesting set of questions regarding the computational goals of regions such as the insula in emotional learning and how neural activity can play a diagnostic or prognostic role in social anxiety, potentially leading to new treatment opportunities that may combine oxytocin and neurofeedback differentially for men and women.
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Affiliation(s)
- Aleya Flechsenhar
- Department of Psychology, Ludwig-Maximilians Universität München, Germany; NeuroImaging Core Unit Munich (NICUM), University Hospital, Ludwig-Maximilians Universität München, Germany
| | - Seth M Levine
- Department of Psychology, Ludwig-Maximilians Universität München, Germany; NeuroImaging Core Unit Munich (NICUM), University Hospital, Ludwig-Maximilians Universität München, Germany
| | - Laura E Müller
- Department of General Psychiatry, Center for Psychosocial Medicine, Heidelberg University, Germany
| | - Sabine C Herpertz
- Department of General Psychiatry, Center for Psychosocial Medicine, Heidelberg University, Germany
| | - Katja Bertsch
- Department of Psychology, Ludwig-Maximilians Universität München, Germany; NeuroImaging Core Unit Munich (NICUM), University Hospital, Ludwig-Maximilians Universität München, Germany; Department of Psychology, Julius-Maximilians-Universität Würzburg, Germany.
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Karth M, Kinzig KP. Adolescent activity-based anorexia has a substantial and prolonged impact on social behavior in young adult female rats. Physiol Behav 2024; 279:114528. [PMID: 38531425 DOI: 10.1016/j.physbeh.2024.114528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2023] [Revised: 03/01/2024] [Accepted: 03/23/2024] [Indexed: 03/28/2024]
Abstract
Activity-based anorexia (ABA) is a rodent model of anorexia nervosa (AN) that induces several key components of AN, including voluntary reduction in food intake, reduced body weight, hyperactivity, and alterations to the hypothalamic-pituitary-adrenal (HPA) axis. Previous research has demonstrated persistently increased anxiety-like behavior in the elevated plus maze (EPM), a test measuring avoidance of novel and open areas in adult female rats that experienced ABA during adolescence and are weight-restored in adulthood. Whether the same behavioral effects of two bouts of adolescent ABA emerge in response to different anxiety-provoking stimuli, however, has not been explored. We used the social partition (SP), novelty suppressed feeding (NSF), marble burying, and EPM tests to explore whether two bouts of adolescent ABA have persistent effects on anxiety-like behavior in weight restored young adult female rats. One-way ANOVA analyses revealed that female rats that experienced two bouts of ABA during adolescence had increased anxiety-like behavior in the EPM and SP tests in young adulthood following weight restoration compared with controls. These data demonstrate that the enduring behavioral effects of two bouts of adolescent ABA are specific to particular anxiety-provoking stimuli and suggest that adolescent ABA has enduring effects on social relationships.
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Affiliation(s)
- Melinda Karth
- Department of Psychological Sciences, Purdue University, West Lafayette, IN, USA
| | - Kimberly P Kinzig
- Department of Psychological Sciences, Purdue University, West Lafayette, IN, USA; Purdue University Ingestive Behavior Research Center, Purdue University, West Lafayette, IN, USA.
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Babington S, Tilbrook AJ, Maloney SK, Fernandes JN, Crowley TM, Ding L, Fox AH, Zhang S, Kho EA, Cozzolino D, Mahony TJ, Blache D. Finding biomarkers of experience in animals. J Anim Sci Biotechnol 2024; 15:28. [PMID: 38374201 PMCID: PMC10877933 DOI: 10.1186/s40104-023-00989-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2023] [Accepted: 12/28/2023] [Indexed: 02/21/2024] Open
Abstract
At a time when there is a growing public interest in animal welfare, it is critical to have objective means to assess the way that an animal experiences a situation. Objectivity is critical to ensure appropriate animal welfare outcomes. Existing behavioural, physiological, and neurobiological indicators that are used to assess animal welfare can verify the absence of extremely negative outcomes. But welfare is more than an absence of negative outcomes and an appropriate indicator should reflect the full spectrum of experience of an animal, from negative to positive. In this review, we draw from the knowledge of human biomedical science to propose a list of candidate biological markers (biomarkers) that should reflect the experiential state of non-human animals. The proposed biomarkers can be classified on their main function as endocrine, oxidative stress, non-coding molecular, and thermobiological markers. We also discuss practical challenges that must be addressed before any of these biomarkers can become useful to assess the experience of an animal in real-life.
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Affiliation(s)
- Sarah Babington
- School of Agriculture and Environment, The University of Western Australia, Crawley, WA, 6009, Australia
| | - Alan J Tilbrook
- Centre for Animal Science, The Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, St Lucia, QLD, 4072, Australia
- School of Veterinary Science, The University of Queensland, Gatton, QLD, 4343, Australia
| | - Shane K Maloney
- School of Human Sciences, The University of Western Australia, Crawley, WA, 6009, Australia
| | - Jill N Fernandes
- School of Veterinary Science, The University of Queensland, Gatton, QLD, 4343, Australia
| | - Tamsyn M Crowley
- School of Medicine, Deakin University, Geelong, VIC, 3217, Australia
- Poultry Hub Australia, University of New England, Armidale, NSW, 2350, Australia
| | - Luoyang Ding
- School of Agriculture and Environment, The University of Western Australia, Crawley, WA, 6009, Australia
- College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, China
| | - Archa H Fox
- School of Human Sciences, The University of Western Australia, Crawley, WA, 6009, Australia
| | - Song Zhang
- School of Human Sciences, The University of Western Australia, Crawley, WA, 6009, Australia
| | - Elise A Kho
- Centre for Animal Science, The Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, St Lucia, QLD, 4072, Australia
| | - Daniel Cozzolino
- Centre for Nutrition and Food Sciences, The Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, St Lucia, QLD, 4072, Australia
| | - Timothy J Mahony
- Centre for Animal Science, The Queensland Alliance for Agriculture and Food Innovation, The University of Queensland, St Lucia, QLD, 4072, Australia
| | - Dominique Blache
- School of Agriculture and Environment, The University of Western Australia, Crawley, WA, 6009, Australia.
- College of Animal Science and Technology, Yangzhou University, Yangzhou, 225009, China.
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Aygün O, Mohr E, Duff C, Matthew S, Schoenberg P. Oxytocin Modulation in Mindfulness-Based Pain Management for Chronic Pain. Life (Basel) 2024; 14:253. [PMID: 38398763 PMCID: PMC10890287 DOI: 10.3390/life14020253] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2023] [Revised: 01/31/2024] [Accepted: 02/07/2024] [Indexed: 02/25/2024] Open
Abstract
In the context of chronic pain management, opioid-based treatments have been heavily relied upon, raising concerns related to addiction and misuse. Non-pharmacological approaches, such as Mindfulness-Based Pain Management, offer alternative strategies. We conducted a mechanistic clinical study to investigate the impact of an 8-week Mindfulness-Based Pain Management intervention on chronic pain, the modulation of inflammatory markers, stress physiology, and oxytocin, and their interplay with clinical pain symptoms and perception, in comparison to a patient wait-list active control. A total of 65 participants, including 50 chronic pain patients and 15 healthy controls, underwent salivary assays to assess endocrine markers, oxytocin, interleukin (IL)-1b, IL-6, IL-8, tumor necrosis factor (TNF)-a, and dehydroepiandrosterone sulphate (DHEA-S). Psychological assessments were also conducted to evaluate aspects of pain perception, mindfulness, mood, and well-being. Findings revealed significant differences between chronic pain patients and healthy controls in various clinical metrics, highlighting the psychological distress experienced by patients. Following Mindfulness-Based Pain Management, oxytocin levels significantly increased in chronic pain patients, that was not observed in the patient wait-list control group. In contrast, cytokine and DHEA-S levels decreased (not to statistically significant margins) supporting anti-inflammatory effects of Mindfulness-Based Pain Management. The fact DHEA-S levels, a marker of stress, did attenuate but not to statistically meaningful levels, suggests that pain reduction was not solely related to stress reduction, and that oxytocin pathways may be more salient than previously considered. Psychological assessments demonstrated substantial improvements in pain perception and mood in the intervention group. These results contribute to the growing body of evidence regarding the effectiveness of mindfulness-based interventions in chronic pain management and underscore oxytocin's potential role as a therapeutic target.
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Affiliation(s)
- Oytun Aygün
- Laboratoire DysCo, Université Paris 8 Vincennes-Saint-Denis, 93526 Saint-Denis, France;
| | - Emily Mohr
- Osher Center for Integrative Health, Vanderbilt University Medical Center, Nashville, TN 37203, USA
| | - Colin Duff
- Breathworks Foundation, Manchester M4 1DZ, UK
| | | | - Poppy Schoenberg
- Osher Center for Integrative Health, Vanderbilt University Medical Center, Nashville, TN 37203, USA
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Pongrácz P, Lugosi CA, Szávai L, Gengeliczky A, Jégh-Czinege N, Faragó T. Alarm or emotion? intranasal oxytocin helps determine information conveyed by dog barks for adult male human listeners. BMC Ecol Evol 2024; 24:8. [PMID: 38221611 PMCID: PMC10789012 DOI: 10.1186/s12862-024-02198-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Accepted: 01/03/2024] [Indexed: 01/16/2024] Open
Abstract
BACKGROUND Barks play an important role in interspecific communication between dogs and humans, by allowing a reliable perception of the inner state of dogs for human listeners. However, there is growing concern in society regarding the nuisance that barking dogs cause to the surrounding inhabitants. We assumed that at least in part, this nuisance effect can be explained by particular communicative functions of dog barks. In this study we experimentally tested two separate hypotheses concerning how the content of dog barks could affect human listeners. According to the first hypothesis, barks that convey negative inner states, would especially cause stress in human listeners due to the process called interspecific empathy. Based on the second hypothesis, alarm-type dog barks cause particularly strong stress in the listener, by capitalizing on their specific acoustic makeup (high pitch, low tonality) that resembles to the parameters of a baby's cry. We tested 40 healthy, young adult males in a double-blind placebo controlled experiment, where participants received either intranasal oxytocin or placebo treatment. After an incubation period, they had to evaluate the (1) perceived emotions (happiness, fear and aggression), that specifically created dog bark sequences conveyed to them; and (2) score the annoyance level these dog barks elicited in them. RESULTS We found that oxytocin treatment had a sensitizing effect on the participants' reactions to negative valence emotions conveyed by dog barks, as they evaluated low fundamental frequency barks with higher aggression scores than the placebo-treated participants did. On the other hand, oxytocin treatment attenuated the annoyance that noisy (atonal) barks elicited from the participants. CONCLUSIONS Based on these results, we provide first-hand evidence that dog barks provide information to humans (which may also cause stress) in a dual way: through specific attention-grabbing functions and through emotional understanding.
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Affiliation(s)
- Péter Pongrácz
- Department of Ethology, ELTE Eötvös Loránd University, Pázmány Péter sétány 1/c, Budapest, 1117, Hungary.
| | - Csenge Anna Lugosi
- Department of Ethology, ELTE Eötvös Loránd University, Pázmány Péter sétány 1/c, Budapest, 1117, Hungary
| | - Luca Szávai
- Department of Ethology, ELTE Eötvös Loránd University, Pázmány Péter sétány 1/c, Budapest, 1117, Hungary
| | - Atina Gengeliczky
- Department of Ethology, ELTE Eötvös Loránd University, Pázmány Péter sétány 1/c, Budapest, 1117, Hungary
| | - Nikolett Jégh-Czinege
- Department of Ethology, ELTE Eötvös Loránd University, Pázmány Péter sétány 1/c, Budapest, 1117, Hungary
| | - Tamás Faragó
- Neuroethology of Communication Lab, Department of Ethology, Eötvös Loránd University, Budapest, Hungary
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11
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Kraus J, Výborová E, Silani G. The effect of intranasal oxytocin on social reward processing in humans: a systematic review. Front Psychiatry 2023; 14:1244027. [PMID: 37779612 PMCID: PMC10536251 DOI: 10.3389/fpsyt.2023.1244027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/21/2023] [Accepted: 08/30/2023] [Indexed: 10/03/2023] Open
Abstract
Understanding the neurobiology of social reward processing is fundamental, holding promises for reducing maladaptive/dysfunctional social behaviors and boosting the benefits associated with a healthy social life. Current research shows that processing of social (vs. non-social) rewards may be driven by oxytocinergic signaling. However, studies in humans often led to mixed results. This review aimed to systematically summarize available experimental results that assessed the modulation of social reward processing by intranasal oxytocin (IN-OXY) administration in humans. The literature search yielded 385 results, of which 19 studies were included in the qualitative synthesis. The effects of IN-OXY on subjective, behavioral, and (neuro)physiological output variables are discussed in relation to moderating variables-reward phase, reward type, onset and dosage, participants' sex/gender, and clinical condition. Results indicate that IN-OXY is mostly effective during the consumption ("liking") of social rewards. These effects are likely exerted by modulating the activity of the prefrontal cortex, insula, precuneus, anterior cingulate cortex, amygdala, and striatum. Finally, we provide suggestions for designing future oxytocin studies. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021278945, identifier CRD42021278945.
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Affiliation(s)
- Jakub Kraus
- Department of Clinical and Health Psychology, Faculty of Psychology, University of Vienna, Vienna, Austria
- Department of Psychology, Faculty of Arts, Comenius University in Bratislava, Bratislava, Slovakia
- Department of Psychology, Faculty of Social Studies, Masaryk University, Brno, Czechia
| | - Eliška Výborová
- Department of Psychology, Faculty of Social Studies, Masaryk University, Brno, Czechia
- Faculty of Psychology and Neuroscience, Maastricht University, Maastricht, Netherlands
| | - Giorgia Silani
- Department of Clinical and Health Psychology, Faculty of Psychology, University of Vienna, Vienna, Austria
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Cuesta-Marti C, Uhlig F, Muguerza B, Hyland N, Clarke G, Schellekens H. Microbes, oxytocin and stress: Converging players regulating eating behavior. J Neuroendocrinol 2023; 35:e13243. [PMID: 36872624 DOI: 10.1111/jne.13243] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 01/26/2023] [Accepted: 02/02/2023] [Indexed: 02/17/2023]
Abstract
Oxytocin is a peptide-hormone extensively studied for its multifaceted biological functions and has recently gained attention for its role in eating behavior, through its action as an anorexigenic neuropeptide. Moreover, the gut microbiota is involved in oxytocinergic signaling through the brain-gut axis, specifically in the regulation of social behavior. The gut microbiota is also implicated in appetite regulation and is postulated to play a role in central regulation of hedonic eating. In this review, we provide an overview on oxytocin and its individual links with the microbiome, the homeostatic and non-homeostatic regulation of eating behavior as well as social behavior and stress.
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Affiliation(s)
- Cristina Cuesta-Marti
- Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland
- APC Microbiome Ireland, Cork, Ireland
| | - Friederike Uhlig
- APC Microbiome Ireland, Cork, Ireland
- Department of Physiology, University College Cork, Ireland
| | - Begoña Muguerza
- Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland
- APC Microbiome Ireland, Cork, Ireland
- Universitat Rovira i Virgili, Department of Biochemistry & Biotechnology, Nutrigenomics Research Group, Tarragona, Spain
| | - Niall Hyland
- APC Microbiome Ireland, Cork, Ireland
- Department of Physiology, University College Cork, Ireland
| | - Gerard Clarke
- APC Microbiome Ireland, Cork, Ireland
- Department of Psychiatry & Neurobehavioural Science, University College Cork, Cork, Ireland
| | - Harriët Schellekens
- Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland
- APC Microbiome Ireland, Cork, Ireland
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Dong W, Ding Z, Wu X, Wan R, Liu Y, Pei L, Zhu W. The association between neuropeptide oxytocin and neuropsychiatric disorders after orthopedic surgery stress in older patients. BMC Geriatr 2023; 23:416. [PMID: 37420191 PMCID: PMC10329356 DOI: 10.1186/s12877-023-03989-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2022] [Accepted: 04/22/2023] [Indexed: 07/09/2023] Open
Abstract
BACKGROUND The health outcomes of geriatric patients exposed to surgery were found to be enhanced by social support and stress management. The aim of this study was to characterise the relationship between oxytocin and neuropsychiatric disorders after surgery. METHODS A total of 132 geriatric patients aged ≥ 60 years received orthopedic surgery in the First Affiliated Hospital of Harbin Medical University (Harbin, China) were enrolled in the present study. The salivary levels of stress hormone cortisol and oxytocin were measured by enzyme-linked immunosorbent assay for the screening of the stress state and oxytocin function. Moreover, the Depression Anxiety and Stress Scale (DASS), the Geriatric Anxiety Inventory (GAI), the Geriatric Depression Scale (GDS) and the Montgomery-Åsberg Depression Rating Scale (MADRS) were conducted to identify the severity of anxiety and depression. The association between oxytocin and mental health was performed by linear regression analyses in older patients receiving orthopedic surgery. Finally, the Duke Social Support Index (DSSI) was selected to measure the social support and the potential link to mental outcomes. RESULTS The scores from questionnaires showed that female patients with higher social support and higher levels of oxytocin demonstrated better stress-reducing responses as reflected by lower cortisol and decreased anxiety and depression symptoms. Regression analyses revealed that there was a significant association between oxytocin and scores in DASS, GAI, GDS, MADRS and DSSI, suggesting a potential link between peripheral oxytocin function and mood outcomes after orthopedic surgery. CONCLUSIONS Our findings reveal that oxytocin enhances the stress-protective effects of social support and reduces anxiety and depression states under stressful circumstances, particularly in older women receiving orthopedic surgery.
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Affiliation(s)
- Wanru Dong
- Drug Safety Evaluation Center, Heilongjiang University of Chinese Medicine, Harbin, 150040, China
| | - Zengbo Ding
- National Institute On Drug Dependence and Beijing Key Laboratory of Drug Dependence Research, Peking University, Beijing, 100191, China
| | - Xiao Wu
- National Institute On Drug Dependence and Beijing Key Laboratory of Drug Dependence Research, Peking University, Beijing, 100191, China
| | - Ran Wan
- Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China
| | - Ying Liu
- College of Pharmacy, Hainan Medical College, Haikou, 570100, China
| | - Liubao Pei
- Department of Orthopedics, The First Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
| | - Weili Zhu
- National Institute On Drug Dependence and Beijing Key Laboratory of Drug Dependence Research, Peking University, Beijing, 100191, China.
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Evenepoel M, Moerkerke M, Daniels N, Chubar V, Claes S, Turner J, Vanaudenaerde B, Willems L, Verhaeghe J, Prinsen J, Steyaert J, Boets B, Alaerts K. Endogenous oxytocin levels in children with autism: Associations with cortisol levels and oxytocin receptor gene methylation. Transl Psychiatry 2023; 13:235. [PMID: 37391413 DOI: 10.1038/s41398-023-02524-0] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 06/08/2023] [Accepted: 06/13/2023] [Indexed: 07/02/2023] Open
Abstract
Alterations in the brain's oxytocinergic system have been suggested to play an important role in the pathophysiology of autism spectrum disorder (ASD), but insights from pediatric populations are sparse. Here, salivary oxytocin was examined in the morning (AM) and afternoon (PM) in school-aged children with (n = 80) and without (n = 40) ASD (boys/girls 4/1), and also characterizations of DNA methylation (DNAm) of the oxytocin receptor gene (OXTR) were obtained. Further, cortisol levels were assessed to examine links between the oxytocinergic system and hypothalamic-pituitary-adrenal (HPA) axis signaling. Children with ASD displayed altered (diminished) oxytocin levels in the morning, but not in the afternoon, after a mildly stress-inducing social interaction session. Notably, in the control group, higher oxytocin levels at AM were associated with lower stress-induced cortisol at PM, likely reflective of a protective stress-regulatory mechanism for buffering HPA stress activity. In children with ASD, on the other hand, a significant rise in oxytocin levels from the morning to the afternoon was associated with a higher stress-induced cortisol release in the afternoon, likely reflective of a more reactive stress regulatory release of oxytocin for reactively coping with heightened HPA activity. Regarding epigenetic modifications, no overall pattern of OXTR hypo- or hypermethylation was evident in ASD. In control children, a notable association between OXTR methylation and levels of cortisol at PM was evident, likely indicative of a compensatory downregulation of OXTR methylation (higher oxytocin receptor expression) in children with heightened HPA axis activity. Together, these observations bear important insights into altered oxytocinergic signaling in ASD, which may aid in establishing relevant biomarkers for diagnostic and/or treatment evaluation purposes targeting the oxytocinergic system in ASD.
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Affiliation(s)
- Margaux Evenepoel
- KU Leuven, Department of Rehabilitation Sciences, Research Group for Neurorehabilitation, Leuven, Belgium
- KU Leuven, Leuven Autism Research (LAuRes), Leuven, Belgium
| | - Matthijs Moerkerke
- KU Leuven, Leuven Autism Research (LAuRes), Leuven, Belgium
- KU Leuven, Department of Neurosciences, Center for Developmental Psychiatry, Leuven, Belgium
| | - Nicky Daniels
- KU Leuven, Department of Rehabilitation Sciences, Research Group for Neurorehabilitation, Leuven, Belgium
- KU Leuven, Leuven Autism Research (LAuRes), Leuven, Belgium
| | | | - Stephan Claes
- University Psychiatric Centre, KU Leuven, Leuven, Belgium
| | - Jonathan Turner
- Luxembourg Institute of Health, Department of Infection and Immunity, Esch sur Alzette, Luxembourg
| | - Bart Vanaudenaerde
- KU Leuven, Department of Chronic Illness and Metabolism, Laboratory of Respiratory Diseases and Thoracic Surgery, Leuven, Belgium
| | - Lynn Willems
- KU Leuven, Department of Chronic Illness and Metabolism, Laboratory of Respiratory Diseases and Thoracic Surgery, Leuven, Belgium
| | - Johan Verhaeghe
- KU Leuven, Department of Development and Regeneration, Research Group Woman and Child, Leuven, Belgium
| | - Jellina Prinsen
- KU Leuven, Department of Rehabilitation Sciences, Research Group for Neurorehabilitation, Leuven, Belgium
- KU Leuven, Leuven Autism Research (LAuRes), Leuven, Belgium
| | - Jean Steyaert
- KU Leuven, Leuven Autism Research (LAuRes), Leuven, Belgium
- KU Leuven, Department of Neurosciences, Center for Developmental Psychiatry, Leuven, Belgium
| | - Bart Boets
- KU Leuven, Leuven Autism Research (LAuRes), Leuven, Belgium
- KU Leuven, Department of Neurosciences, Center for Developmental Psychiatry, Leuven, Belgium
| | - Kaat Alaerts
- KU Leuven, Department of Rehabilitation Sciences, Research Group for Neurorehabilitation, Leuven, Belgium.
- KU Leuven, Leuven Autism Research (LAuRes), Leuven, Belgium.
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Plett O, Flasbeck V, Brüne M. Effects of human and animal-assisted skills training on oxytocin und cortisol levels in patients with borderline personality disorder. J Psychiatr Res 2023; 162:156-160. [PMID: 37156130 DOI: 10.1016/j.jpsychires.2023.05.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 05/01/2023] [Indexed: 05/10/2023]
Abstract
OBJECTIVE Borderline Personality Disorder (BPD) is characterised, among other symptoms, by emotional instability and difficulties in regulating proximity to significant others. Many with BPD have difficulties in establishing a trustful therapeutic relationship, which often develop before a background of adverse childhood experiences with caregivers. One way to facilitate therapeutic interaction in psychotherapy incorporates pet animals as "door openers". No study exists, however, that has examined the effect of animal-assisted versus human-guided skills training on neurobiological correlates of affiliation and stress regulation, i.e. oxytocin and cortisol. METHODS Twenty in-patients diagnosed with BPD were recruited to participate in an animal-assisted skills-training. Another 20 in-patients participated in a human-guided skills-training. Salivary samples of both groups were taken for determining oxytocin and cortisol before and immediately after 3 therapeutic sessions at least one week apart from one another. In addition, borderline symptom severity (BSL-23), impulsivity (BIS-15), alexithymia (TAS-20), and fear of compassion (FOCS) were determined by self-rating questionnaires before and after the 6-week interventions. RESULTS Both therapeutic interventions led to a significant reduction in cortisol and an (non-significant) increase in oxytocin, respectively. Importantly, there was a statistically significant interaction between changes in cortisol and oxytocin, independent of group. Both groups further showed clinical improvement as measured using the above-listed questionnaires. CONCLUSION Our findings suggest that both animal-assisted and human-guided interventions have measurable short-term effects on affiliative and stress hormones, with no approach being superior to the other in this regard.
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Affiliation(s)
- Olivia Plett
- LWL University Hospital Bochum, Division of Social Neuropsychiatry and Evolutionary Medicine, Ruhr University, 44791, Bochum, NRW, Germany
| | - Vera Flasbeck
- LWL University Hospital Bochum, Division of Social Neuropsychiatry and Evolutionary Medicine, Ruhr University, 44791, Bochum, NRW, Germany
| | - Martin Brüne
- LWL University Hospital Bochum, Division of Social Neuropsychiatry and Evolutionary Medicine, Ruhr University, 44791, Bochum, NRW, Germany.
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Urinary oxytocin and cortisol concentrations vary by group type in male western lowland gorillas (Gorilla gorilla gorilla) in North American zoos. Primates 2023; 64:65-77. [PMID: 36472720 DOI: 10.1007/s10329-022-01037-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2022] [Accepted: 11/09/2022] [Indexed: 12/12/2022]
Abstract
Evaluating how primates in human care function within their social environment is important for understanding and optimizing their management and welfare. The neuroendocrine hormone oxytocin is associated with affiliation and bonding, suggesting it can be used to evaluate the affiliative nature of social groupings. When paired with cortisol concentrations, social stressors can simultaneously be assessed, providing a more complete picture of primate social environments than if measuring either hormone independently. Here, we measured both oxytocin and cortisol in urine within a large subset of male western lowland gorillas (Gorilla gorilla gorilla; n = 71) living in North American zoos. Both endocrine measures were compared between social group types, with an emphasis on comparing bachelor and mixed-sex groupings to understand how these broad management practices affect male gorillas in zoos. Oxytocin concentrations were greater in bachelor group males than mixed-sex group males and singly housed males, providing physiological evidence that males in bachelor groups form comparatively stronger affiliative relationships than males in other group types. Cortisol concentrations did not differ between bachelor and mixed-sex group males and males in both group types had lower cortisol concentrations than singly housed males. These results indicate that males are similarly capable of coping with group-specific social stressors, and single management may expose males to additional stressors for which further study is needed. These data contribute to a larger body of research highlighting the value of bachelor groups from both a population management and individual welfare perspective.
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Fedurek P, Lacroix L, Aktipis A, Cronk L, Makambi J, Mabulla I, Lehmann J, Berbesque JC. Relationship between proximity and physiological stress levels in hunter-gatherers: The Hadza. Horm Behav 2023; 147:105294. [PMID: 36521419 DOI: 10.1016/j.yhbeh.2022.105294] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 11/02/2022] [Accepted: 11/29/2022] [Indexed: 12/15/2022]
Abstract
In recent years there has been a great deal of documentation on how social relationships are related to various aspects of human wellbeing. However, until recently most studies investigating the effects of social relationships on wellbeing have applied social network measures to reported social contacts. Recent advances in the application of bio-loggers in biological studies have now made it possible to quantify social relationships based on in-person, rather than self-reported, social interactions. We used GPS-derived in-camp and out-of-camp proximity data to analyse how in-person proximity is related to Hair Cortisol Concentration (HCC) among Hadza hunter-gatherers. Time spent in close proximity to other camp members was associated with higher HCC, especially in women. In contrast, individuals who spent more time in close out-of-camp proximity to their best friend experienced lower HCC. Our study suggests that physiological costs related to group living might be mitigated by in-person interactions with close friends. We also find that the location (i.e., in-camp vs out-of-camp) of proximity to others and self-perceived friends is associated with HCC among the Hadza.
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Affiliation(s)
- Piotr Fedurek
- Anthropology Programme, University of Roehampton, London, UK; Department of Anthropology, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland.
| | - Laurent Lacroix
- Health Sciences Research Centre, University of Roehampton, London, UK
| | - Athena Aktipis
- Department of Psychology, Arizona State University, Tempe, AZ, USA
| | - Lee Cronk
- Department of Anthropology, Rutgers University, New Brunswick, NJ, USA
| | - Jerryson Makambi
- Mount Meru Tour Guide and International Language School, Arusha, Tanzania
| | | | - Julia Lehmann
- Anthropology Programme, University of Roehampton, London, UK
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Guo L, Qi YJ, Tan H, Dai D, Balesar R, Sluiter A, van Heerikhuize J, Hu SH, Swaab DF, Bao AM. Different oxytocin and corticotropin-releasing hormone system changes in bipolar disorder and major depressive disorder patients. EBioMedicine 2022; 84:104266. [PMID: 36126617 PMCID: PMC9489957 DOI: 10.1016/j.ebiom.2022.104266] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2022] [Revised: 08/26/2022] [Accepted: 08/28/2022] [Indexed: 11/11/2022] Open
Abstract
Background Oxytocin (OXT) and corticotropin-releasing hormone (CRH) are both produced in hypothalamic paraventricular nucleus (PVN). Central CRH may cause depression-like symptoms, while peripheral higher OXT plasma levels were proposed to be a trait marker for bipolar disorder (BD). We aimed to investigate differential OXT and CRH expression in the PVN and their receptors in prefrontal cortex of major depressive disorder (MDD) and BD patients. In addition, we investigated mood-related changes by stimulating PVN-OXT in mice. Methods Quantitative immunocytochemistry and in situ hybridization were performed in the PVN for OXT and CRH on 6 BD and 6 BD-controls, 9 MDD and 9 MDD-controls. mRNA expressions of their receptors (OXTR, CRHR1 and CRHR2) were determined in anterior cingulate cortex and dorsolateral prefrontal cortex (DLPFC) of 30 BD and 34 BD-controls, and 24 MDD and 12 MDD-controls. PVN of 41 OXT-cre mice was short- or long-term activated by chemogenetics, and mood-related behavior was compared with 26 controls. Findings Significantly increased OXT-immunoreactivity (ir), OXT-mRNA in PVN and increased OXTR-mRNA in DLPFC, together with increased ratios of OXT-ir/CRH-ir and OXTR-mRNA/CRHR-mRNA were observed in BD, at least in male BD patients, but not in MDD patients. PVN-OXT stimulation induced depression-like behaviors in male mice, and mixed depression/mania-like behaviors in female mice in a time-dependent way. Interpretation Increased PVN-OXT and DLPFC-OXTR expression are characteristic for BD, at least for male BD patients. Stimulation of PVN-OXT neurons induced mood changes in mice, in a pattern different from BD. Funding 10.13039/501100001809National Natural Science Foundation of China (81971268, 82101592).
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Gnanadesikan GE, Hammock EAD, Tecot SR, Lewis RJ, Hart R, Carter CS, MacLean EL. What are oxytocin assays measuring? Epitope mapping, metabolites, and comparisons of wildtype & knockout mouse urine. Psychoneuroendocrinology 2022; 143:105827. [PMID: 35714438 PMCID: PMC9807061 DOI: 10.1016/j.psyneuen.2022.105827] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2022] [Revised: 06/02/2022] [Accepted: 06/03/2022] [Indexed: 01/04/2023]
Abstract
Oxytocin has become a popular analyte in behavioral endocrinology in recent years, due in part to its roles in social behavior, stress physiology, and cognition. Urine samples have the advantage of being non-invasive and minimally disruptive to collect, allowing for oxytocin measurements even in some wild populations. However, methods for urinary oxytocin immunoassay have not been sufficiently optimized and rigorously assessed for their potential limitations. Using samples from oxytocin knockout (KO) and wildtype (WT) mice, we find evidence of considerable interference in unextracted urine samples, with similar distributions of measured oxytocin in both genotypes. Importantly, although this interference can be reduced by a reversed-phase solid-phase extraction (SPE), this common approach is not sufficient for eliminating false-positive signal on three immunoassay kits. To better understand the source of the observed interference, we conducted epitope mapping of the Arbor Assays antibody and assessed its cross-reactivity with known, biologically active fragments of oxytocin. We found considerable cross-reactivity (0.5-52% by-molarity) for three fragments of oxytocin that share the core epitope, with more cross-reactivity for longer fragments. Given the presence of some cross-reactivity for even the tripeptide MIF-1, it is likely that many small protein metabolites might be sufficiently similar to the epitope that at high concentrations they interfere with immunoassays. We present a new mixed-mode cation-exchange SPE method that minimizes interference-with knockout samples measuring below the assay's limit of detection-while effectively retaining oxytocin from the urine of wildtype mice. This method demonstrates good parallelism and spike recovery across multiple species (mice, dogs, sifakas, humans). Our results suggest that immunoassays of urine samples may be particularly susceptible to interference, even when using common extraction protocols, but that this interference can be successfully managed using a novel mixed-mode cation exchange extraction. These findings imply that previous conclusions based on urinary oxytocin measurements-especially those involving unextracted samples-may need to be reassessed.
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Affiliation(s)
- Gitanjali E Gnanadesikan
- School of Anthropology, University of Arizona, Tucson, AZ 85721, USA; Cognitive Science Program, University of Arizona, Tucson, AZ 85721, USA.
| | - Elizabeth A D Hammock
- Department of Psychology and Program in Neuroscience, The Florida State University, Tallahassee, FL 32306, USA
| | - Stacey R Tecot
- School of Anthropology, University of Arizona, Tucson, AZ 85721, USA; Laboratory for the Evolutionary Endocrinology of Primates, University of Arizona, Tucson, AZ 85721, USA
| | - Rebecca J Lewis
- Department of Anthropology, University of Texas at Austin, Austin, TX 78712, USA
| | - Russ Hart
- Arbor Assays, Ann Arbor, MI 48108, USA; 21 Grams Assays Inc, Chelsea, MI 48118, USA
| | - C Sue Carter
- Kinsey Institute, Indiana University, Bloomington, IN 47405, USA; Department of Psychology, University of Virginia, Charlottesville, VA 22903, USA
| | - Evan L MacLean
- School of Anthropology, University of Arizona, Tucson, AZ 85721, USA; Cognitive Science Program, University of Arizona, Tucson, AZ 85721, USA; Psychology Department, University of Arizona, Tucson, AZ 85721, USA; College of Veterinary Medicine, University of Arizona, Tucson, AZ 85721, USA
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Moscovice LR, Gimsa U, Otten W, Eggert A. Salivary Cortisol, but Not Oxytocin, Varies With Social Challenges in Domestic Pigs: Implications for Measuring Emotions. Front Behav Neurosci 2022; 16:899397. [PMID: 35677575 PMCID: PMC9169876 DOI: 10.3389/fnbeh.2022.899397] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2022] [Accepted: 04/20/2022] [Indexed: 01/01/2023] Open
Abstract
Animals respond to inherently rewarding or punishing stimuli with changes in core affective states, which can be investigated with the aid of appropriate biomarkers. In this study we evaluate salivary cortisol (sCORT) and salivary oxytocin (sOXT) concentrations under baseline conditions and in response to two negatively- and two positively-valenced social challenges in 75 young pigs (Sus scrofa domesticus), housed and tested in eight social groups. We predicted that: (1) Relative to baseline, weaning and brief social isolation would be associated with increases in sCORT, due to psychosocial stress, and reductions in sOXT, due to a lack of opportunities for social support; and (2) Opportunities for social play, and reunions with group members after a separation would be associated with weaker sCORT responses, and increases in sOXT concentrations compared to baseline and to negative social challenges. Testing and sample collection occurred between 28 and 65 days of age and involved a within-subject design, in which every subject was sampled multiple times in neutral (baseline), negative and positive social contexts. We also recorded behavioral data and measured rates of agonism, play and affiliative interactions in the different contexts, prior to saliva sampling. As expected, negative social challenges were associated with robust cortisol responses. Relative to baseline, pigs also had higher sCORT responses to positive social challenges, although these differences were only significant during reunions. Salivary oxytocin concentrations did not differ between the different social conditions, although sOXT was lowest during the brief social isolation. Behavioral analyses confirmed predictions about the expected changes in social interactions in different social contexts, with increases in agonism following weaning, increases in coordinated locomotor play in the play context and high rates of affiliative interactions during reunions. Relative sCORT reactivity to different contexts may reflect the intensity of emotional responses, with greater increases occurring in response to challenges that involve more psychosocial stress. Our results suggest that sOXT is not a reliable indicator of emotional valence in pigs, although more research is needed to characterize sOXT responses to various challenges with and without access to social support.
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Affiliation(s)
- Liza R. Moscovice
- Psychophysiology Unit, Institute of Behavioural Physiology, Research Institute for Farm Animal Biology (FBN), Dummerstorf, Germany
- *Correspondence: Liza R. Moscovice
| | - Ulrike Gimsa
- Psychophysiology Unit, Institute of Behavioural Physiology, Research Institute for Farm Animal Biology (FBN), Dummerstorf, Germany
| | - Winfried Otten
- Psychophysiology Unit, Institute of Behavioural Physiology, Research Institute for Farm Animal Biology (FBN), Dummerstorf, Germany
| | - Anja Eggert
- Service Group Statistical Consulting, Institute of Genetics and Biometry, Research Institute for Farm Animal Biology (FBN), Dummerstorf, Germany
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Maikoo S, Wilkins A, Qulu L. The effect of oxytocin and an enriched environment on anxiety-like behaviour and corticosterone levels in a prenatally stressed febrile seizure rat model. IBRO Neurosci Rep 2022; 13:47-56. [PMID: 36590100 PMCID: PMC9795298 DOI: 10.1016/j.ibneur.2022.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 04/30/2022] [Accepted: 05/03/2022] [Indexed: 02/01/2023] Open
Abstract
Background Febrile seizures (FS) are a neurological abnormality which occur following a fever that has resulted from a systemic infection and are characterised by convulsions. These convulsions occur due to abnormally increased signalling of interleukin-1 beta, resulting in increased neuronal hyper-excitability. Furthermore, exposure to prenatal stress has been shown to exacerbate seizure duration, elicit anxiety-like behaviour and corticosterone levels. Oxytocin is a neuropeptide with anxiolytic, social bonding, and stress regulation effects. Therefore, the aim of the study was to assess whether oxytocin can attenuate the anxiety-like behaviour and increased corticosterone in rat offspring exposed to prenatal stress and FS. Method Sprague Dawley rats were mated. On GND14, prenatal stress was induced on pregnant dams for 1 hr/7 days. On PND 14, rat pups were injected with lipopolysaccharide (LPS, 200 μg/kg, i.p.) followed 2.5 h later by an i.p. injection of kainic acid (KA, 1.75 mg/kg). Oxytocin (1 mg/kg) was induced via different routes (intraperitoneal or intranasal) as well an enriched environment between PND 22-26. The enriched environment included larger cages (1560 cm2) with only 4 pups per cage, compared to those groups not receiving enrichment (646 cm2), as well as cardboard rolls and plastic toys. On PND 27-33 the light/dark box and elevated plus maze were used to assess anxiety-like behaviour. On PND 34 all rats were euthanized using a sharp guillotine, trunk blood and hypothalamic tissue were collected for neurochemical analysis (ELISA kit). Results Our findings confirmed that exposure to both prenatal stress and febrile seizures resulted anxiety-like behaviour and significantly higher plasma corticosterone concentrations compared to their counterparts. Environmental enrichment was significantly effective in attenuating the increased basal corticosterone levels and anxiety-like behaviour seen in the prenatally stressed FS rat. Although direct administration of oxytocin showed higher significance in reducing corticosterone plasma levels when compared to the enriched environment. Furthermore, hypothalamic oxytocin levels were not significant in rat exposed to environmental enrichment while oxytocin treatment showed a significant effect when compared to their counterparts. Conclusion Therefore, oxytocin administration during early postnatal development shows great potential in reversing the effects of prenatal stress and its subsequent exacerbation of FS.
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Affiliation(s)
- Shreyal Maikoo
- HIV Pathogenesis Programme, Doris Duke Medical Research Institute, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa
| | - Andria Wilkins
- University of KwaZulu-Natal, College of Health Sciences, Department of Human Physiology, Durban, South Africa
| | - Lihle Qulu
- Stellenbosch University - Tygerberg Campus: Stellenbosch University Faculty of Medicine and Health Sciences, Capetown, South Africa,Corresponding author.
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Flanagan J, Chatzittofis A, Boström ADE, Hallberg J, Öberg KG, Arver S, Jokinen J. High Plasma Oxytocin Levels in Men With Hypersexual Disorder. J Clin Endocrinol Metab 2022; 107:e1816-e1822. [PMID: 35108393 PMCID: PMC9016473 DOI: 10.1210/clinem/dgac015] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Indexed: 01/23/2023]
Abstract
CONTEXT Hypersexual disorder (HD) involves excessive, persistent sexual behaviors related to various mood states and the diagnosis compulsive sexual behavior disorder is included as an impulse control disorder in the 11th revision of the International Classification of Diseases. Although the neurobiology behind the disorder is not clear, some studies suggest dysregulated hypothalamic-pituitary-adrenal axis. Oxytocin acts as counterregulatory neuroendocrine hormone to cortisol and is also involved in sexual behavior. OBJECTIVE We hypothesized that oxytocin may play a role in the pathophysiology of HD with compensatory actions to cortisol. DESIGN Longitudinal. SETTING ANOVA clinic (Karolinska University Hospital). PATIENTS OR OTHER PARTICIPANTS 64 males with HD and 38 age-matched healthy volunteers. MAIN OUTCOME MEASURES Plasma oxytocin levels, measured with radioimmunoassay; Hypersexual Disorder Screening Inventory; and Hypersexual Disorder: Current Assessment Scale for assessing hypersexual symptoms. INTERVENTIONS A patient subgroup (n = 30) completed the manual-based group-administered cognitive-behavioral therapy (CBT) program for HD, and posttreatment oxytocin levels were measured. RESULTS Hypersexual men (n = 64) exhibited significantly higher oxytocin plasma levels (mean ± SD: 31.0 ± 9.9 pM) compared with healthy volunteers (16.9 ± 3.9 pM; P < 0.001). There were significant positive correlations between oxytocin levels and the rating scales measuring hypersexual behavior. Patients who completed CBT treatment (n = 30) had a significant reduction of oxytocin plasma levels from pretreatment (30.5 ± 10.1 pM) to posttreatment (20.2 ± 8.0 pM; P < 0.001). CONCLUSIONS The results suggest that the hyperactive oxytocinergic system in hypersexual men may be a compensatory mechanism to attenuate hyperactive stress.
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Affiliation(s)
- John Flanagan
- Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Andreas Chatzittofis
- Medical School, University of Cyprus, Nicosia, Cyprus
- Department of Clinical Sciences/Psychiatry, Umeå University, Umeå,Sweden
- Correspondence: Andreas Chatzittofis, MD, PhD, University of Cyprus, Medical School, Palaios dromos Lefkosias Lemesou No.215/6 2029 Aglantzia, Nicosia, Cyprus.
| | - Adrian Desai E Boström
- Department of Clinical Sciences/Psychiatry, Umeå University, Umeå,Sweden
- Neuropaediatric Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden
| | - Jonas Hallberg
- Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Katarina Görts Öberg
- Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Stefan Arver
- Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
| | - Jussi Jokinen
- Department of Clinical Sciences/Psychiatry, Umeå University, Umeå,Sweden
- Department of Clinical Neuroscience/Psychiatry, Karolinska Institutet, Stockholm, Sweden
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Neurochemical and Hormonal Contributors to Compulsive Sexual Behavior Disorder. CURRENT ADDICTION REPORTS 2022. [DOI: 10.1007/s40429-021-00403-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Abstract
Purpose of Review
Compulsive sexual behavior disorder has been recently included in the 11th revision of the International Classification of Diseases (ICD-11), and the possible contribution of neurochemical and hormonal factors have been reported. However, relatively little is known concerning the neurobiology underlying this disorder. The aim of this article is to review and discuss published findings in the area.
Recent Findings
Evidence suggests that the neuroendocrine systems are involved in the pathophysiology of compulsive sexual behavior. The hypothalamus-pituitary adrenal axis, the hypothalamus-pituitary–gonadal axis, and the oxytocinergic system have been implicated.
Summary
Further studies are needed to elucidate the exact involvement of neuroendocrine and hormonal systems in compulsive sexual behavior disorder. Prospective longitudinal studies are particularly needed, especially those considering co-occurring psychiatric disorders and obtaining hormonal assessments in experimental circumstances with appropriate control groups.
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Preckel K, Trautmann S, Kanske P. Medication-Enhanced Psychotherapy for Posttraumatic Stress Disorder: Recent Findings on Oxytocin's Involvement in the Neurobiology and Treatment of Posttraumatic Stress Disorder. CLINICAL PSYCHOLOGY IN EUROPE 2021; 3:e3645. [PMID: 36398286 PMCID: PMC9667220 DOI: 10.32872/cpe.3645] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2020] [Accepted: 08/25/2021] [Indexed: 11/25/2022] Open
Abstract
Background Traumatic experiences may result in Posttraumatic Stress Disorder (PTSD), which is characterized as an exaggerated fear response that cannot be extinguished over time or in safe environments. What are beneficial psychotherapeutic treatment options for PTSD patients? Can oxytocin (OXT), which is involved in the stress response, and safety learning, ameliorate PTSD symptomatology and enhance psychotherapeutic effects? Here, we will review recent studies regarding OXT's potential to enhance psychotherapeutic therapies for PTSD treatment. Method We conducted a literature review on the neurobiological underpinnings of PTSD especially focusing on OXT's involvement in the biology and memory formation of PTSD. Furthermore, we researched successful psychotherapeutic treatments for PTSD patients and discuss how OXT may facilitate observed psychotherapeutic effects. Results For a relevant proportion of PTSD patients, existing psychotherapies are not beneficial. OXT may be a promising candidate to enhance psychotherapeutic effects, because it dampens responses to stressful events and allows for a faster recovery after stress. On a neural basis, OXT modulates processes that are involved in stress, arousal and memory. OXT effectively counteracts memory impairments caused by stress and facilitates social support seeking which is a key resilience factor for PTSD and which is beneficial in psychotherapeutic settings. Conclusion OXT has many characteristics that are promising to positively influence psychotherapy for PTSD patients. It potentially reduces intrusions, but preserves memory of the event itself. Introducing OXT into psychotherapeutic settings may result in better treatment outcomes for PTSD patients. Future research should directly investigate OXT's effects on PTSD, especially in psychotherapeutic settings.
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Affiliation(s)
- Katrin Preckel
- Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
| | - Sebastian Trautmann
- Institute of Clinical Psychology and Psychotherapy, Department of Psychology, Medical School Hamburg, Hamburg, Germany
| | - Philipp Kanske
- Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany
- Clinical Psychology and Behavioral Neuroscience, Faculty of Psychology, Technische Universität Dresden, Dresden, Germany
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McDonald SE, Tomlinson CA, Applebaum JW, Moyer SW, Brown SM, Carter S, Kinser PA. Human-Animal Interaction and Perinatal Mental Health: A Narrative Review of Selected Literature and Call for Research. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2021; 18:10114. [PMID: 34639416 PMCID: PMC8508333 DOI: 10.3390/ijerph181910114] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 09/21/2021] [Accepted: 09/23/2021] [Indexed: 12/13/2022]
Abstract
There is a paucity of research exploring how relationships with household pets may impact maternal mental health. We are unaware of any study to date that has examined associations between individuals' relationships with their pets and psychological adjustment in the perinatal period. Using a biobehavioral lens, this paper provides a narrative overview of the literature on perinatal mental health and human-animal interaction (HAI). We focus on the role of social relationships, stress, and stress reduction in relation to perinatal mental health; the role of HAI in perceptions of social support, stressors, and stress reduction; and gaps in empirical knowledge concerning the role of HAI in perinatal mental health. Finally, we integrate contemporary biobehavioral models of perinatal mental health and HAI (i.e., Comprehensive Model of Mental Health during the Perinatal Period and the HAI-HPA Transactional Model) to propose a new conceptual framework that depicts ways in which HAI during the perinatal period may influence maternal and child health and wellbeing. To our knowledge, this is the first paper to consider the role of HAI in biobehavioral responses and mental health during the perinatal period. We conclude with recommendations for future research and improved perinatal care.
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Affiliation(s)
- Shelby E. McDonald
- Children, Families, and Animals Research (CFAR) Group, LLC, Richmond, VA 23223, USA
| | - Camie A. Tomlinson
- School of Social Work, Virginia Commonwealth University, Richmond, VA 23284, USA
| | - Jennifer W. Applebaum
- Department of Sociology and Criminology & Law, University of Florida, Gainesville, FL 32611, USA;
| | - Sara W. Moyer
- School of Nursing, Virginia Commonwealth University, Richmond, VA 23298, USA; (S.W.M.); (P.A.K.)
| | - Samantha M. Brown
- School of Social Work, Colorado State University, Fort Collins, CO 80523, USA;
| | - Sue Carter
- The Kinsey Institute, Indiana University, Bloomington, IN 47405, USA;
| | - Patricia A. Kinser
- School of Nursing, Virginia Commonwealth University, Richmond, VA 23298, USA; (S.W.M.); (P.A.K.)
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La Fratta I, Franceschelli S, Speranza L, Patruno A, Michetti C, D'Ercole P, Ballerini P, Grilli A, Pesce M. Salivary oxytocin, cognitive anxiety and self-confidence in pre-competition athletes. Sci Rep 2021; 11:16877. [PMID: 34413428 PMCID: PMC8376920 DOI: 10.1038/s41598-021-96392-7] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2021] [Accepted: 07/30/2021] [Indexed: 12/14/2022] Open
Abstract
It is well known that soccer sport has the potential for high levels of stress and anxiety and that these are linked to Cortisol (C) variations. To date, much research has been devoted to understanding how Oxytocin (OT) can affect anxiety in response to a challenge. The aim of this study was to investigate, in 56 young male soccer players, the psychophysiological stress response 96 and 24 h before one soccer match of a tournament, in order to establish whether athletes who won or lost, show different levels of C and OT or expressions of competitive state anxiety subcomponents. We found that winners had significantly lower Cognitive anxiety and higher Self-confidence scores than losers. Also, significant differences between winners and losers in C and OT concentrations were observed, with higher OT levels in who has won and higher C levels in who has lost. Our results showed interesting associations between OT, C, anxiety feelings, and the outcome of competition.
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Affiliation(s)
- Irene La Fratta
- Medicine and Health Science School, University G. d'Annunzio, Via dei Vestini, 31, 66100, Chieti, Italy
| | - Sara Franceschelli
- Medicine and Health Science School, University G. d'Annunzio, Via dei Vestini, 31, 66100, Chieti, Italy
| | - Lorenza Speranza
- Medicine and Health Science School, University G. d'Annunzio, Via dei Vestini, 31, 66100, Chieti, Italy
| | - Antonia Patruno
- Medicine and Health Science School, University G. d'Annunzio, Via dei Vestini, 31, 66100, Chieti, Italy
| | - Carlo Michetti
- Medicine and Health Science School, University G. d'Annunzio, Via dei Vestini, 31, 66100, Chieti, Italy
| | - Paolo D'Ercole
- Medicine and Health Science School, University G. d'Annunzio, Via dei Vestini, 31, 66100, Chieti, Italy
| | - Patrizia Ballerini
- Medicine and Health Science School, University G. d'Annunzio, Via dei Vestini, 31, 66100, Chieti, Italy
| | - Alfredo Grilli
- Medicine and Health Science School, University G. d'Annunzio, Via dei Vestini, 31, 66100, Chieti, Italy.
| | - Mirko Pesce
- Medicine and Health Science School, University G. d'Annunzio, Via dei Vestini, 31, 66100, Chieti, Italy
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Associations between oxytocin and empathy in humans: A systematic literature review. Psychoneuroendocrinology 2021; 129:105268. [PMID: 34023733 DOI: 10.1016/j.psyneuen.2021.105268] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2021] [Revised: 04/19/2021] [Accepted: 05/06/2021] [Indexed: 11/24/2022]
Abstract
This is a systematic review about the association between empathic behavior and oxytocin (OXT). Searches were conducted in the electronic databases PubMed, Web of Science, PsycINFO, SciELO, and LILACS using the search terms "oxytocin", "empathy", and "empathic". Forty-four studies were reviewed. Scarce findings point to a lack of association between baseline endogenous OXT levels and empathy traits, and for a trend towards a direct relationship between oxytocinergic reactivity and empathic functioning. The results showed that variations in empathy were related to polymorphisms in the OXT receptor gene, especially in rs53576, and that this relationship seems to mediated by individual, ethnic, and cultural characteristics. Most studies on the exogenous administration of OXT tested a single dose (24 IU) with positive effects mainly on the affective domain of empathy. At the neural level, findings were inconsistent. Taken together, the results of the studies reviewed support the existence of a relationship between OXT and empathy that is complex and multifaceted. Robust evidence is still needed to elucidate existing links. Future investigations could benefit from methodological improvements aimed at increasing the reproducibility and applicability of findings, as well as the systematic assessment of the effects of exogenous OXT considering dose and frequency of administration, genotyping, and hormonal availability at the peripheral and central levels. This should lead to significant progress in the understanding of the therapeutic possibilities of OXT in the domain of empathic behavior.
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Pedretti G, Wirobski G, Range F, Marshall-Pescini S. Artificially elevated oxytocin concentrations in pet dogs are associated with higher proximity-maintenance and gazing towards the owners. Physiol Behav 2021; 237:113451. [PMID: 33974958 DOI: 10.1016/j.physbeh.2021.113451] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2021] [Revised: 04/18/2021] [Accepted: 04/30/2021] [Indexed: 10/21/2022]
Abstract
The relationship between dogs and their owners is characterized by an affective and enduring bond. It has been suggested that oxytocin might be the underlying mechanism driving this relationship, however evidence is mixed. In this study we tested whether intranasally administered oxytocin (compared to saline) would influence dogs' behavioural synchrony and shared attention towards their owners. Each individuals' pre and post administration oxytocin concentrations (measured in urine) were included in the analyses. Urinary oxytocin concentrations after administrations were positively associated with dogs' duration of social proximity and looking behaviours towards their owners supporting the role of oxytocin in modulating dogs' human-directed social behaviours.
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Affiliation(s)
- Giulia Pedretti
- Domestication Lab, Wolf Science Center, Konrad-Lorenz-Institute for Ethology, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria; University of Parma, Department of Medicine and Surgery, Via Gramsci 14, Parma, 43126, Italy; University of Parma, Department of Chemistry, Life Science and Environmental Sustainability, Viale delle Scienze 17/A, 43124, Parma, Italy.
| | - Gwendolyn Wirobski
- Domestication Lab, Wolf Science Center, Konrad-Lorenz-Institute for Ethology, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria
| | - Friederike Range
- Domestication Lab, Wolf Science Center, Konrad-Lorenz-Institute for Ethology, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria
| | - Sarah Marshall-Pescini
- Domestication Lab, Wolf Science Center, Konrad-Lorenz-Institute for Ethology, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria
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29
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Wirobski G, Range F, Schaebs FS, Palme R, Deschner T, Marshall-Pescini S. Endocrine changes related to dog domestication: Comparing urinary cortisol and oxytocin in hand-raised, pack-living dogs and wolves. Horm Behav 2021; 128:104901. [PMID: 33245878 DOI: 10.1016/j.yhbeh.2020.104901] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 10/02/2020] [Accepted: 11/17/2020] [Indexed: 12/25/2022]
Abstract
Dogs are exceptionally well adapted to life close to humans, and alterations in their endocrine system during the domestication process may be an underlying mechanism. In particular, it has been suggested that low circulating cortisol concentrations in conjunction with simultaneously high oxytocin concentrations may have resulted in dogs' increased docility ('selection for tameness' hypothesis) and heightened propensity to interact and form relationships with humans ('hypersociability' hypothesis) compared to wolves. To investigate this, we analyzed cortisol and oxytocin metabolite concentrations from urine samples of hand-raised, pack-living domestic dogs and their non-domestic relatives, grey wolves. Based on the hypotheses outlined above, we predicted lower cortisol but higher oxytocin concentrations in dogs than wolves. In contrast to our prediction, we found higher cortisol concentrations in dogs than wolves. However, oxytocin concentrations were higher in dogs compared to wolves although the effect was relatively small. Indeed, male dogs had the highest oxytocin concentrations while female dogs' oxytocin concentrations were comparable to wolves'. Feeding status, reproductive phase, and conspecific social interactions also significantly affected cortisol and oxytocin concentrations. Furthermore, we compared two methods of correcting for variable water content of urine samples. We discuss our results in light of physiological and behavioral changes during domestication and highlight the importance of accounting for confounding variables in future studies.
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Affiliation(s)
- G Wirobski
- Domestication Lab, Wolf Science Center, Konrad-Lorenz-Institute for Ethology, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria.
| | - F Range
- Domestication Lab, Wolf Science Center, Konrad-Lorenz-Institute for Ethology, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria.
| | - F S Schaebs
- University of Leipzig, ZLS, Prager Str. 34, 04317 Leipzig, Germany.
| | - R Palme
- Unit of Physiology, Pathophysiology and Experimental Endocrinology, Department of Biomedical Sciences, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria.
| | - T Deschner
- Endocrinology Lab, Department of Primatology, Max-Planck-Institute for Evolutionary Anthropology, Deutscher Platz 6, 04103 Leipzig, Germany.
| | - S Marshall-Pescini
- Domestication Lab, Wolf Science Center, Konrad-Lorenz-Institute for Ethology, University of Veterinary Medicine, Veterinaerplatz 1, 1210 Vienna, Austria.
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30
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Chen K, Ye Y, Troje NF, Zhou W. Oxytocin modulates human chemosensory decoding of sex in a dose-dependent manner. eLife 2021; 10:59376. [PMID: 33439831 PMCID: PMC7806258 DOI: 10.7554/elife.59376] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/27/2020] [Accepted: 01/04/2021] [Indexed: 12/17/2022] Open
Abstract
There has been accumulating evidence of human social chemo-signaling, but the underlying mechanisms remain poorly understood. Considering the evolutionarily conserved roles of oxytocin and vasopressin in reproductive and social behaviors, we examined whether the two neuropeptides are involved in the subconscious processing of androsta-4,16,-dien-3-one and estra-1,3,5 (10),16-tetraen-3-ol, two human chemosignals that convey masculinity and femininity to the targeted recipients, respectively. Psychophysical data collected from 216 heterosexual and homosexual men across five experiments totaling 1056 testing sessions consistently showed that such chemosensory communications of masculinity and femininity were blocked by a competitive antagonist of both oxytocin and vasopressin receptors called atosiban, administered nasally. On the other hand, intranasal oxytocin, but not vasopressin, modulated the decoding of androstadienone and estratetraenol in manners that were dose-dependent, nonmonotonic, and contingent upon the recipients’ social proficiency. Taken together, these findings establish a causal link between neuroendocrine factors and subconscious chemosensory communications of sex-specific information in humans.
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Affiliation(s)
- Kepu Chen
- State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Psychology, Chinese Academy of Sciences, Beijing, China
| | - Yuting Ye
- Department of Psychology, University of Chinese Academy of Sciences, Beijing, China
| | | | - Wen Zhou
- State Key Laboratory of Brain and Cognitive Science, CAS Center for Excellence in Brain Science and Intelligence Technology, Institute of Psychology, Chinese Academy of Sciences, Beijing, China.,Department of Psychology, University of Chinese Academy of Sciences, Beijing, China.,Chinese Institute for Brain Research, Beijing, China
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31
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Intranasal oxytocin and the stress-buffering effects of social support during experimentally induced pain: The role of attachment security. J Affect Disord 2021; 278:149-156. [PMID: 32961410 DOI: 10.1016/j.jad.2020.09.057] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2020] [Revised: 09/08/2020] [Accepted: 09/11/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND This study examined whether intranasal oxytocin enhances the stress-buffering effects of social support during experimentally induced pain, taking into account the role of individual differences in attachment security. METHODS Female participants (N = 193) were randomly assigned to oxytocin (24 IU intranasal) or placebo and to receive support or no support from a friend (2 × 2 factorial design with repeated measures)). Participants underwent the Cold Pressor Task (CPT) and were monitored for heart rate variability (HRV: RMSSD) and heart rate and reported pain levels. The Experiences in Close Relationships Questionnaire was used to measure attachment. RESULTS Oxytocin reduced RMSSD (p = 0.003, partial ɳ2 = 0.03) and increased heart rate (p = 0.039, partial ɳ2 = 0.03) in individuals who received support, possibly reflecting an enhanced attentional state. Oxytocin did not enhance beneficial effects of social support on perceived pain, but increased pain intensity in avoidantly attached individuals who were supported by a friend (p = 0.009, partial ɳ2 = 0.06). LIMITATIONS Only female participants were examined. Future studies are needed to determine sex differences in how oxytocin shapes stress-buffering effects of support. CONCLUSIONS Oxytocin may enhance the salience of social proximity and may be a mechanism underlying previously reported social influences on cardiovascular and mental health. However, oxytocin effects depend on interpersonal insecurities and may trigger discomfort in avoidantly attached individuals. Caution about oxytocin's therapeutic promise is warranted.
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Flanagan JC, Mitchell JM, Baker NL, Woolley J, Wangelin B, Back SE, McQuaid JR, Neylan TC, Wolfe WR, Brady KT. Enhancing prolonged exposure therapy for PTSD among veterans with oxytocin: Design of a multisite randomized controlled trial. Contemp Clin Trials 2020; 95:106074. [PMID: 32561468 DOI: 10.1016/j.cct.2020.106074] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2020] [Revised: 06/06/2020] [Accepted: 06/12/2020] [Indexed: 12/17/2022]
Abstract
Posttraumatic stress disorder (PTSD) is the most highly prevalent mental health disorder among U.S. military Veterans. Prolonged Exposure (PE) therapy is one of the most widely used evidence-based treatments for PTSD, but there is substantial room for improvement in outcomes and retention rates. Accumulating data suggest that oxytocin offers a promising pharmacological approach towards achieving this goal. Therefore, the primary objective of this two-site Phase II study is to examine the ability of oxytocin (vs. placebo) administration combined with PE therapy to (1) reduce PTSD symptom severity, (2) accelerate the rate of PTSD symptom improvement, and (3) improve PE adherence and retention rates. To accomplish these objectives, we will employ a randomized, double-blind, placebo-controlled trial and use standardized, repeated dependent measures of change at five time points (baseline, mid-treatment, end of treatment, and 3 and 6 month follow-up). Intranasal oxytocin (40 IU) will be administered directly prior to each PE therapy session. Findings from this study will provide critical new information regarding the efficacy of oxytocin to augment psychosocial treatment for PTSD, as well as information regarding the physiological mechanisms underlying PTSD and positive treatment response. ClinicalTrials.gov Identifier: NCT04228289.
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Affiliation(s)
- Julianne C Flanagan
- Department of Psychiatry and Behavioral Sciences, College of Medicine, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA.
| | - Jennifer M Mitchell
- Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA; Department of Neurology, University of California San Francisco, San Francisco, CA, USA; San Francisco Veterans Affairs Health Care System, San Francisco, CA, USA.
| | - Nathaniel L Baker
- Department of Public Health Sciences, College of Medicine, Medical University of South Carolina, Charleston, SC, USA.
| | - Joshua Woolley
- Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA; San Francisco Veterans Affairs Health Care System, San Francisco, CA, USA.
| | - Bethany Wangelin
- Department of Psychiatry and Behavioral Sciences, College of Medicine, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA.
| | - Sudie E Back
- Department of Psychiatry and Behavioral Sciences, College of Medicine, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA.
| | - John R McQuaid
- Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA; San Francisco Veterans Affairs Health Care System, San Francisco, CA, USA.
| | - Thomas C Neylan
- Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA; Department of Neurology, University of California San Francisco, San Francisco, CA, USA; San Francisco Veterans Affairs Health Care System, San Francisco, CA, USA.
| | - William R Wolfe
- Department of Psychiatry, University of California San Francisco, San Francisco, CA, USA; San Francisco Veterans Affairs Health Care System, San Francisco, CA, USA.
| | - Kathleen T Brady
- Department of Psychiatry and Behavioral Sciences, College of Medicine, Medical University of South Carolina, Charleston, SC, USA; Ralph H. Johnson Veterans Affairs Medical Center, Charleston, SC, USA.
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Leone RM, Jarnecke AM, Back SE, Brady KT, Flanagan JC. The moderating role of infidelity on the relation between oxytocin and conflict behaviors among substance misusing couples. Exp Clin Psychopharmacol 2020; 28:251-257. [PMID: 31556677 PMCID: PMC7096267 DOI: 10.1037/pha0000320] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
The neuropeptide oxytocin (OT) may be beneficial to augmenting behavioral therapies for couples given its ability to alleviate stress reactivity and increase pro-social behavior. However, there is growing evidence demonstrating inconsistent effects of OT on social behavior. Infidelity may represent a relational vulnerability that modulates the OT response. The present study hypothesized that actor and partner emotional and physical infidelity would be associated with less adaptive conflict behaviors, and moderate the OT response, such that participants randomized to a OT condition, compared to placebo, who report more infidelity would show less adaptive conflict behaviors. Participants were 30 couples (N = 60) wherein one or both partners engaged in recent hazardous drinking or illicit drug use. Partners completed a 10-min dyadic conflict task in the laboratory, self-administered a single intranasal dose of OT (40 IU) or placebo, and then completed the same 10-min dyadic conflict task following a 45-min wait period. Couple conflict behaviors were observed during the conflict tasks and assessed using a validated coding system. Actor partner interdependence models detected significant interactions between drug condition and physical infidelity, such that among individuals in the OT group, verses individuals in the placebo group, (a) who reported greater physical infidelity had greater distress maintaining attributions and (b) whose partners reported greater physical infidelity had fewer relationship enhancing attributions. Results are consistent with the social salience hypothesis of OT and suggest that physical infidelity appears to serve as a contextual vulnerability that may decreases positive and increase negative behaviors during conflict. (PsycInfo Database Record (c) 2020 APA, all rights reserved).
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Affiliation(s)
| | | | - Sudie E. Back
- Medical University of South Carolina,Ralph H. Johnson VA Medical Center, Charleston, South Carolina
| | - Kathleen T. Brady
- Medical University of South Carolina,Ralph H. Johnson VA Medical Center, Charleston, South Carolina
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Leslie M, Leppanen J, Paloyelis Y, Treasure J. A pilot study investigating the influence of oxytocin on attentional bias to food images in women with bulimia nervosa or binge eating disorder. J Neuroendocrinol 2020; 32:e12843. [PMID: 32202692 PMCID: PMC8650572 DOI: 10.1111/jne.12843] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 02/17/2020] [Accepted: 03/10/2020] [Indexed: 12/17/2022]
Abstract
BACKGROUND Previous research has found that exogenous oxytocin administration has the potential to modulate attentional biases in women with anorexia nervosa. Recent work has indicated that attentional biases to food may reinforce the recurrent binge eating behaviour characterising bulimia nervosa and binge eating disorder. To date, however, no study has yet investigated the effect of oxytocin on attentional biases to palatable food in women with bulimia nervosa and binge eating disorder. METHODS The present study employed a single-session cross-over design to test the hypothesis that a divided dose of 64 IU of intranasal oxytocin, administered as one intranasal dose of 40 IU of oxytocin followed by a top-up of 24 IU of oxytocin 80 minutes later, vs placebo administration administered in the same dosing schedule would reduce attentional biases towards food images in a dot probe task. We hypothesised that oxytocin administration would reduce vigilance towards food to a greater degree in women with bulimia nervosa or binge eating disorder vs healthy comparison women. Twenty-five women with bulimia nervosa or binge eating disorder and 27 comparison women without history of an eating disorder were recruited to take part in the study. RESULTS In contrast to our hypothesis, there was no main effect of diagnosis on attentional bias to food (fixed effect = 5.70, P = 0.363), nor a significant interaction between diagnosis and drug condition (fixed effect =-14.80, P = 0.645). There was a main effect of drug condition, such that oxytocin increased vigilance towards food vs neutral images in the dot probe task (fixed effect = 10.42, P = 0.044). A correlation analysis revealed that this effect was moderated by attentional bias in the placebo condition, such that greater avoidance of food stimuli in the placebo condition was associated with a greater increase in vigilance induced by oxytocin. CONCLUSIONS The findings of the present study add to a mixed body of literature investigating the therapeutic effects of oxytocin in women. Future research would benefit from dose-response studies investigating the optimal dose of oxytocin for modulating the attentional processing of palatable food in populations with eating disorders.
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Affiliation(s)
- Monica Leslie
- Institute of Psychiatry, Psychology and Neuroscience (IoPPN)King’s College London (KCL)LondonUK
| | - Jenni Leppanen
- Institute of Psychiatry, Psychology and Neuroscience (IoPPN)King’s College London (KCL)LondonUK
| | - Yannis Paloyelis
- Institute of Psychiatry, Psychology and Neuroscience (IoPPN)King’s College London (KCL)LondonUK
| | - Janet Treasure
- Institute of Psychiatry, Psychology and Neuroscience (IoPPN)King’s College London (KCL)LondonUK
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Hinchcliffe JK, Mendl M, Robinson ES. Investigating hormone-induced changes in affective state using the affective bias test in male and female rats. Psychoneuroendocrinology 2020; 115:104647. [PMID: 32179367 PMCID: PMC7193894 DOI: 10.1016/j.psyneuen.2020.104647] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2019] [Revised: 01/16/2020] [Accepted: 03/04/2020] [Indexed: 11/29/2022]
Abstract
Recent clinical and pre-clinical research suggests that affective biases may play an important role in the development and perpetuation of mood disorders. Studies in animals have also revealed that similar neuropsychological processes can be measured in non-human species using behavioural assays designed to measure biases in learning and memory or decision-making. Given the proposed links between hormones and mood, we used the affective bias test to investigate the effects of different hormone treatments in both male and female rats. Animals were pre-treated with acute doses of hormone or vehicle control prior to learning each of two independent substrate-reward associations. During a subsequent choice test, positive or negative biases were observed by animal's preference towards or away from the substrate learnt during drug treatment respectively. In both sexes, oestradiol and the oestrogen-like compound bisphenol A induced positive biases, whilst blockade of oestrogen hormones with formestane induced a negative bias. Progesterone induced a negative bias in both sexes, but testosterone only induced a negative bias in males. Blocking testosterone with flutamide induced a positive bias in both sexes at the higher dose (10 mg/kg). The oxytocin analogue, carbetocin induced positive biases in both sexes but the vasopressin analogue, desmopressin, induced a positive bias in male rats only. These results provide evidence that modulating levels of hormones using exogenous treatments can induce affective biases in rats. They also suggest that hormone-induced affective biases influence cognitive and emotional behaviour and could have longer-term effects in some mood disorders.
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Affiliation(s)
- Justyna K. Hinchcliffe
- University of Bristol, School of Physiology, Pharmacology & Neuroscience, Biomedical Sciences Building, University Walk, Bristol, BS8 1TD, UK
| | - Michael Mendl
- School of Veterinary Sciences, University of Bristol, Langford House, Langford, Bristol BS40 5DU, UK
| | - Emma S.J. Robinson
- University of Bristol, School of Physiology, Pharmacology & Neuroscience, Biomedical Sciences Building, University Walk, Bristol, BS8 1TD, UK,Corresponding author.
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Harricharran T, Ogunwobi OO. Oxytocin and oxytocin receptor alterations, decreased survival, and increased chemoresistance in patients with pancreatic cancer. Hepatobiliary Pancreat Dis Int 2020; 19:175-180. [PMID: 31919036 PMCID: PMC7265130 DOI: 10.1016/j.hbpd.2019.12.002] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Accepted: 12/04/2019] [Indexed: 02/05/2023]
Abstract
BACKGROUND Oxytocin (OXT) and its receptor (OXTR) is associated with cancer. The present study was to investigate the correlation between the genetic expression alterations of OXT and OXTR and the outcomes in patients with pancreatic cancer (PC). METHODS Information regarding OXT and OXTR genetic alterations and changes in gene expression were retrieved from the Cancer Genome Atlas (TCGA) databases and analyzed using the cBioPortal online tool. We assessed the correlation of overall survival and disease/progression-free months to either OXT or OXTR genetic alterations and changes in gene expression using Kaplan-Meier and Cox regression analyses. Quantitative PCR (qPCR) was conducted to assess the mRNA expression levels of OXT and OXTR in human PC cell lines. RESULTS Five percent of PC cases showed mRNA upregulation in the OXT gene. These PC cases also showed genetic alterations and changes in gene expression of OXTR. The median months of survival and disease-free survival were lower for PC cases with genetic alterations and changes in gene expression in the OXT and OXTR genes as compared to those without such alterations. qPCR data showed that OXT and OXTR mRNA expression were 1-fold and 10-fold higher, respectively in PANC-1 cell lines as compared to L3.6pl cell lines in direct negative correlation with responsiveness to gemcitabine. CONCLUSIONS These data suggest that OXT and OXTR may potentially be important in PC progression, chemoresistance, and patient survival, and potentially could have prognostic and therapeutic implications in a subset of PC patients.
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Affiliation(s)
- Trisheena Harricharran
- Department of Biological Sciences, Hunter College of The City University of New York, New York, NY 10065, USA; The Graduate Center Departments of Biology and Biochemistry, The City University of New York, New York, NY 10016, USA; Hunter College Center for Cancer Health Disparities Research (CCHDR), New York, NY 10065, USA
| | - Olorunseun O Ogunwobi
- Department of Biological Sciences, Hunter College of The City University of New York, New York, NY 10065, USA; The Graduate Center Departments of Biology and Biochemistry, The City University of New York, New York, NY 10016, USA; Hunter College Center for Cancer Health Disparities Research (CCHDR), New York, NY 10065, USA; Joan and Sanford I. Weill Department of Medicine, Weill Cornell Medicine, Cornell University, New York, NY 10065, USA.
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Skvortsova A, Veldhuijzen DS, van Middendorp H, Colloca L, Evers AWM. Effects of Oxytocin on Placebo and Nocebo Effects in a Pain Conditioning Paradigm: A Randomized Controlled Trial. THE JOURNAL OF PAIN 2020; 21:430-439. [PMID: 31494273 PMCID: PMC7408480 DOI: 10.1016/j.jpain.2019.08.010] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 02/05/2019] [Revised: 08/06/2019] [Accepted: 08/23/2019] [Indexed: 12/19/2022]
Abstract
Oxytocin has been shown to increase trust, decrease anxiety, and affect learning as has been observed in conditioning paradigms. Trust, anxiety, and learning are important factors that influence placebo effects. In this study, we investigated whether oxytocin can increase placebo analgesia, decrease nocebo hyperalgesia, and influence extinction processes of both. Eighty male volunteers were assigned to a 40 IU of oxytocin nasal spray group, or to a placebo control group. Placebo analgesia and nocebo hyperalgesia were induced by a conditioning procedure in combination with verbal suggestions. The results demonstrate that the conditioning procedure successfully elicited significant placebo analgesia and nocebo hyperalgesia responses (P < .001). Furthermore, extinction was observed (P < .001), although placebo and nocebo responses did not return to baseline and remained significant. Oxytocin did not influence placebo analgesia or nocebo hyperalgesia and had no effect on extinction. This study provides support against the placebo-boosting effects of oxytocin and was the first one to demonstrate that it also did not influence nocebo effects or extinction processes, however, these results pertain to only a male sample. As managing placebo and nocebo effects has widespread clinical implications, further research should investigate other neurobiological or behavioral pathways to boost placebo and decrease nocebo effects. PERSPECTIVE: The present study demonstrated that placebo analgesia and nocebo hyperalgesia can be successfully induced by conditioning and verbal suggestions. We could not confirm the hypothesis that oxytocin affects either of these phenomena. Other pharmacological agents and behavioral manipulations for increasing placebo and decreasing nocebo effects should be investigated.
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Affiliation(s)
- Aleksandrina Skvortsova
- Health, Medical and Neuropsychology Unit, Institute of Psychology, Faculty of Social and Behavioural Sciences, Leiden University, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands.
| | - Dieuwke S Veldhuijzen
- Health, Medical and Neuropsychology Unit, Institute of Psychology, Faculty of Social and Behavioural Sciences, Leiden University, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands
| | - Henriët van Middendorp
- Health, Medical and Neuropsychology Unit, Institute of Psychology, Faculty of Social and Behavioural Sciences, Leiden University, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands
| | - Luana Colloca
- Department of Pain Translational Symptoms Science, School of Nursing and Department of Anaesthesiology, Medicine, University of Maryland Baltimore, Baltimore, Maryland
| | - Andrea W M Evers
- Health, Medical and Neuropsychology Unit, Institute of Psychology, Faculty of Social and Behavioural Sciences, Leiden University, Leiden, The Netherlands; Leiden Institute for Brain and Cognition, Leiden, The Netherlands; Department of Psychiatry, Leiden University Medical Center, Leiden, The Netherlands
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Uysal N, Çamsari UM, ATEş M, Kandİş S, Karakiliç A, Çamsari GB. Empathy as a Concept from Bench to Bedside: A Translational Challenge. Noro Psikiyatr Ars 2020; 57:71-77. [PMID: 32110155 PMCID: PMC7024828 DOI: 10.29399/npa.23457] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/22/2018] [Accepted: 08/25/2019] [Indexed: 01/10/2023] Open
Abstract
Empathy is a multidimensional paradigm, and there currently is a lack of scientific consensus in its definition. In this paper, we review the possibility of compromising data during behavioral neuroscience experiments, including but not limited to those who study empathy. The experimental protocols can affect, and be affected by, empathy and related processes at multiple levels. We discuss several points to help researchers develop a successful translational pathway for behavioral research on empathy. Despite varying in their focus with no widely accepted model, current rodent models on empathy have provided sound translational explanations for many neuropsychiatric proof-of-concepts to date. Research has shown that empathy can be influenced by many parameters, some of which are to be reviewed in this paper. We emphasize the future importance of consistency in modeling proof of concept; efforts to create a multidisciplinary group which would include both bench scientists and clinicians with expertise in neuropsychiatry, and the consideration of empathy as an independent variable in animal behavioral experimental designs which is not the mainstream practice at present.
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Affiliation(s)
- Nazan Uysal
- Department of Physiology, Dokuz Eylül University, İzmir, Turkey
| | - Ulaş M. Çamsari
- Department of Psychiatry, Mayo Clinic, Rochester, Minnesota, USA
| | - Mehmet ATEş
- Department of Pharmacology, Dokuz Eylül University, İzmir, Turkey
| | - Sevim Kandİş
- Department of Physiology, Dokuz Eylül University, İzmir, Turkey
| | - Aslı Karakiliç
- Department of Physiology, Dokuz Eylül University, İzmir, Turkey
| | - Gamze B. Çamsari
- Department of Psychiatry, Mayo Clinic, Rochester, Minnesota, USA
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Hou W, He Z, Yang Y, Yuan W, Wang L, Zhang J, Zhang X, Cai W, Guo Q, Tai F. The involvement of oxytocin in the effects of chronic social defeat stress on emotional behaviours in adult female mandarin voles. Eur J Neurosci 2020; 52:2853-2872. [PMID: 32011013 DOI: 10.1111/ejn.14691] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/22/2018] [Revised: 12/31/2019] [Accepted: 01/23/2020] [Indexed: 12/26/2022]
Abstract
Chronic social defeat stress (CSDS) can induce anxiety and depression in male rodents, but the prevalence of anxiety and depression is much higher in females, and effects of CSDS on adult females and its underlying mechanism remain unclear. Oxytocin is a stress-buffering hormone in the brain that modulates the physiological effects of stress. Strikingly, research regarding the effect of oxytocin on emotional changes caused by CSDS is still lacking in females. Thus, we focused on the involvement of the oxytocin system in changes in emotional regulation induced by CSDS in female voles. Seventy-day-old female mandarin voles (Microtus mandarinus) were exposed to aggressive adult females for 14 days, and the effects of CSDS on emotion and regulation of oxytocin system were characterized. In addition, we injected vehicle, oxytocin and oxytocin receptor antagonist into the nucleus accumbens (Nacc) of female voles to investigate the involvement of Nacc oxytocin in the effect of CSDS on emotion. Herein, we reported that CSDS increased anxiety and depression-like behaviour and the circulating level of corticosterone, but decreased the number of oxytocin projections and the protein and mRNA expression levels of oxytocin receptor in the Nacc. Injection of oxytocin into the Nacc reversed the effects of CSDS on anxiety-like and depressive-like behaviour, whereas combined injections of oxytocin and oxytocin receptor antagonist eliminated these effects. In conclusion, CSDS increases the levels of anxiety and depression possibly via a reduction in oxytocin projections and the oxytocin receptor level in the Nacc. Nacc oxytocin may be involved in the effects of CSDS on emotional behaviours.
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Affiliation(s)
- Wenjuan Hou
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an, China
| | - Zhixiong He
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an, China
| | - Yang Yang
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an, China
| | - Wei Yuan
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an, China
| | - Limin Wang
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an, China
| | - Jing Zhang
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an, China
| | - Xueni Zhang
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an, China
| | - Wenqi Cai
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an, China
| | - Qianqian Guo
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an, China
| | - Fadao Tai
- Institute of Brain and Behavioral Sciences, College of Life Sciences, Shaanxi Normal University, Xi'an, China
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Meijen C, Turner M, Jones MV, Sheffield D, McCarthy P. A Theory of Challenge and Threat States in Athletes: A Revised Conceptualization. Front Psychol 2020; 11:126. [PMID: 32116930 PMCID: PMC7016194 DOI: 10.3389/fpsyg.2020.00126] [Citation(s) in RCA: 37] [Impact Index Per Article: 7.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/10/2019] [Accepted: 01/16/2020] [Indexed: 01/01/2023] Open
Abstract
The Theory of Challenge and Threat States in Athletes (TCTSA) provides a psychophysiological framework for how athletes anticipate motivated performance situations. The purpose of this review is to discuss how research has addressed the 15 predictions made by the TCTSA, to evaluate the mechanisms underpinning the TCTSA in light of the research that has emerged in the last 10 years, and to inform a revised TCTSA (TCTSA-R). There was support for many of the 15 predictions in the TCTSA, with two main areas for reflection identified: to understand the physiology of challenge and to re-evaluate the concept of resource appraisals. This re-evaluation informs the TCTSA-R, which elucidates the physiological changes, predispositions, and cognitive appraisals that mark challenge and threat states. First, the relative strength of the sympathetic nervous system response is outlined as a determinant of challenge and threat patterns of reactivity and we suggest that oxytocin and neuropeptide Y are also key indicators of an adaptive approach to motivated performance situations and can facilitate a challenge state. Second, although predispositions were acknowledged within the TCTSA, how these may influence challenge and threat states was not specified. In the TCTSA-R, it is proposed that one's propensity to appraise stressors is a challenge that most strongly dictates acute cognitive appraisals. Third, in the TCTSA-R, a more parsimonious integration of Lazarusian ideas of cognitive appraisal and challenge and threat is proposed. Given that an athlete can make both challenge and threat primary appraisals and can have both high or low resources compared to perceived demands, a 2 × 2 bifurcation theory of challenge and threat is proposed. This reflects polychotomy of four states: high challenge, low challenge, low threat, and high threat. For example, in low threat, an athlete can evince a threat state but still perform well so long as they perceive high resources. Consequently, we propose suggestions for research concerning measurement tools and a reconsideration of resources to include social support. Finally, applied recommendations are made based on adjusting demands and enhancing resources.
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Affiliation(s)
- Carla Meijen
- Department of Sport and Exercise Science, Faculty of Sport, Health and Applied Science, St Mary’s University, Twickenham, London, United Kingdom
| | - Martin Turner
- Department of Psychology, Faculty of Health, Psychology and Social Care, Manchester Metropolitan University, Manchester, United Kingdom
| | - Marc V. Jones
- Department of Psychology, Faculty of Health, Psychology and Social Care, Manchester Metropolitan University, Manchester, United Kingdom
| | - David Sheffield
- School of Human Sciences, College of Life and Natural Sciences, University of Derby, Derby, United Kingdom
| | - Paul McCarthy
- Department of Psychology, School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, United Kingdom
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Tabbaa M, Hammock EAD. Orally administered oxytocin alters brain activation and behaviors of pre-weaning mice. Horm Behav 2020; 118:104613. [PMID: 31654673 PMCID: PMC7015803 DOI: 10.1016/j.yhbeh.2019.104613] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2019] [Revised: 09/23/2019] [Accepted: 10/07/2019] [Indexed: 02/02/2023]
Abstract
Oxytocin (OXT) regulates adult social behavior and has been implicated in its development. Because mammalian milk contains OXT and we have recently identified OXT receptors (OXTR) in the face and oronasal cavity of pre-weaning mice, we hypothesize that orally applied OXT may impact brain activity and acute behavior in developing mice. Oral OXT may have effects in the absence of sensory stimulation or perhaps by modulating sensory input, such as whisker stimulation. The present study investigates the acute c-Fos response in the paraventricular nucleus of the hypothalamus (PVN) and along whisker sensory processing brain regions (trigeminothalamocortical circuit) to orally applied OXT, compared to saline, with and without whisker stimulation in postnatal day (P) 14 and P21 male and female mice. Acute behavioral responses were also quantified after oral OXT with whisker stimulation in a non-social context. Oral OXT with and without whisker stimulation increased c-Fos activity in the PVN of males and decreased c-Fos in the ventroposterior medial thalamus in both males and females compared to saline. Additionally, oral OXT with whisker stimulation decreased c-Fos activity across whisker sensory processing brain regions in males and females and decreased c-Fos activity in the trigeminal motor nucleus of females. Lastly, oral OXT with whisker stimulation increased males' locomotor behavior and decreased females' oromotor behavior compared to saline-treated controls. These data indicate that orally applied OXT has acute brain and behavioral effects on developing mice. OXT-modulated sensory signals may bias brain and behavior development toward the social world.
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Affiliation(s)
- Manal Tabbaa
- Department of Psychology and Program in Neuroscience, The Florida State University, Tallahassee, FL, 32306, USA
| | - Elizabeth A D Hammock
- Department of Psychology and Program in Neuroscience, The Florida State University, Tallahassee, FL, 32306, USA.
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42
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Gust K, Caccese C, Larosa A, Nguyen TV. Neuroendocrine Effects of Lactation and Hormone-Gene-Environment Interactions. Mol Neurobiol 2020; 57:2074-2084. [PMID: 31927723 DOI: 10.1007/s12035-019-01855-8] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2019] [Accepted: 12/11/2019] [Indexed: 12/12/2022]
Abstract
While correlational studies suggest that lactation may confer a certain level of protection from mental illness, this benefit is not uniformly expressed in all women who choose to breastfeed. We propose here that the neuroendocrine "resetting" induced by lactation may predispose toward positive affect states in a subset of hormone-sensitive mothers, with hormone-gene and hormone-environment interactions determining the ultimate psychological outcome. We find evidence to suggest that higher secretion of prolactin/oxytocin as well as lower secretion of vasopression/androgens in lactating mothers may protect against postpartum depression and anxiety, decrease levels of irritability, and optimize stress responses. On the other hand, while the abrupt withdrawal of estradiol/progesterone in the immediate postpartum period tends to be associated with adverse psychological outcomes, the chronic suppression of estrogens/progestogens induced by lactation may have antidepressant and anxiolytic effects over time. Finally, the hypo-cortisolemic state seen in lactating mothers appears to be associated with improved stress reactivity and circadian rhythms. We also discuss hormone-gene and hormone-environment interactions likely to modulate any potential psychological benefits related to lactation and focus on those factors that are either easy to screen for or known to be modifiable. In sum, neuroendocrine alterations induced by lactation may play a key role in determining reproductive psychiatric risk in a subset of hormone-sensitive women. Using these neuroendocrine factors as an individualized index of risk can help in devising targeted programs to support these women in pursuing lactation or, for those not able or willing, accessing psychological interventions in a timely manner.
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Affiliation(s)
- Kirsten Gust
- Reproductive Psychiatry Program, Departments of Psychiatry and Obstetrics-Gynecology, McGill University Health Centre, Montreal, QC, Canada
| | - Christina Caccese
- Department of Psychiatry, McGill University, 1001 Decarie Blvd., Montreal, QC, H4A 3J1, Canada
| | - Amanda Larosa
- Integrated Program in Neuroscience, McGill University, Montreal, QC, Canada.,Neuroscience Division, Douglas Mental Health University Institute, Montreal, QC, Canada
| | - Tuong-Vi Nguyen
- Reproductive Psychiatry Program, Departments of Psychiatry and Obstetrics-Gynecology, McGill University Health Centre, Montreal, QC, Canada.
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Zhao W, Luo R, Sindermann C, Li J, Wei Z, Zhang Y, Liu C, Le J, Quintana DS, Montag C, Becker B, Kendrick KM. Oxytocin modulation of self-referential processing is partly replicable and sensitive to oxytocin receptor genotype. Prog Neuropsychopharmacol Biol Psychiatry 2020; 96:109734. [PMID: 31415827 DOI: 10.1016/j.pnpbp.2019.109734] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2019] [Revised: 07/18/2019] [Accepted: 08/10/2019] [Indexed: 11/25/2022]
Abstract
Intranasal oxytocin (OXT) has been associated with effects on diverse social-emotional domains in humans, however progress towards a therapeutic application of OXT in disorders with social-emotion impairments is currently hampered by poor replicability. Limited statistical power and individual differences in biological factors, such as oxytocin receptor (OXTR) genetics, may have contributed to these variable findings. To this end, employing a validated oxytocin-sensitive trait judgment paradigm, we present a pharmaco-genetic study aiming at (1) replicating previous findings suggesting that intranasal oxytocin (24 IU) reduces the self-referential bias in a large sample of n = 170 male subjects, (2) determining whether variations in common receptor polymorphisms (rs237887, rs2268491, rs2254298, rs53576, rs2268498) influence sensitivity to oxytocin's behavioral effects. We confirmed that in the whole sample oxytocin influenced self-other distinction in terms of reduced decision time. However, oxytocin only influenced decision time in rs53576 G carriers, whereas effects on subsequent memory performance were only found in rs2268498 TT homozygotes. In summary, the current study partially replicates our previous findings showing that oxytocin reduces the self-referential bias and suggests that sensitivity to its effects in this domain are receptor genotype dependent.
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Affiliation(s)
- Weihua Zhao
- The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu 611731, China
| | - Ruixue Luo
- The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu 611731, China
| | - Cornelia Sindermann
- Department of Molecular Psychology, Institute of Psychology and Education, Ulm University, Helmholtzstr. 8/1, 89081 Ulm, Germany
| | - Jialin Li
- The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu 611731, China
| | - Zhenyu Wei
- The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu 611731, China
| | - Yingying Zhang
- The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu 611731, China
| | - Congcong Liu
- The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu 611731, China
| | - Jiao Le
- The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu 611731, China
| | - Daniel S Quintana
- NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, University of Oslo, and Oslo University Hospital, Oslo, Norway
| | - Christian Montag
- Department of Molecular Psychology, Institute of Psychology and Education, Ulm University, Helmholtzstr. 8/1, 89081 Ulm, Germany
| | - Benjamin Becker
- The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu 611731, China.
| | - Keith M Kendrick
- The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu 611731, China.
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A Preliminary Examination of Endogenous Peripheral Oxytocin in a Pilot Randomized Clinical Trial of Oxytocin-Enhanced Psychotherapy for Posttraumatic Stress Disorder. J Clin Psychopharmacol 2020; 40:401-404. [PMID: 32639293 PMCID: PMC7350551 DOI: 10.1097/jcp.0000000000001226] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
BACKGROUND Preclinical and clinical research suggests that the oxytocin system is implicated in the development and maintenance of stress and anxiety-related psychiatric conditions, such as posttraumatic stress disorder (PTSD). Recent research also suggests that intranasal oxytocin holds promise as a treatment for PTSD. However, little is known about the relationship between levels of peripheral oxytocin and PTSD symptom severity, PTSD treatment response, and repeated intranasal oxytocin administration. METHODS In the current study, we examined associations between PTSD symptom severity and peripheral oxytocin levels measured in plasma before and after a course of prolonged exposure (PE) for PTSD (n = 13); participants were randomized to adjunctive intranasal oxytocin (n = 6) or placebo (n = 7). RESULTS Baseline peripheral oxytocin levels were not associated with baseline PTSD symptom severity. Change in peripheral oxytocin levels did not differ by treatment condition and did not correspond to change in PTSD symptoms. CONCLUSIONS This proof-of-concept study illustrates the acceptability and feasibility of measuring peripheral oxytocin among individuals engaged in psychotherapy for PTSD and informs the utilization of these procedures in future adequately powered studies.
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Zhang J, Zhou C, Yu R. Oxytocin amplifies the influence of good intentions on social judgments. Horm Behav 2020; 117:104589. [PMID: 31593697 DOI: 10.1016/j.yhbeh.2019.104589] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2019] [Revised: 08/25/2019] [Accepted: 09/13/2019] [Indexed: 11/19/2022]
Abstract
Studies have shown that the evolutionarily conserved neuropeptide oxytocin (OT) promotes various prosocial behaviors, yet there are few studies of the effect of OT on social judgments, especially on judgments when the actor's intention and the final outcome are incongruent. In a double-blind, placebo-controlled experiment, participants were asked to play the role of the recipient in a dictator game and to make social judgments about the dictator after intranasal OT administration. To isolate the outcome and the intention of the dictator's allocation, we developed a novel social judgment task in which recipients were told that 50% of the dictators' proposals would be reversed. The results showed that the effect of OT on social judgment was modulated by intention: OT increased goodness ratings only towards dictators with hyperfair intention. Our findings support the affiliative-motivation theory which states that OT enhances the affiliative motivation and recognition of positive-valence social stimuli.
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Affiliation(s)
- Junfeng Zhang
- School of Psychology, Center for Studies of Psychological Application and Key Laboratory of Mental Health and Cognitive Science of Guangdong Province, South China Normal University, Guangzhou, China
| | - Chengyan Zhou
- School of Psychology, Center for Studies of Psychological Application and Key Laboratory of Mental Health and Cognitive Science of Guangdong Province, South China Normal University, Guangzhou, China
| | - Rongjun Yu
- Department of Psychology, National University of Singapore, Singapore.
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Riem MME, Kunst LE, Bekker MHJ, Fallon M, Kupper N. Intranasal oxytocin enhances stress-protective effects of social support in women with negative childhood experiences during a virtual Trier Social Stress Test. Psychoneuroendocrinology 2020; 111:104482. [PMID: 31677411 DOI: 10.1016/j.psyneuen.2019.104482] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/08/2019] [Revised: 09/26/2019] [Accepted: 10/11/2019] [Indexed: 12/25/2022]
Abstract
Oxytocin is considered a biological mechanism underlying stress-protective effects of positive social interactions. It is assumed to underlie the women-specific tend-and-befriend response to stress, although few studies have tested this assertion with female samples. The aim of the present study was, therefore, to test whether oxytocin enhances stress-protective effects of social support during stress in women, taking into account the moderating role of childhood adversity. The sample consisted of 180 female undergraduate students who had reported on experiences of childhood abuse and how often their mother used love withdrawal as an insensitive disciplinary strategy. Women participated in a virtual version of the Trier Social Stress Test (TSST) and were randomly assigned to receive 24 IU oxytocin or a placebo and to receive support or no support from a female friend (sub-groups N = 45). Results showed that oxytocin reduced heart rate variability during the TSST in participants who received support, possibly indicating that oxytocin increases attention and stimulates a challenge motivational state in the presence of a friend. In addition, we found that, in the presence of a friend, oxytocin reduced state anxiety levels and cortisol levels after the TSST, but only in women with higher levels of adverse childhood experiences. Our findings may indicate that oxytocin is a neurobiological means to attain and benefit from social support under stressful circumstances, which may be particularly adaptive for women with a history of adversity. Thus, oxytocin may function as motivator for affiliative disposition during stress exposure in women with a history of childhood adversity. Results should be replicated in clinical samples.
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Affiliation(s)
- M M E Riem
- Center of Research on Psychological and Somatic disorders, Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands; Clinical Child and Family Studies, VU University Amsterdam, Amsterdam, the Netherlands.
| | - L E Kunst
- Center of Research on Psychological and Somatic disorders, Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands
| | - M H J Bekker
- Center of Research on Psychological and Somatic disorders, Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands; Department of Clinical Psychology, VU University Amsterdam, Amsterdam, the Netherlands
| | - M Fallon
- Business School, University of Mannheim, Mannheim, Germany
| | - N Kupper
- Center of Research on Psychological and Somatic disorders, Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands
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Leslie M, Leppanen J, Paloyelis Y, Treasure J. The influence of oxytocin on eating behaviours and stress in women with bulimia nervosa and binge eating disorder. Mol Cell Endocrinol 2019; 497:110354. [PMID: 30579958 DOI: 10.1016/j.mce.2018.12.014] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Revised: 12/18/2018] [Accepted: 12/19/2018] [Indexed: 12/12/2022]
Abstract
The current study aimed to test the influence of oxytocin on palatable food intake, 24-h caloric consumption, and stress in women with bulimia nervosa and binge eating disorder. We recruited 25 women with DSM-5 bulimia nervosa or binge eating disorder, and 27 weight-matched comparison women without history of an eating disorder. We employed a double-blind, placebo-controlled crossover design in which each participant attended the lab for two experimental sessions, receiving a divided dose of 64IU intranasal oxytocin in one session and equivalent volume of placebo nasal spray in the opposite session. The order of administration was pseudo-randomised across participants. We hypothesised that a divided dose of 64IU intranasal oxytocin administration would reduce subjective hunger, the immediate consumption of palatable food, 24-h calorie consumption, and the incidence of binge eating when compared to placebo. We also hypothesised that oxytocin administration would be associated with lower levels of stress and salivary cortisol, and that there would be an interaction with participant group such that oxytocin would reduce eating behaviour and stress to a greater degree in women with bulimia nervosa or binge eating disorder, compared to women without history of an eating disorder. We did not find a significant effect of oxytocin on any of the measurements of eating behaviour, subjective stress, or salivary cortisol. We recommend that future studies test the dose-response effect of oxytocin on eating behaviours and stress in human populations with eating disorders to further clarify the moderating factors for oxytocin's effect on eating.
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Affiliation(s)
- Monica Leslie
- Institute of Psychiatry, Psychology and Neuroscience (IoPPN) - King's College London (KCL), London, United Kingdom.
| | - Jenni Leppanen
- Institute of Psychiatry, Psychology and Neuroscience (IoPPN) - King's College London (KCL), London, United Kingdom
| | - Yannis Paloyelis
- Institute of Psychiatry, Psychology and Neuroscience (IoPPN) - King's College London (KCL), London, United Kingdom
| | - Janet Treasure
- Institute of Psychiatry, Psychology and Neuroscience (IoPPN) - King's College London (KCL), London, United Kingdom
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Weingarten MFJ, Scholz M, Wohland T, Horn K, Stumvoll M, Kovacs P, Tönjes A. Circulating Oxytocin Is Genetically Determined and Associated With Obesity and Impaired Glucose Tolerance. J Clin Endocrinol Metab 2019; 104:5621-5632. [PMID: 31361301 DOI: 10.1210/jc.2019-00643] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/17/2019] [Accepted: 07/22/2019] [Indexed: 01/01/2023]
Abstract
CONTEXT Despite the emerging evidence on the role of oxytocin (OXT) in metabolic diseases, there is a lack of well-powered studies addressing the relationship of circulating OXT with obesity and diabetes. OBJECTIVES AND DESIGN Here, we measured OXT in a study cohort (n = 721; 396 women, 325 men; mean age ± SD, 47.7 ± 15.2 years) with subphenotypes related to obesity, including anthropometric traits such as body mass index [BMI (mean ± SD), 26.8 ± 4.6 kg/m2], waist-to-hip ratio (WHR; 0.88 ± 0.09), blood parameters (glucose, 5.32 ± 0.50 mmol/L; insulin, 5.3 ± 3.3 µU/mL), and oral glucose tolerance test to clarify the association with OXT. We also tested in a genome-wide association study (GWAS) whether the interindividual variation in OXT serum levels might be explained by genetic variation. RESULTS The OXT concentration was increased in subjects with elevated BMI and positively correlated with WHR, waist circumference, and triglyceride levels. The OXT concentration in subjects with BMI <25 kg/m2 was significantly lower (n = 256; 78.6 pg/mL) than in subjects with a BMI between 25 and 30 kg/m2 (n = 314; 98.5 pg/mL, P = 6 × 10-6) and with BMI >30 kg/m2 (n = 137; 106.4 pg/mL, P = 8 × 10-6). OXT levels were also positively correlated with plasma glucose and insulin and were elevated in subjects with impaired glucose tolerance (P = 4.6 × 10-3). Heritability of OXT was estimated at 12.8%. In a GWAS, two hits in linkage disequilibrium close (19 kb) to the OXT reached genome-wide significant association (top-hit rs12625893, P = 3.1 × 10-8, explained variance 3%). CONCLUSIONS Our data show that OXT is genetically affected by a variant near OXT and is associated with obesity and impaired glucose tolerance.
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Affiliation(s)
| | - Markus Scholz
- Institute for Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig, Germany
- LIFE Research Center, University of Leipzig, Leipzig, Germany
| | - Tobias Wohland
- IFB Adiposity Diseases, University of Leipzig Medical Center, Leipzig, Germany
| | - Katrin Horn
- Institute for Medical Informatics, Statistics, and Epidemiology, University of Leipzig, Leipzig, Germany
- LIFE Research Center, University of Leipzig, Leipzig, Germany
| | - Michael Stumvoll
- Medical Department III-Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany
| | - Peter Kovacs
- Medical Department III-Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany
- IFB Adiposity Diseases, University of Leipzig Medical Center, Leipzig, Germany
| | - Anke Tönjes
- Medical Department III-Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany
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Burmester V, Gibson EL, Butler G, Bailey A, Terry P. Oxytocin reduces post-stress sweet snack intake in women without attenuating salivary cortisol. Physiol Behav 2019; 212:112704. [PMID: 31628930 DOI: 10.1016/j.physbeh.2019.112704] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/26/2019] [Revised: 09/30/2019] [Accepted: 10/07/2019] [Indexed: 10/25/2022]
Abstract
Intranasal oxytocin produces anorectic effects on snack intake in men when tested in the absence of deprivation-induced hunger, but its effects on food intake in women without eating disorders have not been reported. Oxytocin may reduce food intake by reducing stress eating, since it inhibits ACTH release. The present study adopted a double-blind, repeated measures and fully concealed crossover protocol in which 38 women self-administered 24 IU of oxytocin or placebo intranasally, ate lunch, and underwent two consecutive stress tests. Snack intake was assessed 15-20 min after lunch, via a sham taste test. Salivary cortisol was measured throughout the test period every 15 min. Oxytocin significantly reduced sweet fatty snack intake independently of any effect on salivary cortisol, which declined over time at a similar rate after either drug or placebo. Ratings of sweet taste were slightly reduced by oxytocin, but only in self-reported stress eaters. These results differ from previous studies with men that found an effect of oxytocin on postprandial cortisol levels. However, previous research assayed the less active form of plasma cortisol and did not control for protein intake, which can drive elevated cortisol. The finding that oxytocin reduces snack intake in females after acute stress has important implications for appetite regulation and its treatment in obese people and in those with eating disorders.
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Affiliation(s)
- V Burmester
- Department of Psychology, School of Law, Social and Behavioural Sciences, Kingston University, Penrhyn Road, Kingston upon Thames, Surrey KT1 2EE, UK
| | - E L Gibson
- Department of Psychology, Whitelands College, University of Roehampton, London SW15 4JD, UK
| | - G Butler
- Department of Psychology, School of Law, Social and Behavioural Sciences, Kingston University, Penrhyn Road, Kingston upon Thames, Surrey KT1 2EE, UK
| | - A Bailey
- Institute of Medical and Biomedical Education, St George's, University of London, Cranmer Terrace, London SW17 0RE, UK
| | - P Terry
- Department of Psychology, School of Law, Social and Behavioural Sciences, Kingston University, Penrhyn Road, Kingston upon Thames, Surrey KT1 2EE, UK.
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50
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Bradley ER, Seitz A, Niles AN, Rankin KP, Mathalon DH, O'Donovan A, Woolley JD. Oxytocin increases eye gaze in schizophrenia. Schizophr Res 2019; 212:177-185. [PMID: 31416746 PMCID: PMC6791758 DOI: 10.1016/j.schres.2019.07.039] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Revised: 05/23/2019] [Accepted: 07/25/2019] [Indexed: 12/18/2022]
Abstract
Abnormal eye gaze is common in schizophrenia and linked to functional impairment. The hypothalamic neuropeptide oxytocin modulates visual attention to social stimuli, but its effects on eye gaze in schizophrenia are unknown. We examined visual scanning of faces in men with schizophrenia and neurotypical controls to quantify oxytocin effects on eye gaze. In a randomized, double-blind, crossover study, 33 men with schizophrenia and 39 matched controls received one dose of intranasal oxytocin (40 IU) and placebo on separate testing days. Participants viewed 20 color photographs of faces while their gaze patterns were recorded. We tested for differences in fixation time on the eyes between patients and controls as well as oxytocin effects using linear mixed-effects models. We also tested whether attachment style, symptom severity, and anti-dopaminergic medication dosage moderated oxytocin effects. In the placebo condition, patients showed reduced fixation time on the eyes compared to controls. Oxytocin was associated with an increase in fixation time among patients, but a decrease among controls. Higher attachment anxiety and greater symptom severity predicted increased fixation time on the eyes on oxytocin versus placebo. Anti-dopaminergic medication dosage and attachment avoidance did not impact response to oxytocin. Consistent with findings that oxytocin optimizes processing of social stimuli, intranasal oxytocin enhanced eye gaze in men with schizophrenia. Further work is needed to determine whether changes in eye gaze impact social cognition and functional outcomes. Both attachment anxiety and symptom severity predicted oxytocin response, highlighting the importance of examining potential moderators of oxytocin effects in future studies.
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Affiliation(s)
- Ellen R Bradley
- University of California, San Francisco, CA, United States of America; San Francisco Veteran's Affairs Medical Center, San Francisco, CA, United States of America.
| | - Alison Seitz
- University of California, San Francisco, CA, United States of America
| | - Andrea N Niles
- University of California, San Francisco, CA, United States of America; San Francisco Veteran's Affairs Medical Center, San Francisco, CA, United States of America
| | | | - Daniel H Mathalon
- University of California, San Francisco, CA, United States of America; San Francisco Veteran's Affairs Medical Center, San Francisco, CA, United States of America
| | - Aoife O'Donovan
- University of California, San Francisco, CA, United States of America; San Francisco Veteran's Affairs Medical Center, San Francisco, CA, United States of America
| | - Joshua D Woolley
- University of California, San Francisco, CA, United States of America; San Francisco Veteran's Affairs Medical Center, San Francisco, CA, United States of America
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