Original articleSocial support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress
Introduction
There is substantial evidence indicating that psychosocial risk factors (e.g., lack of social contact, death of a spouse) contribute to a wide spectrum of somatic, psycho-somatic, and psychiatric disorders with major public health significance, such as depression or coronary heart disease Bruce 2002, Ehlert and Straub 1998, Kraemer et al 2001, Rozanski et al 1999, Ruberman et al 1984, Smith and Ruiz 2002. Positive social interactions have in turn been shown to exert powerful beneficial effects on health outcomes and longevity. Social support is the most intensively investigated social factor in humans Broadhead et al 1983, House et al 1988, Knox and Uvnas-Moberg 1998, MacMahon and Lip 2002, Paykel 2001, Schwarzer and Leppin 1991, Seeman 2000, Seeman and McEwen 1996, Uchino et al 1996, Veiel and Baumann 1992. A growing body of research in clinical populations has provided support for the hypothesis that higher reported levels of social support are associated with positive effects on various diseases, such as cardiovascular reactivity and blood pressure Evans and Steptoe 2001, Gallo et al 2000, Spitzer et al 1992, Steptoe 2000, Uchino et al 1999, Uno et al 2002, depression Hays et al 2001, Sayal et al 2002, and schizophrenia Buchanan 1995, Erickson et al 1998, Macdonald et al 1998. In addition, physiologic stress reactivity in experimental studies has also been shown to be responsive to social support. The availability of social support has been associated with attenuated free cortisol concentrations in saliva (Kirschbaum et al 1995) and lower cardiovascular reactivity Gerin et al 1992, Lepore et al 1993, Uchino and Garvey 1997 in response to acute laboratory stress.
Although there is considerable knowledge concerning the positive effects of social support on morbidity and mortality risks, to date, less attention has been given to the underlying physiologic mechanisms or pathways. More specifically, it is not clear how positive social interactions suppress stress-responsive physiologic systems or stimulate other internal regulatory systems involved in the attenuation of stress reactivity. A better understanding of these mechanisms would undoubtedly have important clinical implications for differential diagnosis and specific psychological and pharmacologic treatments for numerous disorders.
In animals, the neuropeptide oxytocin has been shown to exert behavioral and physiologic stress-attenuating and anxiolytic effects and, in addition, might prove to promote positive social interaction Carter 1998, Carter and Altemus 1997, Legros 2001, McCarthy and Altemus 1997, Pedersen 1997, Pedersen and Boccia 2002, Uvnas-Moberg 1998. Oxytocin is synthesized in magnocellular neurons of the paraventricular and supraoptic nuclei of the hypothalamus Swaab et al 1975, Vandesande and Dierickx 1975. It is processed from its precursor form, together with the carrier protein, along the axonal projection to the posterior pituitary, from which the peptide is secreted into the systemic circulation (Brownstein et al 1980). In addition, oxytocin is widely distributed throughout the central nervous system from smaller parvocellular neurons, influencing many neurobehavioral functions de Wied et al 1993, McCarthy and Altemus 1997. In experimental studies in animals, oxytocin has been stimulated with both exogenous (e.g., intracerebroventricular injection) and endogenous (e.g., suckling stimulus during lactation) methods of stimulation. Aside from the most well-known peripheral role of oxytocin in parturition and lactation, intracerebral oxytocin inhibits the stress-induced activity of the hypothalamic–pituitary–adrenal (HPA) axis responsiveness, suggesting an inhibitory influence of oxytocin on stress-responsive neurohormonal systems Neumann et al 2000a, Neumann et al 2000b, Uvnas-Moberg et al 1994, Uvnas-Moberg et al 1999, Windle et al 1997b. Moreover, the neuropeptide has been shown to function as a central regulator in social attachment and in related prosocial behaviors Carter 1998, Insel 1997, Insel and Young 2001, Pedersen 1997.
In contrast to the very active investigation in recent years into the effects of oxytocin on physiologic and behavioral stress and anxiety responses in animals, research in humans remains relatively limited; however, initial studies suggest similar stress-reducing effects of the neuropeptide in humans. Similar to the aforementioned studies in lactating rodents, the lactation paradigm for endogenous stimulation has also been used in human studies. In lactating women, a suppression of endocrine stress responses has been observed if breast-feeding starts 30–60 min before stress exposure, depending on the kind of stressor Altemus et al 1995, Altemus et al 2001, Heinrichs et al 2001, Heinrichs et al 2002. Within this context, however, it should be noted that there are a variety of confounding factors, in particular the release of other hormones, that are difficult to control for in endogenous stimulation paradigms. Thus, the specific effects of central oxytocin as an underlying biological mechanism for the reduction of stress and anxiety and for positive social interactions in humans are yet to be determined. Alternatively, studies on central effects of oxytocin and vasopressin in healthy humans and patients have been carried out with exogenous stimulation with intranasal administration Born et al 1998, Bruins et al 1992, Heinrichs 2000, Pitman et al 1993. Neuropeptides have recently been shown to enter the cerebrospinal fluid directly after intranasal administration (Born et al 2002). To date, there have been no human studies that directly address effects of oxytocin administration and social support on stress and anxiety. With these considerations in mind, we set out to study the effects of oxytocin and social support on mood, anxiety, and neuroendocrine responses to psychosocial stress (public speaking and mental arithmetic in front of an audience) in healthy men.
Section snippets
Participants
Thirty-seven healthy men (mean ± SD age, 23.8 ± 3 years) were recruited by advertisements posted at the university and were paid for participation. The study was conducted at the University of Trier, Germany. All subjects underwent a physical evaluation to screen out chronic diseases, mental disorders, medication, smoking, and drug or alcohol abuse. Participants abstained from food and drink (other than water) for 2 hours before the experiment, and from exercise, caffeine, and alcohol during
Description of the study groups
As described in Methods and Materials, all participants were randomly assigned to receive intranasal oxytocin (24 IU) or placebo 50 min before stress, and either no social support or social support from their best friend during the 10-min preparation period (placebo-controlled, double-blind, 2 × 2 factorial design). As shown in Table 1, subjects of the four study groups did not differ significantly with respect to age and body mass index. There were no differences in the perceived availability
Discussion
This is the first study on the effects of social support and oxytocin on endocrine, mood, and anxiety responses to psychosocial stress in humans. Participants who received both protective factors of social support and oxytocin exhibited the lowest cortisol concentrations during stress exposure, whereas subjects who received no social support and placebo demonstrated the highest cortisol response (Figure 1). Most notably, we found corresponding results in psychological measures, indicating that
Acknowledgements
We thank the study participants and acknowledge the technical contributions and assistance of (in alphabetical order) Jutta Bennecke, Uta Berger, Begga Beyersmann, Ulrike Bucerius, Bernhild Doll, Anuschka Enzler, Annemarie Fritzen, Sarah Mannion, Gunther Meinlschmidt, Rita Praprotnik, Ingrid Rummel-Frühauf, Katrin Ruwisch, Silke Welter, Cornelia Zenglein, and Britta Zimmermann. The study was conducted at the Center for Psychobiological and Psychosomatic Research, University of Trier, Germany.
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