Social interactions shape humans from early development through senescence and have a strong impact on many aspects of physiology and behavior. Indeed, social interaction is essential for proper cognitive, affective and behavioral development (1
). Among adults, the social environment remains an important determinant of health and well being; ample evidence suggests that positive social support accelerates and improves patient recovery from cancer, cerebrovascular and cardiovascular disease (CVD), atherosclerosis, and other chronic diseases with an inflammatory component (2
). This has led to a substantial interest in the capacity to which the social environment affects physiological systems, particularly during health challenges. The benefits of a positive social environment are particularly salient in chronic disease states, in which emotional social support can be perceived as being equally or more important than instrumental and informational support (6
). In contrast, social isolation and loneliness can have profoundly detrimental effects on mental and physical health (7
). While this observation is not novel in the medical community (8
), it has only relatively recently begun to gain momentum in both clinical and animal research. The addition of evaluating patients’ social, along with cognitive and physical states, while not yet considered common practice, is gaining acceptance in hospitals and clinics worldwide (11
); however, despite growing evidence implicating the social environment as a modifying factor in disease outcomes, little is known regarding the mechanisms through which psychosocial factors influence disease pathogenesis. Converging evidence from experimental research suggests that socially isolated animals mount a quantitatively and qualitatively different pathophysiological response to disease and physical trauma compared to socially housed animals. Moreover, the benefits of social housing in animal models are remarkably consistent with clinical findings, and are evident in a diverse set of disease and injury models. The aim of this review is to further illustrate the need for integrative clinical and experimental research that encompasses a more complete understanding of the qualitative and quantitative consequences of social experiences on disease physiology.
Chronic diseases such as cardiovascular and cerebrovascular disease, diabetes, cancer, and autoimmune disorders accounted for 70% of all deaths in the United States in 2005 (13
). A substantial research effort has elucidated a number of risk factors (e.g. smoking, alcohol consumption, high blood pressure, cholesterol, etc) that are common across most chronic disease states, as well as identified causal relationships and mechanisms by which these factors influence disease onset and outcome. Interestingly, even after statistically controlling for these risk factors, there still exists substantial inter-individual variability in susceptibility to disease and recovery. This naturally occurring variability can be accounted for in part by an additional class of risk factors: psychological stress (including social isolation or perceived lack of social support), that is predictive of disease outcome independently of other traditional risk factors (14
). Importantly, the impact of the social environment is not only evident during the course of disease, but also influences the development of potentially debilitating consequences such as chronic pain, long-term physical disability, and psychological distress such as anxiety/depression (16
A prevailing hypothesis is that social support improves health by promoting healthy behaviors. Indeed, social support is associated with better medical compliance, increased physical exercise, improved nutrition and low-to-moderate tobacco and alcohol consumption (17
). While it is not surprising that social and peer support increases the likelihood of engaging in health behaviors (whether because of the pressure to conform to social norms or a potential increase of tangible resources), statistically controlling for these behavioral changes indicates that the benefits of social support remain substantial (15
). The major implication of these findings is the need to identify an endogenous physiological mechanism through which social behaviors influence physiological parameters that have important health implications.
To date, it has been difficult to definitively establish a causal relationship between psychosocial factors and disease among the clinical population, however, a number of successful longitudinal studies have identified social isolation as a predictor of physiological measures that are known risk-factors for disease, including onset of CVD, even 20 years following initial assessment (19
). Indeed, childhood social isolation is associated with a greater number of CVD and stroke risk factors, including high body mass index, high blood pressure and cholesterol, and low oxygen consumption in adulthood (19
). These data demonstrate that the relationship between social isolation and disease is not strictly correlational; rather, early experiences of social isolation can predict the development of risk factors well into adulthood.
Two important questions emerge in light of these studies. (1) What are the shared pathophysiological features among the disease states that are influenced by social experiences, and (2) in what way are they modifiable by the psychosocial environment? Inflammatory processes represent one common mechanism of disease that underlies the multiple pathophysiologies described in this review. Indeed, chronic inflammation increasingly ranks as an important risk factor for stroke and CVD, as well as many cancers, Alzheimer’s disease and major depression disorder (21
). For example, patients presenting with systemic inflammation, such as systemic lupus erythematosus and rheumatoid arthritis, have a 4–10 fold increased risk of developing CVD (reviewed in 26
). This relationship is particularly evident in coronary and cerebral ischemia, as inflammation is relevant both as an indicator of an underlying cause (i.e. atherosclerosis 27
) and as an important mediator (22
), rather than just a biomarker of ischemia. As such, chronic inflammation has become a main focus for monitoring and prevention of stroke and CVD. In particular, systemic levels of acute phase proteins such as C-reactive protein (CRP) and proinflammatory cytokines (primarily interleukin 6; IL-6) predict the risk and prognosis of stroke and CVD (21
). Importantly, circulating CRP and IL-6 levels are reduced in patients with sufficient social support, thus presenting one mechanism by which social experiences could influence stroke and CVD (29
); however, the intermediate signal that interprets and translates the social environment into an altered inflammatory response remains unknown.
One signal that may serve to transduce social experiences into an altered physiology is oxytocin (OT). OT is a neuropeptide that is released during social interactions. Exogenous OT administration has been shown to increase pro-social behaviors in humans, including the ability to interpret emotions of others (31
), interpersonal communication and social approach behavior (32
). Anxiolytic properties of OT are also evident in clinical studies. Indeed, a particularly robust finding in the clinical literature is the relationship between endogenous OT (which is elevated during lactation) and stress hyporesponsiveness. Lactating and nursing women have attenuated stress responses (33
) and lower blood pressure (34
) compared to non-lactating controls. Moreover, this stress buffering effect of social interaction can be mimicked with exogenous OT administration (35
). Taken together, the role of OT in meditating social behaviors as well as stress physiology makes it an attractive potential endogenous signaling mechanism by which social behaviors influence health.
Overall, the precise mechanisms through which psychosocial factors influence the pathophysiological response to disease remain unknown because (1) the relevant clinical studies are inconsistent in the way they define social support and often don’t distinguish between the various types of social support (i.e. functional, emotional, informational, etc) and importantly (2) the manipulations necessary to establish a causal link between social support and health outcomes cannot be conducted ethically in humans. On the other hand, environmental factors such as social housing are easily modifiable in laboratory animals and produce reliable and quantifiable physiological effects, and as such can be used to establish causation as well as to allow extensive characterization of the physiological mechanisms underlying social influences on disease.