McEwen BS. Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators. Eur J Pharmacol 583: 174-185

Laboratory of Neuroendocrinology, The Rockefeller University, 1230 York Avenue Box 165, New York, NY 10065, United States.
European Journal of Pharmacology (Impact Factor: 2.53). 05/2008; 583(2-3):174-85. DOI: 10.1016/j.ejphar.2007.11.071
Source: PubMed


Stress begins in the brain and affects the brain, as well as the rest of the body. Acute stress responses promote adaptation and survival via responses of neural, cardiovascular, autonomic, immune and metabolic systems. Chronic stress can promote and exacerbate pathophysiology through the same systems that are dysregulated. The burden of chronic stress and accompanying changes in personal behaviors (smoking, eating too much, drinking, poor quality sleep; otherwise referred to as "lifestyle") is called allostatic overload. Brain regions such as hippocampus, prefrontal cortex and amygdala respond to acute and chronic stress and show changes in morphology and chemistry that are largely reversible if the chronic stress lasts for weeks. However, it is not clear whether prolonged stress for many months or years may have irreversible effects on the brain. The adaptive plasticity of chronic stress involves many mediators, including glucocorticoids, excitatory amino acids, endogenous factors such as brain neurotrophic factor (BDNF), polysialated neural cell adhesion molecule (PSA-NCAM) and tissue plasminogen activator (tPA). The role of this stress-induced remodeling of neural circuitry is discussed in relation to psychiatric illnesses, as well as chronic stress and the concept of top-down regulation of cognitive, autonomic and neuroendocrine function. This concept leads to a different way of regarding more holistic manipulations, such as physical activity and social support as an important complement to pharmaceutical therapy in treatment of the common phenomenon of being "stressed out". Policies of government and the private sector play an important role in this top-down view of minimizing the burden of chronic stress and related lifestyle (i.e. allostatic overload).

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Available from: Bruce S Mcewen, Jun 01, 2015
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    • "Social disruption, isolation, and neglect are major sources of stress and can negatively impact health and well-being (McEwen, 2008), as well as contribute to dysregulation of the hypothalamicpituitary-adrenal (HPA) axis (Smith and Wang, 2012). Long-lasting social relationships and positive social interactions can serve as resilience factors against stressors. "
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    ABSTRACT: Social isolation is a major source of stress and can lead to activation of the hypothalamic-pituitary-adrenal (HPA) axis. The presence of a close social partner can reduce the magnitude of the HPA-axis response during a stressor, a phenomenon known as social buffering. The oxytocin (OXT) system has been identified as one candidate for mediating social buffering due to its role in the facilitation of social bonding and the expression of prosocial behavior. The goal of the present study was to determine whether the OXT system contributes to social buffering of HPA-axis activity in response to stressor exposure in marmoset monkeys (Callithrix jacchus). Male and female marmosets experienced a standardized psychogenic stressor with and without their long-term mate under OXT-treatments (Pro8-OXT, Leu8-OXT, OXT antagonist, and saline); we assessed HPA-axis activity by measuring urinary cortisol across the stressor. We found that blocking, but not augmenting, the OXT system altered patterns of cortisol and proximity behavior in response to a stressor. We demonstrated that (1) the presence of a mate during a stressor significantly attenuated HPA-axis activity in female, but not male, marmosets; (2) male, but not female, marmosets treated with an OXT antagonist had significantly higher HPA-axis activity across the stressor than when they were treated with saline, suggesting that the OXT system may reduce the stressor-induced rise in cortisol levels; (3) male and female marmosets treated with an OXT antagonist spent significantly less time in close proximity to their mate during the first 30 min of the stressor than when they were treated with saline, suggesting that the OXT system may be important for the expression of partner-seeking behavior during a stressor. Thus, the OXT system and social context differentially influenced how the HPA-axis responded to a stressor in male and female marmosets, and may modulate HPA-axis activity by promoting the expression of proximity behavior with a close social partner.
    Full-text · Article · Apr 2016 · Psychoneuroendocrinology
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    • "Buffardi et al. 2008; Krieger 2012; Leslie and Lentle 2006; Yamada and Palmer 2007), Latin American Social Medicine (e.g. de Almeida-Filho 2000; Granda 2008; Krieger 2011; Muntaner 2013; Tajer 2003), theorisation of psychosocial determinants of health and disease (e.g. Marmot 2004; McEwen 2008; Wilkinson and Pickett 2009) and complex systems frameworks (e.g. Diez-Roux 2007; Jayasinghe 2011). "
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    ABSTRACT: The discipline of epidemiology, which holds major influence on public health policy as well as on clinical medical practice, has in recent decades to a large extent been concerned with the identification of factors and markers of risk for disease. Much health information and intervention is thus informed by a wealth of studies on a variety of risk factors, of which the individual is encouraged to keep informed and to be responsible about. Meanwhile, risk factor epidemiology has been subject to intense debate, both within and outside the discipline. The following review offers an overview of critical intradisciplinary debates. It then opens discussion on three partially overlapping areas where social theory has been called upon to contribute to epidemiological inquiry, namely analysis of macro-social determinants of health and disease, of categories of human difference and of embodiment. The review ends with, and is motivated by, a plea for further integration of and dialogue between epidemiology and social theory.
    Full-text · Article · Feb 2016 · Sociology Compass
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    • "It influences the desire to work, performance at work and attitude toward life. Chronic stress has been linked to a range of health problems [2]. Previous studies have shown a correlation between long-term exposure to stress and risk factors such as cardiovascular diseases [3] [4]. "

    Full-text · Conference Paper · Dec 2015
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