similarly, social stressors in the micro-environment are also linked to increased mortality. a seminal longitudinal study of nearly 7,000 people found that socially isolated people had greater risk of dying from any cause. social support, which is defined as "the comfort, assistance, and/or information one receives through formal or informal contacts with individuals or groups", has been linked to physical health outcomes. research shows the three aspects of social support, available attachments, perceived social support, and frequency of social interactions, can predict mortality thirty months after assessment. morbidity social stress also makes people more sick. people who have fewer social contacts are at greater risk for developing illness, including cardiovascular disease. the lower one's social status, the more likely he or she is to have a cardiovascular, gastrointestinal, musculoskeletal, neoplastic, pulmonary, renal, or other chronic diseases. these links are not explained by other, more traditional risk factors such as race, health behaviors, age, sex, or access to health care. in one laboratory study, researchers interviewed participants to determine whether they had been experiencing social conflicts with spouses, close family members and friends. they then exposed the participants to the common cold virus and found that participants with conflict-ridden relationships were two times more likely to develop a cold than those without such social stress. social support, especially in terms of support for socioeconomic stressors, is inversely related to physical morbidity. a study that investigated social determinants of health in an urban slum in india found that social exclusion, stress, and lack of social support are significantly related to illnesses, such as hypertension, coronary heart disease, and diabetes. long-term effects exposure to social stress in childhood can also have long-term effects, increasing risk for developing diseases later in life. in particular, adults who were maltreated (emotionally, physically, sexually abused or neglected) as children report more disease outcomes, such as stroke, heart attack, diabetes, and hypertension or greater severity of those outcomes. the adverse childhood experiences study (ace), which includes over seventeen thousand adults, also found that there was a 20% increase in likelihood for experiencing heart disease for each kind of chronic familial social stressor experienced in childhood, and this was not due to typical risk factors for heart disease such as demographics, smoking, exercise, adiposity, diabetes, or hypertension. recovery and other disease social stress has also been tied to worse health outcomes among patients who already have a disease. patients with end-stage renal disease faced a 46% increased risk for mortality when there was more relationship negativity with their spouse even when controlling for severity of disease and treatment. similarly, women who had experienced an acute coronary event were three times more likely to experience another coronary event if they experienced moderate to severe marital strain. this finding remained even after controlling for demographics, health behaviors, and disease status. with regard to hiv/aids, stress may affect the progression from the virus to the disease. research shows the hiv-positive males who have more negative life events, social stress, and lack of social support progress to a clinical aids diagnosis more quickly than hiv-positive males who do not have as high levels of social stress. for hiv-positive females, who have also contracted the hsv virus, stress is a risk factor for genital herpes breakouts. physiology social stress leads to a number of physiological changes that mediate its relationship to physical health. in the short term, the physiological changes outlined below are adaptive, as they enable the stressed organism to cope better. dysregulation of these systems or repeated activation of them over the long-term can be detrimental to health. sympathetic nervous system the sympathetic nervous system (sns) becomes activated in response to stress. sympathetic arousal stimulates the medulla of the medulla to secrete epinephrine and norepinephrine into the blood stream, which facilitates the fight-or-flight response. blood pressure, heart rate, and sweating increase, veins constrict to allow the heart to beat with more force, arteries leading to muscles dilate, and blood flow to parts of the body not essential for the fight or flight response decreases. if stress persists in the long run, then blood pressure remains elevated, leading to hypertension and atherosclerosis, both precursors to cardiovascular disease. a number of animal and human studies have confirmed that social stress increases risk for negative health outcomes by increasing sns activity. studies of rodents show that social stress causes hypertension and atherosclerosis. studies of non-human primates also show that social stress clogs arteries. although humans cannot be randomized to receive social stress due to ethical concerns, studies have nevertheless shown that negative social interactions characterized by conflict lead to increases in blood pressure and heart rate. social stress stemming from perceived daily discrimination is also associated with elevated levels of blood pressure during the day and a lack of blood pressure dipping at night. hypothalamic-pituitary adrenocortical axis (hpa) in response to stress, the hypothalamus releases corticotropin-releasing hormone (crh), stimulating the anterior pituitary to release adrenocorticotropic hormone (acth). acth then stimulates the adrenal cortex to secrete glucocorticoids, including cortisol. social stress can lead to adverse health outcomes by chronically activating the hpa axis or disrupting the hpa system. there are a number of studies that link social stress and indications of a disrupted hpa axis; for instance, monkey infants neglected by their mothers show prolonged cortisol responses following a challenging event. in humans, abused women exhibit a prolonged elevation in cortisol following a standardized psychosocial laboratory stressor compared to those without an abuse history. maltreated children show higher morning cortisol values than non-maltreated children. their hpa systems also fail to recover after a stressful social interaction with their caregiver. over time, low-ses children show progressively greater output of cortisol. although these studies point to a disrupted hpa system accounting for the link between social stress and physical health, they did not include disease outcomes. nevertheless, a dysfunctional hpa response to stress is thought to increase risk for developing or exacerbating diseases such as diabetes, cancer, cardiovascular disease, and hypertension. inflammation inflammation is an immune response that is critical to fighting infections and repairing injured tissue. although acute inflammation is adaptive, chronic inflammatory activity can contribute to adverse health outcomes, such as hypertension, atherosclerosis, coronary heart disease, depression, diabetes, and some cancers. research has elucidated a relationship between different social stressors and cytokines (the markers of inflammation). chronic social stressors, such as caring for a spouse with dementia, lead to greater circulating levels of cytokine interleukin-6 (il-6), whereas acute social stress tasks in the laboratory have been shown to elicit increases in proinflammatory cytokines. similarly, when faced with another type of social stress, namely social evaluative threat, participants showed increases in il-6 and a soluble receptor for tumor necrosis factor-α. increases in inflammation may persist over time, as studies have shown that chronic relationship stress has been tied to greater il-6 production 6 months later and children reared in a stressful family environment marked by neglect and conflict tend to show elevated levels of c-reactive protein, a marker of il-6, in adulthood. interactions of physiological systems there is extensive evidence that the above physiological systems affect one another's functioning. for instance, cortisol tends to have a suppressive effect on inflammatory processes, and proinflammatory cytokines can also activate the hpa system. sympathetic activity can also upregulate inflammatory activity. given the relationships among these physiological systems, social stress may also influence health indirectly via affecting a particular physiological system that in turn affects a different physiological system.