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Psychoneuroimmunology (PNI) is a field that investigates the interactions between the brain and the immune system. PNI takes an interdisciplinary approach, incorporating psychology, neuroscience, immunology, physiology, pharmacology, molecular biology, psychiatry, behavioural medicine, infectious diseases, endocrinology, and rheumatology. The main interests of PNI are the interactions between the nervous and immune systems and the relationships between mental processes and health. One important goal of this field of research is to translate basic research in order to understand how behaviour affects health and resistance to disease in humans.

Depression is associated with complex patterns of changes in immune cell number and function; immune activation with the excessive secretion of pro-inflammatory cytokine found in depressed persons is coupled with a loss of nonspecific and specific cellular immune responses (Irwin, 1999). Depression is correlated with increased in vivo and ex vivo secretion of the pro-inflammatory cytokine, IL-6 (Zorrilla et al, 2001). Psychological response to the stressor (e.g., increases in anxiety and depressive symptoms) is critical; those who have increases in depressive symptoms following exposure to acute examination stress show greater production of TNF, IFN, and IL- 6 as compared to students with low perceived stress (Maes et al, 1998).

Stressor characteristics, such as severity and type of stressor and/or time response, partly determine alterations of a wide range of cellular and/or humoural immune parameters. However, the psychological state in response to the stressor has also been related to the immunological consequences of the stress. It was found that rats exposed to inescapable, uncontrollable electric tail shock have reduced lymphocyte activity, whereas animals that received the same total amount of shock but were able to terminate it did not show altered immunity (Irwin, 2000).

Although depressed individuals tended to display increased cortisol and adrenocorticotropic hormone levels they did not display elevations in corticotropin-releasing hormone. Studies that included older hospitalized individuals reported significantly greater cortisol differences between depressed and non-depressed groups compared with studies with younger outpatient samples. Important cortisol differences also emerged for atypical, endogenous, melancholic, and psychotic forms of depression. The current study suggests that the degree of HPA hyperactivity can vary considerably across patient groups. Results are consistent with HPA hyperactivity as a link between depression and increased risk for conditions, such as diabetes, dementia, coronary heart disease, and osteoporosis. Such a link is strongest among older inpatient that displays melancholic or psychotic features of depression (Stetler and Miller, 2011).

Research has provided growing evidence of links between the social environment and cancer progression (Spiegel et al, 1998). The body’s psychophysiological reactions to tumour invasion are mediated by brain/body mechanisms, including the endocrine, neuroimmune, and autonomic nervous systems (Spiegal and Giese-Davis, 2003). For example, men with few social connections showed significantly poorer cancer survival rates (Reynolds & Kaplan, 1990). Clinical studies have revealed that social support improves the outcome of cancer patients, whereas epidemiologic studies suggest that social isolation increases the risk of death associated with several chronic diseases (Williams et al, 2009). There is growing evidence that stress and other behavioural factors may affect cancer progression and patient survival, and direct experimental evidence that stress hormones can enhance the invasive potential of ovarian cancer cells (Sood et al, 2006). Experiments in mouse models of cancer are identifying aspects of tumour biology that may be regulated by hormones such as glucocorticoids released during psychosocial stress (Trainor et al, 2009).

Rat studies have demonstrated strong connections between stress and cancer. Strong maternal behaviour, involving licking and grooming of the offspring, produces a “neophilic” animal that is more exploratory of novel environments and less emotionally reactive and produces a lower and more contained glucocorticoid stress response in novel situations; poor maternal care leads to a “neophobic” phenotype with increased emotional and HPA reactivity and less exploration of a novel situation (Meaney et al, 1994).
Increased emotional reactivity and fear of novelty in young rats, whatever its cause, has consequences for longevity and for cognitive function. A study of female rats focused on tumours as the likely cause of death of neophobic females, which died 6 months sooner than neophilic females (Cavigelli et al, 2003; Cavigelli et al, 2006).

Psychosocial Stress
For many years, anecdotal evidence and clinical observations have suggested that exposure to psychosocial stress can affect disease outcomes in immune-related disorders such as viral infections, chronic autoimmune diseases and tumours. Acute and chronic psychological stress can induce pronounced changes in innate and adaptive immune responses and that these changes are predominantly mediated via neuroendocrine mediators from the hypothalamic–pituitary–adrenal axis and the sympathetic–adrenal axis (Kemeny and Schedlowski, 2007).

Fig. 1. Acute and sustained psychosocial stress affects the circulation and activity of immuncompetent cells via the release of neuroendocrine mediators.
The major neural efferent pathways, through which stress can affect peripheral immune functions, are the neocortical–sympathetic–immune axis, the hypothalamus–pituitary–adrenal immune axis, and the brain stem–vagus–cholinergic pathway with the release of the major mediators noradrenaline, cortisol and acetylcholine. These hormones and neurotransmitters can subsequently modulate the inflammatory process in autoimmune diseases such as rheumatoid arthritis, multiple sclerosis or skin disease, affect the immune response during infection and may influence tumor development and progression.

ACTH, adrenocorticotropic hormone; Ach, acetylcholine; NE, noradrenaline.

Immune Disorders
The interactions between the immune system and psychological states are both intricate and intriguing. Research at a molecular level has thrown considerable light on the previously ill-defined area of psychoneuroimmunology. Rogers and Fozdar (1996) explored the psychoneuroimmunology of autoimmune disorders, particularly rheumatoid arthritis and lupus erythematosus and these diseases have provided a particularly useful window on complex psychoneuroimmunological interactions.

Chronic stress may increase vulnerability to infectious disease; however, the role of stress in the course of inflammatory bowel disease remains unclear. Because there are large individual differences in psychological response to stress, it is important to consider the role of cognitive and affective responses to stress. Depression has been associated with functional immune decrements and immune over-activation. Cognitive states such as perceived control, views of the self, and views of the future have been associated with immune parameters and health in some studies (Kemeny and Gruenewald, 1999).

Glucocorticoids and catecholamines, the end-products of the stress system, and histamine, a product of activated mast cells, might selectively suppress cellular immunity, and favour humoral immune responses. This is mediated by a differential effect of stress hormones and histamine, on T helper 1 (Th1)/Th2 patterns and type 1/type 2-cytokine production. Thus, systemically, stress might induce a Th2 shift, while, locally, under certain conditions, it might induce pro-inflammatory activities through neural activation of the peripheral corticotropin-releasing factor-mast cell-histamine axis (Elenkov and Chrousos, 1999).

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