REVIEW
Emotion and immunity

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Abstract

Earlier studies have suggested that depression is associated with decreased immune function, but a recent literature review has revealed that a majority of studies reached inconsistent or conflicting conclusions. On the other hand, studies on immune function in anxiety disorders are sparse, and their findings are also inconsistent. Despite a few contradictory results, a clinical level of anxiety seems to reduce immune function, whereas a subclinical level of anxiety seems to enhance immunity. The latter may be a transient phenomenon occurring prior to the downregulation of immune function, reflecting the body’s defense to a stressor. Thus, research needs to be conducted to elucidate the relationship between those hormones related to hypothalamic–pituitary–adrenal axis and a variety of immune measures at the subclinical level of anxiety. In addition, to confirm the interaction between emotion and immune function, the effectiveness of treatment with medication and psychotherapy on immunity should be investigated.

Introduction

Some studies indicate that anxiety and depression are associated with disease recurrence in patients with genital and oral herpes [1]. Emotional factors (e.g., depression) are thought to play a role in numerous diseases, including Graves disease, rheumatoid arthritis, systemic lupus erythematosus, asthma, and diabetes [2].

Psychosocial factors associated with decreased immune responsiveness produce states of arousal, anxiety, and negative affect 3, 4, 5, 6, 7. These psychological states have been linked to increased neural activity in limbic circuits involving the amygdala and the hippocampus (arousal and anxiety) 8, 9, as well as to imbalances in neocortical activity favoring the right hemisphere(negative affect) 10, 11, 12.

It has been suggested that an emotional state, such as anxiety and depression, could play a key role in triggering immune alterations 13, 14. Theoretically, it can be assumed that negative events (stressors) lead to negative affective states (distress), consequently producing alterations in human immunity [13]. However, mild, brief, and controllable states of challenged homeostasis could actually be perceived as pleasant or exciting, and could be positive stimuli for emotional and intellectual growth and development. The immune response has also been reported to be enhanced when the stressful condition is mild to moderate in intensity [15]. Thus, it is likely to be the more severe, protracted, and uncontrollable situations of psychological and physical distress that lead to overt disease states [16], apparently resulting from immunosuppression.

Immunosuppression has been reported in human subjects who experience symptoms of anxiety and depression in response to situations such as examinations, bereavement, separation, and divorce 17, 18, 19, 20, 21, 22, 23. In animals, immunosuppression has also been demonstrated in response to a variety of stressors 15, 17, 24.

The relationship between emotion and the hypothalamic–pituitary–adrenal (HPA) axis has been studied extensively. Dysregulation of the HPA axis is the best documented example of a neurobiological abnormality in depresson. The main findings have been an elevation of cortisol levels, often during the night 25, 26, and a relative resistence of cortisol suppression to dexamethasone administration 26, 27, 28. Thus, hypercortisolemia has been suggested as a possible explanation for reduced immune function in depressed individuals. However, dissociation between the HPA axis and immune function has been reported in depression, with the suggestion that corticotropin-releasing hormone (CRH) and corticoid hypersecretion are not directly responsible for immunosuppression in affective disorders 29, 30.

An anxiety disorder such as panic disorder is accompanied by an activation of the HPA axis, which seems to correlate with the degree of anxiety experienced by the patients. On the other hand, the decrease of anxiety after alprazolam therapy occurs in concert with the normalization of the HPA axis function [31]. In panic disorder, however, there may be a dissociation between HPA axis and immune systems. This hypothesis is reinforced by the observation that administration of CRH with the ensuing ACTH-cortisol hypersecretion failed to modify the lymphocyte proliferative response to PHA [31].

Several methods have been employed to obtain quantitative indices of an individual’s immune responsiveness 3, 7, 32, 33, 34, 35. The most frequently used methods include quantification of T-helper and T-suppressor lymphocyte subpopulations; measurement of the ability of lymphocytes to synthesize and release lymphokines; quantification of T-lymphocyte proliferation in response to mitogens such as phytohemagglutinin (PHA), pokeweed mitogen (PWM) and concanavaline A (Con A); quantification of the cytotoxic activity of natural killer cells and other lymphocytes; measurement of total immunoglobulin levels; and measurement of specific antibody titers.

Recently, several prospective studies have addressed the question of whether emotions are accompanied by reduced immune responsiveness [1]. These studies have initiated the following review on the relationship between emotion and immunity.

Section snippets

Depression and immunity

Many studies suggest that, compared with normal controls, patients with depression show reduced immune function in a variety of immune measures. Clinically significant levels of depression are associated with poorer immunocompetence in psychiatric populations. For example, in-patients suffering from depression have a poorer blastogenic response than nondepressed controls 36, 37. Depressed patients have also been shown to have a lower percentage of helper T-lymphocytes than nondepressed controls

Loneliness and immunity

Loneliness is also a construct related to depression. In separate studies, both medical students [32] and psychiatric patients suffering from loneliness [67] have been shown to have lower NK activity. Kiecolt-Glaser et al. 32, 67 assessed lymphocyte responses to PHA and PWM activity and reported that a subgroup of patients with high scores on the UCLA Loneliness Scale showed confluence of hypercortisolism, reduced lymphocyte responses to PHA, and decreased NK cell activity.

In a prospective

Anxiety and immunity

Whereas there are numerous immunological studies on depression, studies that examine the relationship between anxiety and immunity are sparse. Recurrent lesions of genital herpes were preceded by higher levels of anxiety and a concomitant blunting of T-cell blastogenesis [69]. In another study, lymphocyte response was found to correlate negatively with anxiety among hospitalized patients [70]. In a recent study [71], untreated patients with anxiety disorders showed significantly reduced

Humor and immunity

Although the relationship between humor and immune function is an interesting topic, there is limited research available. According to one study, salivary IgA concentration increased significantly after subjects viewed a humorous videotape but did not change significantly after viewing a didactic videotape [78]. Thus, enhancement of the immune system could be one link between anecdotal claims of the relationship between positive emotional state and healing.

Limitation in research on the relationship between emotion and immunity

The existing literature is highly controversial and fraught with methodologic problems. These problems limit the interpretation and the generalizability of most of the studies. The limitations include diagnostic heterogeneity, sample size, control group composition, and assay techniques [44]. In particular, diagnostic heterogeneity is a potential confounding element that interferes with the attempts to evaluate this body of research.

The sample sizes were small in a majority of the studies, and

Conclusion

Earlier studies have suggested that depression is associated with immunosuppression, but a recent literature review has revealed that many studies reached inconsistent or conflicting conclusions. Few studies have investigated the relationship between anxiety and immunity, in contrast to the numerous immunological studies on depression. Despite a few contradictory reports, a clinical level of anxiety seems to reduce immune function, whereas a subclinical level of anxiety seems to enhance immune

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