In psychiatry, the practical import of connections between brain outflow pathways and the immune system has been best documented in the effects of stress-related disorders, especially major depression, on immune functioning. Despite a significant degree of heterogeneity across individual studies, significant evidence suggests that patients with major depression demonstrate a number of immune changes similar to those seen in individuals undergoing chronic and/or severe stress (Herbert and Cohen 1993; Zorrilla et al. 2001). This is hardly surprising, given the many indices of stress system hyperactivity that are apparent in patients with major depression, including increased corticotropin-releasing hormone (CRH) and cortisol production (Pariante et al. 1995) and augmented sympathetic nervous system (SNS) activity as manifested in part by increased peripheral blood catecholamines (Veith et al. 1994; Wong et al. 2000). Enumerative immune changes shared by major depression and chronic/severe stress include a decrease in lymphocytes, B cells, and T cells and an increase in the ratio of CD4 to CD8 T cell subsets (Herbert and Cohen 1993). Shared functional changes include a decrease in NK cell activity and lymphocyte proliferation in response to nonspecific mitogens (Herbert and Cohen 1993; Zorrilla et al. 2001).
In a meta-analysis examining the issue, major depression was found to have a larger effect than stress on these immune variables (Zorrilla et al. 2001) (Table 9-2). It is important to note, however, that major depression is a heterogeneous condition and that immune changes are not uniform across all patients. Indeed, inhibited lymphocyte responses tend to be most striking in patients who are older, are hospitalized, or have more severe and/or melancholic types of depression (Miller 1998; Schleifer et al. 1989). In addition, the sleep changes common in depression are known to alter lymphocyte responses, especially NK cell activity (NKCA), even in the absence of other depressive symptoms (Irwin et al. 1996). Nonetheless, it does not appear that these factors completely account for the association between major depression and alterations in measures of the number and function of lymphocyte subsets (Herbert and Cohen 1993).
TABLE 9-2. Immune alterations in major depression
Increased white blood cells
Increased neutrophil percentage
Decreased lymphocyte percentage
Increased CD4-to-CD8 ratio
Decreased natural killer cell activity
Decreased mitogen-induced lymphocyte proliferation
Compared with chronic/severe stress, major depression has been less well characterized in terms of effects on in vivo functional immunity; however, the little evidence that is available suggests that depression, like chronic/severe stress, may impair T-cell function in ways that are relevant to disease vulnerability. For example, although it is not known whether major depression is associated with an increase in antibody titers to latent viruses, one study reports that patients with major depression have a marked decrease in the ability to generate lymphocytes that respond to the herpes zoster virus (Irwin et al. 1998). Also consistent with impaired T-cell function in depression is the observation that depressed patients, especially those with melancholia, demonstrate impaired DTH (Hickie et al. 1993).
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