Immune suppression and immune activation in depression

Abstract

Depression has been characterized as a disorder of both immune suppression and immune activation. Markers of impaired cellular immunity (decreased natural killer cell cytotoxicity) and inflammation (elevated IL-6, TNFα, CRP) have been associated with depression. These immunological markers have been associated with other medical illnesses, suggesting that immune dysregulation may be a central feature common to both depression and to its frequent medical comorbidities. Yet the significant associations of findings of both immune suppression and immune activation with depression raise questions concerning the relationship between these two classes of immunological observations. Depressed populations are heterogeneous groups, and there may be differences in the immune profiles of populations that are more narrowly defined in terms of symptom profile and/or demographic features. There have been few reports concurrently investigating markers of immune suppression and immune activation in the same depressed individuals. An emerging preclinical literature suggests that chronic inflammation may directly contribute to the pathophysiology of immune suppression in the context of illnesses such as cancer and rheumatoid arthritis. This literature provides us with specific immunoregulatory mechanisms mediating these relationships that could also explain differences in immune disturbances between subsets of depressed individuals We propose a research agenda emphasizing the assessment of these immunoregulatory mechanisms in large samples of depressed subjects as a means to define the relationships among immune findings (suppression and/or activation) within the same depressed individuals and to characterize subsets of depressed subjects based on shared immune profiles. Such a program of research, building on and integrating our knowledge of the psychoneuroimmunology of depression, could lead to innovation in the assessment and treatment of depression and its medical comorbidities.

Pathogenetic insights from the treatment of rheumatoid arthritis

“…These effects are considered to result from the action of proinflammatory cytokines, particularly TNF and IL-6 on the central nervous system. In accordance, TNF inhibition rapidly reduces pain sensitization in the brain and also normalizes the dysbalance of the serotonin homeostasis in the brain of RA patients [86][87][88]. Similar effects are also emerging for IL-6R inhibition.…”

Salvianolic acid B ameliorates depressive-like behaviors in chronic mild stress-treated mice: involvement of the neuroinflammatory pathway

“…SalB has been shown to provide anti-inflammatory, antioxidant, and neuroprotective activity by regulating microglial activation [17,35] . According to recent studies, besides functioning as a monoaminergic neurotransmitter, neuroinflammation may also have a key role in the pathogenesis of MDD [13,36] . Growing evidence suggests that there is a causative link between depressive-like behaviors and life events, inflammation and apoptosis in the brain [37] .…”

The Association of Mental Health over Time with Cardiac Outcomes in HEMO Study Patients

“…It has been reported that markers of impaired cellular immunity (decreased natural killer cell cytotoxicity) and inflammation (elevated IL-6, TNF-a, and C-reactive protein) are associated with psychological stress and depression (14). These immunologic markers have been associated with other medical illnesses such as cardiac disease, cancer, stroke, HIV/AIDS, and ESRD, suggesting that immune dysregulation may be a fundamental feature to both mental illness and its medical comorbidities (15). Dialysis patients with cardiac disease have a higher case fatality rate than nondialysis patients with heart disease, and the mortality rates secondary to sepsis in dialysis patients are several hundred-fold higher compared with the general population (16,17).…”