Stress and depression-induced immune dysfunction: Implications for the development and progression of cancer

Abstract

The persistent activation of the hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal-medullary axes in chronic stress response and in depression impairs the immune response and contributes to the development and progression of some types of cancer. This overview presents results from experimental animal models, human studies, and clinical evidence that various cellular and molecular immunological parameters are compromised in chronic stress and depression. At the cellular level, stressed and depressed patients had overall leukocytosis, high concentrations of circulating neutrophils, reduced mitogen-stimulated lymphocyte proliferation and neutrophil phagocytosis. At the molecular level, high levels of serum basal cortisol, acute phase proteins, specific antibodies against herpes simplex virus type 1 and Epstein Barr virus, plasma concentration of interleukins IL-1, IL-6, and TNF-alpha, and a shift in the balance of Th1 and Th2 immune response were observed. Both stress and depression were associated with the decreased cytotoxic T-cell and natural killer cell activities affecting the processes of the immune surveillance of tumours, and the events that modulate the development and the accumulation of somatic mutations and genomic instability. DNA damage, growth and angiogenic factors, proteases, matrix metalloproteinases, and reactive oxygen species were also related to the chronic stress response and depression. Behavioural strategies, psychological, and psychopharmacotherapeutic interventions that enhance effective coping and reduce affective distress showed beneficial effects in cancer patients. A better understanding of the bidirectional communication between the neuroendocrine and immune systems could contribute to novel clinical and treatment strategies in oncology.

Type 1 diabetes mellitus and major depressive disorder: evidence for a biological link

“…In addition to reduced hippocampal volume, neuroimaging studies of individuals with MDD have revealed atrophy of the prefrontal cortex and biphasic changes of the amygdala based on illness chronicity [112]. These findings correlate with those of studies of cerebral perfusion and glucose metabolism in individuals with MDD, which demonstrated both a decrease in these factors in the prefrontal cortex and an increase in the amygdala in affected individuals [113]. These findings are reminiscent of those reported in type 1 diabetes above.…”

Aging of the Immune System as a Prognostic Factor for Human Longevity

“…Increased psychological stress in aging occurs in parallel with significant activation of the HPA axis (19,64,111). The persistent activation of the SAM axis in chronic stress responses and in depression impairs the immune response and contributes to the development and progression of some types of cancer (92). Stressed and depressed patients have reduced mitogen-stimulated lymphocyte proliferation, high levels of acutephase proteins, IL-1, IL-6, and TNF-␣.…”

Psychological vulnerability and stress: The effects of self-affirmation on sympathetic nervous system responses to naturalistic stressors.

“…Examination stress can also lead to increased SAM activation as assessed by cardiovascular reactivity (Loft et al, 2007) and such naturalistic stressors can suppress cellular immunity (Segerstrom & Miller, 2004) and increase vulnerability to diseases such as cancer (Antoni & Lutgendorf, 2007;Reiche, Morimoto, & Nunes, 2005). For example, Glaser et al (1985) found that during final exams, medical students showed a decrease in natural killer cells and an increase in psychological distress relative to a baseline period 6 weeks earlier.…”