Links among depression, stress and inflammation. An explosion of research has documented the link between the experience of stressful conditions, markers of inflammation in the blood, and the experience of depressive feelings and behaviors. Inflammatory hormones (called cytokines) are elevated in persons diagnosed with depression (Raison, Capuron, & Miller, 2006). Persons undergoing the stress of caring for a loved one with Alzheimer’s disease show elevations in inflammatory markers (Kiecolt-Glaser, et al., 2003). In the Whitehall studies of employees in the British Civil Service system, those who were paid less and had less control over their work schedules, as a group, were higher on inflammatory markers even after controlling for possible differences in diet and smoking (Steptoe et al., 2003). Most recently, Setiawan et al. (2015), using brain imaging strategies, measured the level of activated white blood cells in brain and found a correlation between level of depression and activation of microglia, the brain’s major type of white blood cell. About 1/3 of persons diagnosed with major depressive disorder exhibit elevations in inflammatory white blood cell hormones (cytokines) in blood (Tartter, Hammen, Bower, Brennan, & Cole, 2015).
Showing Causal Association between Stress and Inflammation. Beyond the correlational studies, there is research in which animals have been manipulated in some way and then inflammation has been measured. Animals have been subjected to bouts of foot shock that they were unable to control. Subsequently, these animals displayed depressed behavior (not eating sweet foods, avoiding other animals, moving less). They also had higher amounts of inflammatory cytokines in brain and when the researchers put in a molecular sponge to bind up the inflammatory cytokine in brain, the animals reverted to normal behavior (Maier & Watkins, 1998). These studies showed that stressing the animal results in more depressive behaviors and that these depressive behaviors are caused by the brain inflammatory factors.
Showing a causal link between infection and depression. Researchers also know that another way to cause inflammatory factors to rise in the brain is by inducing infection in the periphery. A number of experimenters have placed the wall of a bacterium into the paw of a rodent. Subsequently, inflammatory cytokines increase in brain and the animal loses preference for sweet liquids, avoids other animals and moves less. Again, if the researcher puts in a molecular sponge to bind up the inflammatory factor, the behavior reverts to normal (Maier & Watkins, 1998).
Showing causal link between inflammation and distress in people. The accumulation of the animal findings has prompted similar studies in people. Researchers have placed the wall of a bacterium into the periphery. The wall of the bacterium in the body results in activation of areas of the brain associated with alarm, less response to money in reward areas, and stronger activation in the amygdala (an anxiety center) in response to scary images (Eisenberger et al., 2009, 2011; Inagaki et al., 2012). In another approach, researchers arranged for research-participants to feel bad. They had their research-participants play a computer game with others tossing a frisbee type object around. Then suddenly the research-participant gets excluded. Again, activation in the brain’s alarm area is noted. However, if the research-participant had taken acetaminophen (Tylenol), an anti-inflammatory, prior to the study, then the alarm area remained quiet and people reported less distress (Dewall et al., 2010).
The causal role that inflammation plays in producing depression and anxiety has many implications. Many reports of depression preceding dementia, heart disease, strokes, cancer have been published in samples of persons who were not taking antidepressants. The common factor in all of these conditions is inflammatory processes.
A flood of new information on the immune system has emerged in the last several decades. New fields, such as psychoneuroimmunology and psychoneuroendocrinology, have initiated research into how various systems, once thought to operate somewhat independently, are linked. I cover topics in these fast-changing areas of research in Neuroscience for Psychologists and Other Mental Health Professionals. Chapters 6 and 7 also covers disorders associated with hearing voices and how inflammation plays a role here as well. On this web-site, I will be updating the latest findings in the research areas covered in Neuroscience for Psychologists and Other Mental Health Professionals. We’ll examine the impact of psychiatric medications on inflammation. We’ll also examine how dietary factors, exercise, salubrious social relationships, yoga and meditation can tame inflammation. A picture of how the various systems in the body are coordinated is emerging in various literatures. Integrating these diverse findings is the objective of this website.
Dewall, C. N, Macdonald, G., Webster, G. D., Masten, C. L., Baumeister, R. F., Powell, C., . . . Eisenberger, N. I. (2010). Acetaminophen reduces social pain: behavioral and neural evidence. Psychological Science, 21 (7), 931-947
Eistenberger, N. L., Berkman, E. T., Inagaki, T. K., Rameson, L. T., Mashal, N. M., & Irwin, M. R. (2100) Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward. Biological Psychiatry, 68(8), 748-754.
Eisenberg, N., Inagaki, T. K., Rameson, L. T., Marshal, N. M., & Irwin, M. R. (2009). An fMRI study of cytokine-induced depressed mood and social pain: the role of sex differences. Neuroimage, 47(3), 881-890.
Inagki, T. K., Muscatell, K. A., Irwin, M. R., Cole, S. W., & Eisenberger, N. I. (2012). Inflammation selectively enhances amygdala activity to socially threatening images. Neuroimage 59(4), 3222-3226.
Kiecolt-Glaser, J. K., Preacher, K. J., MacCallum, R. C., Atkinson, C., Marlarkey, W. B., Emery, C. F., & Glaser, r. (2003). Chronic stress and age-related increases in proinflammatory cytokine IL-6. PNAS, 100(15), 9090-9095.
Maier, S. F., & Watkins, L. R. (1998). Cytokines for psychologists: implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition. Psychological Review, 105(1), 83-107.
Raison, C. L., Capuron, L., & Miller, A. H. (2006). Cytokine sing the blues: inflammation and the pathogenesis of depression. Trends in Immunology, 27(1), 24-31.
Setiawan, E., Wilson, A. A., Mizrahi, R., Rusjan, P. J., Miller, L., Rajkowska, G., Suridjan, I., Kennedy, J. L., Rekkas, P. V., Houle, S., & Meyer, J. H. (2015). Role of translocator protein density, a marker of neuroinflammation in the rain during major depressive episodes. JAMA Psychiatry, 72 (3), 268-275.
Steptoe, A., Kunz-Ebrecht, S., Owen, N., Feldman, P. J., Rumley, A., Lowe, G. D., & Marmot, M. (2003). Influence of socioeconomic status and job control of plasma fibrinogen responses to acute mental stress. Psychosomatic Medicine, 65(1), 137-144.
Tartter, M., Hamman, C., Bower, J. E., Brennan, P. A., & Cole, S. (2015). Effects of chronic interpersonal stress exposure on depressive symptoms are moderated by genetic variation at IL6 and Il1β in youth. Brain, Behavior, and Immunity, 46, 104-111.