Neurobiology of inflammation
The inflammatory system can be classified into either the innate or the adaptive immune system. The innate system is primordial with low memory capacity present throughout much of the animal species and comprising multiple cellular populations including but not limited to monocytes. The adaptive and/or humoral immune system is responsible for humoral immunity (eg, antibodies) and is comprised of cellular populations (B and T cells) that are capable of recognizing billions of different antigens.
The primary role of the inflammatory system dating back to early humanity was to fight off pathogens, which often came from wounding at the hands of predators and other humans. Inflammation was also key for wound healing. The agricultural revolution occurred approximately 10,000 to 12,000 years ago and brought humanity into close proximity with animal-borne pathogens. While this had the negative effect of increased mortality in the short term, in the longer term, it may have also fortuitously augmented immune-inflammatory capability. Advances in food production, agriculture, hygiene, sanitation, urbanization, as well as vaccination, all have contributed to the shift away from infectious disease, and to chronic non-communicable diseases as the principle source of morbidity and mortality.
Notwithstanding the fact that predators and pathogens are no longer the principle instigators of the inflammatory system, the system is still wired to react to “threat” without regard to cause. For much of the past century, causes such as urbanization, dissolution of family structure, social alienation, air pollution, and exposure to refined high-glycemic high-calorie foods, along with financial stressors, have become principles triggers of the inflammatory system.2 Consequently, “low-grade” inflammation is now implicated as cause, consequence, and comorbidity of many noncommunicable diseases, including mood disorders.
Findings indicates that many individuals with mood disorders exhibit alterations in both innate and adaptive immune systems in both the peripheral and central compartments. For example, comprehensive reviews and meta-analyses indicate that proinflammatory cytokines and acute phase proteins (eg, C-reactive protein (CRP), interleukin-1, interleukin-6, tumor necrosis factor-α), are abnormal in individuals with mood disorders.3 Rather than conceptualize mood disorders as associated with elevated proinflammatory markers, it is more accurate to state that mood disorders are associated with a proinflammatory balance (ie, relative increase in proinflammatory markers associated with relative decrease in select anti-inflammatory markers). The consequence is an abnormal “inflammatory biosignature.”
Dr. McIntyre reports that he is on the Speakers Bureau for AstraZeneca, Bristol-Myers Squibb, Janssen-Ortho, Eli Lilly, Lundbeck, Pfizer, Shire, Otsuka, Purdue, Takeda, and Allergan; he has received research support/grants from Stanley Medical Research Institute, National Alliance for Research on Schizophrenia and Depression (NARSAD), and National Institutes of Mental Health. Dr. Rong reports no conflicts of interest concerning the subject matter of this article.
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