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By David Warmflash

David WarmflashOver the last few decades, inflammation has been implicated as a prime factor in the pathophysiology of an increasing number of conditions. These include allergies, transplant rejection, autoimmune diseases with notable joint inflammation (e.g., rheumatoid arthritis, ankylosing spondylitis, fibromyalgia, and systemic lupus erythematosus) and a range of other diseases, like sarcoidosis, Addison disease, Graves disease, and Hashimoto disease, where the problem manifests mostly in organs and glands.

At the same time, Crohn disease, ulcerative colitis, and celiac disease are caused by inflammation focused on the gastrointestinal tract. The various complications of diabetes also work through inflammatory mechanisms, plus inflammation is thought to lie at the foundation of several types of cancer. There also is atherosclerosis, where inflammation is a key factor leading to coronary and cerebrovascular disease. But in addition to all of this, research based at the U.K.’s Cambridge University also suggests a connection between inflammation and mental illness, suggesting that psychiatry will be the next area to benefit from a growing armament of anti-inflammatory drugs.

Brain InflammationAt the most dramatic level, the connection between inflammation and psychiatry has been recognized in a type of autoimmune encephalitis resulting from antibodies against a subcategory of a receptor known as NMDA. Recognized only a few years ago, this condition is easily misdiagnosed as any of a handful of psychiatric or psychological disorders, and has been popularized in the book Brain on Fire: My Month of Madness by Susannah Cahalan. Notwithstanding the severity of anti–NMDA receptor encephalitis, inflammation also appears to be involved in the pathology of more commonly diagnosed psychiatric conditions, including mood disorders and psychotic disorders. Consequently, the Cambridge study examined 4,500 people, consisting of parents and their children. From the latter group, blood samples were taken at age 9 and again at age 18 to check levels of interleukin-6 (IL-6), a mediator for inflammation. IL-6 levels were categorized as low, medium, or high, and these results were compared with the number of episodes of depression or psychosis experienced by the subjects. For children with IL-6 levels in the high category, the likelihood of a depressive or psychotic episode was shown to be double that for subjects with low IL-6 levels.

According to Professor Peter Jones, senior author of the study, the inflammation underlying psychiatric illness may be part of the same mechanism behind the various chronic medical conditions mentioned above. Thus, increased IL-6 levels are also associated with elevated risk for cardiovascular disease and diabetes type 2, while the risk of these two conditions is elevated in schizophrenia and in people with a depressed mood.

Combining anti-inflammatory drugs with psychiatric medication is one emerging strategy that could be expanded as a result of this work. Adding aspirin, which has anti-inflammatory function, has been shown to improve the efficacy of antipsychotic agents in the setting of schizophrenia, for instance. The antibiotic minocycline is known to have anti-inflammatory effects and also permeates the blood-brain barrier (BBB), which normally blocks most drugs from entering the central nervous system. Studies on mice suggest that, despite the BBB, the presence of inflammation throughout the body is also reflected in the brain, causing psychiatric effects: the autonomic nervous system, especially the vagus nerve, links the brain with the gastrointestinal tract. Because of the BBB, the armament of brain active drugs—whether for psychiatry or neurology—has always been limited. Thus, agents like minocycline that are both BBB-permeable and anti-inflammatory look promising, particularly if the inflammation hypothesis for psychiatric illness proves to be correct.

David Warmflash, M.D., is an astrobiologist, science writer, and physician. He is principal investigator on a Planetary Society-sponsored investigation of the effects of the space environment on organisms.