Inflammation in the Brain as a Trigger for Depression

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Andrew Miller, M.D., Emory University Director of Psychiatric Oncology Winship Cancer Institute
Andrew Miller, M.D.

An important new development in psychiatry is the growing body of research pointing to the involvement of the immune system in brain and behavior disorders, including depression. It has long been known that depression and stress negatively affect the immune system and increase vulnerability to illness. Recently, there has been growing awareness that, conversely, inflammation and the release of immune-system chemicals called cytokines can get into the brain and induce depression: the higher the level of inflammation, the greater the severity of the depression.

In the brain, cytokines act on growth factors like brain-derived neurotrophic factor (BDNF) that support the development of new neurons. They exert influence on neurotransmitters; for example, reducing levels of serotonin and dopamine, key players in depression, and increasing glutamate, a cytotoxic (aka, cell-killing) neurotransmitter.

A recent study with cancer patients reinforced the hypothesis that inflammation in the brain can cause depression. The cytokines involved in inflam-mation are interferon (IFN) alpha, interleukin-1 and interleukin-6 (IL-1 and IL-6) and tumor necrosis factor (TFN) alpha. The cancer patients in the study were given IFN alpha as part of their treatment protocol for melanoma and/or renal cell carcinoma. IFN alpha triggers other cytokines, TNF-alpha and IL-6. After 12 weeks, all the cancer patients showed marked symptoms of depression.

A large percentage of people with depression fail to respond to the currently available antidepressant medications; patients with depression and with high markers of inflammation are often among those. Dr. Miller has been leading a study with treatment-resistant patients with increased inflammatory markers to test the effect of blocking TNF-alpha as one of perhaps multiple potential targets for treatment along the inflammatory signaling pathways. Further brain and behavior research will be needed to explore deeper into immunology and to better understand how cytokines work and which ones might be the best candidates for treatment development.

On the practical level of prevention, it has been shown that a Mediterranean diet, long recommended for heart health, can lower blood levels of IL-6. Having too many fat cells can contribute to inflammation, as does sleep deprivation, stress and alcohol. Also, in the push-pull between the sympathetic nervous system that drives inflammation and the parasympathetic nervous system that puts a brake on it, strategies, like meditation, exercise, and yoga can help to pump up the parasympathetic system.

Andrew Miller, M.D.    
1997 NARSAD  Independent Investigator Grantee
William P. Timmie Professor of Psychiatry and Behavioral Sciences
Emory University
Director of Psychiatric Oncology
Winship Cancer Institute

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