Cytokines and Depression

How your immune system causes depression

by Ronald S. Smith

About Ronald S. Smith

Ronald Stephen Smith was the author of numerous biomedical papers on the immune→brain connection, cytokines, depression, schizophrenia, psychosocial disease and headache. He was Professor of Chemistry and Nutrition at Gavilan College for many years and was also a Research Chemist at Shell Development's Biological Sciences Research Center. For the last two decades of his life, he researched the biomedical literature on immunology, neuroscience, nutrition and cardiovascular disease while lecturing nationwide in continuing education seminars for health care professionals.

Professor Smith spent 1996 and 1997 writing this book on Cytokines and Depression but died unexpectedly of an aortic aneurism in June 1997 with 9 of 11 chapters written. This website was created by his son, Brent Smith, in order to share the book and its insights with the world. The material has been left alone with almost no editing. If you have questions, comments, suggestions, or find errors in the text, please feel free to contact Brent at smithbr@gmail.com. He also enjoys hearing from people who've found these ideas helpful. The contents of this website are also available as a Kindle e-Book on Amazon.com.

What others are saying about Ronald Smith's work

"In the early 1990's a significant breakthrough was made when several research groups recognized that sickness behaviours were remarkably similar to the symptoms of depression...The first to propose explicitly that depression was driven by PI molecules was Ronald Smith in a seminal paper published in 1991."

F.R. Walker et al. Stress Nutrition and Physical Activity in Inflammatory Diseases. Chapter 15: Stress and Inflammation: An Emerging Story. p266.

"The link to depression was made in Smith’s ‘macrophage theory of depression’ in which he noted the similarities between sickness behavior and depression, and proposed specifically that IL-1 secreted by macrophages was responsible for the depression. This exciting series of proposals caught the imagination of many researchers, and has achieved folklore status."

Adrian J. Dunna, Artur H. Swiergiel, Renaud de Beaurepaire. Cytokines as mediators of depression: What can we learn from animal studies? Neuroscience & Biobehavioral Reviews 29:891-909, 2005.

"The etiology of depression is still controversial, and several theories have emerged to explain it. Taking into account the communication between the immune and central nervous systems, Smith, in the early 1990s, proposed a role for cytokines in depression. The 'cytokine theory of depression', that has been widely studied in the last two decades, proposes that enhanced production of proinflammatory cytokines is associated with the pathogenesis of depression. Indeed, several studies show a significant increase in the production of proinflammatory cytokines among depressed patients." "The 'cytokine theory of depression' has also been supported by a large set of results in animals models."

Susana Roque et al. Interleukin-10: A Key Cytokine in Depression? Cardiovascular Psychiatry and Neurology Volume 2009 (2009), Article ID 187894, 5 pages.

"The macrophage theory of depression was formulated by Smith in 1991. This hypothesis proposes that excessive secretion of macrophage cytokines such as interleukin (IL) -I, tumour necrosis factor-a (TNF-a), and interferon-a (IFN-a) are a cause of some cases of major depression. To date, there are several lines of evidence that arise from both clinical and experimental studies to support this hypothesis."

Thomas J. Connor, Brian E. Leonard. Depression, Stress, and Immunological Activation: The Role of Cytokines in Depressive Disorders. Life Sciences, Vol. 62, No. 7, pp. 583-606. 1998.

Scientific Publications of Ronald S. Smith