Depression Is an Inflammatory Disease

Summary and Comment |
March 29, 2010

Depression Is an Inflammatory Disease

  1. Steven Dubovsky, MD

A meta-analysis shows higher levels of two cytokines in depressed patients.

  1. Steven Dubovsky, MD

People who are chronically ill often get depressed; depressed people are prone to a variety of medical illnesses; and pro-inflammatory cytokines can alter mood and promote illness. To determine whether these proteins play a role in the overlap between depression and inflammation-associated medical disorders, researchers conducted a meta-analysis of 24 case–control studies of basal cytokine levels in a total of 438 unmedicated subjects with major depression and no comorbid illnesses and 350 medically and psychiatrically healthy controls.

Concentrations of tumor necrosis factor-alpha (TNF-α) and interleukin (IL)-6 were significantly higher in depressed patients than in controls. The groups showed no significant differences in other interleukins (IL-1β, IL-4, IL-2, IL-8, or IL-10) or in interferon-gamma.


IL-6 stimulates differentiation and proliferation of immunoglobulin-secreting B-lymphocytes, and TNF-α stimulates the release of other pro-inflammatory cytokines and inflammatory prostaglandins. In the brain, these substances inhibit hippocampal neurogenesis; activate the hypothalamic-pituitary-adrenal axis, thus increasing cortisol production; and indirectly increase production of agonists of the N-methyl-d-aspartate receptor, which promotes apoptosis. The central actions of these proteins reduce resiliency of the brain and contribute to the hyperactive stress response that is characteristic of depression, which is further aggravated by loss of hippocampal cells. And, the peripheral actions of these proteins can exacerbate inflammatory diseases, such as diabetes and coronary heart disease. By the same token, the effects of cytokines in the brain can induce depression in patients with these medical diseases. To the extent that inflammation is a component of depression and other systemic conditions, anti-inflammatory drugs might prove helpful (JW Psychiatry Feb 8 2006).


Reader Comments (18)


Gosh when I read all the latest medical info th Iat has been coming out I wonder if I will ever find relief in my lifetime.I am 31 have had Major Depressive Disorder since I was a young girl. Following that Borderline Personity Disorder, and the mostv recent RRMS, Fibromyalgia, Periodic Limb Movement, Upper Airway Resistance Syndrome. From this article it gives pause to a rational link between all the above. Thanks too all who research and give of themselves in the name of truth and science.

Competing interests: None declared

andy besso

Dear friends am new to this online journal & I must say I find this topic very interesting...I was wondering if the fact that depression implies "lower mobility potential" of the person involved may in fact somhow explain the higher values of some inflammatory markers like IL-1 or IL-6....(this would imply the fact that activity has some sort of anti- inflammatory affect..)

Competing interests: None declared

Gail A Simon

What are your comments re: the above mentioned disorders? How do you feel about Drs./PNP's completely removing meds with the belief that only CBT/DBT is the only cure for such diseases?

I find it somewhat disconcerting that this is happening more and more frequently. My personal research shows that meds are essential for living a full, resourceful life. Do you know of other research that is (supposedly) indicative that behavioral therapy is better than medication?

Competing interests: None declared

Steven Dubovsky, MD

It is always gratifying when one of our summaries generates a lot of discussion. Since these are of necessity brief summaries of a few salient points in what may be very complex original research by an investigator other than us, Journal Watch summaries are meant to stimulate further interest and highlight one or two implications or limitations of the research so that those with an interest in the area can go on to the actual paper in detail and look at other research in the area.

Competing interests: Summary author

Shannon K Brown ND LAc

This is fantastic data, but I'm not sure that it supports the conclusions. There is just as much data that suggests that outlook changes body chemistry as there is that body chemistry changes outlook. And even if it is true, we should seek an underlying imbalance before leaping to the use of suppressive, anti-inflammatory drugs.

Competing interests: None declared

Mary Hanessian MD

I am interested in the link between autoimmune disease and early sexual trauma. I find that if middle aged female pts who are seeking treatment of depression and anxiety tell me that they have rheumatoid arthritis, fibromyalgia, or other diseases with chronic pain associated with inflammation, I will later get a history of early sexual abuse/assault. Somehow, the immune system response has become part of their Post Traumatic Stress Disorder and is often the most disabling part of the illness. I am interested in doing research in this area and would be happy to hear from others who might like to look at this.

Competing interests: None declared

Trevor Webber

This is very promising, although case-control studies are notoriously subject to biases and confounding. Before I am convinced I will need to look at the details of the methodology.

Competing interests: None declared

Neal F Devitt

Patients with affective disorders are more likely than controls to test positive for antibodies to borna disease virus. Perhaps it is not depression that is an inflammatory condition but that at least in some depression is the symptom of an infection.

Competing interests: None declared

Deborah Rund

IL-6 can also cause anemia by induction of hepcidin production. It would be interesting to know if the depressed patients were also anemic.

Competing interests: None declared

Rogerio Luz Coelho

IF the inflammatory pathways are activated in Depression, and IF the inflammation progresses we can be seeing the beginning of a new understanding in pain mechanisms, even an explanation to such diseases as Fibromialgia and Chronic Fatigue Syndrome.

But we should be very careful not to over-extend this first finding,

Does the inflammation CAUSE Depression or is it the other way around ? Were these patients checked on a Well-being scale ? On a pain scale ? On a Depression scale ? What criteria were used to define Depression ? If the diagnosis was clinical (no scales used) how well trained were the doctors to make such a diagnosis ?

Lots of questions need answering before this could have any practical / clinical use. However a very nice piece of information no doubt.

Competing interests: None declared

Phillip Harper

I suggest you add more advertising on your site to pay for your needs/desires so the general public can learn from your knowledge when they cannot afford to pay a subscription fee. Knowledge shouldn't have a fee when you want to learn for the need for yourself or your loved ones.

Thank you,

Phillip E Harper

Competing interests: None declared

raul a reichard

Taking into account this phenmenom together with Sleep Breathing Disorders, it is why MDD should not be confused with Mood Disorders due to a General Medical Condition-Obstructive Sleep Apnea, Dysomnia, etc. These pts. don't present psychomotor retardation, genuine, severe life stressor, self-injurious thoughts and that flat affect real MDD pts do.Their bottomline collective disturbance is a sleep disorder.This is why psychotropics(antidepressant) result undoubtedly in treatment failure and /or partial remission of sx.Combination Tx compunds further the condition Dearranged neurophisiology will never be supplanted/corrected with SRRI'S.

Competing interests: None declared

Jon Wilcox

This is quite important I think. When on an SSRI Committee some years ago I noticed that anti-depressant prescribing peaked every year in NZ in spring.

Competing interests: None declared

Kostantinos E. Panagiotopoulos

Brain feels first the upcomming disease before the physician does. Depression should be recognised as introductory step for major systemic diseases.

Competing interests: None declared

G L Florentin-Lee

The biochemistry is interesting and confirmatory. The conclusion trite and unhelpful. The cohort suffered from inflammaory diseases and certainly would normally be treated with one antiinflammatory regime or other. Thus the remedial suggestion is less than helpful.

Competing interests: None declared

Maria Humphrey

interesting fact and useful to know.

Competing interests: None declared

raul a reichard

all awhile during NREM hypoxemia from sleep breathing disorders in addition to nocturnal sleep movement disorders engage the CNS sympathetic system to comensate for lack of O2 and also engage the cytokines & pro -antiinflamatory system.And voila....we develop resistant htn, left heart enlargement, t2DM, etc etc and the rest of the endocrine disorders.

Competing interests: None declared

Marilyn Vach�

Tons of evidence from all over the place confirms this, but psychiatrists rarely hear of it (ref: Hedaya &Quinn, "Depression: Advancing the Treatment Paradigm," Institute for Functional Medicine, 2008). But we have to go beyond anti-inflammatories and look for the underlying causes of inflammation.

Competing interests: None declared

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