Is Depression a Physical Illness? - Inflammation, Cytokines, Stress, and All That

Patient Expert

Is depression a kind of allergic reaction? read the title to an article in The Guardian earlier this month. The answer is rather involved. Let's break it down "

Inflammation and the immune system ...

Inflammation is the body's response to cellular injury, be it from banging your shin against the edge of a coffee table or inhaling too much pollen or being invaded by pathogens. The term is frequently used interchangeably with the immune system response.

Biological processes are engaged to destroy or isolate any injurious agents and to control damage. Initially, the subject may feel swelling or pain or redness or other symptoms. When everything goes right, the injury eventually heals. Sometimes, though, the inflammation process spirals out of control, which may lead to a host of diseases, from arthritis to hypothyroidism to cancer.

Cytokines ...

Cytokines are one part of the inflammation/immune system response. These are signaling proteins involved in dispatching a cellular army against foreign invaders. These molecules perform the task so well that they play a major role in many medical interventions. For instance, one type of cytokine - interferon - is administered via injection to treat, amongst other things, melanoma and hepatitis C.

But here is the catch   - about one in three of melanoma and hepatitis C patients treated with interferon develop major depression.

**The depression connection ...  **

It may be that depression is a natural part of healing. Integrative medicine guru Andrew Weil, in a piece in The Huffington Post, speculates that loss of interest in pleasurable activities such as eating frees up the energy used for digesting food and makes it available for defending against infection.

Once the immune system gains the upper hand, cytokine production slows down and the brain renews its interest in food and other pleasures.

But not always. Inflammatory and autoimmune diseases - ranging from Crohn's disease to rheumatoid arthritis - involve a failure of the inflammation/immune response to return to normal. By now, the cytokines have spread throughout the body, into places where they are not welcome, leaving symptoms of depression in their destructive wake.

Rodents injected with cytokines become listless and essentially give up on taking care of themselves - as close as you can get to diagnosing depression in animals. In humans, raised cytokine levels are associated with both depression and bipolar disorder. There is much to learn, but researchers are now sufficiently confident to be talking about the "inflammation hypothesis" of depression.

The stress connection ...

Fine, but where does the inflammation come from? A 2013 review article in BMC Medicine by Michael Berk of the University of Melbourne et al asked precisely this question. Never mind inflammatory illnesses, they concluded in effect. We need to be looking at environmental factors, and there can be little doubt that stress and trauma are Public Enemy Number One. Higher cytokine levels - particularly interleukin - have been found in both lab animals and humans exposed to stress.

The authors cite a study that has tracked a thousand-strong birth cohort from Dunedin, New Zealand over the course of three decades. Previous findings from this cohort have linked childhood stress and trauma to adult depression and antisocial behavior. A 2011 finding revealed that those who suffered stress in childhood were twice as likely to suffer chronic inflammation.

The authors caution that it would be a mistake to give stress sole credit. It may be that maladaptive responses learned in childhood could play a significant role in how we react to, say, economic hardship in adulthood. But, yes, put stress high on your list.

Other factors ...

Diet also looms large. The authors of the review article cite a study that found that a diet rich in fruits and vegetables, whole grains, fish and legumes, was associated with lower concentrations of inflammatory markers, including interleukin-6.

The authors also reel off a number of lifestyle considerations, including exercise, obesity, smoking, and sleep. They also note that the gut and its flora may have a profound effect.

Meanwhile ...

A handful of small studies suggests that adding anti-inflammatory agents to antidepressants may have a beneficial effect. Nevertheless, it's far too soon to ask your doctor to write a prescription.

In the meantime, we have our own lifestyle choices to consider. Dr Weil recommends foods that may control inflammation (such as green tea), together with nutritional supplements.

But more important, I would submit, is to manage your stress. The links between stress and depression are well-documented. Its pathways are many and its middlemen legion. From our own perspective, familiarity with these middleman is far less important than the knowledge that depression is a highly complex physical condition, one that not only affects the brain but involves biological processes that take place outside the brain.

Related to this is the knowledge we are not helpless. By managing our stress, we can manage our depression. Presumably, our cytokine levels will drop as a result. Like any regimen that yields long-term benefits, this is no quick fix. Be smart, live well "

John McManamy is the award-winning author of Living Well With Depression and Bipolar Disorder: What Your Doctor Doesn't Tell You That You Need to Know.