Depression and Inflammation

The practice of obstetrics and gynaecology is normally a kaleidoscope of colours –from the pale red blush of an embarrassed face, the bright green flash of twinkling eyes, to the panoply of skin colours proudly arrayed like just-washed clothes in the waiting room. There is no rank to the colours, no special prize for the one most displayed, no arbitrary preference, but I am wary of grey…

You don’t have to be a psychiatrist to spot the clouds, nor possess a doctorate in psychology to feel the angst. Depression is a fog whose periphery shades and obtunds everything and everyone nearby. Its boundary is indistinct and to approach is to be enveloped. Obscured. Affected. It has the strange property of contagion.

Not to pretend an exact analogy, but I have often wondered about the resemblance of depression to how many of us react to an acute illness like, say, a ‘cold’ or even a headache –so-called ‘sickness behaviour’: fatigue, apathy, loss of focus, withdrawl… All of these are vaguely reminiscent of the psychological behaviour in depression, although I suspect most of us have not really thought about it in those terms. Admittedly, the resemblance is tenuous and terribly non specific, and yet I find the correspondence intriguing –not least because the symptoms are caused by some physical malfunction and seem almost designed to isolate and rest the body to allow healing.

So I was excited to read about the work being done investigating the link between depression and inflammation. One of the more informative evidence based reviews I have found was published in the June 2013 edition of Current Psychiatry and the author was Dr. Maria Almond from the University of Michigan:

The concept of inflammation having a role in what has always been considered a mental maladjustment reminds me of the story of stomach ulcers. Remember, it was not so long ago that ulcers were attributed to stress. It seemed intuitively obvious that it would –and should- be so. And then Helicobacter pylori was discovered in a large percentage of these patients and when treated, seemed to alleviate the symptoms. Mind you, not everone with Helicobacter was symptomatic, but its undisputed role in the disease process changed our thinking about psychosomatic illnesses –opened our minds… Or at least should have.

And then there is the oft refuted contention that cardiovascular diseases may have their origin in infectious –or at least inflammatory- processes. The arterial plaques that can narrow or block important blood vessels and lead to strokes or heart attacks have been commonly attributed to cholesterol levels –too much ‘bad’ cholesterol (LDL) will form these plaques and impede blood flow past them. Observational science at its finest; but seeing them and recognizing their significance, still does not answer the question of why they formed in the first place. There have been attempts to attribute the reason for their formation to inflammation and underlying damage to the arterial wall. But it is a chicken-and-egg observation: did the damage result from inflammation –ie some infectious, or other agent- or did some other cause for damage engender inflammation and attract the cholesterol to form the plaque in an ongoing attempt to heal it?

But as a gynaecologist I admit that I am straying into uncomfortable territory here, so I will merely leave it as a sort of illustration of the There are more things in heaven and earth, Horatio, than are dreamt of in your philosophy type assertion.

The article on depression is exciting because it opens up entirely new ways of thinking of mental illness. It proves nothing, to be sure, and there are no doubt many ways of refuting the evidence it provides –including the fact that the causes of depression are likely as multifactorial as are, say, headaches or abdominal pain. One interpretation is unlikely to explain them all, I agree, but I am still beguiled by the way the observations seem to hint at commonalities. As the article points out:

In our progression toward understanding depression’s pathophysiology, we see factors that point to a relationship between depression and inflammation:

  • depression frequently is comorbid with many inflammatory illnesses
  • increased inflammatory biomarkers are associated with major depressive disorder (MDD) 
  • exposure to immunomodulating agents may increase the risk of developing depression 
  • stress can activate proinflammatory pathways
  • antidepressants can decrease inflammatory response
  • inhibition of inflammatory pathways can improve mood.

I’m not sure how this would explain the increased risk of antepartum –and especially postpartum– depression. Would the ever-changing level of hormones in pregnancy play some role in facilitating an inflammatory process? Or would the physiologic stresses engendered by the increasing needs of the developing foetus play a role? As another observation pointed out in the paper explains:

Acute and chronic stress is associated with increased availability of proinflammatory cytokines and decreases in anti-inflammatory cytokines.3,24 One theory looks to glucocorticoid response to stress as an explanation. Miller et al25 found glucocorticoid sensitivity decreased among depressed women after exposure to a mock job interview stressor and increased among nondepressed controls. Because glucocorticoids normally stop the inflammatory cascade, this finding suggests depressed individuals may not be able to control inflammation during stress.26 At the level of genetic expression, there is increased transcription of proinflammatory genes in response to stress  […]

Heuristic, to be sure, and certainly thought-provoking, but still a long way from convincing. But in Medicine, as in Science, it pays to have an open mind; to look around as you wander along long the well-trodden path. We haven’t seen everything yet; sometimes we have not even left the trail. There is something written by Lao Tzu that I have always remembered from my youthful philosophical journeys: If you do not change direction, you may end up where you are heading. Perish the thought.

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