Depression – Caused by Inflammation, Thus Like Other Diseases of Civilization

http://www.psychologytoday.com/print/57915

Depression – Caused by Inflammation, Thus Like Other Diseases of Civilization

From the page: “From the page: “Part of the possible connection between diet and mental illness is how a bad diet can lead to a generalized inflammatory state. The theory goes like so: first you eat a ton of vegetable oil in processed food that fills the body with inflammatory molecules derived from the omega-6 fatty acids, then you add a lot of grains or legumes with lectins and immunoreactive proteins, and top it off lots of modern chronic stress. Do this for a long period of time, and your body gets irritated – obesity, cardiovascular disease, and autoimmune diseases are all related to inflammation. Turns out your brain can get pretty irritated too.

It is well known that symptoms of clinical depression are likely mediated by inflammation in the brain. A number of lines of evidence support this idea, including that depressed people, old and young, have elevated levels of certain inflammatory proteins in the plasma and cerebrospinal fluid. Anti-inflammatory agents treat depression, and pharmacologic agents such as interferon, that cause depression, also lead to increases in the inflammatory proteins IL-6 and TNF-alpha. In addition, when someone who is depressed responds to an antidepressant treatment, these same inflammation markers decrease (1). People with generalized inflammatory syndromes (such as acute viral illness, rheumatoid arthritis, insulin resistance, and cardiovascular disease) have higher rates of depression than the general population too. I also notice in my clinic that people who have had bone surgery tend to get depressed for a few weeks after the operation, more so than people who had other kinds of surgery. I always wonder if sawing through the bones releases an enormous wave of inflammatory cytokines.

There are several suspected mechanisms of how this inflammation leads to depression, many of them very intriguing. Here’s one – the amino acid tryptophan is a precursor to the neurotransmitter serotonin. Turns out that tryptophan is also the precursor to another, far less famous neurotransmitter, kynurenic. When the inflammatory cascade is activated, more tryptophan is made into kynurenic, which leaves less tryptophan around to make into serotonin. And everyone knows that without serotonin, we’re unhappy (and angry). SSRIs work (when they do), it is thought, by undermining the effect of the inflammatory cytokines, pushing more tryptophan to be made into serotonin rather than kynurenic.

Here’s another mechanism – inflammatory cytokines also interfere with the regulation of another neurotransmitter, glutamate. Glutamate is an excitatory neurotransmitter that, if left to go wild, can pound our NMDA receptors in the brain and wreak major havoc. No one wants overexcited NMDA receptors, and clinical depression is one among many nasty brain issues that can be caused by overexcitement. Astrocytes, little clean-up cells in the brain, are supposed to mop up excess glutamate to keep it from going nutso on the NMDA. Turns out inflammatory cytokines interfere with the clean-up process. The horse tranquilizer (and club drug) ketamine, when administered IV, can eliminate symptoms of severe depression pretty much immediately in some cases (do NOT try this at home) (2). Ketamine helps the astrocytes mop up glutamate, and it is assumed that this is how ketamine instantly cures depression. Unfortunately, the effects of ketamine don’t last, otherwise it would be a nifty tool, indeed.

Finally, inflammatory cytokines also push the brain from a general environment of happy “neuroplasticity” (mediated in part by a type of natural brain fertilizer called “BDNF”) towards an environment of neurotoxicity (sounds bad, and it is!).

At this point It shouldn’t surprise you that psychological interventions (such as therapy) have been shown to reduce chemical markers of inflammation. Yoga has also been shown to do the same. I think it makes sense to assume that any successful antidepressant treatment will also be anti-inflammatory.

Well, an absolute flurry of research has been done in this area in the last decade or so, because omega 3 fish oils would be a nifty, natural, presumably no or low side effect, and inexpensive treatment for depression, if it worked. Some studies have been disappointing (3)(4). However, the largest study yet does show benefit (equal to a prescription antidepressant) for those who have depression, but not concurrent anxiety, at a daily dose of 150mg DHA and about 1000mg EPA. (DHA and EPA are fish oil omega 3 fatty acids).””

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