There are lots of different models of depression. One of them is sickness behavior, i.e. the way that you act when your immune system is fighting off particularly foul bacteria or viruses. Symptoms of sickness behavior include anhedonia, anorexia, fever, sleep changes, and decreased social interaction. In depression that looks like sickness behavior, presumably, your body's immune response is over-active for some reason to the detriment of other mental and behavioral faculties.
What causes sickness behavior? Dysregulation of inflammatory cytokines maybe.
What's that? Your body produces both inflammatory cytokines and anti-inflammatory cytokines. They fight each other a bit. When there's an infection in your body, inflammatory cytokines cause local inflammation, like swelling and redness, and pain, and elevated temperature of the body part. If a bacterial colony colonizes a person's body, the person can have low-grade peripheral inflammation all the time without obvious redness or swelling. The same immune processes are still going on. in the blood and tissues, involving cytokines and lots of other chemicals that have longs names full of numbers.
People with depression that looks like sickness behavior generally don't have swollen, red, infected body parts, so why are inflammatory cytokines relevant to depression? In addition to peripheral inflammation, there's also central inflammation: neuroinflammation.
Neuroinflammation? Isn't the brain immunologically privileged? Isn't there a barrier of immuno-competent cells (astrocytes and endothelial cells) surrounding the brain and preventing infectious agents from crossing into the cerebrospinal fluid via the blood? Yes, and there are like a hundred guesses about how neuro-inflammation happens despite the blood-brain barrier, and honestly, a bunch of them might be right. The main thing to know is that it's not the infectious agents that are passing over the blood-brain barrier, it's the inflammatory cytokines (and other chemicals that are downstream of cytokines in chemical reaction pathways) that get into the brain. Or they at least trigger the brain to produce its own cytokines.
Why does this matter again? Because acute administration of inflammatory cytokines in healthy people produces sickness behavior: anhedonia, anorexia, fever, sleep changes, and decreased social interaction. Also, cytokines are found at elevated levels in people with some types of depression, like depression with anhedonia, anorexia, fever, sleep changes, and decreased social interaction. There's a consensus that those sickness behaviors are adaptations of the immune system. How they are all individually adaptive, I don't know. The consensus is that jointly they help a sick person to conserve energy and allocate internal resources to either combat infection or to repair tissues that have been damaged by injuries. And maybe they help you to limit contact with other people? I think I've heard that too.
So cytokines = sickness behavior = depression? No, not all depression is thought to involve cytokines: post-partum depression and depression which follows drug withdrawal, for example, are thought not to involve elevated inflammatory cytokines in the brain or the blood. But if you're depressed and your depression doesn't look like those, then yeah, maybe. Maybe the topic of inflammatory cytokines is worth some of your attention.
What does neuroinflammation even mean? Is it redness and swelling in the brain, or is it the low-level kind of inflammation that isn't necessarily visible? As near as I can tell, neuroinflammation does not involve swelling in the brain, at least not in the normal case where infectious agents haven't crossed the blood-brain barrier. The normal non-infectious version of neuroinflammation is just a continuation of the production of chemicals like cytokines and their less easily pronounced relatives, but now in the brain. In the brain, those chemicals do different things than in the rest of the body. Fevers, as a component of sickness behavior, are the result of cytokines acting on the hypothalamus. The other symptoms of sickness behavior (anhedonia, anorexia, sleep changes, and decreased social interaction) aren't as well linked to the action of cytokines on brain regions, so far as I know, but I don't know much. Less behaviorally direct, lots of things are known about how the chronic production of cytokines in the brain messes up other chemical processes, like the production of neurotransmitters and neural growth factors. I keep saying just "cytokines", but it's the inflammatory ones specifically.
So these chemicals are important for immune function, but their chronic production has bad effects, and they're found in elevated levels in people with some kinds of chronic neuropathology: especially depression that looks like being sick, without the swelling, but also other pathologies like multiple sclerosis.
What can be done about it? Probably we first want to figure out why it's there in the first place: why is there is a background level of inflammatory response? That would be the ideal things to treat. I don't know enough about that. We could call it inflammatory cytokine dysregulation for short. Other than figuring out why it's happening, we could also just treat the symptoms: anti-inflammatories are the treatment for inflammation, and these are generally NSAIDs or anti-cytokines.
I don't know much of anything about anti-cytokines, or cytokine inhibitors, except that they increase the risk of infections, which makes sense, given that they're suppressing an immune response.
There is mixed-to-positive support in drug trials for the antidepressant effect of non-steroidal anti-inflammatory drugs, NSAIDS, generally usually used in conjunction with regular anti-depressants that directly target neurotransmitter production. NSAIDs are a drug class that includes aspirin and ibuprofen among others. They target chemicals called COX1 or COX2, which I think are like downstream messengers of cytokines, but don't trust me on that. I've heard that selective-COX2 inhibitors do much better as anti-inflammatories and anti-depressants than other NSAIDs. Celebrex is a COX2-selective NSAID. It's mainly advertised and indicated for arthritis. I don't know whether aspirin hits COX1 or COX2 or both, but you shouldn't be taking it in large regular doses for depression, even though it seems like a cheap readily available solution to inflammation. It's got all sorts of terrible side effects, not limited to intestinal bleeding. Also, if taking lots of aspirin could fix a big class of depression, wouldn't people have figured that out by now? They would have. For every analgesic on the market, there are already people taking unsafe amounts, and they would have figured it out.
But it's interesting, right? Inflammatory cytokines: not yet a target of any depression treatment, but maybe one day.
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