# Could depression be an autoimmune disorder? **URL:** \ **Category:** Factual Questions\ **Created:** [November 14, 2010, 8:54pm UTC](https://boards.straightdope.com/t/could-depression-be-an-autoimmune-disorder/560673 "2010-11-14T20:54:52Z")\ **Posts on this page:** 7\ **Page:** 2
**Author:** ![maggenpye](https://avatars.discourse-cdn.com/v4/letter/m/ecc23a/32.png) [@maggenpye](https://boards.straightdope.com/u/maggenpye)\ **Post date:** [May 29, 2011, 4:02am UTC](https://boards.straightdope.com/t/could-depression-be-an-autoimmune-disorder/560673/21 "2011-05-29T04:02:16Z")
> [@AskNott](#): > > Seriously, as a depressed man, I’m interested in this thread, and in the Hay Diet. > > Non-seriously, I remember that Lewis Carroll’s Red Queen told Alice that there’s nothing like eating _hay_ for a headache. > > Alice disagreed, saying that eating hay wouldn’t help a headache. > > The Red Queen said, “I didn’t say it would help. I said there’s nothing like it.” :smack: I laughed. Wikipedia has a [link](http://en.wikipedia.org/wiki/Hay_diet), and you could probably learn quite a bit from the links to Alkaline diet etc on the main page. I found a couple of books in a local second hand shop that had (Hay) meal plans and combo’s that were helpful. Edgar Casey took it one step further and said at least one meal every day should be made of entirely raw ingredients and there are some who’ve taken \*that \*even further and said every meal should be raw, including meat. I just try to eat balanced meals and watch my portion sizes, I’m such a wimp. ---
**Author:** ![DSeid](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/dseid/32/20194_2.png) [@DSeid](https://boards.straightdope.com/u/DSeid)\ **Post date:** [May 29, 2011, 4:19am UTC](https://boards.straightdope.com/t/could-depression-be-an-autoimmune-disorder/560673/22 "2011-05-29T04:19:44Z")
Not being very helpful here I guess but remember that correlation does not mean causation. It is well established that immune dysregulation is correlated with depression. The difficult bit is to determine if depression causes the immune dysrgulation, if the effect of immune dysregulation on function triggers the depression, or if there is more of a direct etiologic role going from immune dysregulation to depression as you postulate. Or, of course all of the above to varying degrees and in some possible feedback interactions that also include endocrine and of course genetic factors. It is also established that immune responses to infections, both viral and bacterial (most famously influenza for an example in the first camp and strep for the second) can have neurologic and neuropsychiatric effects. So the speculation has real biologic plausibility. [This study](http://care.diabetesjournals.org/content/27/2/429.short) also provides some fodder for discussion. Diabetes is an autoimmune disease. Those who are depressed are significantly more likely to develop diabetes over the next six years. > [@](#): > > This relation persisted after adjustment for stress-associated lifestyle factors (smoking, physical activity, caloric intake, and adiposity) (1.28, 1.02–1.60) and metabolic covariates (fasting insulin and glucose, lipids, blood pressure, and adiposity) [Other studies](http://care.diabetesjournals.org/content/33/4/792.full) confirm this result. > [@](#): > > In a national sample of men and women aged ≥50 years, we found that elevated depressive (CES-D) symptoms at baseline were associated with a higher risk of developing type 2 diabetes. This association did not vary according to age and sex and was largely independent of known correlates of diabetes and depression and cardiovascular, psychiatric, and other comorbidities. Hypothesized mechanisms through which elevated depressive symptoms might affect incident diabetes involving health behaviors, BMI, and use of antidepressants explained little or nothing of the association. Other studies however, like [this one](http://jama.ama-assn.org/content/299/23/2751.full#T2), find no relationship to a limited selection of inflammatory markers. (IL-6 and CRP in that study.) That study also found that being pre-diabetic was not correlated with future risk of depression. Now again, it is impossible to say whether the increased risk was because some immune dysregulation increased the risk of both, or the depression caused some immune dysregulation that increased the risk of diabetes. But it does show that the correlation exists without the disease causing functional impairments that lead to psychological distress that lead to depression. So it is one step closer. But the fact that pre-diabetes was not correlated with future depression, while depression was correlated with future diabetes, argues that the stronger effect is depression to immune function rather than the other way around. ---
**Author:** ![phouka](https://avatars.discourse-cdn.com/v4/letter/p/c5a1d2/32.png) [@phouka](https://boards.straightdope.com/u/phouka)\ **Post date:** [May 30, 2011, 2:54am UTC](https://boards.straightdope.com/t/could-depression-be-an-autoimmune-disorder/560673/23 "2011-05-30T02:54:16Z")
**DSeid** , you’re totally helping with that reminder. We only really learn the facts when we keep in mind the logical fallacies that can lead us astray. More and more, I’m aware that what we think of as different systems - central nervous system, respiratory system, immune system, endocrine system - are far more interconnected than we ever knew. Bone cells talk to fat cells. Genes are turned on and off by environmental stressors. A person with a genetically identical twin has a 50% chance of developing Type I diabetes if their twin has it, but a 90% chance of developing Type II diabetes if their twin has it. Type I is without a doubt an autoimmune disease. Type II? We’re still trying to figure it out. We know it has correlations to mood, environment, job type, genetics, high blood pressure, high cholesterol, race, and geography. I can see where already having symptoms of MDD could cause a higher incidence of Type II diabetes. Classic symptoms of MDD include hypersomnia (not burning calories), loss of interest in activities (not burning calories), and a change in appetite (often taking in more calories). But I can’t help but wonder if there isn’t an initial immune reaction to an infection - especially viral, like influenza - that causes sickness behavior, which then is increased by some immune dysregulation, and becomes depression. What, though? An inability to produce immune moderating cytokines? A heightened sensitivity to immune stimulating cytokines? An underlying food allergy, sensitivity, or intolerance that causes chronic inflammation? I know at this point that I do not have Rheumatoid Arthritis. The autoimmune blood panel I had done indicated a positive anti-nucleus antibody (lab talk for “why, yes, your immune system does seem to be wonky”), but nothing else was positive. After the course of prednisone, the joint and muscle pain and exhaustion faded, but it will come back as soon as I eat any gluten, and it likes to bring suicidal ideation with it. Currently, my symptoms point more towards Sjogren’s than anything else, but I just figured out that my diet has been extremely deficient in protein the past few months. There are no quick answers. Most studies are predicated on only one or two variables, because following more variables complicates things beyond what researchers can track. There are a couple of on-going, extremely long term studies still under way - one on nurses, and one on people in a specific town - that have already provided a goldmine of information. I suspect what we really need to do is expand our research to larger populations over longer periods of time, and I hope the ubiquity of technology will make that possible. ---
**Author:** ![joey\_101](https://avatars.discourse-cdn.com/v4/letter/j/a587f6/32.png) [@joey\_101](https://boards.straightdope.com/u/joey_101)\ **Post date:** [March 16, 2012, 2:47pm UTC](https://boards.straightdope.com/t/could-depression-be-an-autoimmune-disorder/560673/24 "2012-03-16T14:47:52Z")
@Phouka: Now that nearly a year has passed, have you discovered anything new? I suffer from RA and have been having a major flare since giving birth last July. I’ve also been suffering a major depression at the same time. Hadn’t put the two together until very recently but I’m interested in understanding what’s happening to me in order to prevent it after future pregnancies. I’m just curious if you’ve continued your research into the subject. ---
**Author:** ![md2000](https://avatars.discourse-cdn.com/v4/letter/m/73ab20/32.png) [@md2000](https://boards.straightdope.com/u/md2000)\ **Post date:** [March 16, 2012, 3:04pm UTC](https://boards.straightdope.com/t/could-depression-be-an-autoimmune-disorder/560673/25 "2012-03-16T15:04:33Z")
The problem is that we know an awful lot about nothing. We don’t\*\*\* really\*\*\* know what causes schizophrenia, for example, let alone depression. We don’t know what really causes type I diabetes, except to say, “yep, you have it.” We don’t know what causes autoimmune diseases. We don’t even know if some conditions are diseases, and what they are. heck, we don’t even know why some people get high blood presure. Back when everyone died of plague or tuberculosis, etc. - who cared about depression? Your other problems were bigger. I have a theory that a lot of the odd diseases we see are a result of subtle infections; just as measles or polio (or cold sores) can recurr to bother you years later, maybe some sort of infection is (peripherally, maybe long after the fact) responsible for everything from depression to autoimmune problems like diabetes and arthritis, inflamations that produce blood clots around the heart, parkinsons, alzheimers or other deteriroration disease, etc. When somethings strikes the body randomly and unpredictably, I suppose it’s either cellular mutation or infection. Heck, 25 years ago stomach ulcers were believed to be psychologically induced. Some doctors still don’t credit neck vein blockage for MS. What’s astounding is how little we actually know about the human body. The easy answers, we’ve found. The rest of the questions are tough. ---
**Author:** ![DSeid](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/dseid/32/20194_2.png) [@DSeid](https://boards.straightdope.com/u/DSeid)\ **Post date:** [March 16, 2012, 3:41pm UTC](https://boards.straightdope.com/t/could-depression-be-an-autoimmune-disorder/560673/26 "2012-03-16T15:41:53Z")
> [@md2000](#): > > … The easy answers, we’ve found. The rest of the questions are tough. Meh. Those answers are only easy in retrospect. None of them were easy at the time. Not the op but I will offer [this](http://www.ediver.be/ediver/latest%20news/Depression's%20multiple%20comorbidities,%20Maes%20M.pdf) pdf up (published online 2011-02-25) as a review of the current support for the hypothesis: > [@](#): > > Depression’s multiple comorbidities explained by (neuro)inflammatory and oxidative & nitrosative stress pathways > > There is now evidence that depression, as characterized by melancholic symptoms, anxiety, and fatigue and somatic (F&S) symptoms, is the clinical expression > of peripheral cell-mediated activation, inflammation and induction of oxidative > and nitrosative stress (IO&NS) pathways and of central microglial activation, > decreased neurogenesis and increased apoptosis. This review gives an explanation for the multiple “co-morbidities” between depression and a large variety of > a) brain disorders related to neurodegeneration, e.g. Alzheimer’s, Parkinson’s > and Huntington’s disease, multiple sclerosis and stroke; b) medical disorders, > such as cardiovascular disorder, chronic fatigue syndrome, chronic obstructive > pulmonary disease, rheumatoid arthritis, psoriasis, systemic lupus erythematosus, > inflammatory bowel disease, irritable bowel syndrome, leaky gut, diabetes type 1 > and 2, obesity and the metabolic syndrome, and HIV infection; and c) conditions, > such as hemodialysis, interferon-α-based immunotherapy, the postnatal period > and psychosocial stressors. The common denominator of all those disorders/ > conditions is the presence of microglial activation and/or activation of peripheral IO&NS pathways. There is evidence that shared peripheral and / or central > IO&NS pathways underpin the pathophysiology of depression and the previously > mentioned disorders and that activation of these IO&NS pathways contributes > to shared risk … ---
**Author:** ![DSeid](https://sea3.discourse-cdn.com/straightdope/user_avatar/boards.straightdope.com/dseid/32/20194_2.png) [@DSeid](https://boards.straightdope.com/u/DSeid)\ **Post date:** [March 16, 2012, 4:08pm UTC](https://boards.straightdope.com/t/could-depression-be-an-autoimmune-disorder/560673/27 "2012-03-16T16:08:50Z")
Another [recent review](http://www.ncbi.nlm.nih.gov/pubmed/21110802) of the hypothesis (but full article not available free on line). > [@](#): > > The latest advancement in neurobiological research provided an increasing evidence that inflammatory and neurodegenerative pathways play a relevant role in depression. Preclinical and clinical studies on depression highlighted an increased production of inflammatory markers, such as interleukin (IL)-1, IL-6, tumor necrosis factor-α and interferon- α and γ. On the other hand, acute and chronic administration of cytokines or cytokine inducers were found to trigger depressive symptoms. According to the cytokine hypothesis, depression would be due to a stress-related increased production of pro-inflammatory cytokines that, in turn, would lead to increased oxidative and nitrosative brain damage and to indoleamine 2,3 dioxygenase (IDO) induction, with production of tryptophan (TRP) catabolites along the IDO pathway (TRYCATs) and consequent reduced availability of TRP and serotonin (5-HT). Cytokines would also play a role in the onset of the glucocorticoid resistance, underlying the overdrive of the hypothalamic-pituitary-adrenal axis. Therefore, the activation of the inflammatory and neurodegenerative pathways would lead to the brain damage observed in depression through both reduced neurogenesis and increased neurodegeneration. … **phouka** ’s thought has a lot to back it up and the concept may lead to both new medications to treat depression, and perhaps to investigations as to whether or not diets associated with decreased inflammation can reduce the risk of depression in at risk populations. [Previous page](https://boards.straightdope.com/t/could-depression-be-an-autoimmune-disorder/560673.md?page=1)