We know that many cases of fibromyalgia and chronic fatigue syndrome (ME/CFS) start with an infection and that those infections result in what is called “sickness behavior”. The fatigue, pain, difficulty concentrating, problems with sleep and apathy found during an infection, are intended to force an individual to withdraw from society and stop spreading an infection.
We know that higher than normal rates of mood disorders (for a chronic illness) are present in ME/CFS and FM and that ME/CFS, FM and depression, share many symptoms that are associated with sickness behavior.
That brings up the question where the immune system fits in. Could it be causing or contributing to the elevated rates of mood disorders seen in FM and ME/CFS? Is it causing mood disorders found outside of ME/CFS and FM? Could depression in some cases, be just a case of sickness behavior that never lets up?
The very large study below doesn’t answer the questions about ME/CFS and FM but it does help to clarify the immune systems role in producing neuropsychiatric symptoms like depression. The study asks if having a significant immune response; i.e. a serious infection or an autoimmune disorder increases ones risk of becoming depressed.
That’s a very interesting question given the high incidence of infection triggered ME/CFS and FM and the high rates of mood disorders found in both illnesses.
Autoimmune diseases and severe infections as risk factors for mood disorders: a nationwide study. Benros ME, Waltoft BL, Nordentoft M, Ostergaard SD, Eaton WW, Krogh J, Mortensen PB. JAMA Psychiatry. 2013 Aug;70(8):812-20. doi: 10.1001/jamapsychiatry.2013.1111.
The study involved tracking the history of 3.5 million people visiting Danish hospitals (normal and psychiatric) between 1977 and the end of 2010. It examined the incidence of psychiatric diagnoses and severe infections (sepsis, central nervous system infections, urogenital infections, etc. ) and thirty types of autoimmune disorders. It asked whether having visited a hospital for an infection or autoimmune disorder increased one’s risk of being diagnosed with a mood disorder later.
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The study calculated what’s called an incidence rate ratio (IRR). An IRR of 1.0 would mean there’s no increased risk of getting diagnosed with a mood disorder after visiting a hospital for an infection. An IRR of 2.0 would mean a doubling of your risk.
Overall the study indicated that having an infection or an autoimmune disorder increased one’s risk of being diagnosed later with a mood disorder by about 50%.
Infections had the most significant impact. Simply being seen in the hospital for a serious infection increased one’s risk of being diagnosed with a mood disorder by 62%. Prior to being diagnosed with a mood disorder, thirty-two percent of individuals had been seen in the hospital for a serious infection. That’s an amazing figure, given that, unlike autoimmune disorders, most infections are time-limited – people do get over them. The initial inflammatory response associated with an infection appears to be uniquely powerful.
This result, of course, brings to mind the Dubbo study findings which indicated that a wide variety of infections trigger ME/CFS in about ten percent of individuals. Just as in the Dubbo studies, this study suggested that severe infections that produce more inflammation are more likely to result in later illness (i.e. a mood disorder). (Infection severity and cytokine levels early in an infection were the only factors found in the Dubbo studies that significantly predisposed individuals to coming down with ME/CFS. Having a prior mood disorder, interestingly enough, does not).
Being seen in the hospital for multiple infections significantly increases one’s risk of subsequent mood disorders, in a dose-response manner. If you were unlucky enough to have to go to the hospital five times for an infection your risk of being diagnosed with a mood disorder later goes up fivefold. The study suggested that 12% of all mood disorders might be avoided if an initial infection had never occurred.
Getting an autoimmune diagnosis increases ones risk of having a mood disorder by about 45%. That mostly time-limited infections puts one at greater risk of having a mood disorder than an ongoing autoimmune process, is intriguing to say the least.
The risk of being diagnosed with a mood disorder is highest in the year or two following a diagnosis with an autoimmune disorder. Having an autoimmune disorder that produces autoantibodies known to effect the central nervous system, increases one’s risk more.
Having a history of two significant immune events; an infection and an autoimmune disorder almost doubled the risk of being diagnosed with a mood disorder later. A person with an infection and Sjogren’s Syndrome was 2 1/2 times more likely to come down with a mood disorder later.
An examination of timing indicated that the risk of being diagnosed with a mood disorder is significantly higher in the year after being diagnosed with an autoimmune disorder, perhaps because of the high rate of inflammation present.
Exactly how inflammation in the body is increasing the risk for mood disorders is not clear but possibilities exist. Increased rates of inflammation could be damaging the blood brain barrier – allowing cytokines and infectious agents entry into the brain. Inflammation can also disrupt serotonin and glutamate activity via the tryptophan kynurenine pathway. Microglia sensitized by the initial immune reaction may be putting out sickness-behavior producing chemicals at the slightest signs of stress.
The Long Arm of the Immune Response
Many people with ME/CFS and FM vividly know how infections can change everything from functioning, to cognition, to mood. The research community is finally waking up to the fact that infections are not necessarily time-limited affairs but can have long term health consequences.
Infections – even when the virus or bacteria is apparently vanquished – can have life-changing consequences. Being exposed to giardia in ones drinking water repeatedly, has life-altering effects for some. Infectious mononucleosis increases the risk of ME/CFS in the short-term and multiple sclerosis in the longer term. Cytomegalovirus infections were recently shown to result in an extraordinary amount of immune system remodeling -even in the healthy. Hepatitis C infections bring with them an increased risk of encephalopathy, myelitis, encephalomyelitis and depression, anxiety and fatigue.
The Ebola outbreak is highlighting this fact. Vincent Raccanielo recently posted the outcome of a study examining survivors of an earlier outbreak in his Virology blog.
The results show that survivors of Bundibugyo ebolavirus infection are at significantly greater risk than controls for long term health problems. These include ocular problems (pain, blurred vision), loss of hearing, sleep difficulty, and joint pain. Other issues are abdominal and back pain, fatigue, impotence, severe headaches, memory problems and confusion. No differences in results of blood analyses were observed between the two groups.
If they’d encountered a flu instead of one of the most dangerous viruses in the world, and these symptoms lingered, the survivors would have undoubtedly been accused of being malingerers, and not worthy of study. The post viral consequences of Ebola are getting some press because it was Ebola, but it’s clearly not necessary to encounter an Ebola-like virus to have serious after-effects. The common cold will do quite nicely at times.
The research community has a long, long way to go to catch up to the possible long-term consequences of infection. Some progress is being made. A recent review identified three ways ( activation and expansion of self-reactive T and B cells, lower threshold for self-tolerance breakdown, and enhanced autoreactive B-cell survival) an Epstein-Barr infection might increase one’s risk of coming down with multiple sclerosis later in life.
Much, much more research is needed. The real breakthroughs will occur when the specific processes occurring during infection or autoimmunity that produce often lifelong struggles with fatigue, depression, pain, etc. are identified.
- Up on the Health Rising Forums – Have you been diagnosed with a mood disorder? If so was it before or after you got ME/CFS or FM. Take the The Fibromyalgia and ME/CFS Mood Disorders Poll here.
- Next up – Anti-inflammatory Sparks A Renewal in an ME/CFS Patient
I Was diagnosed major depression cfs and fibro nu prof maes . Bloodtest shows antibodies against serotonine
There you go – antibodies hitting your serotonin…
I use 1500mg of Source Naturals Tryptopthan for low serotonin, it seems to improve mood and raises melatonin levels at night, which definitely improves my sleep.
I completely concur. The other part of the picture, is that many of us were high, type A achievers, and athletes in our former lives. I was a personal trainer, fitness instructor and soccer coach. I can still dance, but can’t afford classes due to having to survive on Disability. Sickness itself is depressing – knowing that it may stick around forever is doubly depressing!
The other side of this issue is the social alienation of having a disease that, in America, most DOCTORS do not even recognize! Most of us look perfectly normal. Recognition is a MAJOR ISSUE in this country – where many of us are accused of being hypochondriac, phsychotic, self absorbed or just plain lazy.
Aly: My theory is the reason many of us with this illness may look perfectly normal (healthy) is that we are not sick in the conventional way that doctors think of sickness. Our immune systems are not failing. We are not down-regulated and prone to illnesses of a less-than-optimal immune system, such as cancer, diabetes, viruses, or infections. Our bodies are actually over-performing, sending out far too many disease fighting proteins, against agents, that are often considered harmless. The vast majority of people don’t possess this innate, exaggerated immune response. We, unfortunately, keep sending out disease fighting chemicals, long after the battle is over. This constant immune system activation lends us to feel very ill.
Indeed. We’re almost done with a program to help with this….
Although I don’t believe chronic infection plays a central role in CFS, I thought this 2014 paper on infection / Vitamin D / autoimmunity was quite interesting:
Thanx for this cort. Am really looking forward to your upcoming blog on the use of anti inflammatories as I’ve found them useful. I take slow release voltaren 75 mg. I’ve recently found out that adding Celebrex to antidepressants increases their response so I thought that was why I’d been helped. I still have the ME but it’s not as bad. I think LDN and adding voltaren to Prozac has shifted the illness. I used to be terrible in the mornings , now not so bad, but by late arvo I’m toast. I still get the glands and the throats and the attacks of wonkiness ( which are prob orthostatic issues), so it’s hard to say whether I’m ‘better’ but the despair doesn’t hit so badly, that’s despite having a bedridden partner for whom the NSAIDs helped but then he became allergic and he’s progressed to being totally dependent. I got a dr free sample pack of Celebrex as its unfounded in NZ, and that worked much better. They are saying that depression is now inflammation in the brain. I just want my partner to get onto something that might help him. Are there any other anti inflammatory meds that aren’t NSAIDs ???
There may be two very different reasons for sickness behavior. One form of sickness behavior may be the result of a poor-functioning, inferior immune system, which is chronically activated because it cannot defeat a virus, or infection. This immune system keeps trying , but just isn’t successful at sending out enough fighters to defeat an invader – a slow, but constant burn – trying hard, but not succeeding.
The other form of sickness behavior is more likely the result of an immune system, that just doesn’t know when to quit. This immune system is always on high alert and quickly defeats viruses, and infections, but tends to over-react to just about everything else in the environment (chemicals etc). This type of immune system is in a perpetual state of activation against things most immune systems wouldn’t even notice.
I suffer from the second type of sickness behavior, which I believe is an autoimmune illness. My superior, but truly annoying immune system is in a constant state of activation against anything, and everything it believes is a threat to my body. It just never lets up.
I just had to laugh at your “superior but truly annoying immune system” 🙂 🙂
Seems to me common sense would tell you that being ill with a disease that’s unacknowledged by most doctors; that has no chance of being cured; of living a socially isolated life; of being unable to pursue activities one loved in ones “former life” would equal depression. I led an extremely active life before ME (40+ years ago), but now can do nothing. Just 5 minutes on my elliptical machine recently, put me “to bed” for 2 weeks. I was a positive person who looked forward to doing all sorts of wonderful things of which I can not “do” a one! Depression is a given!
Yes, indeed it is…Or rather I think at least a subclinical form of depression is a given. I think that’s almost inescapable. Whether inflammation is adding to it in a substantial number of cases – I’ll bet it is.
Again, I take issue with the term “sickness behavior” when referring to SYMPTOMS. A behavior is something we can choose, a symptom is not. When this terminology coined by sociologists and psychologists goes unquestioned it should be no surprise that those schools perpetuate the idea that ME/CFS is a somatoform or psycho-social disorder, the CBT, GET, and anti-depressants are all that is offered to us by the medical establishment. If we join this chorus there will be no funding for bio-organic research that we need. Please stop perpetuating that phrase! Re-phrase it if you must in your articles.
Sorry for the scolding, but again my mantra is “I will accept the term ‘sickness behavior’ for ME/CFS when it is equally used to describe coughing in COPD and clutching the chest in heart attack.”
Have you looked sickness behavior up? It’s not coined by sociologist and has nothing to do a somatoform condition – and contrary to the usual meaning of “behavior” it is not under our control. Instead it’s a well recognized response to an infection that is driven by pro-inflammatory cytokines produced by the immmune system. In fact it’s now clear that none of the symptoms we associate with colds are caused by the pathogen per se; they are all produced by an immune system that is bent on making an individual so miserable that they take to bed and stop interacting with others – and hence stop spreading the infection.
It has nothing at all to do with CBT or GET….
“The behavioral repertoire of humans and animals changes dramatically following infection. Sick individuals have little motivation to eat, are listless, complain of fatigue and malaise, loose interest in social activities and have significant changes in sleep patterns. They display an inability to experience pleasure, have exaggerated responses to pain and fail to concentrate. Proinflammatory cytokines acting in the brain cause sickness behaviors. These nearly universal behavioral changes are a manifestation of a central motivational state that is designed to promote recovery. ”
Lipopolysaccharides trigger the immune system to produce proinflammatory cytokines IL-1, IL-6, and tumor necrosis factor (TNF). These peripherally released cytokines act on the brain via a fast transmission pathway involving primary input through the vagus nerves, and a slow transmission pathway involving cytokines originating from the choroid plexus and circumventricular organs and diffusing into the brain parenchyma by volume transmission. Peripheral cytokines may enter the brain directly. They may also induce the expression of other cytokines in the brain that cause sickness behavior.[20
I appreciate so much the research you do, how you find the bio-organic roots of the history of this term–for it’s there–yet “sickness behavior” is an unfortunate choice of words. I have looked at the history of the phrase, from the first time it irked me, and it’s there that I find the slippery slope toward social and psychological interpretation that concerns me. The intentions of those who coined it are well and good if everyone reads the fine print, but terms are short-hand, and that’s where the problem with “sickness behavior” comes in.
In the Century of Freud, as someone has called it, choosing “behavior” as part of any terminology is loaded. Looking up “behavior” in my Thesaurus, the three classifications of synonyms it offers are “conduct,” “action,” and “way.” There is no mention of “symptoms” in the major synonym classifications nor the full listings of related synonyms for “behavior.” Synonym classifications for terms using “behavioral” include sociology, psychological theories, social environment, study of conduct, anthropology. Looking up “symptom,” the main classifications are “signs,” “indication,” “prediction,” “concomitant,” “forewarning,” and “manifestation.” If those who coined “sickness behavior” had chosen “sickness signs,” “sickness indicators,” or “sickness manifestations” it would have been more based in observation, medically dispassionate.
Where you wisely see a term related to a pathogenic process, the average person will know that “behaviors” are what “behavioral scientists” study. The preponderance of use skews the meaning, even if the intentions for coining the term were otherwise. And that seems unscientific at least, and for our population perhaps harmful. Someone curious about the term may turn first to Wikipedia, where it says:
“Sickness behavior is a coordinated set of adaptive behavioral changes that develop in ill individuals during the course of an infection. They usually (but not necessarily) accompany fever and aid survival. Such illness responses include lethargy, depression, anxiety, loss of appetite, sleepiness, hyperalgesia, reduction in grooming and failure to concentrate. Sickness behavior is a motivational state that reorganizes the organism’s priorities to cope with infectious pathogens. It has been suggested as relevant to understanding depression, and some aspects of the suffering that occurs in cancer.”
“Motivational state” links to:
“Motivation is a theoretical construct used to explain behavior. It represents the reasons for people’s actions, desires, and needs. Motivation can also be defined as one’s direction to behavior or what causes a person to want to repeat a behavior and vice versa. A motive is what prompts the person to act in a certain way or at least develop an inclination for specific behavior. For example, when someone eats food to satisfy the need of hunger, or when a student does his/her work in school because he/she wants a good grade. Both show a similar connection between what we do and why we do it. According to Maehr and Meyer, “Motivation is a word that is part of the popular culture as few other psychological concepts are”. ”
“Sickness behavior” does not have to be the term used to describe this concept. The idea of “reasons for people’s actions” suggests that we can “reason” them, and that’s where I think we have SYMPTOMS rather than behavior; we can’t reason with our symptoms as much as most of us have tried! Using the word “behavior” muddies the waters rather than clarifying them–not unlike the word “stress” which can refer to exercising to exhaustion at Pacific Fatigue Lab or the mental state of feeling pressure from an outside source, a response that can be conditioned as well as reconditioned through therapy.
Cort, I am so very grateful that you see the strengths in so many approaches, and I depend on you for that. I take no issue with your analysis of the study, yet maybe this discussion puts into words an unease that others feel when they this term and wonder if we have to embrace it. Our narrative makes a difference in the trajectory of our story. Language matters.
Well, I must take some of my own medicine! Language does matter–and today I see that when I wrote yesterday my language was angry, blaming, and polarizing. You don’t need that energy slung your way. Please accept my apologies and gratitude rather than animosity. We’re on the same team!
I also agree that “sickness behavior” isn’t justified for our group. The implication is wrong. With all due respect, of course!
Hello Cort, sorry my english is not so good but can you tell me what blood test I need to find if I have this problem. I was diagnosed EM in 1999. Know I cannot work anymore. A had HHV-6, Einpstein-Barr, Cytomegalovirus, my IGA are high and many more infections.
Thank you for your help
It sounds like you had some good tests Marie-Josee…I think you need to find a really good doctor (??).
What kind of specialist do you recommend?