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.

sickness behavior

Infections cause sickness behavior but do they also set some people up for depression as well?

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.

The Study

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.

Biol Psychiatry. 2014 Feb 15;75(4):300-6. doi: 10.1016/j.biopsych.2013.09.023. Epub 2013 Oct 3.The epidemiologic evidence linking autoimmune diseases and psychosis. Benros ME1, Eaton WW2, Mortensen PB3.

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.

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.

A serious infection can have long lasting central nervous system effects in some people.

Even an vanquished infection can have long-lasting central nervous system effects in some people.

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.

breaking-chainInfections – 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


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