Stress management skills, cortisol awakening response, and post-exertional malaise in Chronic Fatigue Syndrome Daniel L. Hall a,∗, Emily G. Lattie a, Michael H. Antonia, Mary Ann Fletcherb, Sara Czajac, Dolores Perdomoc, Nancy G. Klimasb. Psychoneuroendocrinology (2014) 49, 26—31

 “Given the paucity of effective treatments for CFS, there is an ongoing search for potential intervention targets based on the limited understanding of the mechanisms that govern symptom expression.”

Noting the “paucity” of effective treatments and their “limited understanding” of its disease mechanisms, the authors didn’t pull their punches about how in the dark we are regarding understanding and treating Chronic Fatigue Syndrome.

One area we do pretty much understand about ME/CFS is cortisol – the subject of dozens of studies.  It’s pretty clear now that it’s the cortisol awakening response, not total cortisol levels, that’s primarily off in Chronic Fatigue Syndrome.

Low cortisol  has been associated with increased fatigue in ME/CFS. This  study determined whether it was also associated with PEM.

Low cortisol has been associated with increased fatigue in ME/CFS. This study determined whether it was also associated with PEM.

Since cortisol regulates several functions associated with energy production, it could play a role in the fatigue and post-exertional malaise seen in ME/CFS.  (Cortisol also suppresses the immune system, and regulates fat, protein, and carbohydrate metabolism.)  Studies do, in fact, indicate that lowered cortisol levels are associated with increased fatigue in ME/CFS, but nobody has looked at its association with post-exertional malaise until now.

Since stress management skill could take the pressure, so to speak, off a damaged stress response system and help it to function better – thereby increasing ones energy – the study authors also examined the participants’ perceived stress management skills (PSMS).

In all three hypotheses were tested:

  1. Higher cortisol awakening responses are associated with less post-exertional malaise(PEM) severity.
  2. Greater Perceived Stress Management Skills (PSMS) are associated with a higher cortisol awakening response.
  3. Greater Perceived Stress Management Skills increase the cortisol awakening response and reduce post-exertional malaise.

The Study

In this large study, the 117 participants took salivary cortisol samples upon waking and 30 minutes later, and they rated their perceived stress  management  skills  (PSMS) using the “Measure of Current Status” questionnaire. The PEM section from the CDC CFS Symptom Inventory was used to assess post-exertional malaise. Participants were asked to rate on two separate five-point scales the frequency (1 — A Little of the Time to 5 — All of the Time) and intensity (1 — Very Mild to 5— Very Severe) of ‘‘Unusual fatigue following exertion that lasts for at least 24 hours”.

This was a typical ME/CFS group: average age about 50 with 90% women who’d had ME/CFS for an average of about 7 years. Their major symptoms included PEM, muscle pain, cognitive difficulties, and unrefreshing sleep.


The finding that lower cortisol awakening levels were associated with greater post-exertional malaise suggested that low cortisol does play a role in the “payback” ME/CFS patients suffer from after exertion.

The study suggested that more skill at managing stress was associated with reduced (but still present) PEM  and higher cortisol.

The study suggested that more skill at managing stress was associated with reduced (but still present) PEM and higher levels of cortisol in ME/CFS.

The finding that higher Perceived Stress  Management Skills were associated with an increased cortisol awakening  response suggested that better stress management may increase cortisol  levels, which in turn reduces post-exertional malaise; i.e., stress management can help with PEM.

A recent study found that higher cortisol values are associated with improved health in ME/CFS.  This isn’t surprising in that cortisol is used for energy metabolism, and low cortisol is associated with reduced mitochondrial activity.

This study followed a similar one by the same group in 2012 which found that greater PSMS was associated with less emotional distress, greater diurnal cortisol slope, and reduced IL-2 levels. The fact that patients with high Il-6 levels received the most benefit suggested that researchers at some future time may be able to identify the patients mostly likely to improve using such techniques.

The Low Cortisol Inflammation Link


Studies suggest that lowered cortisol in ME/CFS is associated with increased levels of inflammation.

Because cortisol also helps shut down inflammation, low cortisol levels could result in increased inflammation – particularly after exercise.  Low cortisol could also contribute to the increased levels of pro-inflammatory cytokines some studies have found.  A modeling  study by the Klimas group recently found that women with ME/CFS were trapped in an “alternate homeostatic state” characterized by low cortisol,  high estradiol, and a Th2 immune balance.

Given the effects the immune system can have on mood, mood alterations might be expected in  low cortisol states and, in fact,  Subclinical hypocortisolism was associated with “dysfunctional mood states” in elite water polo players.

Stress Management Skills Normal – For the Chronically Ill

The ME/CFS patients were not particularly poor at Perceived Stress Management Skills: their PSMS scores were similar to those of people with cancer. It may be that stress management skills may be a good thing to have in a disorder with documented problems in both of the stress response systems (HPA axis and autonomic nervous system).

It’s also not true, in my understanding, that the cortisol levels in ME/CFS are particularly low; they’re simply a bit lower than normal. There is disagreement, however, about what constitutes “low” cortisol levels.  The same is true, by the way, with inflammation.  Although both findings, in general, are in the “mildly low” category, both can produce quite negative effects over time. Low levels of inflammation, for instance, affect disease progression in a variety of diseases.


People with ME/CFS with higher Perceived Stress Management Skills had higher cortisol levels and decreased PEM, as well as more immune issues.

It’s important to understand what this study did not suggest. It did not suggest that better stress management skills can cure ME/CFS  or remove post-exertional malaise (PEM). All the patients, whether or not they had high PSMS skills, still had ME/CFS.  The study simply suggested that more stress management skills are associated with improved cortisol and reduced (but obviously still present) levels of PEM in ME/CFS.

(A Lenny Jason study, on the other hand, suggested that while many ME/CFS patients can benefit from stress management skills and pacing, a subset of the more severely ill may not.)

The level of Perceived Stress Management Skills in patients with ME/CFS does not appear to be different from patients suffering from other chronic illnesses.


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