Abnormal levels

From: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730359/">The associations between basal salivary cortisol and illness symptomatology in chronic fatigue syndrome</a>

Those participants rated to be ‘abnormal’ in their daily cortisol pattern self-reported higher mean levels of fatigue (m=80.51) when compared to individuals with normal cortisol levels (m=70.46). The η2 = .08, indicating that group membership accounted for 8% of the variance in the fatigue severity measure.

Contrary to what was hypothesized, cortisol mean, cortisol slope, or abnormal cortisol levels were not related to neurocognitive symptoms, psychiatric status, or sleep difficulties. Regarding neurocognitive levels, although some analyses approached significance, there were no statistically significant associations between cognitive functioning, as measured by a brief cognitive testing battery, and baseline salivary cortisol levels. These non-significant findings contrast with <a id="tag_223092392" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730359/#R42">Sephton and colleagues (2003)</a>, who found associations between cortisol and memory functioning in a group of fibromyalgia patients. However, differences between the two studies may be due to the fact that the current investigation and the <a id="tag_223092376" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730359/#R42">Sephton et al. (2003)</a> study sampled from CFS and from fibromyalgia, respectively, two overlapping but distinct patient groups. Second, the current investigation did not measure salivary cortisol levels on the same day that the neurocognitive measures were administered, and it is possible that examining the concordance of cortisol levels and neurocognitive functioning at the same time might yield associations that occur on a daily or even hourly basis. However, it is also possible that salivary cortisol levels and general neurocognitive functioning are not directly associated in CFS.

In addition, cortisol levels were not associated with psychiatric status, as measured by either a history of or current diagnosis of depressive disorder or PTSD; or with current depression and anxiety. CFS frequently co-occurs with depression (<a id="tag_223092379" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730359/#R37">Parker, et al. 2001</a>). However, past or current depressive disorder was not associated with changes in baseline cortisol. One reason for a lack of association might be that the type of depression experienced in CFS may be different than individuals with a primary depressive disorder, such as melancholic depression. For instance, CFS patients have been found to be less likely to endorse the self-reproach items of the Beck Depression Inventory, and were more likely to endorse items indicating somatic complaints of depression (i.e. sleeplessness, appetite/weight change) that are confounded with the symptoms of CFS (<a id="tag_223092369" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730359/#R22">Hawk, Jason, & Torres-Harding, 2006</a>). Similarly, there was no difference in cortisol levels with individuals with a history of current or past post-traumatic stress disorder. However, given than both CFS and PTSD are associated with low levels of cortisol and hypofunctioning of the HPA axis, it is possible that further exacerbations or alterations in hypercortisolism could not be obtained if one had both CFS and history of PTSD when compared to having CFS only.

Finally, there were no statistically significant associations between sleep difficulties and cortisol levels in CFS. This finding was unexpected, given the severe disruptions in sleep patterns that some with CFS report. These individuals frequently report a great deal of variability in their wake-up times, and it might be expected that this could alter the diurnal pattern of cortisol secretion. However, when looking at all overall production (mean), change over the course of the day (slope), and the overall normality of the pattern of salivary cortisol, as judged by a study physician, no association was found. <a id="__tag_223092393" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730359/#R6">Buckley & Schatzberg (2005)</a>suggest that nighttime awakenings may be associated with increased pulsative cortisol levels, but that night time awakenings might not have any impact on awakening cortisol levels. In addition, it is possible that measuring alterations in cortisol levels during the daytime may not capture nighttime levels, which may be more affected by sleep disruptions. In addition, this study only measured overall sleep quality, and cortisol production may be associated with specific aspects of sleep dysfunction, such as the duration of slow-wave sleep.

Potential limitations of this study included the fact that this study measured only baseline cortisol over the course of one day, and there may have been inter-individual variability that was not measured due to this sampling methodology. However, when measuring between-subject variability, <a id="__tag_223092359" class=" bibr popnode tag_hotlink tag_tooltip" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730359/#R47">Stone et al. (2001)</a> found consistency of results among different sampling protocols of salivary cortisol measurement, and the sampling protocols in their set of studies varied from 1 day to 24 days. Thus, it is expected that the use of between-subject comparisons in the current investigations over the course of one day is appropriate. Second, <a class=" bibr popnode" href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2730359/#R8">Cleare (2003)</a> noted that examining activation of the HPA axis after exposure to stress may yield important information about HPA functioning in CFS; however, HPA axis reactivity after stress could not be inferred from the current study, as only baseline cortisol measurement was employed. Another limitation was that the salivary cortisol measurements and the other measures were not sampled on the same day, and sometimes there was a span of days or weeks between cortisol sampling and completion of the other measures. Thus, direct concordance in time between salivary cortisol and other physiological variables, such as neurocognitive functioning, could not be measured, and no direction of causality could be established. Finally, due to the number of analyses conducted, the likelihood of obtaining a Type 1 error might have increased. In order to minimize the likelihood of Type 1 error, significance level was set at the p=.01 level. However, the analyses presented in this investigation should be considered exploratory, and replication of these results in other samples of people with CFS would lend support to the validity of these findings.

In summary, baseline levels of salivary cortisol appeared to be associated with illness parameters in CFS, including fatigue severity and pain. These findings are particularly important, given that fatigue and pain are two of the hallmark symptoms of CFS. These findings are consistent with the hypothesis that hypocortisolism may underlie some of the frequently reported aspects of CFS. Future research should focus on delineating the connections between available cortisol levels and potential effects on neurological and immunological systems. In addition, attention needs to be paid to those individuals who exhibit diurnal dysregulation of cortisol as these individuals may be the ones most likely to experience significant CFS symptoms of fatigue and pain.