Diurnal Cortisol
Patterns and Psychological Stress:
Relationships in Cancer Progression
Project Description
Physical, emotional, and mental stress all initiate a cascade of physiological events to help our bodies prepare for immediate stress, as well as long-term recovery. This is accomplished by the activation of the hypothalamic-pituitary-adrenal (HPA) axis. This process is the stress response, and its products are epinephrine, norepinephrine, and cortisol. Cortisol is a hormone produced by the adrenal cortex that helps the body adapt and recover from long-term stress; it is therefore appropriately referred to as a stress hormone and is most often used as the biological measure of stress.
Free cortisol levels in the saliva and blood have been shown to be a direct marker of an increase in overall cortisol production in times of stress in normal subjects. Studies have found that cortisol levels increase with the severity of the stress (Kirschbaum, et al 1992; Nelson, et al 2003; Wuest, et al 2000). Malarkey et al (1995) found that subjects that report the most perceived psychological distress from an imposed stress exhibited the largest increases in serum cortisol levels. In other words, those that were least able to cope with the stress showed the most exaggerated physiological response. This finding, as well as common sense, leads one to believe that if a stressor is unanticipated and the individual is unable to prepare for it, the resulting stress response may be more dramatic. In this study, stress will be assessed using the Perceived Stress Scale (Cohen, Kamarck, & Mermelstein, 1983). and the Taylor Manifest Anxiety Scale (Bendig, 1956). These batteries were chosen because they address the participants own perception of their stress levels, and actual physical manifestations of stress. Both have been shown to reliable and valid.
The diagnosis of cancer is a sudden, heart-wrenching situation that that no one is able to prepare for. As such, it brings about intense levels of distress. The public views cancer as a killer and the first association that is made with the term “cancer” is death. In addition to the stress of the initial diagnosis, physical and emotional strains are caused by repeated, aggressive, and prolonged cancer treatments. The occurrence of cancer has been recently described by many investigators as an event that fulfills the DSM-IV criteria for a “traumatic event” that has been demonstrated in some cases to be linked with the subsequent development of post-traumatic stress disorder (PTSD; Luecken & Compas, 2002). Yehuda (2003) also found that the neuroendocrine alterations observed in PTSD are similar to those found in cancer. This finding lends credence to the idea that stress is involved in the etiology and progression of cancer.
Neuroendocrine abnormalities
associated with cancer and PTSD have been compared to those seen in depression.
Spiegel and Giese-Davis (2003) report several
psychophysiological
mechanisms that link depression and cancer progression, namely dysregulation of
the hypothalamic-pituitary-adrenal axis. This causes diurnal variation in
cortisol and melatonin in those suffering from depression, as well as in cancer
patients. Another similarity these diseases share is the symptom of sleep
disturbance (Koopman, et al,
2002). A decrease in the amount or quality of sleep can increase cortisol
levels, and thus potentially affect the immune response and the course of
disease. Researchers believe sleep disturbance to be a symptom of an underlying
neuroendocrine alteration related to both cancer and depression
(Blackburn-Munro & Blackburn-Munro, 2001; Koopman et al., 2002).
Cancer victims also demonstrate an
increased basal cortisol level, as well as an exaggerated physiological
response to stress. This was displayed by significantly higher levels of
cortisol released by the activation of the HPA axis following a stressor in
cancer patients than in healthy controls (Mazzoccoli, et al, 2003;
Porter, Mishel, et al, 2003). This recent research has linked exposure
to chronic stress (such as dealing with cancer) to altered acute stress
responses and suggests a sensitizing effect of chronic stress, leading to a
stronger endocrine and cardiovascular response to acute stressors (Gold, et
al, 2003). These increased levels of circulating cortisol actually have a
down-regulating effect on the immune system, including components of immune
function that participate in cancer surveillance (i.e. antigenic processes) and
eradication (Brunda et al, 1993; Spiegel & Giese-Davis, 2003). In addition,
cortisol produces a suppression of T1-helper (Th1) cells (Elenkov et al,
1996), whose response may be most important to antitumor immune responses
(Brunda et al., 1993). Septhton et al (2003) showed that cancer-stricken
subjects who displayed the typical declining pattern of cortisol levels from
morning to evening had better survival (60%) versus individuals whose slopes
had patterns of slower declines, abnormally timed peaks, or increasing levels
during the day (77%). I hypothesize that the reason prior studies have found that abnormal
diurnal variation of cortisol predicts mortality is due to cortisol’s direct
suppression of Th1 cells. Th1 cell activity has been found to have a circadian
rhythm, in which activity peaks in the evening (Petrovsky, 2001). However,
since cancer victims tend to have increased evening levels of cortisol, the
activity of the Th1 cells (the very cells that have the most antitumor
properties) is suppressed during the time they would normally be most active.
This opposite variation and obvious connection was not stated in any of the
studies that tested the circadian rhythm of cortisol in cancer patients.
In combination, these studies provide suggestive evidence of the adverse effects of stress on endocrine (i.e. cortisol) and immune responses. No research, to my knowledge, has explored whether the alteration of cortisol’s circadian rhythm variation plays a role in the progression of non-hormonally mediated cancers. The premise of the currently proposed study is to test the following hypotheses: Subjects who report a higher level of perceived stress will show an abnormal diurnal cortisol variation; the stage of cancer will have an effect on cortisol variation and stress assessment; and subjects who exhibit more abnormal cortisol patterns will experience comparatively accelerated cancer progression.
I am
a senior at
Specifically for this project, I believe my own personal experience with cancer will enable me to have and express empathy and gratitude to my participants and truly grasp the subject matter I am dealing with. My goal is not to be a removed “investigator”, but to truly make a contribution to the field of Psychooncology and share my findings with as many as possible of the 1.2 million Americans that will be diagnosed with cancer this year (American Cancer Society, 1998).
The sample pool will be a heterogeneous group of volunteers that have been diagnosed with cancer. Cancer types, location, and stage of the disease will vary. Large amounts of studies researching the stress-cancer relationship have tended to sample middle-aged, middle-class female breast cancer patients. To have increased external validity, it is pertinent to have a more diverse group of subjects with cancer.
March 1: Purchase cortisol assay kits.
March 8-10: Approximately twenty-five participants
will be recruited from the Cancer Wellness House in
April 5-7: All the same measurements will be gathered in the same procedure once again to test for any change over one month’s period in diurnal cortisol variation and/or stress. At this time, subjects will be asked if their condition has improved, stayed the same, or worsened.
April 12-25: Analysis of data: The degree to which their diurnal cortisol pattern varies from that of a healthy individual will be recorded and associated with their results from the questionnaires. A 4(stages of cancer) x 2 (times of testing) factorial MANOVA will be used to test for effects on diurnal cortisol variation and stress assessment.
April 26-30: The findings of this study will be presented to the Psychology Department.
I also plan on presenting the results of this study at a regional or national conference during fall of 2004, and if the results merit they will be submitted for publication to a regional or national journal.
Item Cost Quantity Total Funds
Needed
AM/PM Diurnal $60.00 50 $3000.00
Cortisol Test
Product # CD82530X2
Rationale for requested supplies: Since this study is assessing altered circadian rhythms of cortisol secretion, it is mandatory to use an assay that has a test for both AM and PM measures. Also, in order for this study to be statistically reliable, a minimum of 25 subjects must be used.
References are available for above citations upon request.