Alterations in morning cortisol associated with PTSD in women with breast cancer

doi:10.1016/S0022-3999(03)00561-0

Journal of Psychosomatic Research

Volume 56, Issue 1, January 2004, Pages 13-15

https://doi.org/10.1016/S0022-3999(03)00561-0 Get rights and content

Abstract

Objective

Diagnosis and treatment of breast cancer can be a stressful experience, putting women at risk of posttraumatic stress disorder (PTSD). The current study investigated morning cortisol levels in newly diagnosed (i.e., within 6 months) breast cancer patients.

Methods

Structured DSM-IV interviews determined current and past incidence of PTSD and major depressive disorder (MDD) in 71 women with Stage 0–3 breast cancer.

Results

Significantly decreased plasma cortisol was found in women meeting current or lifetime criteria for PTSD or past diagnosis of MDD.

Conclusions

These results reinforce the importance for both psychological and physiological outcomes of a clinical evaluation of both current and past psychiatric status in newly diagnosed cancer patients.

Introduction

Although a diagnosis of posttraumatic stress disorder (PTSD) requires exposure to an extreme traumatic stressor, surprisingly large percentages of the population have been exposed to traumatic events. Resnick et al. [1] found that approximately two thirds of women in the United States had experienced a significant traumatic event, with PTSD prevalence rates of 12.3% lifetime diagnosis and 4.6% current diagnosis. Recent research has found symptoms of PTSD in women with breast cancer, and estimates of the prevalence of PTSD in newly diagnosed patients range from 3% to 10% [2], [3]. Elevated symptoms of anxiety and depression near the time of diagnosis are also common and have been reported in 30% to 40% of patients [4]. Although few studies of the prevalence of clinically diagnosed major depressive disorder (MDD) have been reported, Dausch et al. [5] found prevalence rates of 6.7% for a current diagnosis and 23% for a lifetime diagnosis in women newly diagnosed with breast cancer.

The level of emotional distress of breast cancer patients may have physiological consequences relevant to cancer [6]. Numerous investigations have shown cortisol and immune alterations associated with distress. Neuroendocrine function can be influenced by a variety of genetic or environmental factors, including trauma exposure. In noncancer populations, lower cortisol has been associated with PTSD [7]. In contrast, increased cortisol has been associated with MDD, although decreased cortisol has been reported in “atypical depression” [8]. Variations in cortisol levels can directly impact neoplastic growth and immune parameters (e.g., T-cell proliferation) relevant to the progression of breast cancer, suggesting that psychological factors that influence immune function may also influence cancer outcomes [6].

This study evaluated cortisol levels associated with PTSD and MDD in women newly diagnosed with breast cancer. Women with MDD were expected to show elevated cortisol relative to those with no diagnosis. In contrast, women with PTSD were expected to show lower cortisol. High rates of comorbid PTSD and MDD have been found [9]; thus, it was anticipated that women with PTSD would show high rates of comorbid MDD.

Section snippets

Participants

Participants included 71 women (age 34–82, mean 53; 98% Caucasian) newly diagnosed (i.e., within the last 6 months) with breast cancer. The sample included women participating in a larger study of psychosocial intervention. Data reported represent preintervention measures. Cancer stage at diagnosis included 14% Stage 0 (in situ), 38% Stage 1, 42% Stage 2, and 6% Stage 3.

Measures and procedure

PTSD and MDD prevalence were determined with structured DSM-IV diagnostic interviews developed as an adaptation of the DSM-IV

Rates of PTSD and MDD in the sample

Current or past PTSD was diagnosed in 18.3% of the women (5.6% current, 12.7% past). Diagnoses were attributable to abuse or assault (57%), the diagnosis and treatment of breast cancer (15%), witnessing a death (14%), or other causes (13%). Comparable to previous studies, 3% of women in the entire sample met criteria for current PTSD due to breast cancer. No women met criteria for a current diagnosis of MDD, although a past diagnosis was found in 25%. A high level of comorbidity was found; 39%

Discussion

A diagnosis of PTSD (current or past) was found in 18% of women in this sample of newly diagnosed breast cancer patients. Psychobiological correlates were evident, including lower cortisol in women with current or past PTSD. The number of PTSD symptoms endorsed was negatively correlated with cortisol, suggesting that the amount of HPA disruption varies with the severity of the PTSD symptoms experienced. Surprisingly, cortisol levels did not differ between women with a current or a past

References (16)

BL Green et al.
Prevalence of posttraumatic stress disorder in women with breast cancer
Psychosomatics
(1998)
JJ Hudziak et al.
The use of the DSM-III-R checklist for initial diagnostic assessments
Comp Psychiatry
(1993)
ML Laudenslager et al.
Elevated cytotoxicity in combat veterans with long-term post-traumatic stress disorder: preliminary observations
Brain Behav Immun
(1998)
HS Resnick et al.
Prevalence of civilian trauma and posttraumatic stress disorder in a representative sample of women
J Consult Clin Psychol
(1993)
MA Andrykowski et al.
Posttraumatic stress disorder after treatment for breast cancer: prevalence of diagnosis and use of the PTSD Checklist-Civilian Version (PCL-C) as a screening instrument
J Consult Clin Psychol
(1998)
JE Epping-Jordan et al.
Psychological adjustment in breast cancer: processes of emotional distress
Health Psychol
(1999)
Dausch BM, Compas BE, Luecken LJ, Anderson-Hanley C, Sherman M, Grossman C. Rates and Correlates of DSM-IV Diagnoses in...
LJ Luecken et al.
Stress, coping, and immune function in breast cancer
Ann Behav Med
(2002)

There are more references available in the full text version of this article.

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Being diagnosed with and treated for cancer is highly stressful and potentially traumatic. An extensive literature has evaluated the prevalence, predictors, and correlates of cancer-related post-traumatic stress disorder (PTSD) symptoms and diagnoses. In this qualitative review of cancer-related PTSD literature, we highlight conceptual, methodological, and diagnostic issues, and identify clinical implications and areas for future research. Cancer-related PTSD has been documented in a minority of patients with cancer and their family members, is positively associated with other indices of distress and reduced quality of life, and has several correlates and risk factors (eg, prior trauma history, pre-existing psychiatric conditions, poor social support). The literature on treatment of cancer-related PTSD is sparse. Existing literature on cancer-related PTSD has used DSM-IV-TR diagnostic criteria; the revised DSM-5 PTSD criteria have important implications for the assessment of cancer-related distress. Application of PTSD diagnosis to patients with cancer has been critiqued on conceptual and methodological grounds, and important differential diagnosis considerations should be taken into account. Psychosocial assessment of patients with cancer should include careful evaluation of pre-cancer diagnosis trauma and psychiatric history, and diagnostic interviewing should consider concurrent conditions (eg, adjustment disorder). Treatment of cancer-related PTSD should be approached with caution and be informed by existing evidence-based approaches for traumatic stress.
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However, as a host of calculations exist in the extant literature of cortisol rhythm and overall output [14], we included 5 cortisol output calculations in addition to ICV (described below) which are commonly reported. Specifically, given their previously reported relationship with psychosocial factors in cancer populations, we chose to calculate the following: 1) cortisol slope [33], 2) evening cortisol [23], 3) morning cortisol [22], 4) the cortisol awakening response [24] and 5) total cortisol area under the curve (with respect to ground [30]). This approach to aggregating data has been shown to increase the reliability of cortisol data [21].
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View full text

Alterations in morning cortisol associated with PTSD in women with breast cancer

Abstract

Objective

Methods

Results

Conclusions

Introduction

Section snippets

Participants

Measures and procedure

Rates of PTSD and MDD in the sample

Discussion

Psychosomatics

Comp Psychiatry

Brain Behav Immun

Prevalence of civilian trauma and posttraumatic stress disorder in a representative sample of women

J Consult Clin Psychol

Posttraumatic stress disorder after treatment for breast cancer: prevalence of diagnosis and use of the PTSD Checklist-Civilian Version (PCL-C) as a screening instrument

J Consult Clin Psychol

Psychological adjustment in breast cancer: processes of emotional distress

Health Psychol

Stress, coping, and immune function in breast cancer

Ann Behav Med