Psychobiological Concomitants: Bereaved Women at Br Ca Risk

Institution: University of California, Los Angeles
Investigator(s): David Wellisch, Ph.D. -
Award Cycle: 2004 (Cycle 10) Grant #: 10IB-0048 Award: $94,738
Award Type: IDEA
Research Priorities
Community Impact of Breast Cancer>Sociocultural, Behavioral, and Psychological Issues: the human side



Initial Award Abstract (2005)
In our decade of clinical and research experience with a population of women at high risk for breast cancer at UCLA, it has become apparent that grief is a central, enduring and profound emotional dynamic in their lives. Because of their family history of breast cancer, many of these women have lost a sister and/or a mother. Our prior research indicates that grief is a central issue to these women. Specifically, traumatic grief is known to be associated with occurrence of cancer. We formed a research team that can integrate research from several diverse areas to compose a model of how this may happen. Our prior research shows that grief activates particular emotion centers, primarily the limbic system. The limbic system is known to influence the production of a stress hormone called cortisol. Additionally, our prior research shows that the level of cortisol is related to distress levels in high-risk women. Finally, cortisol is known to suppress immune system functioning, which is important to cancer resistance.

The central question of this study is whether traumatic grief confers increased psychobiological risk for women already at high risk for breast cancer. Specifically, the question is whether grief-driven activation of emotion centers of the brain leads to cortisol dysregulation. The effects of the chronic stress of traumatic grief, brain activation and cortisol dysregulation may be a pathway to immune system compromise, and, hence, higher risk for breast cancer. This model has never before been integrated and tested.

We propose to recruit 24 women from a pool of 1200 women at the UCLA Revlon Breast Center those with traumatic grief (according to newly developed diagnostic criteria) and those with normal grief. Both groups of women will have fMRI brain scanning while looking at a picture of their deceased loved one. Before, during and after the scanning, salivary cortisol levels will be obtained. It is expected that the areas of brain activation and the cortisol levels will differ between these two groups. In addition, increased cortisol should predict specific brain activation patterns (e.g., greater limbic activation).

The proposed project is designed to systematically examine the psychobiological concomitants of grief at several levels in a sample of women at high risk for breast cancer in a way that has never been done before. While prior research suggests parts of the proposed model, no study has looked at all of them simultaneously. If the expected links between grief, brain activation and the stress hormone cortisol can be shown, this will form a definitive rationale for attending to grief in high-risk women as a critical issue in their care.


Final Report (2007)
Grief affects the lives of many women who have are at high risk for breast cancer because of a family history of breast cancer. While many women adjust with relatively little trauma after the death of a mother or a sister, others have a much more complicated course. The chronic stress that complicated grief confers may increase the psychobiological risk for women already at high risk for breast cancer. Our question is whether grief-driven activation of emotion centers of the brain leads to cortisol dysregulation. Cortisol dysregulation may be a pathway to immune system compromise, and, hence, higher risk for breast cancer. In order to test this question, we are interviewing women who have lost a mother or a sister in the past five years. Subsequently, they provide daily saliva samples from which cortisol levels are derived. Last, the participants have a functional magnetic resonance imaging (fMRI) scan while they look at pictures of their deceased loved one, to measure their brain activation during the feeling of grief.

Significant progress has been made on this project. We have obtained the authorization from the Office for the Protection of Research Subjects, and a Certificate of Confidentiality. Approximately 64 potential participants were screened over the telephone, and 35 came to UCLA for an initial interview. This included a standardized clinical interview for psychiatric and medical history, and a standardized interview for Complicated Grief. The interviewees also had an opportunity to tell their experience of the death of their loved one, in a supportive and open-ended format. The participants provided photographs of their deceased loved one, and their autobiographical story was documented.

The brain scanning portion of the study has been fully implemented; this has included successfully digitizing photographs and programming the scanner. Twenty-three participants have been scanned and made subjective ratings of their emotional experience in the scanner. Review of these ratings suggests that grief is successfully being elicited in the scanner. An overview of the scans suggests that we successfully recorded brain activity, without a high level of artifacts or movement. Salivettes (for collection of the stress hormone cortisol from saliva) were ordered, and packages for participants to take home have been organized. Twenty-four participants have successfully followed the directions for saliva sampling, including phoning a voicemail program after each collection for time-stamped documentation and daily questionnaires. Participants returned them to the investigators and they have been analyzed by a laboratory at UCLA. These hormone values have been entered into a computer database, and the data has been checked for errors or irregularities.

Data collection has been completed, and data analysis is being performed. An initial manuscript will be written for publication this spring, and a talk was given at the UCLA Semel Institute Grand Rounds in April, 2007 that includes some of these results. Additional publications will be written in the fall of 2007.

Preliminary results demonstrate differences in the regional brain activity between those who are resilient and those with Complicated Grief. These include differences in limbic areas, as hypothesized. Early analysis also suggests that there are group differences in the diurnal pattern of the stress hormone cortisol between the groups; those with Complicated Grief appear to be more dysregulated.

This is the very first time that we have known that there are physiological differences in the way that those with Complicated Grief and those who are more resilient process grief in the brain. This provides evidence that attending to grief in high-risk women as a critical issue in their care.