Dr. Michael Irwin

[UCLA] – UCLA researchers have received a $5 million grant from the National Cancer Institute for a study aimed at developing a risk profile for breast cancer survivors likely to suffer from depression. The prevalence of depression among survivors is three to five times greater than in the general population.

UCLA will be teaming on the five-year study with Kaiser Permanente, which will provide the 300 volunteers needed for the study by culling through electronic patient records to locate women who have been treated for breast cancer and have not had a history of depression.

Researchers believe that cancer and its treatment induce inflammation, which in turn leads to sleep disturbance and depression. Sleep disturbance occurs in more than half of breast cancer survivors and is thought to contribute to the elevated risk of depression in these women. Depression negatively impacts quality of life and increases the risk of death, possibly due to an increased chance of cancer recurrence.

Through the study, researchers hope to find out if certain sub-sets of breast cancer survivors are at greater risk for depression by examining their DNA for potential biomarkers and genetic anomalies. If they can identify a risk profile, a study would be launched later to evaluate prevention measures, said the study’s principal investigator, Dr. Michael Irwin, a professor of psychiatry and biobehavioral sciences at the Cousins Center for Psychoneuroimmunology, part of the Semel Institute for Neuroscience and Human Behavior at UCLA.

“Depression in breast cancer survivors is a huge problem. It often goes undiagnosed and is undertreated,” Irwin said. “If we can identify those breast cancer survivors at elevated risk for sleep disturbance and, therefore, depression, we can diagnose and treat it earlier, with better outcomes. Additionally, if we can identify those at greatest risk, efforts can be implemented early to prevent the occurrence of depression in the first place.

“Because depression is so prevalent and difficult to treat in breast cancer survivors, prevention of depression will dramatically improve the quality of their life.”

For many cancer patients, their survival is complicated by long-term physical and behavioral late effects of their treatment, especially depression, Irwin said. Yet despite the high prevalence of depression among breast cancer survivors, the unique clinical, behavioral and biological factors that contribute to this increased depression risk is not known.

“There are no published prospective data that have examined the independent contribution of sleep disturbance on depression occurrence in breast cancer survivors,” Irwin said. “Increasing evidence implicates that sleep disturbance is activating inflammatory signaling, which serves as a biological mechanism that contributes to depression. We hope to define the genomic and biologic processes that results in this depression.”

Irwin’s ultimate goal is preventing the cascade of events that lead to depression — inflammation and sleep disturbance — but more information is needed first.  This study is vital to providing valuable clues as to how that cascade occurs, he said.

“You can’t design a prevention trial unless you know the risk profile and the magnitude of the problem,” Irwin said. “What makes this so exciting is that by partnering with Kaiser Permanente, we can do this work in a primary care sample, which will significantly help speed recruitment.”

Study volunteers, once identified, will come in for an interview, give a blood sample that will measure levels of inflammation and provide DNA for examination. This process will be repeated every six months for two years. The volunteers also will be called once a month and asked a series of questions to determine if they are becoming depressed.

“If depression is suspected, we can bring them in immediately and evaluate them,” Irwin said. “That will be a big benefit for volunteers as they’ll get diagnosed and treated much sooner than they normally would be.”

Irwin said he expects it will take two to three years to successfully recruit the 300 volunteers needed.

The UCLA Cousins Center for Psychoneuroimmunology encompasses an interdisciplinary network of scientists working to advance the understanding of psychoneuroimmunology by linking basic and clinical research programs and by translating findings into clinical practice. The center is affiliated with the Semel Institute for Neuroscience and Human Behavior and the David Geffen School of Medicine at UCLA.