UCSF Researchers Seek Volunteers for Study on Connections Between Stress and Sleep

Thomas Neylan

A study underway at the San Francisco Veterans Affairs Medical Center (SFVAMC) and UCSF is probing the connection between post-traumatic stress disorder (PTSD), sleep disturbances and stress hormones. Investigators hope the study will reveal a new potential method for treating PTSD, as well as shed light on the biology of sleep. The study is currently recruiting volunteers. Thomas Neylan, MD, is leading the study on the role of hormones in sleep disturbances in men and women with and without PTSD. "Disturbed sleep - insomnia - is the most frequently reported symptom of PTSD. It's the number one complaint," observes Neylan, who is medical director of the PTSD treatment program at SFVAMC and an associate professor of psychiatry at UCSF. Neylan and his research group are investigating corticotropin-releasing factor, or CRF, which controls the release of several stress-related hormones in the brain. "When you stimulate CRF, it tends to make for lighter, more fragmented sleep," he explains. "Our hypothesis is that chronically elevated CRF may help explain chronic sleep problems in people with PTSD." Study volunteers are asked to sleep for three consecutive nights in the General Clinical Research Center at UCSF Moffitt Hospital. The first night allows subjects to adapt to sleeping at the GCRC. On the second night, researchers monitor the subjects' hormone levels as they sleep. On the final night, the volunteers are given metyrapone, a medication that stimulates production of CRF in the brain. Neylan predicts that "when we stimulate CRF, all subjects will have less deep sleep and more sleep fragmentation. However, we think that subjects with PTSD will actually have less of a response to metyrapone than our controls without PTSD, because they have adapted to chronically higher levels of CRF." The study has several goals, he says. "First, we have data suggesting that CRF is implicated in stress-related insomnia, and this is a more direct way of measuring that. Second, we hope to observe a relationship between chronic PTSD and elevated CRF during sleep, which may lead to new treatments." Additionally, says Neylan, "The implications of this study go beyond PTSD. We can actually learn more about the relationship between this particular hormone pathway and insomnia." He notes that sleep problems have been associated with a propensity to gain weight and to develop insulin resistance and type 2 diabetes, "so we're carefully measuring the metabolism of people admitted to the study, including whole body fat distribution, insulin sensitivity, fasting lipids and triglycerides, and other factors associated with weight gain." Ultimately, Neylan hopes the study will lead to a new way to treat sleep problems in general by targeting CRF. "The NIH and several pharmaceutical companies are developing CRF antagonists right now," he says. "They're not available yet, but they will be soon." The study is recruiting healthy men and women, age 20 to 50, with and without post-traumatic stress disorder and not taking medication regularly. Volunteers are compensated for their time, assessed for PTSD, and referred to treatment if appropriate. People interested in participating in the study should call Tracy at 415/418-4360 or 888/567-6337, or email. Co-investigators include Charles Marmar, MD, of SFVAMC and UCSF, Mary Dallman, PhD, of UCSF, and Rachel Yehuda, PhD, of Bronx VAMC and Mount Sinai School of Medicine, New York. Related Links: Posttraumatic Stress Disorder Research Program San Francisco Veterans Affairs Medical Center Common PTSD Drug Is No More Effective Than Placebo UCSF News Release, December 1, 2006