Although current research indicates an important role for sleep disturbance in the pathophysiology of PTSD, our understanding of PTSD-related sleep physiology is based primarily on studies of male subjects (8, 9, 15). This is highly concerning: evidence of gender differences in neurobiology and behavior suggests that research on sleep in males with PTSD may not pertain to females (12, 16-18). Dr. Richards proposes to examine sexual dimorphism in PTSD by examining sex differences in the role of REM sleep on a fundamental component of the disorder: negative emotional memory. Strong evidence indicates that REM sleep plays an essential part in consolidating memory for negative emotional stimuli (6, 11, 20-22). Research also indicates that women have better recall of negative emotional material than men (12-14). Surprisingly, such research has not been conducted in PTSD subjects. Dr. Richards recently published findings showing increased REM sleep in women with PTSD which has potential relevance for explaining sexual dimorphism in memory mechanisms in PTSD and increased PTSD risk in women. Dr. Richards' long-term objective is to gain a better understanding of the pathophysiology of PTSD in both men and women. Her current objective is to examine the contribution of REM sleep to PTSD disease mechanisms in male and female subjects. She expects that insights gained from her research will ultimately contribute to the development of targeted treatments for PTSD symptoms in both men and women. She will benefit from exceptional training resources at UCSF, UC Berkeley, UC Davis, Stanford University and the San Francisco VA Medical Center and an outstanding team of mentors within the VA to develop her expertise in a unique area of inquiry: the measurement of sex differences in PTSD-related sleep physiology and their relationship to negative emotional memory. Her research will build on solid clinical experience with male and female veterans, on the research training and experience she acquired during public health and psychiatry residency training, and on her PTSD and sleep research as a VA staff psychiatrist under the mentorship of Dr. Thomas Neylan. The Stress and Health Research Program, directed by her primary mentor Dr. Neylan, and her co-mentor Dr. Daniel Mathalon, will ensure the adequacy of staff and equipment resources to accomplish the proposed objectives. The San Francisco VA Medical Center will provide the necessary sleep laboratory space. The research study will assess the relationship of sex and REM sleep on negative emotional memory in subjects with PTSD and age- and sex-matched trauma-exposed PTSD-negative controls. Twenty (20) male and 20 female veterans with PTSD and 20 male and 20 female controls between the ages of 18 and 40 will be enrolled. All participants will participate in a sleep laboratory admission involving an adaptation night and a night of undisturbed sleep. A subsample of forty participants (10 in each group) will participate in a second admission involving a REM-deprivation condition, in a counter-balanced cross-over design. The International Affective Picture System (IAPS) will be used to assess recall of negative emotional images in the undisturbed sleep and REM-deprived sleep conditions (23). Subjective arousal responses and the late positive component (LPC) of event-related potentials (ERPs) will also be used to study emotional arousal reactions to IAPS images and to compare the impact of arousal on memory across groups. Sleep of female subjects will be studied in the follicular phase of the menstrual cycle. Her primary hypotheses examine the relationship of sex and REM sleep with consolidation of negative emotional memory in male and female PTSD and control subjects. Her secondary hypotheses examine sex differences in negative emotional memory following REM-deprivation sleep in PTSD and control subjects.

Public Health Relevance

PTSD is highly prevalent in modern deployment veterans and is a large contributor to VA healthcare utilization (1-5). Women have up to twice the risk of PTSD as men (7). Compelling research on sleep and PTSD indicates that abnormal sleep plays a significant role in the pathophysiology of the disorder (8-10). Increasing evidence also indicates that sleep may impact memory for emotionally upsetting material (6, 11), and that women may have better memory for upsetting material than men (12-14), findings of major relevance to PTSD. Unfortunately, our understanding of the neurobiology of PTSD-related sleep disturbance is derived from studies of male, or predominantly male, samples (15). This creates profound barriers to understanding PTSD in women (12, 16-18). Increasing numbers of women are serving in the military, and are exposed to combat and potentially traumatic life events (19). Enhancing our understanding of sex differences in PTSD-related sleep disturbance is vital to developing treatments that adequately address the needs of both men and women veterans.

National Institute of Health (NIH)
Veterans Affairs (VA)
Veterans Administration (IK2)
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Mental Health and Behavioral Science A (MHBA)
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Veterans Affairs Medical Center San Francisco
San Francisco
United States
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Richards, Anne; Inslicht, Sabra S; Metzler, Thomas J et al. (2017) Sleep and Cognitive Performance From Teens To Old Age: More Is Not Better. Sleep 40:
Richards, Anne; Inslicht, Sabra S; Metzler, Thomas J et al. (2016) SLEEP AND COGNITIVE PERFORMANCE FROM TEENS TO OLD AGE: MORE IS NOT BETTER. Sleep :