Cognitive deficits remain prevalent among HIV+ individuals in the era of combination antiretroviral therapies, inhibiting adherence to life-saving treatments and lowering quality of life. HIV-infected women report high rates of exposure to acute and chronic stressors such as those resulting from the high prevalence of early childhood trauma as well as challenges related to HIV disease management in adulthood. These stressors can lead to profound and sustained negative physiological and psychological consequences including cognitive deficits and brain dysfunction. The primary goal of this project is to develop an independent scholarly program of research that addresses the role of stress and stress hormones on cognitive dysfunction among HIV+ women, with the ultimate objective of designing an intervention that lowers stress and improves cognition. This four- year program of training and research includes: 1) application of epidemiological and biostatistical methods to analysis of cognitive data from a large, longitudinal, multi-site cohort of HIV+ and HIV- women to study dysfunction associated with HIV status, especially among women with post-traumatic stress disorder (PTSD);and 2) conducting a pharmacological challenge study to better understand the mechanisms underlying stress and related cognitive dysfunction, and then using newly acquired knowledge to design an intervention to enhance cognitive function among HIV+ women. Training will include coursework, mentoring, and practical experience in advanced methods in epidemiology, biostatistics, pharmacological challenge studies, and intervention science in the context of HIV. Two studies are proposed. The first will characterize relationships between stress and cognition in HIV+ vs. HIV- women in the Women's Interagency HIV Study (WIHS), the largest prospective multicenter cohort study of at-risk women in the U.S. and the longest ongoing study of HIV disease progression in women. Based on preliminary results from data on ~1000 HIV+ women and uninfected controls, we will test the hypothesis that perceived stress and PTSD symptom severity are more strongly related to cognitive impairment in HIV+ than HIV- women, and that HIV-associated vulnerability to stress is most evident on tasks involving the prefrontal cortex. The second study is a hydrocortisone challenge study among HIV+ women contrasting those with (n=15) and without (n=15) a PTSD diagnosis to determine whether the former group shows greater prefrontal task impairment than the latter following hydrocortisone administration. Results of these two studies will provide a foundation for designing subsequent mechanistic and treatment studies (R01s) to improve cognition among HIV+ women, and submission of grant proposals to fund this line of inquiry.
HIV+ women's exposure to acute and chronic stressors is associated with cognitive and brain dysfunction that interferes with treatment adherence and lowers quality of life. Interventions based on a better understanding of neuroendocrine processes have the potential to enhance treatment adherence, lower morbidity and mortality, and reduce treatment costs, resulting in greater well-being for their these women and their families, and improved public health for our nation.
|Rubin, Leah H; Meyer, Vanessa J; J Conant, Rhoda et al. (2016) Prefrontal cortical volume loss is associated with stress-related deficits in verbal learning and memory in HIV-infected women. Neurobiol Dis 92:166-74|
|Vance, David E; Rubin, Leah H; Valcour, Victor et al. (2016) Aging and Neurocognitive Functioning in HIV-Infected Women: a Review of the Literature Involving the Women's Interagency HIV Study. Curr HIV/AIDS Rep 13:399-411|
|Valdez, Arielle N; Rubin, Leah H; Neigh, Gretchen N (2016) Untangling the Gordian knot of HIV, stress, and cognitive impairment. Neurobiol Stress 4:44-54|
|Valcour, Victor G; Rubin, Leah H; Obasi, Mary U et al. (2016) Liver Fibrosis Linked to Cognitive Performance in HIV and Hepatitis C. J Acquir Immune Defic Syndr 72:266-73|
|Rubin, Leah H; Pyra, Maria; Cook, Judith A et al. (2016) Post-traumatic stress is associated with verbal learning, memory, and psychomotor speed in HIV-infected and HIV-uninfected women. J Neurovirol 22:159-69|
|Rubin, Leah H; Wu, Minjie; Sundermann, Erin E et al. (2016) Elevated stress is associated with prefrontal cortex dysfunction during a verbal memory task in women with HIV. J Neurovirol 22:840-851|
|Maki, Pauline M; Mordecai, Kristen L; Rubin, Leah H et al. (2015) Menstrual cycle effects on cortisol responsivity and emotional retrieval following a psychosocial stressor. Horm Behav 74:201-8|
|Bishop, Jeffrey R; Najjar, Fedra; Rubin, Leah H et al. (2015) Escitalopram pharmacogenetics: CYP2C19 relationships with dosing and clinical outcomes in autism spectrum disorder. Pharmacogenet Genomics 25:548-54|
|Maki, Pauline M; Rubin, Leah H; Valcour, Victor et al. (2015) Cognitive function in women with HIV: findings from the Women's Interagency HIV Study. Neurology 84:231-40|
|Sundermann, Erin E; Bishop, Jeffrey R; Rubin, Leah H et al. (2015) Genetic predictor of working memory and prefrontal function in women with HIV. J Neurovirol 21:81-91|
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