This is an application for a K02 Independent Scientist Award for Dr Helen Fox, who is currently an Assistant Professor in Psychiatry at Yale University School of Medicine. In 2010, Dr Fox received a NIH-NIDA funded Mentored Research Scientist Development Award which allowed her to received unparalleled training in cognitive pharmacotherapy and medications development. It was also instrumental in helping Dr Fox secure subsequent funding and establish a solid research trajectory. Dr Fox has received independent funding to examine immune system changes underpinning stress-induced alcohol craving and cognitive control in early abstinent alcoholics with and without depressive symptomatology (R01: AA 20095). She is also Co-PI of a 12 week clinical Prazosin trial in alcoholics with and without anxiety symptomatology (R01: AA 20504). Other projects include assessing discreet and converging mechanisms underlying stress and immune system changes in dependent individuals with and without depressive symptomatology (R03:AA022500) and hazardous non- dependent drinkers (Peter F MacManus Charitable Trust). On the basis of this research program, her career development goals are: 1) To characterize stress and immune system adaptations in alcoholics with and without anxiety and depressive comorbidity in order to provide novel treatment targets for medications development; 2) to subsequently develop better-tailored medications that target these systems in co-morbid populations. Attaining these goals via the focused research time afforded by the K02 award will be critical for Dr Fox to maintain her current level of productivity and transition to a fully independent scientist. A 5- year Career Development Plan is also proposed, comprising 4 training modules: 1. Didactic components: intramural and extramural courses and workshops; 2. Practical components: overseeing research projects and funding securement 3.Preceptorships 4. Symposia & Meetings. The proposed K02 research represents a supplementary project conducted within the framework of the applicants funded projects (R01: AA 020504 / R01: AA 020095). Objectives are to a) assess the efficacy of 3-weeks prazosin (16mgs t.i.d) versus placebo in improving cognitive control (Stroop, Go/No Go, Stop Signal performance), following a personalized imagery stressor in alcoholics with and without anxiety, and b) examine the utility of cognitive control measures as markers of outcome in the same population. The proposed exploratory aims will additionally examine cytokine changes underlying cognitive control processes following a personalized stressor in alcoholics with and without depressive symptomatology. The objectives of both parent studies and the proposed supplementary neurocognitive research are compatible with Dr Fox's career goals and training plan. Examining the utility of inhibitory control in predicting outcome and the efficacy of prazosin versus placebo in strengthening these mechanisms is compatible with both goals. In addition, elucidating immune system changes underpinning these mechanisms also complements the need to development novel targets for treatment development.
The proposed study aims to establish whether prazosin versus placebo strengthens ability to regulate in the face of stress to a greater extent in alcoholics with anxiety symptoms compared to those without. In addition, we also propose to explore some of the immune system changes underlying these regulatory processes in alcoholics with and without depressive symptoms. As ability to regulate successfully during stress is associated with many factors which affect alcohol treatment outcome, better understanding of the mechanisms underlying such processes may provide important targets for medications development in different populations of alcoholics.
| Milivojevic, Verica; Ansell, Emily; Simpson, Christine et al. (2017) Peripheral Immune System Adaptations and Motivation for Alcohol in Non-Dependent Problem Drinkers. Alcohol Clin Exp Res 41:585-595 |
| Fox, Helen C; Milivojevic, Verica; Angarita, Gustavo A et al. (2017) Peripheral immune system suppression in early abstinent alcohol-dependent individuals: Links to stress and cue-related craving. J Psychopharmacol 31:883-892 |
| Milivojevic, Verica; Fox, Helen C; Jayaram-Lindstrom, Nitya et al. (2017) Sex differences in guanfacine effects on stress-induced stroop performance in cocaine dependence. Drug Alcohol Depend 179:275-279 |
