This K23 Mentored Patient-Oriented Research Career Development Award will significantly advance the candidate's long-term career goal of becoming an independent investigator in the field of alcohol research by providing new knowledge and training in the neurobiology of alcohol use disorders and oxytocin, as well as cue reactivity and clinical pharmacology paradigms. Over the past 10 years, Dr. Flanagan's research has focused on behavioral correlates of alcohol use disorders (AUD) and intimate partner aggression (IPA). The health and economic burdens associated with AUD and co-occurring IPA are staggering, and alcohol use is consistently identified as a precipitant to IPA. Significant gaps in the treatment of AUD and IPA exist and there is an immediate need for research in this area. Dr. Flanagan is trained as a clinical psychologist and has a strong background in research design, statistical analysis, and behavioral interventions for AUD and co-occurring problems. Under the K23 award, she will gain new knowledge and training to significantly expand her current level of expertise and research skills. Dr. Flanagan's immediate career development goals are: (1) to develop a solid foundation in the neurobiology of AUD, (2) master the literature on the neurobiology of oxytocin, (3) obtain new training in the conduct of human laboratory paradigms, (4) enhance understanding of the interrelationship between AUD and IPA, and (5) hone scientific and grant writing skills. These goals represent a logical and synergistic expansion of her current expertise. Under the outstanding mentorship of experienced translational researchers, Dr. Flanagan will conduct a human laboratory study to examine the effects of the neuropeptide oxytocin on alcohol craving and aggression among couples with co-occurring AUD and IPA. In previous studies, oxytocin has been shown to mitigate craving among individuals with alcohol, cocaine, and marijuana use disorders, and to promote prosocial behavior. The proposed study will utilize a standardized alcohol cue reactivity paradigm and a well-established laboratory aggression paradigm (i.e., the Taylor Aggression Paradigm) and will include assessment of subjective (e.g., craving, anger, stress), physiological (e.g., heart rate, skin conductance) and neuroendocrine (e.g., cortisol, Adrenocorticotropic hormone [ACTH]) reactivity. The findings from this study will directly inform treatment and prevention strategies for AUD and IPA. Results of the study will also help direct future treatment research efforts in which pharmacological agents are combined with behavioral interventions to attenuate AUD and IPA. Dr. Flanagan has assembled a highly accomplished, multidisciplinary team of mentors with the expertise and experience necessary to ensure the K23 career development goals are achieved. The mentoring team is comprised of two on-site mentors at the Medical University of South Carolina (MUSC), including Dr. Sudie Back (Primary Mentor) and Dr. Howard Becker (Co-Mentor), and two off-site co-mentors, including Dr. Sue Carter at the Kinsey Institute and Dr. Gregory Stuart at the University of Tennessee. The K23 award will provide formal coursework and workshops, directed readings, individual tutoring and consultation with leaders in the field, hands-on training in alcohol cue reactivity paradigms and clinical pharmacology paradigms, and new training in advanced statistical analysis methodology. In summary, the overarching goal of this K23 application is to promote the candidate's successful transition to research independence in the alcohol field, with an emphasis on the development of evidence-based interventions to reduce AUD and co-occurring IPA. The K23 award will provide the protected time necessary to fully engage in the training activities outlined in the career development plan, enabling Dr. Flanagan to take full advantage of the expertise at MUSC in the areas of AUD, neurobiology, and human laboratory paradigms. The new training afforded by the K23 will allow Dr. Flanagan to apply multimodal assessment methods in future research studies to identify novel targets for treatment and test the efficacy of treatments for AUD and IPA. The outstanding mentorship, hands-on experience, and formal coursework proposed in the training plan will provide a rich training experience and critical preliminary data on which to build an NIH R01 application.

Public Health Relevance

Alcohol use disorders (AUD) and intimate partner aggression (IPA) frequently co-occur. There are significant health and economic burdens associated with AUD and co-occurring IPA, and little empirical data to guide treatment efforts. The neuropeptide oxytocin may help mitigate both AUD and IPA. However, clinical data examining oxytocin's effects on human aggression is scant. The proposed study is designed to address these gaps in the literature by utilizing a human laboratory paradigm to test the effects of oxytocin on craving and aggression among couples with AUD and co-occurring IPA. The career development and research training activities afforded by the K23 award will significantly enhance the candidate's long-term career goal of becoming a successful independent investigator and a leading expert in the field of alcohol research.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Mentored Patient-Oriented Research Career Development Award (K23)
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Study Section
National Institute on Alcohol Abuse and Alcoholism Initial Review Group (AA)
Program Officer
Grakalic, Ivana
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Medical University of South Carolina
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United States
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Flanagan, Julianne C; Hand, Anne; Jarnecke, Amber M et al. (2018) Effects of oxytocin on working memory and executive control system connectivity in posttraumatic stress disorder. Exp Clin Psychopharmacol 26:391-402
Back, Sudie E; Flanagan, Julianne C; Jones, Jennifer L et al. (2018) Doxazosin for the treatment of co-occurring PTSD and alcohol use disorder: Design and methodology of a randomized controlled trial in military veterans. Contemp Clin Trials 73:8-15
Flanagan, Julianne C; Fischer, Melanie S; Nietert, Paul J et al. (2018) Effects of oxytocin on cortisol reactivity and conflict resolution behaviors among couples with substance misuse. Psychiatry Res 260:346-352
Jarnecke, Amber M; Allan, Nicholas P; Badour, Christal L et al. (2018) Substance use disorders and PTSD: Examining substance use, PTSD symptoms, and dropout following imaginal exposure. Addict Behav 90:35-39
Bountress, Kaitlin E; Badour, Christal; Flanagan, Julianne et al. (2018) Treatment of co-occurring posttraumatic stress disorder and substance use: Does order of onset influence outcomes? Psychol Trauma 10:662-665
Flanagan, Julianne C; Sippel, Lauren M; Wahlquist, Amy et al. (2018) Augmenting Prolonged Exposure therapy for PTSD with intranasal oxytocin: A randomized, placebo-controlled pilot trial. J Psychiatr Res 98:64-69
Flanagan, Julianne C; Allan, Nicholas P; Calhoun, Casey D et al. (2018) Effects of oxytocin on stress reactivity and craving in veterans with co-occurring PTSD and alcohol use disorder. Exp Clin Psychopharmacol :
Jarnecke, Amber M; Barden, Eileen; Back, Sudie E et al. (2018) Intimate partner violence moderates the association between oxytocin and reactivity to dyadic conflict among couples. Psychiatry Res 270:404-411
Flanagan, Julianne C; Fischer, Melanie S; Badour, Christal L et al. (2017) The Role of Relationship Adjustment in an Integrated Individual Treatment for PTSD and Substance Use Disorders Among Veterans: An Exploratory Study. J Dual Diagn 13:213-218
Szafranski, Derek D; Snead, Alexandra; Allan, Nicholas P et al. (2017) Integrated, exposure-based treatment for PTSD and comorbid substance use disorders: Predictors of treatment dropout. Addict Behav 73:30-35