The goals of this fellowship are to further develop the applicant's knowledge and research skills in comorbid psychopathology, psychophysiology, and advanced statistical methods. In line with these goals, the cornerstone of the applicant's training will be the daily activities associated with the proposed study of psychophysiological processes underlying comorbid alcohol dependence (AD) and panic disorder (PD). The project will serve as the applicant's dissertation work and allow her to pursue her goal of becoming an independent investigator with a translational program of research on biobehavioral processes associated with comorbid substance use and internalizing disorders. As the skills of an academic clinical psychologist are multidimensional, the proposed training plan also includes course work, regular sponsor meetings, clinical practica, and professional development activities. In addition to the skills to be gained by the applicant, the project also has the potenial to greatly advance our understanding of the processes underlying comorbid AD and PD, a goal consistent with several facets of both NIAAA's and NIMH's strategic plans. This area of research is also noteworthy given that AD-PD is associated with costly social and economic consequences and thus, is of the utmost public health significance. It has recently been postulated that alcohol's ability to dampen anticipatory anxiety between unpredictable panic attacks may be a core mechanism in AD-PD. Evidence also suggest that individuals with AD-PD may exhibit heightened aversive reactivity in response to anticipatory anxiety relative to PD-only individuals. However, this question has yet to be directly examined and few studies have assessed how aversive responses change over time. Research further suggests that prolonged alcohol use causes deficits in respiratory sinus arrhythmia (RSA), an important factor associated with aversive responding, which may subsequently lead to heightened reactivity/responding to anticipatory anxiety. As such, the specific aims of the study are to examine whether: 1) AD-PD individuals exhibit increased reactivity to unpredictable threat (i.e., anticipatory anxiety) compared with PD-only individuals, 2) AD-PD individuals exhibit a different time course of aversive responding during unpredictable threat (e.g., less habituation) compared with PD-only individuals, and 3) RSA mediates these associations. Forty-five individuals with AD-PD and 45 individuals with PD-only will be recruited for the present study and responses to unpredictable threat will be assessed using a well-established EMG startle paradigm. Mentorship for this project will be provided by experts in the areas of psychophysiology and comorbid psychopathology. The sponsors are Drs. Shankman and Kassel and the consultants are Drs. Curtin and Porges. This fellowship will not only be an important step in the applicant's research career, but if the hypotheses are supported, it would suggest that reactivity/responding to anticipatory anxiety may be a potential risk factor or consequence of AD- PD and thus, may aid in the development of targeted interventions for this difficult-to-treat population.