Rates of alcohol use disorders are high among combat Veterans, and alcohol use disorder (AUD) is the most prevalent and costly substance use disorder among Veterans (SAMSHA, 2012). Current AUD is estimated at 16% in recently deployed veterans seeking VA care (VHA, 2011), and is approximately four times as common among combat Veterans than in the general population (Kessler et al., 2005). Care for individuals with AUD is standardized for across Veterans. An objective care framework that identifies individuals at highest risk for relapse may improve clinical outcomes. In addition, women may be more susceptible to consequences of problematic drinking behaviors than men, despite fewer years of drinking and less total drinks consumed yet research on AUD in women Veterans is sparse. Individuals with psychiatric co-morbidities have poorer outcomes than those with AUD alone, yet most research to date has excluded those with co-morbidities, leading to research results that are not generalizable to all Veterans with AUD. Evidence suggests that one component of the neurobiological mechanisms underlying AUD include dysregulation of emotional salience and reward circuits. It is not yet known exactly how dysfunction in brain circuits contribute to AUD, and how gender and co-morbidities moderate these effects, but research that answers these questions is critical. The current diagnostic and assessment system does not provide a model for objectively identifying individuals at highest risk for relapse following treatment. The checklist of symptoms that defines AUD does not reflect underlying neurobiology, yet brain circuit function predisposes individuals to AUD (e.g., to relieve anxiety or seek reward) and the effects of AUD can produce chronic changes to these circuits even after abstinence. We also know that these circuits may be moderated by other individual characteristics such as gender and/or the presence of a psychiatric co-morbidity. Technological advances in brain imaging have revolutionized our capacity to understand the brain circuits that underlie complex behaviors such as addiction. The most significant advancement in brain imaging research has been to identify core nodes of the large-scale circuits that are dysfunctional in mental health disorders. Despite this advance, there is a critical gap in integrated brain-based models of addiction. The proposed CSR&D CDA-2 seeks to fill this gap by conducted a neuroimaging study to assess the degree to which disconnections in networks implicated in reward and emotion circuits contribute to risk of relapse following treatment. We will achieve this via three specific aims:
Aim 1 : Define the neural circuits of emotion and reward processing that underlie AUD in Veterans.
Aim 2 : Test the relationship between defined neural circuits and treatment outcome (abstinence vs. relapse) and probability of relapse risk.
Aim 3 : Explore the impact of gender, psychiatric co-morbidities, and craving on the model developed in Aim 2. To test these aims, we will recruit 100 Veterans (50 men and 50 women) from outpatient and residential substance use treatment programs. In order to provide the most generalizable information, we will not exclude female Veterans or those with co-occurring depression, anxiety and PTSD. Currently there are no neuroimaging studies that have examined brain circuits as they relate to relapse risk in men and women Veterans with AUD. Findings from the proposed study will be the first to determine if brain circuits underlying in AUD can be used to predict relapse in this population. This study is a foundational first step and will lay the groundwork in using innovative neuroimaging technology to identify individuals at greatest risk who may need prolonged or more precise treatment strategies. This neuroscience based translational program of research will help vulnerable Veteran populations obtain more effective treatments and achieve better outcomes.

Public Health Relevance

The proposed CDA-2 will provide Dr. Padula with the training, expertise and data needed to advance research aimed at improving the prediction of treatment outcomes for men and women Veterans with alcohol use disorders. The proposed project will examine the relationship between brain circuits of emotion and reward and risk of relapse. Technological advances in brain imaging have revolutionized our capacity to understand the brain circuits that underlie complex behaviors, like addiction. Utilizing such technologies will make rapid progress toward improving objective measures of future success and eventually creating a more precise care model of treatment. Improved assessment and precise treatments will help Veterans with alcohol use disorders lead a better and more productive quality of life. These goals are consistent with the VA's mission to sponsor research examining variables related to pathogenesis, diagnosis, and treatment of neuropsychiatric disorders, and VA priorities of high risk behaviors (i.e., substance use) and women Veterans.

National Institute of Health (NIH)
Veterans Affairs (VA)
Veterans Administration (IK2)
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Neurobiology A (NURA)
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Veterans Admin Palo Alto Health Care Sys
Palo Alto
United States
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