Dongju Seo, Ph.D. - US grants

DESCRIPTION (provided by applicant): Dr. Dongju Seo is an associate research scientist in the Department of Psychiatry at Yale University specializing in functional magnetic resonance imaging (fMRI). Dr. Seo received a Ph.D. in Clinical Psychology from the University of Minnesota, Twin Cities in 2008 and subsequently completed postdoctoral training at Yale University with a focus on stress and addiction. The long-term goal of the candidate is to develop an interdisciplinary program of research to competitively conduct and interpret translational neuroscience research on alcoholism using multimodal neuroimaging and connectivity mapping. Specifically, her research focuses on stress- and autonomic nervous system (ANS)- related neural dysregulation associated with heavy alcohol use, discovering vulnerability markers for alcoholism risk, and developing effective prevention and treatment strategies. Her short-term goal is to obtain the skills and resources required to achieve her long-term goals and to become an independent researcher through the training and support provided by this K08 Award. Her preliminary findings indicate that binge and heavy alcohol use is influenced by a functional disconnectivity between the VmPFC regulatory system and the ANS arousal regions, brain areas involved in the modulation of emotions and rewarding states. Based on this result, it is hypothesized that decreased functional connectivity in the VmPFC-ANS circuit contributes to emotional and ANS disruption and alcohol intake in heavy social drinkers. The candidate aims to test this hypothesis in a larger sample and seeks support to learn new skills for this study. Her research strategy will be to examine brain and ANS response in heavy and light social drinkers using simultaneous fMRI and ANS recording, functional connectivity mapping, and combined clinical design to identify neural measures associated with risk for alcohol abuse. Her training program will cover the following topics relating to the interdisciplinary neuroscience of alcoholism: 1) learning fMRI connectivity mapping and translational neuroscience of alcoholism 2) combining fMRI and ANS techniques and analysis, and 3) developing expertise in longitudinal study design and analysis for alcohol research. Her mentors include internationally prominent experts in translational research on alcoholism (Rajita Sinha, Ph.D.; John H. Krystal, M.D.), multimodal neuroimaging and connectivity mapping (Todd Constable, Ph.D.) and longitudinal research on alcoholism (Howard Tennen, Ph.D.; Ralitza Gueorguieva, Ph.D.). The K08 Award will allow the candidate to acquire new skills and resources to test the hypothesis and provide Dr. Seo with a valuable opportunity to grow into an independent clinical investigator, with expertise in the application of state-of-the art, multimoda neuroimaging techniques to conduct translational neuroscience research on alcoholism.

Project Summary/Abstract Early trauma (ET) is a significant obstacle to alcohol recovery. Patients with alcohol use disorder (AUD) who experienced early trauma are at a higher risk of frequent and early relapse and suffer from severe clinical symptoms including emotion and stress-related difficulties. However, neural mechanisms linking alcoholism, early trauma and high relapse risk remain unclear. Two biological systems, stress-related brain circuits and the hypothalamic?pituitary?adrenal (HPA) axis system, are implicated in the pathologies of both AUD and ET. Concurrent examination of these two systems using multimodal neuroimaging techniques (e.g., simultaneous brain and stress hormone monitoring) may clarify the relationship between AUD and ET. Using this novel approach, our prior study showed that a lack of dynamic increase in the ventromedial prefrontal cortex (VmPFC) during stress was a critical predictor of ineffective coping, disrupted HPA axis response to stress, and increased alcohol consumption. Preliminary results also indicated that impaired dynamic VmPFC recovery during stress was associated with comorbid AUD/ET and early relapse. This pattern of findings leads us to hypothesize that impaired dynamic VmPFC response to stress may be a novel marker of comorbid alcoholism and early trauma, which underlies high relapse risk. Using functional magnetic resonance imaging (fMRI) combined with a prospective clinical outcome design, the proposed study aims to utilize brain-HPA axis markers of co-occurring alcoholism and early trauma and to examine whether these markers contribute to early relapse after treatment. We propose a 5-year study with four demographically-matched groups (total N=160; N=40 each; equal sex ratio); these groups will include AUD patients with and without ET and moderate drinkers with and without ET. Participants will complete an fMRI session while viewing a series of stress, alcohol, and neutral cues. After the multimodal scan, AUD patients will be engaged in eight weeks of standard, empirically-validated outpatient treatment and then prospectively followed for 90 days. To accurately capture relapse rate, we will conduct face-to-face follow-up interviews at 14, 30, and 90 days after treatment in conjunction with daily monitoring of stress and alcohol related behaviors using a smartphone app. Successful completion of the proposed aims has the potential to identify the neural mechanisms underlying comorbid alcoholism and early trauma and associated relapse risk, which may be further explored to develop new treatment targets and to improve clinical outcomes in AUD patients with early trauma.

ABSTRACT/SUMMARY In times of national crisis, the prevalence of stress- and alcohol- related disorders increases substantially. In particular, risky drinkers with high levels of stress tend to have lasting binge drinking habits even after the crisis is resolved, highlighting the importance of timely interventions. During the COVID-19 pandemic, there has been a significant rise in mental health symptoms including emotional distress and alcohol/substance misuse, presenting unprecedented public health challenges. Immediate clinical interventions are exigent to reach out to vulnerable individuals in high-risk areas to evaluate and treat those at risk for alcohol- and stress- related disorders. However, the infectious nature of the pandemic is a significant obstacle to these efforts. Digital interventions have emerged as an effective tool to overcome this difficulty by allowing access to those residing in high-risk zones stricken with COVID-19. In response to NOT-AA-20-011/PA-18-591 requesting the investigation of the impact of the COVID-19 pandemic on alcohol misuse, this project aims to study the influence of COVID-19 related stress on increasing risk of alcohol misuse and relapse after digital interventions. This project proposes a 1-year digital intervention study using a prospective clinical outcome design with two demographically-matched groups of risky drinkers (total N=40; equal gender ratio) with high versus low COVID-19 related stress. We will utilize a digital intervention method that combines telehealth- and smartphone app- based interventions, allowing concurrent treatment and daily monitoring in a real-life setting. All participants will receive a 4-week telehealth intervention after which they will be prospectively followed for 30 days to monitor stress, alcohol use, social functioning, and other health-related behaviors via a smartphone app. A Specific Aim is to assess the impact of COVID-19 related stress on increasing risk of alcohol misuse and relapse after digital interventions during and in the aftermath of the COVID-19 pandemic. This project will also examine the impact of COVID-19 related social isolation on alcohol misuse and relapse. If successful, the proposed research has the potential to make a difference in clinical care by (1) establishing digital healthcare protocols for individuals at risk of alcohol use disorders; (2) providing timely telehealth access for those who suffer from stress-related drinking in times of national crisis; and (3) identifying the impact of the COVID-19 pandemic on stress, emotion, and social interactions and risk of alcohol misuse and relapse to prevent future risky drinking associated with traumatic events.