David C. Knight, PhD - US grants

The long term goal of this project is to improve our understanding of how neural systems in the human brain subserve aversive emotional states like fear and anxiety by assessing the brain metabolic activity of healthy volunteers with Functional Magnetic Resonance Imaging (fMRI). Specifically, this project will focus on the acquisition and performance of Pavlovian fear conditioning by assessing dynamic changes in regional activation during the learning process and when a fear response is expressed. These goals will be achieved with two experiments. In the first experiment, volunteers will be initially trained (acquisition) to fear a neutral stimulus. Then their memory for the previous training (performance) will be assessed. Functional and anatomical images will be obtained during both acquisition and performance phase. In the second experiment, volunteers will be differentially trained to fear one stimulus (Csplus) and not to fear a second stimulus (CS-). In this experiment, subjects will serve as their own control, and Probe trials will be used to make comparisons without UCS presentation. These experiments will answer questions about which neural structures are involved in learning and expression of conditional fear, will describe the temporal pattern of activation within these structures, will provide insights into how the involvement of various structures change as learning occurs and fear is expressed, and will comparisons with learning animal model systems. The data to be collected will substantially advance our understanding of neuroanatomical mechanisms of human fear and anxiety, and may directly contribute to improvements in the assessment and treatment of affective disorders.

DESCRIPTION (provided by applicant): Compared to Non-Hispanic Whites, Black Americans carry a disproportionate burden of social risk factors for poor mental health, such as living in violent urban environments and experiencing economic deprivation and discrimination. Despite these risks, Black Americans have lower lifetime prevalence of depressive and anxiety disorders than Whites. The reasons for Black Americans' resilience to these mental health disorders are unknown. This proposal aims to examine cumulative adversity and subsequent diminished neurobiological stress response as a possible explanation of Black Americans' resilience to anxiety and depression. It also aims to investigate the neural mechanisms underlying this resilience. These aims will be accomplished by conducting research interviews with 1,306 young adults (age 20-21; 60% Black, 40% White; 50% female) from an existing community sample who have been previously assessed three times during childhood and adolescence. These research interviews will provide information on adversity experienced by the participants, categorical diagnoses and dimensional measures of internalizing distress, and physiological indicators of reactivity to stress. Neural bases of stress response will be evaluated with functional magnetic resonance imaging (fMRI) for a subset of 120 Black and 120 White participants from the larger study. This study is innovative because it proposes to test a novel mechanism explaining the resilience of Black Americans to depression and anxiety, incorporates both categorical and dimensional measures of internalizing problems, and examines the role of physiological stress response and regulatory neural circuit in the resilience process. The results will have important implications for our understanding of racial disparities i anxiety and depression, neurobiological mechanisms underlying resilience to stress, and relationships between environmental stress, neural and physiological response, and negative affect. These findings will point to novel ways to diagnose and treat mental health problems in Black and White Americans. PUBLIC HEALTH RELEVANCE: Black Americans are exposed to more adversity than White Americans, yet they experience lower rates of anxiety and depressive disorders. The proposed project investigates cumulative adversity and diminished neurobiological stress response as causal mechanisms underlying Black Americans' resilience to anxiety and mood disorders. The findings will improve our understanding of the role of adversity and neurobiological stress system in anxiety and depression and suggest novel approaches to diagnose and treat these mental health problems in Black and White Americans.