Anxiety disorders are characterized by exaggerated and perserverant fear responses and have been previously characterized to show functional impairment in a number of brain regions. These brain regions include the amygdala, ventromedial prefrontal cortex, dorsal anterior cingulate, and the hippocampus. Importantly, these brain regions are involved in fear learning, its expression, and its subsequent extinction. The function of this fear extinction network is impaired in PTSD within the context of de novo fear extinction. Is the function of this fear extinction network also impaired in the other anxiety disorders? If yes, is the functional impairment equivalent across all the disorders or is there a distinct pattern of dysfunction within the context of fear extinction that could help distinguish oe disorder from another? The research proposed in this application will employ state- of-the-art neuroimaging tools, psychophysiological tools, and a well-validated two- day fear conditioning and extinction paradigm to begin to answer the above stated questions. Specifically, patients diagnosed with social anxiety disorder (SAD), generalized anxiety disorders (GAD), specific phobia (SP), and panic disorder (PD) will undergo the fear conditioning and extinction paradigm while in a 3T fMRI scanner. Previously acquired data from posttraumatic stress disorder (PTSD), obsessive compulsive disorder (OCD), and a large cohort of healthy controls will be used to compare across the anxiety disorders to compile a large matrix of data. This matrix will be used to conduct a conjunction analysis to examine the commonalities and differences between disorders regarding the dysfunction of the fear extinction network. These data could lead to better understanding of the psychopathology of the anxiety disorders within the context of one single paradigm.
Anxiety disorders are characterized by exaggerate fear responses. A number of brain regions have been implicated in the psychopathology of anxiety disorders using different experimental tools. This proposal will examine the psychopathology of all anxiety disorders within the context of fear extinction using functional MRI and psychophysiological tools. If successful, this approach could lead to developing a better understanding of the psychopathology of the different anxiety disorders within the context of fear inhibition.
|Alexandra Kredlow, M; Pineles, Suzanne L; Inslicht, Sabra S et al. (2017) Assessment of skin conductance in African American and Non-African American participants in studies of conditioned fear. Psychophysiology 54:1741-1754|
|Sierra-Mercado, Demetrio; McAllister, Lauren M; Lee, Christopher C H et al. (2015) Controlled cortical impact before or after fear conditioning does not affect fear extinction in mice. Brain Res 1606:133-41|
|Marin, Marie-France; Lonak, Sylwia Fowler; Milad, Mohammed R (2015) Augmentation of Evidence-Based Psychotherapy for PTSD With Cognitive Enhancers. Curr Psychiatry Rep 17:39|
|Pace-Schott, Edward F; Germain, Anne; Milad, Mohammed R (2015) Effects of sleep on memory for conditioned fear and fear extinction. Psychol Bull 141:835-57|
|Rosenbaum, Blake L; Bui, Eric; Marin, Marie-France et al. (2015) Demographic factors predict magnitude of conditioned fear. Int J Psychophysiol 98:59-64|
|Linnman, Clas; Zeidan, Mohamed A; Furtak, Sharon C et al. (2012) Resting amygdala and medial prefrontal metabolism predicts functional activation of the fear extinction circuit. Am J Psychiatry 169:415-23|
|Graham, Bronwyn M; Milad, Mohammed R (2011) The study of fear extinction: implications for anxiety disorders. Am J Psychiatry 168:1255-65|