Anxiety disorders (ADs) may be more similar than different in terms of neural dysfunction. Examining phenotypic variability that is independent of specific diagnoses may help explicate fundamental biobehavioral substrates of psychopathology in the ADs, leading to improved classification and treatment. For instance, comorbidity in the ADs is common and is known to relate to severity and measures of emotional reactivity such as self-reported negative affectivity (NA), yet evidence of its underlying neurobiology is scarce. The primary goal of this K23 is to provide the candidate with training in brain (functional magnetic resonance imaging, fMRI) and behavior (eyeblink startle) measures of negative emotion processing, in order to launch the candidate's career as an independent clinical neuroscientist with expertise in the multi-level, neurobiological, dimensional analysis of emotional dysfunction in anxiety. The proposal has three components: 1) a mentorship team with complementary expertise, 2) didactics to fill gaps in the candidate's previous education and 3) hands-on experience critical to the candidate's growth. The research plan tests the utility of a dimensional transdiagnostic approach in linking neural and behavioral measures of dysregulated negative emotion processing to clinically relevant anxiety burden characterized by comorbidity load and self-reported NA. Participants in the proposed project will comprise 90 adults with a 'simple' phobia (specific phobia or performance-only social anxiety) recruited to fill 3 comorbidity load cells: 1) n = 30 with no comorbidity; 2) n = 30 with 1 other anxiety or depressive (AnxDep) disorder; and 3) n = 30 with 2 or more other AnxDep disorders, all compared to psychiatrically healthy controls (HCs, n = 30). This K23 leverages the recruitment infrastructure of mentor Phan's NIH-funded R01 (MH101497 [08/2013-07/2017]) study, but is distinct practically (different tasks and scan sessions) and scientifically. Participants will undergo simultaneous fMRI and electromyographic (EMG) startle recording during: a) anticipation of; and b) response to aversive stimuli. Consonant with candidate's training goals in fMRI affective neuroscience, startle methodology and their clinical application to dimensional constructs relevant to ADs, the project's aims are to: 1) examine the relationship between brain measures of negative emotion processing, comorbidity load and NA; 2) examine the relationship between behavioral (startle) measures of negative emotion processing, comorbidity load and NA; and 3) examine the interrelationships between brain and behavioral measures of negative emotion processing in relation to comorbidity load and NA. Comorbidity load, a marker of disease burden, may aid understanding of dimensional and categorical internalizing psychopathology. Through completion of this project and the coordinated training plan, the candidate will build upon her prior expertise in event-related potentials (ERPs) and anxiety to emerge as a multi-modal, neurobiological expert using complementary, layered methodologies (fMRI, ERPs, startle) to close gaps between neurobiology and clinical profiles, in order to improve diagnosis and guide new treatments.
Comorbidity in anxiety disorders is common, exerts tremendous personal and societal costs, is difficult to treat and is associated with increased negative affectivity. Little is known about the brain and behavioral mechanisms that promote anxiety comorbidity and negative affectivity. A better understanding of these brain and behavior mechanisms could lead to better ways to diagnose and treat anxiety disorders that co-occur with other anxiety disorders and depression.
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