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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23MH105553-04
Application #
9551075
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Chavez, Mark
Project Start
2016-08-01
Project End
2019-08-31
Budget Start
2018-09-01
Budget End
2019-08-31
Support Year
4
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Texas A&M University
Department
Type
DUNS #
020271826
City
College Station
State
TX
Country
United States
Zip Code
77845
MacNamara, Annmarie; Barley, Blake (2018) Event-related potentials to threat of predictable and unpredictable shock. Psychophysiology 55:e13206
MacNamara, Annmarie; Rabinak, Christine A; Kennedy, Amy E et al. (2018) Convergence of fMRI and ERP measures of emotional face processing in combat-exposed U. S. military veterans. Psychophysiology 55:
MacNamara, Annmarie (2018) In the mind's eye: The late positive potential to negative and neutral mental imagery and intolerance of uncertainty. Psychophysiology 55:e13024
MacNamara, Annmarie; Jackson, T Bryan; Fitzgerald, Jacklynn M et al. (2018) Working Memory Load and Negative Picture Processing: Neural and Behavioral Associations With Panic, Social Anxiety, and Positive Affect. Biol Psychiatry Cogn Neurosci Neuroimaging :
MacNamara, Annmarie; Klumpp, Heide; Kennedy, Amy E et al. (2017) Transdiagnostic neural correlates of affective face processing in anxiety and depression. Depress Anxiety 34:621-631
Xing, Mengqi; Tadayonnejad, Reza; MacNamara, Annmarie et al. (2017) Resting-state theta band connectivity and graph analysis in generalized social anxiety disorder. Neuroimage Clin 13:24-32
Stange, Jonathan P; MacNamara, Annmarie; Barnas, Olga et al. (2017) Neural markers of attention to aversive pictures predict response to cognitive behavioral therapy in anxiety and depression. Biol Psychol 123:269-277
Stange, Jonathan P; MacNamara, Annmarie; Kennedy, Amy E et al. (2017) Brain-behavioral adaptability predicts response to cognitive behavioral therapy for emotional disorders: A person-centered event-related potential study. Neuropsychologia :
Waszczuk, Monika A; Zimmerman, Mark; Ruggero, Camilo et al. (2017) What do clinicians treat: Diagnoses or symptoms? The incremental validity of a symptom-based, dimensional characterization of emotional disorders in predicting medication prescription patterns. Compr Psychiatry 79:80-88
Fitzgerald, Jacklynn M; MacNamara, Annmarie; Kennedy, Amy E et al. (2017) Individual differences in cognitive reappraisal use and emotion regulatory brain function in combat-exposed veterans with and without PTSD. Depress Anxiety 34:79-88

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