Difficulty down-regulating negative affect is a prominent feature of anxiety disorders and impairment in the extinction of an aversively-conditioned response, long an important model of anxiety, is a likely mechanism underlying this form of anxiety-related emotion dysregulation. A separate line of inquiry has indicated that specific genes are associated with both extinction deficits and the functional neuroanatomy of emotion regulation. Specifically the serotonin transporter promoter gene (5-HTTLPR) is associated with greater amygdala and reduced rostral anterior cingulate activation during affective challenge and the DRD4 dopamine receptor gene has been linked with extinction learning. Imaging genetics studies of extinction will be useful for understanding the mechanisms underlying affect dysregulation in anxiety and risk for anxiety.
SPECIFIC AIMS : The proposed research project will integrate findings from these domains by assessing how the 5-HTTLPR and DRD4 genes influence neural circuitry previously implicated in emotion dysregulation and extinction learning in a sample of those at risk for anxiety. CAREER DEVELOPMENT PLAN: The candidate's long term goal is to become an independent investigator in the area of imaging genetics of emotion regulation and affective psychopathology. The proposed research and training activities will focus on building expertise in three domains: 1) conditioning as a model for anxiety, 2) genetics and imaging genetics of affect-related traits, and 3) further development of previously established neuroimaging skills. The candidate will work closely with a team of mentors and consultants with expertise spanning these three domains. In addition to the proposed research project, the candidate will complete formal coursework and lab-based training, along with advisor-directed didactics in each area. SIGNIFICANCE: This project and the candidate's subsequent work will utilize the power of the imaging genetics approach to more precisely specify the mechanisms via which genes modulate emotion dysregulation and confer risk for anxiety and affective psychopathology.

Public Health Relevance

I will examine how specific genes influence brain regions activated when attempting to down- regulate responses to previously threatening stimuli among individuals at risk for anxiety disorders. These data will further our understanding of neurobiological factors associated with vulerability to anxiety and provide an important step toward identifying appropriate prevention and intervention measures for clinical anxiety.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
1K01MH086809-01A1
Application #
7893407
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Wynne, Debra K
Project Start
2010-07-01
Project End
2015-03-31
Budget Start
2010-07-01
Budget End
2011-03-31
Support Year
1
Fiscal Year
2010
Total Cost
$165,167
Indirect Cost
Name
University of Wisconsin Milwaukee
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
627906399
City
Milwaukee
State
WI
Country
United States
Zip Code
53201
Belleau, Emily L; Pedersen, Walker S; Miskovich, Tara A et al. (2018) Cortico-limbic connectivity changes following fear extinction and relationships with trait anxiety. Soc Cogn Affect Neurosci 13:1037-1046
Weis, Carissa N; Belleau, Emily L; Pedersen, Walker S et al. (2018) Structural Connectivity of the Posterior Cingulum Is Related to Reexperiencing Symptoms in Posttraumatic Stress Disorder. Chronic Stress (Thousand Oaks) 2:
Bennett, Ken P; Dickmann, Jacqueline S; Larson, Christine L (2018) If or when? Uncertainty's role in anxious anticipation. Psychophysiology 55:e13066
Miskovich, Tara A; Anderson, Nathaniel E; Harenski, Carla L et al. (2018) Abnormal cortical gyrification in criminal psychopathy. Neuroimage Clin 19:876-882
Pedersen, Walker S; Muftuler, L Tugan; Larson, Christine L (2017) Disentangling the effects of novelty, valence and trait anxiety in the bed nucleus of the stria terminalis, amygdala and hippocampus with high resolution 7T fMRI. Neuroimage 156:293-301
Pedersen, Walker S; Balderston, Nicholas L; Miskovich, Tara A et al. (2017) The effects of stimulus novelty and negativity on BOLD activity in the amygdala, hippocampus, and bed nucleus of the stria terminalis. Soc Cogn Affect Neurosci 12:748-757
Stout, Daniel M; Shackman, Alexander J; Pedersen, Walker S et al. (2017) Neural circuitry governing anxious individuals' mis-allocation of working memory to threat. Sci Rep 7:8742
Miskovich, Tara A; Pedersen, Walker S; Belleau, Emily L et al. (2016) Cortical Gyrification Patterns Associated with Trait Anxiety. PLoS One 11:e0149434
Pedersen, Walker S; Larson, Christine L (2016) State anxiety carried over from prior threat increases late positive potential amplitude during an instructed emotion regulation task. Emotion 16:719-729
Taubitz, Lauren E; Pedersen, Walker S; Larson, Christine L (2015) BAS Reward Responsiveness: A unique predictor of positive psychological functioning. Pers Individ Dif 80:107-112

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