Anxiety disorders are a debilitating form of mental illness that affect many people and carry a high societal and economic burden. A central feature of these disorders is the excessive anticipation of potential adverse outcomes. Considerable work in the candidate's and others'labs has identified multiple brain areas recruited during the anticipation of aversive events. The primary research objectives of this application are to probe these areas for abnormalities during anticipation in anxiety disorder patients and to examine the impact of uncertainty and uncontrollability, which figure prominently in anxiety. The planned research will also assess functional associations and white matter connections among the brain networks identified. In service of that, training in functional and structural connectivity methods is the major focus of the career development plan. These rapidly developing areas examining connectivity are an obvious next step for the candidate's research program and career development and will be crucial in his efforts to continue contributing to our developing knowledge base about brain function in anxiety. The environment is ideal for the pursuit of these research and career development objectives, with outstanding facilities, collaborators, and resources as well as a high degree of support from both the Department of Psychiatry and the Waisman Center. The proposed research will examine anticipatory function in generalized anxiety disorder and social anxiety disorder using a picture paradigm designed and developed in the candidate's laboratory over the past 7 years. The high levels of comorbidity with depression for these two anxiety disorders will be systematically investigated by including patients with major depressive disorder. The discovery of neural abnormalities in anticipatory processes should add to the body of work already being used in developing new clinical tools for directly targeting specific brain regions in anxiety and depression, such as transcranial magnetic stimulation, epidural electrocortical stimulation, and deep brain stimulation. Psychotherapy clients may benefit from greater focus of intervention strategies on anticipatory processes relevant to their symptoms. Research findings from the proposed project might have implications for determining which individuals would be likely to benefit from a particular treatment, building on recent findings by the candidate and his colleagues that greater anticipatory activity in the anterior cingulate predicts better response to an 8-week medication trial.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research (K02)
Project #
5K02MH082130-05
Application #
8301684
Study Section
Adult Psychopathology and Disorders of Aging Study Section (APDA)
Program Officer
Meinecke, Douglas L
Project Start
2008-09-01
Project End
2014-01-31
Budget Start
2012-08-01
Budget End
2014-01-31
Support Year
5
Fiscal Year
2012
Total Cost
$97,811
Indirect Cost
$7,245
Name
University of Wisconsin Madison
Department
Psychiatry
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
McFarlin, Daniel R; Kerr, Deborah L; Nitschke, Jack B (2013) Upsampling to 400-ms resolution for assessing effective connectivity in functional magnetic resonance imaging data with Granger causality. Brain Connect 3:61-71
Grupe, Dan W; Nitschke, Jack B (2013) Uncertainty and anticipation in anxiety: an integrated neurobiological and psychological perspective. Nat Rev Neurosci 14:488-501
Oathes, Desmond J; Squillante, Christian M; Ray, William J et al. (2010) The impact of worry on attention to threat. PLoS One 5:e13411
Sarinopoulos, I; Grupe, D W; Mackiewicz, K L et al. (2010) Uncertainty during anticipation modulates neural responses to aversion in human insula and amygdala. Cereb Cortex 20:929-40