Neural Substrates of Anticipation and Interoception in Anxiety Disorders

Summary

Principal Investigator: M B Stein
Affiliation: University of California
Country: USA
Abstract: This proposal is the competing renewal of our ongoing work into the neural substrates of anxiety. In a natural progression of this work, we now propose to test key aspects of a neural circuit model for anxiety disorders. We will use BOLD fMRI in conjunction with emotion processing tasks to compare healthy controls subjects (HC) to patients with panic disorder (PD) and generalized anxiety disorder (GAD), who will be studied before and after cognitive behavioral treatment (CBT). This proposal brings together methods and approaches from behavioral and cognitive neuroscience, functional neuroimaging imaging, and psychological clinical therapeutics to outline a series of studies with the long-term objective of delineating the neural substrates of anxiety disorders. The principal objective of this competitive renewal is to build on the applicants' previously accomplished work in non-clinical individuals with anxiety proneness and apply this to patients with anxiety disorders with the following specific aims: (1) To develop a basic systems neuroscience endophenotype for anxiety disorders. Based on our prior work, we hypothesize that, compared to healthy controls (HC), patients with GAD or PD will show increased activation of the anterior insula during various types of emotion processing that engage interoceptive systems. Moreover, we hypothesize that there is less functional coupling between the insular cortex and both the amygdala and the medial prefrontal cortex (mPFC) in patients with anxiety disorders. (2) To evaluate effects of CBT on the neural systems hypothesized to be dysfunctional in patients with anxiety disorders. We expect that successful treatment will be associated with attenuation of insular cortex activity and increased coupling between insula and both amygdala and mPFC, respectively. In the case of GAD, we also expect to see a reduction in task-related dorsolateral prefrontal cortex (DLPFC) activity. Anxiety disorders are early onset, prevalent, serious conditions that impact adversely on individual and societal functioning. Improved understanding of the neural circuitry of anxiety disorders will inform diagnostic conceptualizations and enable the more directed development and testing of novel therapies that are based on a more thorough understanding of pathophysiology, thereby conveying new therapeutic options to the many patients with anxiety disorders for whom existing treatments are inadequate.
Funding Period: 2002-04-01 - 2012-05-31
more information: NIH RePORT

Top Publications

  1. pmc Role of functional magnetic resonance imaging in drug discovery
    Martin P Paulus
    Department of Psychiatry, University of California, San Diego UCSD, 8950 Villa La Jolla Drive, Suite C 213, La Jolla, CA 92037, USA
    Neuropsychol Rev 17:179-88. 2007
  2. ncbi Heritability of anterior cingulate response to conflict: an fMRI study in female twins
    Scott C Matthews
    Laboratory of Biological Dynamics and Theoretical Medicine, CA, USA
    Neuroimage 38:223-7. 2007
  3. pmc Intolerance of uncertainty correlates with insula activation during affective ambiguity
    Alan Simmons
    Laboratory of Biological Dynamics and Theoretical Medicine, USA
    Neurosci Lett 430:92-7. 2008
  4. doi Influence of RGS2 on anxiety-related temperament, personality, and brain function
    Jordan W Smoller
    Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Arch Gen Psychiatry 65:298-308. 2008
  5. pmc Functional activation and neural networks in women with posttraumatic stress disorder related to intimate partner violence
    Alan N Simmons
    Department of Psychiatry, University of California San Diego, and VA San Diego Healthcare System, San Diego, California 92037, USA
    Biol Psychiatry 64:681-90. 2008
  6. pmc Association between individual differences in self-reported emotional resilience and the affective perception of neutral faces
    Estibaliz Arce
    Department of Psychiatry, University of California San Diego, La Jolla, CA 92037 0985, United States
    J Affect Disord 114:286-93. 2009

Detail Information

Publications6

  1. pmc Role of functional magnetic resonance imaging in drug discovery
    Martin P Paulus
    Department of Psychiatry, University of California, San Diego UCSD, 8950 Villa La Jolla Drive, Suite C 213, La Jolla, CA 92037, USA
    Neuropsychol Rev 17:179-88. 2007
    ....
  2. ncbi Heritability of anterior cingulate response to conflict: an fMRI study in female twins
    Scott C Matthews
    Laboratory of Biological Dynamics and Theoretical Medicine, CA, USA
    Neuroimage 38:223-7. 2007
    ..These results suggest an endophenotype that may be applied to various psychiatric disorders that are both highly heritable and associated with altered dACC function...
  3. pmc Intolerance of uncertainty correlates with insula activation during affective ambiguity
    Alan Simmons
    Laboratory of Biological Dynamics and Theoretical Medicine, USA
    Neurosci Lett 430:92-7. 2008
    ..Previously observed insula hyperactivity in anxiety disorder individuals may therefore be directly linked to altered processes of uncertainty...
  4. doi Influence of RGS2 on anxiety-related temperament, personality, and brain function
    Jordan W Smoller
    Center for Human Genetic Research, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA
    Arch Gen Psychiatry 65:298-308. 2008
    ..The gene encoding regulator of G protein signaling 2 (Rgs2) is a quantitative trait gene that influences mouse anxiety behavior, making its human ortholog (RGS2) a compelling candidate gene for human anxiety phenotypes...
  5. pmc Functional activation and neural networks in women with posttraumatic stress disorder related to intimate partner violence
    Alan N Simmons
    Department of Psychiatry, University of California San Diego, and VA San Diego Healthcare System, San Diego, California 92037, USA
    Biol Psychiatry 64:681-90. 2008
    ..Victims of IPV are often preoccupied by the anticipation of impending harm. This investigation tested the hypothesis that IPV-related PTSD individuals show exaggerated insula reactivity to the anticipation of aversive stimuli...
  6. pmc Association between individual differences in self-reported emotional resilience and the affective perception of neutral faces
    Estibaliz Arce
    Department of Psychiatry, University of California San Diego, La Jolla, CA 92037 0985, United States
    J Affect Disord 114:286-93. 2009
    ..We used a novel experimental paradigm to test the hypothesis that highly resilient individuals show a judgment bias towards positive emotions...