Panic disorder is among the most common psychiatric disorders and is particularly prevalent among women. There is significant morbidity and mortality associated with panic disorder. Although effectively treated with medication or cognitive-behavioral therapy (CBT), an approximately 60 percent relapse rate after treatment discontinuation suggests that panic disorder is a chronic illness for a subpopulation of affected individuals. Relapse rates off treatment also appear to be influenced by treatment duration as longer treatment with medication reduces the risk for subsequent relapse when medication-free. Our studies to date suggest that individuals with panic disorder have brain metabolic abnormalities, manifested as abnormal lactate elevations in response to challenges, such as lactate infusion or hyperventilation, that appear to have a trait-specific component. There also is evidence that the magnitude of abnormal brain lactate response decreases in relationship to duration of treatment. The goal of this research is to apply a recently developed dynamic, metabolic imaging technique, protein echo- planar spectroscopic imaging (PEPSI), to measure brain metabolic changes in response to lactate infusion in order to better understand neuropathological mechanisms underlying panic disorder, treatment response and relapse both during treatment and after treatment discontinuation. Symptomatic, mediation-free panic subjects (n=80) and healthy controls (n=32) will be studied with PEPSI during a standard lactate infusion, and then again at 12 weeks following randomization of the panic subjects into treatment with CBT (n=40) or fluvoxamine (n=40). Panic subjects will be restudied during lactate reinfusion at 1 year while in ongoing treatment and then followed clinically for 1 year after discontinuation of treatment. A clinical rater blinded to treatment will be responsible for independent assessment of clinical status. It is hypothesized that persistence of brain metabolic abnormalities during medication treatment, but not CBT treatment, is predictive of treatment course and vulnerability to relapse following treatment discontinuation. An attempt will be made to reassign treatment nonresponders to the opposite treatment arm and restudy those individuals (not included as additional subjects in the opposite treatment arm), in order to better understand mechanisms underlying treatment failure.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
2R01MH050579-04A2
Application #
6129358
Study Section
Special Emphasis Panel (ZRG1-BDCN-6 (01))
Program Officer
Hsiao, John
Project Start
1994-09-30
Project End
2005-06-30
Budget Start
2000-07-01
Budget End
2001-06-30
Support Year
4
Fiscal Year
2000
Total Cost
$384,087
Indirect Cost
Name
University of Washington
Department
Psychiatry
Type
Schools of Medicine
DUNS #
135646524
City
Seattle
State
WA
Country
United States
Zip Code
98195
Dager, Stephen R (2010) The vexing role of baseline: implications for neuroimaging studies of panic disorder. Int J Psychophysiol 78:20-6
Corrigan, Neva M; Richards, Todd L; Friedman, Seth D et al. (2010) Improving 1H MRSI measurement of cerebral lactate for clinical applications. Psychiatry Res 182:40-7
Dager, Stephen R; Corrigan, Neva M; Richards, Todd L et al. (2008) Research applications of magnetic resonance spectroscopy to investigate psychiatric disorders. Top Magn Reson Imaging 19:81-96
Giardino, Nicholas D; Friedman, Seth D; Dager, Stephen R (2007) Anxiety, respiration, and cerebral blood flow: implications for functional brain imaging. Compr Psychiatry 48:103-12
Friedman, Seth D; Mathis, C Mark; Hayes, Cecil et al. (2006) Brain pH response to hyperventilation in panic disorder: preliminary evidence for altered acid-base regulation. Am J Psychiatry 163:710-5
Layton, M E; Friedman, S D; Dager, S R (2001) Brain metabolic changes during lactate-induced panic: effects of gabapentin treatment. Depress Anxiety 14:251-4
Friedman, S D; Dager, S R; Richards, T L et al. (2000) Modeling brain compartmental lactate response to metabolic challenge: a feasibility study. Psychiatry Res 98:55-66
Dager, S R; Friedman, S D (2000) Brain imaging and the effects of caffeine and nicotine. Ann Med 32:592-9
Dager, S R; Friedman, S D; Heide, A et al. (1999) Two-dimensional proton echo-planar spectroscopic imaging of brain metabolic changes during lactate-induced panic. Arch Gen Psychiatry 56:70-7
Posse, S; Dager, S R; Richards, T L et al. (1997) In vivo measurement of regional brain metabolic response to hyperventilation using magnetic resonance: proton echo planar spectroscopic imaging (PEPSI). Magn Reson Med 37:858-65

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