A PET Study of Tiagabine Treatment Implicates Ventral Medial Prefrontal Cortex in Generalized Social Anxiety Disorder
Abstract
Corticolimbic circuitry has been implicated in generalized social anxiety disorder (gSAD) by several neuroimaging symptom provocation studies. However, there are limited data regarding resting state or treatment effects on regional cerebral metabolic rate of glucose uptake (rCMRglu). Given evidence for anxiolytic effects conferred by tiagabine, a gamma-aminobutyric acid (GABA) reuptake inhibitor, the present [(18)F] fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) study sought to (1) compare resting rCMRglu between healthy control (HC) and pretreatment gSAD cohorts, (2) examine pre- to post-tiagabine treatment rCMRglu changes in gSAD, and (3) determine rCMRglu predictors of tiagabine treatment response. Fifteen unmedicated individuals with gSAD and ten HCs underwent a baseline (pretreatment) resting-state (18)FDG-PET scan. Twelve of the gSAD individuals completed an open, 6-week, flexible dose trial of tiagabine, and underwent a second (posttreatment) resting-state (18)FDG-PET scan. Compared to the HC subjects, individuals with gSAD demonstrated less pretreatment rCMRglu within the anterior cingulate cortex and ventral medial prefrontal cortex (vmPFC) at baseline. Following tiagabine treatment, vmPFC rCMRglu increased significantly in the gSAD group. Further, the magnitude of treatment response was inversely correlated with pretreatment rCMRglu within vmPFC. Taken together the present findings converge with neuroimaging findings from studies of social cognition in healthy individuals and symptom provocation in gSAD to support a role for the vmPFC in the pathophysiology of gSAD. Given the pharmacological profile of tiagabine, these findings suggest that its therapeutic effects in gSAD may be mediated by GABAergic modulation within the vmPFC.
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Both the amygdala and rostral ACC/mPFC are putative neural targets of psychosocial and pharmacological treatments known to be effective in generalized social anxiety disorder.
“Both the amygdala and rostral ACC/mPFC are putative neural 'targets' of psychosocial and pharmacological treatments known to be effective in GSAD (Evans et al, 2009;Goldin et al, 2013;Klumpp et al, 2013a;Phan et al, 2013).”
From Modulation of Resting-State Amygdala-Frontal Functional Connectivity by Oxytocin in Generalized Social Anxiety Disorder (2014) · cites this paper as Evans et al, 2009
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- Authors
- Evans, K. C., Simon, N. M., Dougherty, D. D., Hoge, E. A., Worthington, J. J., Chow, C., Kaufman, R. E., Gold, A. L., Fischman, A. J., Pollack, M. H., & Rauch, S. L.
- Affiliations
- Harvard University (US)
- Corresponding author
- Evans, Karleyton C
- ORCID
- Venue
- Neuropsychopharmacology
- Published
- 2008-06-04
- Volume
- 34
- Issue
- 2
- Pages
- 390-398
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- OpenAlex
- W2050476668
- Cited by
- 68
- References
- 54
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 6 · 2017: 2 · 2016: 9 · 2015: 3 · 2014: 9 · 2013: 4 · 2012: 6
- FWCI
- 4.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Abbott Laboratories
- Bristol-Myers Squibb
- Eli Lilly and Company
- Pfizer
- GlaxoSmithKline
- Medtronic
- Beth Israel Deaconess Medical Center
- National Institutes of Health (5t32eb001632-05, 5r01mh060219-05)
- National Institute of Mental Health (MH T32 19126, R01MH60219, R01MH074848, R01MH070730, T32MH019126)
- National Institute of Biomedical Imaging and Bioengineering (EB T32 1632-03)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Keywords
- generalized social anxiety disorder, tiagabine, ventromedial prefrontal cortex, GABA reuptake inhibition, treatment response prediction, anterior cingulate cortex, corticolimbic circuitry, GABAergic modulation
- MeSH terms
- Tiagabine, Adult, Anxiety Disorders, Brain, Brain Mapping, Female, Glucose, Humans, Magnetic Resonance Imaging, Male, Nipecotic Acids, Neurotransmitter Uptake Inhibitors, Prefrontal Cortex, Fluorodeoxyglucose F18, Positron-Emission Tomography
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