A PET Study of Tiagabine Treatment Implicates Ventral Medial Prefrontal Cortex in Generalized Social Anxiety Disorder

• Published in: Neuropsychopharmacology (New York, N.Y.) Vol. 34; no. 2; pp. 390 - 398
• Main Authors: Evans, Karleyton C, Simon, Naomi M, Dougherty, Darin D, Hoge, Elizabeth A, Worthington, John J, Chow, Candice, Kaufman, Rebecca E, Gold, Andrea L, Fischman, Alan J, Pollack, Mark H, Rauch, Scott L
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.01.2009; Nature Publishing Group
• Subjects: Adult; Adult and adolescent clinical studies; Anxiety; Anxiety Disorders - drug therapy; Anxiety Disorders - physiopathology; Anxiety disorders. Neuroses; Behavioral Sciences; Biological and medical sciences; Biological Psychology; Brain - diagnostic imaging; Brain - metabolism; Brain - physiopathology; Brain Mapping; Female; Fluorodeoxyglucose F18; Glucose - metabolism; Humans; Magnetic Resonance Imaging; Male; Medical sciences; Medicine; Medicine & Public Health; Miscellaneous; Neurosciences; Neurotransmitter Uptake Inhibitors - administration & dosage; Neurotransmitter Uptake Inhibitors - therapeutic use; Nipecotic Acids - administration & dosage; Nipecotic Acids - therapeutic use; original-article; Pharmacotherapy; Phobia; Positron-Emission Tomography; Prefrontal Cortex - diagnostic imaging; Prefrontal Cortex - drug effects; Prefrontal Cortex - metabolism; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; positron emission tomography; tiagabine; prefrontal cortex; social anxiety disorder; neuroimaging; Social phobia; Central nervous system; Anxiety disorder; Anticonvulsant; Prefrontal cortex; Reuptake inhibitor; Encephalon; Tiagabine; Treatment; Generalized anxiety disorder; Medial frontal cortex; GABA; Neurotransmitter; Emission tomography
• ISSN: 0893-133X; 1740-634X; 1740-634X
• DOI: 10.1038/npp.2008.69

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 γ-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.