A PET study of tiagabine treatment implicates ventral medial prefrontal cortex in generalized social anxiety disorder.
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.
Department of Psychiatry, Psychiatric Neuroscience Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02129, USA. kcevans@partners.org
Karleyton C
KC
Evans
Naomi M
NM
Simon
Darin D
DD
Dougherty
Elizabeth A
EA
Hoge
John J
JJ
Worthington
Candice
C
Chow
Rebecca E
RE
Kaufman
Andrea L
AL
Gold
Alan J
AJ
Fischman
Mark H
MH
Pollack
Scott L
SL
Rauch
D000328:Adult; D001008:Anxiety Disorders / Q000188:drug therapy* / Q000503:physiopathology; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D001931:Brain Mapping; D005260:Female; D019788:Fluorodeoxyglucose F18; D005947:Glucose / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D014179:Neurotransmitter Uptake Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D009557:Nipecotic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism; D000078308:Tiagabine
D014179:Neurotransmitter Uptake Inhibitors; D009557:Nipecotic Acids; D019788:Fluorodeoxyglucose F18; D005947:Glucose; D000078308:Tiagabine