Positron emission tomographic imaging of neural correlates of a fear acquisition and extinction paradigm in women with childhood sexual-abuse-related post-traumatic stress disorder

• Type of Material: Article
• Authors: J. Douglas Bremner, Emory University; Eric Vermetten, Emory University; Christian G. Schmahl, Emory University; Viola Vaccarino, Emory University; Meena Vythilingam, National Institute of Mental Health; Nadeem Afzal, Emory University; Christian Grillon, National Institute of Mental Health; Dennis S. Charney, National Institute of Mental Health
• Language: English
• Date: 2005-06
• Publisher: Cambridge University Press (CUP)
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2004 Cambridge University Press
• Title of Journal or Parent Work: Psychological Medicine
• ISSN: 0033-2917
• Volume: 35
• Issue: 6
• Start Page: 791
• End Page: 806
• Grant/Funding Information: This study was supported by NIMH 1R01MH56120-01A1 and a Veterans Administration Career Development Award to Dr Bremner, the Emory Conte Center for the Neurosciences of Mental Health (1P50 MH58922), and the VA National Center for Post-Traumatic Stress Disorder.
• Research Categories: Health Sciences, Mental Health

Abstract

Background In the conditioned fear paradigm, repeated pairing of an aversive unconditioned stimulus (US) (e.g. electric shock) with a neutral conditioned stimulus (CS) (e.g. bright light) results in a conditioned fear response to the light alone. Animal studies have shown that the amygdala plays a critical role in acquisition of conditioned fear responses, while the medial prefrontal cortex (including anterior cingulate), through inhibition of amygdala responsiveness, has been hypothesized to play a role in extinction of fear responses. No studies have examined neural correlates of fear conditioning and extinction in patients with post-traumatic stress disorder (PTSD). Method Women with early childhood sexual-abuse-related PTSD (n=8) and women without abuse or PTSD (n=11) underwent measurement of psychophysiological (skin conductance) responding as well as positron emission tomographic (PET) measurement of cerebral blood flow during habituation, acquisition and extinction conditions. During habituation subjects were repeatedly exposed to a blue square on a screen. During acquisition, exposure to the blue square (CS) was paired with an electric shock to the forearm (US). With extinction, subjects were again exposed to the blue squares without shock. On a different day subjects went through the same procedure with electric shocks administered randomly in the absence of the blue square. Results Skin conductance responding to the CS was consistent with the development of conditioned responses with this paradigm. PTSD patients had increased left amygdala activation with fear acquisition, and decreased anterior cingulate function during extinction, relative to controls. Conclusions These findings implicate amygdala and anterior cingulate in the acquisition and extinction of fear responses, respectively, in PTSD.