Psychological Medicine



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


J. DOUGLAS BREMNER a1a2a4a5c1, ERIC VERMETTEN a1, CHRISTIAN SCHMAHL a1, VIOLA VACCARINO a3a5, MEENA VYTHILINGAM a6, NADEEM AFZAL a1, CHRISTIAN GRILLON a6 and DENNIS S. CHARNEY a6
a1 Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA
a2 Department of Radiology, Emory University School of Medicine, Atlanta, GA
a3 Department of Internal Medicine (Cardiology), Emory University School of Medicine, Atlanta, GA
a4 Emory Center for Positron Emission Tomography, Emory University School of Medicine, Atlanta, GA
a5 Atlanta VAMC, Decatur, GA
a6 Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, MD, USA

Article author query
bremner jd   [PubMed][Google Scholar] 
vermetten e   [PubMed][Google Scholar] 
schmahl c   [PubMed][Google Scholar] 
vaccarino v   [PubMed][Google Scholar] 
vythilingam m   [PubMed][Google Scholar] 
afzal n   [PubMed][Google Scholar] 
grillon c   [PubMed][Google Scholar] 
charney ds   [PubMed][Google Scholar] 

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.


Correspondence:
c1 Dr J. Douglas Bremner, Emory Clinical Neuroscience Research Unit, Emory University – Emory West Campus, 1256 Briarcliff Road, Atlanta, GA 30306, USA. (Email: jdbremn@emory.edu)


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