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.
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).


METHODS
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.
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30306, USA. jdbremn@emory.edu
J Douglas
JD
Bremner
Eric
E
Vermetten
Christian
C
Schmahl
Viola
V
Vaccarino
Meena
M
Vythilingam
Nadeem
N
Afzal
Christian
C
Grillon
Dennis S
DS
Charney
D000328:Adult; D000679:Amygdala / Q000098:blood supply; D001921:Brain / Q000098:blood supply* / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D002648:Child; D002650:Child Abuse, Sexual / Q000523:psychology*; D005108:Extinction, Psychological; D005239:Fear; D005260:Female; D005712:Galvanic Skin Response / Q000502:physiology; D006801:Humans; D007858:Learning; D049268:Positron-Emission Tomography; D011594:Psychometrics / Q000379:methods; D013313:Stress Disorders, Post-Traumatic / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*