Deficient fear extinction memory in posttraumatic stress disorder.
BACKGROUND
Posttraumatic stress disorder (PTSD) might be maintained by deficient extinction memory. We used a cued fear conditioning design with extinction and a post-extinction phase to provoke the return of fear and examined the role of the interplay of amygdala, hippocampus and prefrontal regions.


METHODS
We compared 18 PTSD patients with two healthy control groups: 18 trauma-exposed subjects without PTSD (nonPTSD) and 18 healthy controls (HC) without trauma experience. They underwent a three-day ABC-conditioning procedure in a functional magnetic resonance imaging scanner. Two geometric shapes that served as conditioned stimuli (CS) were presented in the context of virtual reality scenes. Electric painful stimuli were delivered after one of the two shapes (CS+) during acquisition (in context A), while the other (CS-) was never paired with pain. Extinction was performed in context B and extinction memory was tested in a novel context C.


RESULTS
The PTSD patients showed significantly higher differential skin conductance responses than the non-PTSD and HC and higher differential amygdala and hippocampus activity than the HC in context C. In addition, elevated arousal to the CS+ during extinction and to the CS- throughout the experiment was present in the PTSD patients but self-reported differential valence or contingency were not different. During extinction recall, differential amygdala activity correlated positively with the intensity of numbing and ventromedial prefrontal cortex activity correlated positively with behavioral avoidance.


CONCLUSIONS
PTSD patients show heightened return of fear in neural and peripheral measures. In addition, self-reported arousal was high to both danger (CS+) and safety (CS-) cues. These results suggest that a deficient maintenance of extinction and a failure to identify safety signals might contribute to PTSD symptoms, whereas non-PTSD subjects seem to show normal responses.
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159 Mannheim, Germany. Electronic address: manon.wicking@yahoo.de.
Manon
M
Wicking
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159 Mannheim, Germany. Electronic address: frauke.steiger@zi-mannheim.de.
Frauke
F
Steiger
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159 Mannheim, Germany. Electronic address: frauke.nees@zi-mannheim.de.
Frauke
F
Nees
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159 Mannheim, Germany. Electronic address: slawomira.diener@gmail.com.
Slawomira J
SJ
Diener
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159 Mannheim, Germany; Klinik für Psychiatrie, Psychosomatik und Psychotherapie, Klinikum der J.W. Goethe-Universität, Heinrich-Hoffmann-Str. 10, 60528 Frankfurt am Main, Germany. Electronic address: oliver.grimm@kgu.de.
Oliver
O
Grimm
Computer Assisted Clinical Medicine, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. Electronic address: Michaela.ruttorf@medma.uni-heidelberg.de.
Michaela
M
Ruttorf
Computer Assisted Clinical Medicine, Medical Faculty Mannheim, Heidelberg University, Theodor-Kutzer-Ufer 1-3, 68167 Mannheim, Germany. Electronic address: lothar.schad@medma.uni-heidelberg.de.
Lothar R
LR
Schad
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159 Mannheim, Germany. Electronic address: tobias.winkelmann@zi-mannheim.de.
Tobias
T
Winkelmann
Department of Psychiatry and Psychotherapy, SRH Klinikum Karlsbad-Langensteinbach GmbH, Guttmannstr. 1, 76307 Karlsbad, Germany. Electronic address: gustav.wirtz@KKL.srh.de.
Gustav
G
Wirtz
Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, J5, 68159 Mannheim, Germany. Electronic address: herta.flor@zi-mannheim.de.
Herta
H
Flor
D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging / Q000503:physiopathology*; D003214:Conditioning, Classical / Q000502:physiology*; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D005712:Galvanic Skin Response / Q000502:physiology*; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D011939:Mental Recall / Q000502:physiology*; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000502:physiology*; D000067073:Psychological Trauma / Q000000981:diagnostic imaging / Q000503:physiopathology*; D013313:Stress Disorders, Post-Traumatic / Q000000981:diagnostic imaging / Q000503:physiopathology*
Amygdala; Fear conditioning; Hippocampus; Posttraumatic stress disorder (PTSD); Renewal; Safety learning