Extinction Memory Is Impaired in Schizophrenia

被引:132
作者
Holt, Daphne J. [1 ,2 ]
Lebron-Milad, Kelimer [1 ,2 ]
Milad, Mohammed R. [1 ,2 ]
Rauch, Scott L. [3 ]
Pitman, Roger K. [1 ,2 ]
Orr, Scott P. [1 ,2 ,4 ]
Cassidy, Brittany S. [1 ,2 ]
Walsh, Jared P. [1 ]
Goff, Donald C. [1 ]
机构
[1] Harvard Univ, Sch Med, Dept Psychiat, Massachusetts Gen Hosp, Boston, MA 02115 USA
[2] Athinoula A Martinos Ctr Biomed Imaging, Charlestown, MA USA
[3] McLean Hosp, Belmont, MA 02178 USA
[4] Dept Vet Affairs Med Ctr, Manchester, NH USA
关键词
Conditioning; emotion; extinction; fear; memory; schizophrenia; VENTROMEDIAL PREFRONTAL CORTEX; FEAR EXTINCTION; CONDITIONED FEAR; PERSECUTORY DELUSIONS; NEGATIVE SYMPTOMS; D-CYCLOSERINE; ELECTRODERMAL ACTIVITY; EMOTION RECOGNITION; REALITY DISTORTION; DECLARATIVE MEMORY;
D O I
10.1016/j.biopsych.2008.09.017
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Background: Schizophrenia is associated with abnormalities in emotional processing and social cognition, which might result from disruption of the underlying neural mechanism(s) governing emotional learning and memory. To investigate this possibility, we measured the acquisition and extinction of conditioned fear responses and delayed recall of extinction in schizophrenia and control subjects. Methods: Twenty-eight schizophrenia and 18 demographically matched control subjects underwent a 2-day fear conditioning, extinction learning, and extinction recall procedure, in which skin conductance response (SCR) magnitude was used as the index of conditioned responses. Results: During fear acquisition, 83% of the control subjects and 57% of the patients showed autonomic responsivity ("responders"), and the patients showed larger SCRs to the stimulus that was not paired with the unconditioned stimulus (CS-) than the control subjects. Within the responder group, there was no difference between the patients and control subjects in levels of extinction learning; however, the schizophrenia patients showed significant impairment, relative to the control subjects, in context-dependent recall of the extinction memory. In addition, delusion severity in the patients correlated with baseline skin conductance levels. Conclusions: These data are consistent with prior evidence for a heightened neural response to innocuous stimuli in schizophrenia and elevated arousal levels in psychosis. The finding of deficient extinction recall in schizophrenia patients who showed intact extinction learning suggests that schizophrenia is associated with a disturbance in the neural processes supporting emotional memory.
引用
收藏
页码:455 / 463
页数:9
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