title: Deficits in conditioned fear extinction in obsessive-compulsive disorder and neurobiological changes in the fear circuit.
abstract: OBJECTIVE
  Obsessive-compulsive disorder (OCD) may be characterized by impaired self-regulation and behavioral inhibition. Elevated fear and anxiety are common characteristics of this disorder. The neurobiology of fear regulation and consolidation of safety memories have not been examined in this patient population.
  
  
  OBJECTIVE
  To examine the psychophysiological and neurobiological correlates of conditioned fear extinction in patients with OCD.
  
  
  METHODS
  Cross-sectional, case-control, functional magnetic resonance imaging study.
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  Twenty-one patients with OCD and 21 healthy participants.
  
  
  METHODS
  Skin conductance responses and blood oxygenation level-dependent responses.
  
  
  RESULTS
  The between-group difference noted in our psychophysiological measure (skin conductance responses) was during extinction recall: patients with OCD showed impaired extinction recall relative to control subjects. Regarding the functional magnetic resonance imaging data, patients with OCD showed significantly reduced activation in the ventromedial prefrontal cortex across training phases. Moreover, reduced activation in the patients with OCD was noted in the caudate and hippocampus during fear conditioning, as well as in the cerebellum, posterior cingulate cortex, and putamen during extinction recall. Contrary to our prediction, OCD symptom severity was positively correlated with the magnitude of extinction memory recall. Also contrary to our prediction, functional responses of the ventromedial prefrontal cortex were positively correlated with symptom severity, and functional responses of the dorsal anterior cingulate cortex were inversely correlated with symptom severity.
  
  
  CONCLUSIONS
  As expected, our study showed that fear extinction and its neural substrates are impaired in patients with OCD. However, this study also yielded some surprising and unexpected results regarding the correlates between extinction capacity and its neural substrates and the severity of symptoms expressed in this disorder. Thus, our data report neural correlates of deficient fear extinction in patients with OCD. The negative correlations between fear extinction deficits and Yale-Brown Obsessive-Compulsive Scale symptoms in OCD suggest that there may be other factors, in addition to fear extinction deficiency, that contribute to the psychopathology of OCD.
authors.affiliation: Department of Psychiatry, Harvard Medical School, Massachusetts General Hospital, Charlestown 02129, USA. milad@nmr.mgh.harvard.edu
authors.forename: Mohammed R
authors.initials: MR
authors.lastname: Milad
authors.forename: Sharon C
authors.initials: SC
authors.lastname: Furtak
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Greenberg
authors.forename: Aparna
authors.initials: A
authors.lastname: Keshaviah
authors.forename: Jooyeon J
authors.initials: JJ
authors.lastname: Im
authors.forename: Martha J
authors.initials: MJ
authors.lastname: Falkenstein
authors.forename: Michael
authors.initials: M
authors.lastname: Jenike
authors.forename: Scott L
authors.initials: SL
authors.lastname: Rauch
authors.forename: Sabine
authors.initials: S
authors.lastname: Wilhelm
mesh_terms: D000328:Adult; D001921:Brain / Q000503:physiopathology; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005108:Extinction, Psychological / Q000502:physiology*; D005239:Fear / Q000502:physiology*; D005260:Female; D059907:Functional Neuroimaging; D005712:Galvanic Skin Response / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000503:physiopathology*; D055815:Young Adult