title: Effect of cognitive-behavioral therapy on neural correlates of fear conditioning in panic disorder.
abstract: BACKGROUND
  Learning by conditioning is a key ability of animals and humans for acquiring novel behavior necessary for survival in a changing environment. Aberrant conditioning has been considered a crucial factor in the etiology and maintenance of panic disorder with agoraphobia (PD/A). Cognitive-behavioral therapy (CBT) is an effective treatment for PD/A. However, the neural mechanisms underlying the effects of CBT on conditioning processes in PD/A are unknown.
  
  
  METHODS
  In a randomized, controlled, multicenter clinical trial in medication-free patients with PD/A who were treated with 12 sessions of manualized CBT, functional magnetic resonance imaging (fMRI) was used during fear conditioning before and after CBT. Quality-controlled fMRI data from 42 patients and 42 healthy subjects were obtained.
  
  
  RESULTS
  After CBT, patients compared to control subjects revealed reduced activation for the conditioned response (CS+ > CS-) in the left inferior frontal gyrus (IFG). This activation reduction was correlated with reduction in agoraphobic symptoms from t1 to t2. Patients compared to control subjects also demonstrated increased connectivity between the IFG and regions of the "fear network" (amygdalae, insulae, anterior cingulate cortex) across time.
  
  
  CONCLUSIONS
  This study demonstrates the link between cerebral correlates of cognitive (IFG) and emotional ("fear network") processing during symptom improvement across time in PD/A. Further research along this line has promising potential to support the development and further optimization of targeted treatments.
authors.affiliation: Department of Psychiatry and Psychotherapy, Philipps-University Marburg, Rudolf-Bultmann-Straße 8, Marburg, Germany. psychiat@med.uni-marburg.de
authors.forename: Tilo
authors.initials: T
authors.lastname: Kircher
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.forename: Andreas
authors.initials: A
authors.lastname: Jansen
authors.forename: Martin
authors.initials: M
authors.lastname: Pyka
authors.forename: Isabelle
authors.initials: I
authors.lastname: Reinhardt
authors.forename: Thilo
authors.initials: T
authors.lastname: Kellermann
authors.forename: Carsten
authors.initials: C
authors.lastname: Konrad
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lueken
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Gloster
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Gerlach
authors.forename: Andreas
authors.initials: A
authors.lastname: Ströhle
authors.forename: André
authors.initials: A
authors.lastname: Wittmann
authors.forename: Bettina
authors.initials: B
authors.lastname: Pfleiderer
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Wittchen
authors.forename: Benjamin
authors.initials: B
authors.lastname: Straube
mesh_terms: D000328:Adult; D000379:Agoraphobia / Q000150:complications / Q000503:physiopathology / Q000628:therapy; D001921:Brain / Q000503:physiopathology*; D016022:Case-Control Studies; D015928:Cognitive Behavioral Therapy / Q000379:methods; D003214:Conditioning, Classical / Q000502:physiology*; D005239:Fear / Q000502:physiology* / Q000523:psychology*; D005260:Female; D059907:Functional Neuroimaging / Q000379:methods / Q000523:psychology; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods / Q000523:psychology; D008297:Male; D009434:Neural Pathways / Q000503:physiopathology; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D016584:Panic Disorder / Q000150:complications / Q000503:physiopathology* / Q000628:therapy*; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data