title: Association among clinical response, hippocampal volume, and FKBP5 gene expression in individuals with posttraumatic stress disorder receiving cognitive behavioral therapy.
abstract: BACKGROUND
  Posttraumatic stress disorder (PTSD) is characterized by a reduced expression of FKBP5, a key modulator of the glucocorticoid receptor. Smaller hippocampal volume has also been documented in PTSD. We explored possible changes in FKBP5 gene expression and brain structure in patients with PTSD after cognitive behavioral therapy (CBT).
  
  
  METHODS
  We measured peripheral FKBP5 RNA and volumes of the hippocampus, amygdala, and medial orbitofrontal cortex in 39 patients with PTSD before and after CBT. The control subjects were 31 trauma-exposed individuals without PTSD who were also assessed twice. Gene expression changes were screened with a microarray toolkit, which was followed by quantitative polymerase chain reaction for FKBP5 RNA. Brain volumes were measured using FreeSurfer.
  
  
  RESULTS
  At baseline, patients with PTSD showed lower FKBP5 gene expression and smaller hippocampal and medial orbitofrontal cortex, but not amygdala, volumes relative to control subjects. At follow-up, we found significantly increased FKBP5 expression and increased hippocampal volume in patients with PTSD. At follow-up, patients did not differ from control subjects in hippocampal volume. Improvement in PTSD symptoms was predicted by increased FKBP5 expression and increased hippocampal volume, but the primary predictor was FKBP5 expression. The most significantly altered gene expression in patients with PTSD relative to control subjects was found for ribosomal protein S6 kinase, which did not change after CBT and did not correlate with hippocampal volume.
  
  
  CONCLUSIONS
  Clinical improvement in individuals with PTSD was associated with increased expression of FKBP5 and increased hippocampal volume, which were positively correlated.
authors.affiliation: National Psychiatry Center, Budapest, Hungary; Institute for the Study of Affective Neuroscience, University of Haifa, Haifa, Israel.
authors.forename: Einat
authors.initials: E
authors.lastname: Levy-Gigi
authors.forename: Csilla
authors.initials: C
authors.lastname: Szabó
authors.forename: Oguz
authors.initials: O
authors.lastname: Kelemen
authors.forename: Szabolcs
authors.initials: S
authors.lastname: Kéri
mesh_terms: D000328:Adult; D000679:Amygdala / Q000473:pathology; D015928:Cognitive Behavioral Therapy; D005260:Female; D005625:Frontal Lobe / Q000473:pathology; D015870:Gene Expression; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D013313:Stress Disorders, Post-Traumatic / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D022021:Tacrolimus Binding Proteins / Q000235:genetics / Q000378:metabolism*; D000099159:Tacrolimus Binding Protein 5
chemical_list: D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5
keywords: Cognitive behavioral therapy; FKBP5; gene expression; hippocampus; posttraumatic stress disorder; structural brain imaging