Association among clinical response, hippocampal volume, and FKBP5 gene expression in individuals with posttraumatic stress disorder receiving cognitive behavioral therapy

Einat Levy-Gigi, Csilla Szabó, O. Kelemen, S. Kéri

Research output: Contribution to journalArticle

78 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)793-800
Number of pages8
JournalBiological Psychiatry
Volume74
Issue number11
DOIs
Publication statusPublished - Dec 1 2013

Fingerprint

Cognitive Therapy
Post-Traumatic Stress Disorders
Gene Expression
Amygdala
Prefrontal Cortex
RNA
Ribosomal Protein S6 Kinases
Glucocorticoid Receptors
Brain
Hippocampus
Polymerase Chain Reaction
Wounds and Injuries

Keywords

  • Cognitive behavioral therapy
  • FKBP5
  • gene expression
  • hippocampus
  • posttraumatic stress disorder
  • structural brain imaging

ASJC Scopus subject areas

  • Biological Psychiatry

Cite this

@article{c398189b099e406398750dea256d0339,
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.",
keywords = "Cognitive behavioral therapy, FKBP5, gene expression, hippocampus, posttraumatic stress disorder, structural brain imaging",
author = "Einat Levy-Gigi and Csilla Szab{\'o} and O. Kelemen and S. K{\'e}ri",
year = "2013",
month = "12",
day = "1",
doi = "10.1016/j.biopsych.2013.05.017",
language = "English",
volume = "74",
pages = "793--800",
journal = "Biological Psychiatry",
issn = "0006-3223",
publisher = "Elsevier USA",
number = "11",

}

TY - JOUR

T1 - Association among clinical response, hippocampal volume, and FKBP5 gene expression in individuals with posttraumatic stress disorder receiving cognitive behavioral therapy

AU - Levy-Gigi, Einat

AU - Szabó, Csilla

AU - Kelemen, O.

AU - Kéri, S.

PY - 2013/12/1

Y1 - 2013/12/1

N2 - 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.

AB - 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.

KW - Cognitive behavioral therapy

KW - FKBP5

KW - gene expression

KW - hippocampus

KW - posttraumatic stress disorder

KW - structural brain imaging

UR - http://www.scopus.com/inward/record.url?scp=84887223481&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84887223481&partnerID=8YFLogxK

U2 - 10.1016/j.biopsych.2013.05.017

DO - 10.1016/j.biopsych.2013.05.017

M3 - Article

C2 - 23856297

AN - SCOPUS:84887223481

VL - 74

SP - 793

EP - 800

JO - Biological Psychiatry

JF - Biological Psychiatry

SN - 0006-3223

IS - 11

ER -