title: The role of FKBP5 genotype in moderating long-term effectiveness of exposure-based psychotherapy for posttraumatic stress disorder.
abstract: Exposure-based therapies are considered the state-of-the-art treatment for Posttraumatic Stress Disorder (PTSD). Yet, a substantial number of PTSD patients do not recover after therapy. In the light of the well-known gene × environment interactions on the risk for PTSD, research on individual genetic factors that influence treatment success is warranted. The gene encoding FK506-binding protein 51 (FKBP5), a co-chaperone of the glucocorticoid receptor (GR), has been associated with stress reactivity and PTSD risk. As FKBP5 single-nucleotide polymorphism rs1360780 has a putative functional role in the regulation of FKBP5 expression and GR sensitivity, we hypothesized that this polymorphism influences PTSD treatment success. We investigated the effects of FKBP5 rs1360780 genotype on Narrative Exposure Therapy (NET) outcome, an exposure-based short-term therapy, in a sample of 43 survivors of the rebel war in Northern Uganda. PTSD symptom severity was assessed before and 4 and 10 months after treatment completion. At the 4-month follow-up, there were no genotype-dependent differences in therapy outcome. However, the FKBP5 genotype significantly moderated the long-term effectiveness of exposure-based psychotherapy. At the 10-month follow-up, carriers of the rs1360780 risk (T) allele were at increased risk of symptom relapse, whereas non-carriers showed continuous symptom reduction. This effect was reflected in a weaker treatment effect size (Cohen's D=1.23) in risk allele carriers compared with non-carriers (Cohen's D=3.72). Genetic factors involved in stress response regulation seem to not only influence PTSD risk but also responsiveness to psychotherapy and could hence represent valuable targets for accompanying medication.
authors: Clinical and Biological Psychology, Institute for Psychology and Education, University of Ulm, Ulm, Germany.
authors: S
authors: S
authors: Wilker
authors: Clinical Psychology and Neuropsychology, University of Konstanz, Konstanz, Germany.
authors: A
authors: A
authors: Pfeiffer
authors: SAP Switzerland AG, Tägerwilen, Switzerland.
authors: S
authors: S
authors: Kolassa
authors: Clinical Psychology and Neuropsychology, University of Konstanz, Konstanz, Germany.
authors: T
authors: T
authors: Elbert
authors: Clinical Psychology and Neuropsychology, University of Konstanz, Konstanz, Germany.
authors: B
authors: B
authors: Lingenfelder
authors: Faculty of Medicine, Gulu University, Gulu, Uganda.
authors: E
authors: E
authors: Ovuga
authors: Division of Molecular Neuroscience, University of Basel, Basel, Switzerland.
authors: A
authors: A
authors: Papassotiropoulos
authors: Division of Cognitive Neuroscience, University of Basel, Basel, Switzerland.
authors: D
authors: D
authors: de Quervain
authors: Clinical and Biological Psychology, Institute for Psychology and Education, University of Ulm, Ulm, Germany.
authors: I-T
authors: 0000000178471847
authors: IT
authors: Kolassa
mesh_terms: D000328:Adult; D005260:Female; D005838:Genotype; D006801:Humans; D007171:Implosive Therapy / Q000379:methods*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012008:Recurrence; D013313:Stress Disorders, Post-Traumatic / Q000209:etiology / Q000235:genetics* / Q000628:therapy*; D017741:Survivors / Q000523:psychology; D022021:Tacrolimus Binding Proteins / Q000235:genetics*; D016896:Treatment Outcome; D014857:Warfare; D000099159:Tacrolimus Binding Protein 5
chemical_list: D022021:Tacrolimus Binding Proteins; D000099159:Tacrolimus Binding Protein 5