The role of FKBP5 genotype in moderating long-term effectiveness of exposure-based psychotherapy for posttraumatic stress disorder

Translational Psychiatry

Volumn 4, Issue , 2014, Pages

  Wilker, S ^a   Pfeiffer, A ^b   Kolassa, S ^c   Elbert, T ^b   Lingenfelder, B ^b   Ovuga, E ^d   Papassotiropoulos, A ^e   De Quervain, D ^e   Kolassa, I T ^a  

^a UNIVERSITY OF ULM   (Germany)

^b UNIVERSITY OF KONSTANZ   (Germany)

^c SAP AG   (Switzerland)

^d GULU UNIVERSITY   (Uganda)

^e UNIVERSITY OF BASEL   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ADULT; AGE DISTRIBUTION; ALLELE; ARTICLE; AVOIDANCE BEHAVIOR; CLINICAL ARTICLE; DISEASE SEVERITY; DNA POLYMORPHISM; EXPOSURE BASED PSYCHOTHERAPY; FEMALE; FKBP 5 GENE; FOLLOW UP; GENE; GENE FUNCTION; GENETIC RISK; GENOTYPE; HETEROZYGOTE; HUMAN; MALE; OUTCOME ASSESSMENT; POSTTRAUMATIC STRESS DISORDER; PSYCHOTHERAPY; SEX RATIO; SHORT COURSE THERAPY; SUICIDAL BEHAVIOR; SURVIVOR; THERAPY EFFECT; UGANDA; BEHAVIOR THERAPY; GENETICS; MIDDLE AGED; PROCEDURES; PSYCHOLOGY; RECURRENT DISEASE; SINGLE NUCLEOTIDE POLYMORPHISM; STRESS DISORDERS, POST-TRAUMATIC; TREATMENT OUTCOME; WAR; EFFECT SIZE; EXPOSURE; HEREDITY; NARRATIVE EXPOSURE THERAPY; RELAPSE; STRESS;

FK 506 BINDING PROTEIN; TACROLIMUS BINDING PROTEIN 5; FK 506 BINDING PROTEIN 51; UNCLASSIFIED DRUG;

ADULT; FEMALE; GENOTYPE; HUMANS; IMPLOSIVE THERAPY; MALE; MIDDLE AGED; POLYMORPHISM, SINGLE NUCLEOTIDE; RECURRENCE; STRESS DISORDERS, POST-TRAUMATIC; SURVIVORS; TACROLIMUS BINDING PROTEINS; TREATMENT OUTCOME; WAR;

EID: 84902684521     PISSN: None     EISSN: 21583188     Source Type: Journal    
DOI: 10.1038/tp.2014.49     Document Type: Article

References (70)

1. Kolassa IT, Ertl V, Kolassa S, Onyut LP, Elbert T. The probability of spontaneous remission from PTSD depends on the number of traumatic event types experienced. Psychol Trauma 2010; 3: 169-174.
2. Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry 1995; 52: 1048-1060.
3. Kessler RC, Berglund P, Demler O, Jin R, Merikangas KR, Walters EE. Lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the National Comorbidity Survey Replication. Arch Gen Psychiatry 2005; 62: 593-602.
4. Neuner F, Schauer M, Karunakara U, Klaschik C, Robert C, Elbert T. Psychological trauma and evidence for enhanced vulnerability for posttraumatic stress disorder through previous trauma among West Nile refugees. BMC Psychiatry 2004; 4: 34.
5. Kubzansky LD, Bordelois P, Jun HJ, Roberts AL, Cerda M, Bluestone N et al. The weight of traumatic stress: a prospective study of posttraumatic stress disorder symptoms and weight status in women. JAMA Psychiatry 2013; 71: 44-51.
6. Glaesmer H, Brahler E, Gundel H, Riedel-Heller SG. The association of traumatic experiences and posttraumatic stress disorder with physical morbidity in old age: a German population-based study. Psychosom Med 2011; 73: 401-406.
7. Jakupcak M, Cook J, Imel Z, Fontana A, Rosenheck R, McFall M. Posttraumatic stress disorder as a risk factor for suicidal ideation in Iraq and Afghanistan War veterans. J Trauma Stress 2009; 22: 303-306.
8. Bisson JI, Ehlers A, Matthews R, Pilling S, Richards D, Turner S. Psychological treatments for chronic post-traumatic stress disorder. Systematic review and meta-analysis. Br J Psychiatry 2007; 190: 97-104.
9. Ehlers A, Bisson J, Clark DM, Creamer M, Pilling S, Richards D et al. Do all psychological treatments really work the same in posttraumatic stress disorder? Clin Psychol Rev 2010; 30: 269-276.
10. Bradley R, Greene J, Russ E, Dutra L, Westen D. A multidimensional meta-analysis of psychotherapy for PTSD. Am J Psychiatry 2005; 162: 214-227.
11. Elbert T, Schauer M. Burnt into memory. Nature 2002; 419: 883.
12. Jovanovic T, Ressler KJ. How the neurocircuitry and genetics of fear inhibition may inform our understanding of PTSD. Am J Psychiatry 2010; 167: 648-662.
13. Rothbaum BO, Davis M. Applying learning principles to the treatment of posttrauma reactions. Ann N Y Acad Sci 2003; 1008: 112-121.
14. True WR, Rice J, Eisen SA, Heath AC, Goldberg J, Lyons MJ et al. A twin study of genetic and environmental contributions to liability for posttraumatic stress symptoms. Arch Gen Psychiatry 1993; 50: 257-264.
15. Stein MB, Jang KL, Taylor S, Vernon PA, Livesley WJ. Genetic and environmental influences on trauma exposure and posttraumatic stress disorder symptoms: a twin study. Am J Psychiatry 2002; 159: 1675-1681.
16. Wilker S, Kolassa IT. The formation of a neural fear network in posttraumatic stress disorder: Insights from molecular genetics. Clin Psychol Sci 2013; 1: 452-469.
17. Bryant RA, Felmingham KL, Falconer EM, Pe Benito L, Dobson-Stone C, Pierce KD et al. Preliminary evidence of the short allele of the serotonin transporter gene predicting poor response to cognitive behavior therapy in posttraumatic stress disorder. Biol Psychiatry 2010; 67: 1217-1219.
18. Felmingham KL, Dobson-Stone C, Schofield PR, Quirk GJ, Bryant RA. The brainderived neurotrophic factor Val66Met polymorphism predicts response to exposure therapy in posttraumatic stress disorder. Biol Psychiatry 2013; 73: 1059-1063.
19. Pervanidou P, Chrousos GP. Neuroendocrinology of post-traumatic stress disorder. Prog Brain Res 2010; 182: 149-160.
20. Sapolsky RM, Romero LM, Munck AU. How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev 2000; 21: 55-89.
21. Wochnik GM, Ruegg J, Abel GA, Schmidt U, Holsboer F, Rein T. FK506-binding proteins 51 and 52 differentially regulate dynein interaction and nuclear translocation of the glucocorticoid receptor in mammalian cells. J Biol Chem 2005; 280: 4609-4616.
22. Denny WB, Valentine DL, Reynolds PD, Smith DF, Scammell JG. Squirrel monkey immunophilin FKBP51 is a potent inhibitor of glucocorticoid receptor binding. Endocrinology 2000; 141: 4107-4113.
23. Hubler TR, Scammell JG. Intronic hormone response elements mediate regulation of FKBP5 by progestins and glucocorticoids. Cell Stress Chaperones 2004; 9: 243-252.
24. Vermeer H, Hendriks-Stegeman BI, van der Burg B, van Buul-Offers SC, Jansen M. Glucocorticoid-induced increase in lymphocytic FKBP51 messenger ribonucleic acid expression: a potential marker for glucocorticoid sensitivity, potency, and bioavailability. J Clin Endocrin Metab 2003; 88: 277-284.
25. Binder EB. The role of FKBP5, a co-chaperone of the glucocorticoid receptor in the pathogenesis and therapy of affective and anxiety disorders. Psychoneuroendocrinology 2009; 34: S186-S195.
26. Yehuda R. Status of glucocorticoid alterations in post-traumatic stress disorder. Ann N Y Acad Sci 2009; 1179: 56-69.
27. van Zuiden M, Kavelaars A, Geuze E, Olff M, Heijnen CJ. Predicting PTSD: preexisting vulnerabilities in glucocorticoid-signaling and implications for preventive interventions. Brain Behav Immun 2013; 30: 12-21.
28. de Quervain DJ-F, Aerni A, Schelling G, Roozendaal B. Glucocorticoids and the regulation of memory in health and disease. Front Neuroendocrinol 2009; 30: 358-370.
29. Pitman RK, Rasmusson AM, Koenen KC, Shin LM, Orr SP, Gilbertson MW et al. Biological studies of post-traumatic stress disorder. Nat Rev Neurosci 2012; 13: 769-787.
30. Klengel T, Mehta D, Anacker C, Rex-Haffner M, Pruessner JC, Pariante CM et al. Allele-specific FKBP5 DNA demethylation mediates gene-childhood trauma interactions. Nat Neurosci 2013; 16: 33-41.
31. Binder EB, Salyakina D, Lichtner P, Wochnik GM, Ising M, Putz B et al. Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nat Genet 2004; 36: 1319-1325.
32. Binder EB, Bradley RG, Liu W, Epstein MP, Deveau TC, Mercer KB et al. Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA 2008; 299: 1291-1305.
33. Ising M, Depping AM, Siebertz A, Lucae S, Unschuld PG, Kloiber S et al. Polymorphisms in the FKBP5 gene region modulate recovery from psychosocial stress in healthy controls. Eur J Neurosci 2008; 28: 389-398.
34. Buchmann AF, Holz N, Boecker R, Blomeyer D, Rietschel M, Witt SH et al. Moderating role of FKBP5 genotype in the impact of childhood adversity on cortisol stress response during adulthood. Eur Neuropsychopharmacol 2013; 24: 837-845.
35. Mahon PB, Zandi PP, Potash JB, Nestadt G, Wand GS. Genetic association of FKBP5 and CRHR1 with cortisol response to acute psychosocial stress in healthy adults. Psychopharmacology (Berl) 2013; 227: 231-241.
36. Zimmermann P, Bruckl T, Nocon A, Pfister H, Binder EB, Uhr M et al. Interaction of FKBP5 gene variants and adverse life events in predicting depression onset: results from a 10-year prospective community study. Am J Psychiatry 2011; 168: 1107-1116.
37. Lekman M, Laje G, Charney D, Rush AJ, Wilson AF, Sorant AJ et al. The FKBP5-gene in depression and treatment response - An association study in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) Cohort. Biol Psychiatry 2008; 63: 1103-1110.
38. Papiol S, Arias B, Gasto C, Gutierrez B, Catalan R, Fananas L. Genetic variability at HPA axis in major depression and clinical response to antidepressant treatment. J Affect Disord 2007; 104: 83-90.
39. Minelli A, Maffioletti E, Cloninger CR, Magri C, Sartori R, Bortolomasi M et al. Role of allelic variants of FK506-binding protein 51 (fkbp5) gene in the development of anxiety disorders. Depress Anxiety 2013; 30: 1170-1176.
40. Roy A, Gorodetsky E, Yuan Q, Goldman D, Enoch MA. Interaction of FKBP5, a stress-related gene, with childhood trauma increases the risk for attempting suicide. Neuropsychopharmacology 2010; 35: 1674-1683.
41. Koenen KC, Saxe G, Purcell S, Smoller JW, Bartholomew D, Miller A et al. Polymorphisms in FKBP5 are associated with peritraumatic dissociation in medically injured children. Mol Psychiatry 2005; 10: 1058-1059.
42. Xie P, Kranzler HR, Poling J, Stein MB, Anton RF, Farrer LA et al. Interaction of FKBP5 with childhood adversity on risk for post-traumatic stress disorder. Neuropsychopharmacology 2010; 35: 1684-1692.
43. Sarapas C, Cai G, Bierer LM, Golier JA, Galea S, Ising M et al. Genetic markers for PTSD risk and resilience among survivors of the World Trade Center attacks. Dis Markers 2011; 30: 101-110.
44. Mehta D, Gonik M, Klengel T, Rex-Haffner M, Menke A, Rubel J et al. Using polymorphisms in FKBP5 to define biologically distinct subtypes of posttraumatic stress disorder: evidence from endocrine and gene expression studies. Arch Gen Psychiatry 2011; 68: 901-910.
45. Schauer M, Neuner F, Elbert T. Narrative Exposure Therapy. A Short- Term intervention for Traumatic Stress Disorders after War, Terror or Torture. 2nd edn, Hogrefe & Huber: Göttingen, Germany, 2011.
46. Robjant K, Fazel M. The emerging evidence for narrative exposure therapy: a review. Clin Psychol Rev 2010; 30: 1030-1039.
47. Ertl V, Pfeiffer A, Schauer E, Elbert T, Neuner F. Community-implemented trauma therapy for former child soldiers in Northern Uganda: a randomized controlled trial. JAMA 2011; 306: 503-512.
48. Foa EB, Cashman L, Jaycox L, Perry K. The validation of a self-report measure of posttraumatic stress disorder: The Posttraumatic Diagnostic Scale. Psychol Assess 1997; 9: 445-451.
49. Wilker S, Kolassa S, Vogler C, Lingenfelder B, Elbert T, Papassotiropoulos A et al. The role of memory-related gene WWC1 (KIBRA) in lifetime posttraumatic stress disorder: evidence from two independent samples from African conflict regions. Biol Psychiatry 2013; 74: 664-671.
50. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998; 59: 22-33.
51. Ertl V, Pfeiffer A, Saile R, Schauer E, Elbert T, Neuner F. Validation of a mental health assessment in an African conflict population. Psychol Assess 2010; 22: 318-324.
52. Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MA, Bender D et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 2007; 81: 559-575.
53. R Core Team. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing: Vienna, Austria, 2013.
54. Pinheiro J, Bates D, DebRoy S, Sarkar D and the R Development Core Team. nlme: Linear and Nonlinear Mixed Effects Models. R package version 3.1-111 2013.
55. Pinheiro J, Bates D. Unconstrained parametrizations for variance-covariance matrices. Stat Comput 1996; 6: 289-296.
56. Pinheiro J, Bates D. Mixed-Effects Models in S and S-PLUS. Statistics and Computing: Springer: New York, NY, USA, 2000.
57. Burnham KP, Anderson DR. Model Selection and Multi-Model Inference: A Practical Information-Theoretic Approach. 2nd edn, Springer: New York, NY, USA, 2002.
58. Hothorn T, Bretz F, Westfall P. Simultaneous inference in general parametric models. Biom J 2008; 50: 346-363.
59. Hamacher-Dang TC, Engler H, Schedlowski M, Wolf OT. Stress enhances the consolidation of extinction memory in a predictive learning task. Front Behav Neurosci 2013; 7: 108.
60. Soravia LM, Heinrichs M, Winzeler L, Fisler M, Schmitt W, Horn H et al. Glucocorticoids enhance in vivo exposure-based therapy of spider phobia. Depress Anxiety 2013; 31: 429-435.
61. de Quervain DJ-F, Bentz D, Michael T, Bolt OC, Wiederhold BK, Margraf J et al. Glucocorticoids enhance extinction-based psychotherapy. Proc Natl Acad Sci USA 2011; 108: 6621-6625.
62. Bentz D, Michael T, de Quervain DJ, Wilhelm FH. Enhancing exposure therapy for anxiety disorders with glucocorticoids: from basic mechanisms of emotional learning to clinical applications. J Anxiety Disord 2010; 24: 223-230.
63. Segman RH, Shefi N, Goltser-Dubner T, Friedman N, Kaminski N, Shalev AY. Peripheral blood mononuclear cell gene expression profiles identify emergent posttraumatic stress disorder among trauma survivors. Mol Psychiatry 2005; 10: 500-513, 425.
64. Yehuda R, Cai G, Golier JA, Sarapas C, Galea S, Ising M et al. Gene expression patterns associated with posttraumatic stress disorder following exposure to the World Trade Center attacks. Biol Psychiatry 2009; 66: 708-711.
65. Levy-Gigi E, Szabo C, Kelemen O, Keri S. Association among clinical response, hippocampal volume, and FKBP5 gene expression in individuals with posttraumatic stress disorder receiving cognitive behavioral therapy. Biol Psychiatry 2013; 74: 793-800.
66. Yehuda R, Daskalakis NP, Desarnaud F, Makotkine I, Lehrner AL, Koch E et al. Epigenetic biomarkers as predictors and correlates of symptom improvement following psychotherapy in combat veterans with PTSD. Front Psychiatry 2013; 4: 118.
67. Aerni A, Traber R, Hock C, Roozendaal B, Schelling G, Papassotiropoulos A et al. Low-dose cortisol for symptoms of posttraumatic stress disorder. Am J Psychiatry 2004; 161: 1488-1490.
68. Mollica RF, McInnes K, Poole C, Tor S. Dose-effect relationships of trauma to symptoms of depression and post-traumatic stress disorder among Cambodian survivors of mass violence. Br J Psychiatry 1998; 173: 482-488.
69. Zannas AS, Binder EB. Gene-environment interactions at the FKBP5 locus: sensitive periods, mechanisms and pleiotropism. Genes Brain Behav 2014; 13: 25-37.
70. Schmidt MV, Paez-Pereda M, Holsboer F, Hausch F. The prospect of FKBP51 as a drug target. ChemMedChem 2012; 7: 1351-1359.