Using polymorphisms in FKBP5 to define biologically distinct subtypes of posttraumatic stress disorder: Evidence from endocrine and gene expression studies

Archives of General Psychiatry

Volumn 68, Issue 9, 2011, Pages 901-910

  Mehta, Divya ^a   Gonik, Mariya ^a   Klengel, Torsten ^a   Rex Haffner, Monika ^a   Menke, Andreas ^a   Rubel, Jennifer ^a   Mercer, Kristina B ^e   Pütz, Benno ^a   Bradley, Bekh ^b,c   Holsboer, Florian ^a   Ressler, Kerry J ^b,d,e   Müller Myhsok, Bertram ^a   Binder, Elisabeth B ^a,b  

^a MAX PLANCK INSTITUTE OF PSYCHIATRY   (Germany)

^b EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c VETERANS AFFAIRS MEDICAL CENTER   (United States)

^d EMORY UNIVERSITY   (United States)

^e HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BINDING PROTEIN; DEXAMETHASONE; GLUCOCORTICOID RECEPTOR; HYDROCORTISONE; INTERLEUKIN 18; PROTEIN FKBP5; STAT PROTEIN; STEROID HORMONE; UNCLASSIFIED DRUG;

ADULT; AFRICAN AMERICAN; ALLELE; ARTICLE; BINDING SITE; BLOOD; CONTROLLED STUDY; DEXAMETHASONE SUPPRESSION TEST; DISEASE COURSE; FEMALE; GENE EXPRESSION; GENE EXPRESSION REGULATION; GENE INTERACTION; GENETIC ASSOCIATION; GENETIC RISK; GENETIC TRANSCRIPTION; GENOTYPE; HUMAN; HYDROCORTISONE BLOOD LEVEL; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; MAJOR CLINICAL STUDY; MALE; POSTTRAUMATIC STRESS DISORDER; RECEPTOR SENSITIVITY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SINGLE NUCLEOTIDE POLYMORPHISM; SOCIAL STATUS; UNIVERSITY HOSPITAL; WAITING ROOM;

ADULT; ALLELES; DEXAMETHASONE; DNA; FEMALE; GENE EXPRESSION PROFILING; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HUMANS; HYDROCORTISONE; INTERLEUKIN-18 RECEPTOR ALPHA SUBUNIT; MALE; PITUITARY-ADRENAL FUNCTION TESTS; POLYMORPHISM, SINGLE NUCLEOTIDE; PSYCHIATRIC STATUS RATING SCALES; RNA; SEVERITY OF ILLNESS INDEX; STRESS DISORDERS, POST-TRAUMATIC; TACROLIMUS BINDING PROTEINS;

EID: 80051926419     PISSN: 0003990X     EISSN: 15383636     Source Type: Journal    
DOI: 10.1001/archgenpsychiatry.2011.50     Document Type: Article

References (56)

1. Breslau N. The epidemiology of posttraumatic stress disorder: What is the extent of the problem? J Clin Psychiatry. 2001;62(suppl 17):16-22. (Pubitemid 32720661)
2. Kessler R.C., Sonnega A., Bromet E., Hughes M., Nelson C.B. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry. 1995;52 (12):1048-1060.
3. Koenen K.C., Lyons M.J., Goldberg J., Simpson J., Williams W.M., Toomey R., Eisen S.A., True W., Tsuang M.T. Co-twin control study of relationships among combat exposure, combat-related PTSD, and other mental disorders. J Trauma Stress. 2003;16(5):433-438. (Pubitemid 37280222)
4. Stein M.B., Jang K.L., Livesley W.J. Heritability of social anxiety-related concerns and personality characteristics: A twin study. J Nerv Ment Dis. 2002;190(4): 219-224. (Pubitemid 34326908)
5. True W.R., Rice J., Eisen S.A., Heath A.C., Goldberg J., Lyons M.J., Nowak J. A twin study of genetic and environmental contributions to liability for posttraumatic stress symptoms. Arch Gen Psychiatry. 1993;50(4):257-264. (Pubitemid 23115368)
6. Comings D.E., Muhleman D., Gysin R. Dopamine D2 receptor (DRD2) gene and susceptibility to posttraumatic stress disorder: A study and replication. Biol Psychiatry. 1996;40(5):368-372. (Pubitemid 26301067)
7. Gelernter J., Southwick S., Goodson S., Morgan A., Nagy L., Charney D.S. No association between D2 dopamine receptor (DRD2) "A" system alleles, or DRD2 haplotypes, and posttraumatic stress disorder. Biol Psychiatry. 1999;45(5): 620-625. (Pubitemid 29147371)
8. Segman R.H., Cooper-Kazaz R., Macciardi F., Goltser T., Halfon Y., Dobroborski T., Shalev A.Y. Association between the dopamine transporter gene and posttraumatic stress disorder. Mol Psychiatry. 2002;7(8):903-907.
9. Koenen K.C., Aiello A.E., Bakshis E., Amstadter A.B., Ruggiero K.J., Acierno R., Kilpatrick D.G., Gelernter J., Galea S. Modification of the association between serotonin transporter genotype and risk of posttraumatic stress disorder in adults by countylevel social environment. Am J Epidemiol. 2009;169(6):704-711.
10. Binder E.B., Bradley R.G., Liu W., Epstein M.P., Deveau T.C., Mercer K.B., Tang Y., Gillespie C.F., Heim C.M., Nemeroff C.B., Schwartz A.C., Cubells J.F., Ressler K.J. Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA. 2008;299(11):1291-1305. (Pubitemid 351439075)
11. Xie P., Kranzler H.R., Poling J., Stein M.B., Anton R.F., Farrer L.A., Gelernter J. Interaction of FKBP5 with childhood adversity on risk for post-traumatic stress disorder. Neuropsychopharmacology. 2010;35(8):1684-1692.
12. De Kloet E.R., Joe¨lsM, Holsboer F. Stress and the brain: From adaptation to disease. Nat Rev Neurosci. 2005;6(6):463-475. (Pubitemid 40769171)
13. Yehuda R., Yang R.K., Buchsbaum M.S., Golier J.A. Alterations in cortisol negative feedback inhibition as examined using the ACTH response to cortisol administration in PTSD. Psychoneuroendocrinology. 2006;31(4):447-451. (Pubitemid 43375946)
14. Mason J.W., Giller E.L., Kosten T.R., Ostroff R.B., Podd L. Urinary free-cortisol levels in posttraumatic stress disorder patients. J Nerv Ment Dis. 1986;174(3):145-149. (Pubitemid 16117404)
15. Yehuda R. Neuroendocrine aspects of PTSD. Handb Exp Pharmacol. 2005;(169): 371-403.
16. Yehuda R., Bierer L.M., Sarapas C., Makotkine I., Andrew R., Seckl J.R. Cortisol metabolic predictors of response to psychotherapy for symptoms of PTSD in survivors of the World Trade Center attacks on September 11, 2001. Psychoneuroendocrinology. 2009;34(9):1304-1313.
17. Yehuda R., Southwick S.M., Nussbaum G., Wahby V., Giller E.L. Jr, Mason J.W. Low urinary cortisol excretion in patients with posttraumatic stress disorder. J Nerv Ment Dis. 1990;178(6):366-369. (Pubitemid 20203850)
18. Grad I., Picard D. The glucocorticoid responses are shaped by molecular chaperones. Mol Cell Endocrinol. 2007;275(1-2):2-12. (Pubitemid 47260713)
19. Pratt W.B., Toft D.O. Steroid receptor interactions with heat shock protein and immunophilin chaperones. Endocr Rev. 1997;18(3):306-360. (Pubitemid 27246880)
20. Scammell J.G., Denny W.B., Valentine D.L., Smith D.F. Overexpression of the FK506- binding immunophilin FKBP51 is the common cause of glucocorticoid resistance in three New World primates. Gen Comp Endocrinol. 2001;124(2):152- 165.
21. Wochnik G.M., Rüegg J., Abel G.A., 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(6):4609-4616. (Pubitemid 40288629)
22. Binder E.B., Salyakina D., Lichtner P., Wochnik G.M., Ising M., Pütz B., Papiol S., Seaman S., Lucae S., Kohli M.A., Nickel T., Künzel H.E., Fuchs B., Majer M., Pfennig A., Kern N., Brunner J., Modell S., Baghai T., Deiml T., Zill P., Bondy B., Rupprecht R., Messer T., Köhnlein O., Dabitz H., Brückl T., Müller N., Pfister H., Lieb R., Mueller J.C., Lõhmussaar E, Strom TM, Bettecken T, Meitinger T, Uhr M, Rein T, Holsboer F, Muller-Myhsok B. Polymorphisms in FKBP5 are associated with increased recurrence of depressive episodes and rapid response to antidepressant treatment. Nat Genet. 2004;36(12):1319-1325.
23. Ising M, Depping AM, Siebertz A, Lucae S, Unschuld PG, Kloiber S, Horstmann S, Uhr M, Müller-Myhsok B, Holsboer F. Polymorphisms in the FKBP5 gene region modulate recovery from psychosocial stress in healthy controls. Eur J Neurosci. 2008;28(2):389-398.
24. Gillespie C.F., Bradley B., Mercer K., Smith A.K., Conneely K., Gapen M., Weiss T., Schwartz A.C., Cubells J.F., Ressler K.J. Trauma exposure and stress-related disorders in inner city primary care patients. Gen Hosp Psychiatry. 2009;31(6):505-514.
25. Gillespie C.F., Phifer J., Bradley B., Ressler K.J. Risk and resilience: Genetic and environmental influences on development of the stress response. Depress Anxiety. 2009;26(11):984-992.
26. Jovanovic T., Blanding N.Q., Norrholm S.D., Duncan E., Bradley B., Ressler K.J. Childhood abuse is associated with increased startle reactivity in adulthood. Depress Anxiety. 2009;26(11):1018-1026.
27. Schroeder A., Mueller O., Stocker S., Salowsky R., Leiber M., Gassmann M., Lightfoot S., Menzel W., Granzow M., Ragg T. The RIN: An RNA integrity number for assigning integrity values to RNA measurements. BMC Mol Biol. 2006;7:3.
28. Foa E.B., Tolin D.F. Comparison of the PTSD Symptom Scale-Interview Version and the Clinician-Administered PTSD scale. J Trauma Stress. 2000;13(2):181-191. (Pubitemid 30333790)
29. Blake D.D., Weathers F.W., Nagy L.M., Kaloupek D.G., Klauminzer G., Charney D.S., Keane T.M. A clinician rating scale for assessing current and lifetime PTSD: The CAPS-1. Behav Therapist. 1990;13:187-188.
30. Beck A.T., Ward C.H., Mendelson M., Mock J., Erbaugh J. An inventory for measuring depression. Arch Gen Psychiatry. 1961;4:561-571.
31. Hovens J.E., Bramsen I., Van der Ploeg H.M., Reuling I.E. Test-retest reliability of the trauma and life events self-report inventory. Psychol Rep. 2000;87(3, pt 1): 750-752.
32. Bernstein D.P., Stein J.A., Handelsman L. Predicting personality pathology among adult patients with substance use disorders: Effects of childhood maltreatment. Addict Behav. 1998;23(6):855-868. (Pubitemid 28443197)
33. Kellogg S.H., McHugh P.F., Bell K., Schluger J.H., Schluger R.P., LaForge K.S., Ho A., Kreek M.J. The Kreek-McHugh-Schluger-Kellogg Scale: A new, rapid method for quantifying substance abuse and its possible applications. Drug Alcohol Depend. 2003;69(2):137-150. (Pubitemid 36259776)
34. Huber W., Von Heydebreck A., Sültmann H., Poustka A., Vingron M. Variance stabilization applied to microarray data calibration and to the quantification of differential expression. Bioinformatics. 2002;18(suppl 1):S96-S104. (Pubitemid 41185642)
35. Potter D.M. A permutation test for inference in logistic regression with small- and moderate-sized data sets. Stat Med. 2005;24(5):693-708. (Pubitemid 40298121)
36. Wilcox R.R., Keselman H.J., Muska J., Cribbie R. Repeated measures ANOVA: Some new results on comparing trimmed means and means. Br J Math Stat Psychol. 2000;53(pt 1):69-82.
37. Krawetz S., Epple A., Scherf M. BiblioSphere: Hypothesis Generation in Regulatory Network Analysis. Bioinformatics for Systems Biology. New York, NY: Humana Press; 2009:401-412.
38. Scherf M., Epple A., Werner T. The next generation of literature analysis: Integration of genomic analysis into text mining. Brief Bioinform. 2005;6(3):287-297. (Pubitemid 41614550)
39. Sandelin A., Alkema W., Engström P., Wasserman W.W., Lenhard B. JASPAR: an open-access database for eukaryotic transcription factor binding profiles. Nucleic Acids Res. 2004;32(database issue):D91-D94.
40. Ramakers C., Ruijter J.M., Deprez R.H., Moorman A.F. Assumption-free analysis of quantitative real-time polymerase chain reaction (PCR) data. Neurosci Lett. 2003; 339(1):62-66.
41. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using realtime quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2001; 25(4):402-408.
42. Segman R.H., Shefi N., Goltser-Dubner T., Friedman N., Kaminski N., Shalev AY. Peripheral blood mononuclear cell gene expression profiles identify emergent post-traumatic stress disorder among trauma survivors. Mol Psychiatry. 2005; 10(5):500-513, 425.
43. Yehuda R., Cai G., Golier J.A., Sarapas C., Galea S., Ising M., Rein T., Schmeidler J., Müller-Myhsok B., Holsboer F., Buxbaum J.D. Gene expression patterns associated with posttraumatic stress disorder following exposure to the World Trade Center attacks. Biol Psychiatry. 2009;66(7):708-711.
44. Zieker J., Zieker D., Jatzko A., Dietzsch J., Nieselt K., Schmitt A., Bertsch T., Fassbender K., Spanagel R., Northoff H., Gebicke-Haerter P.J. Differential gene expression in peripheral blood of patients suffering from post-traumatic stress disorder. Mol Psychiatry. 2007;12(2):116-118. (Pubitemid 46160977)
45. Rietkerk T., Boks M.P., Sommer I.E., De Jong S., Kahn R.S., Ophoff R.A. Network analysis of positional candidate genes of schizophrenia highlights myelin-related pathways. Mol Psychiatry. 2009;14(4):353-355.
46. Yehuda R. Advances in understanding neuroendocrine alterations in PTSD and their therapeutic implications. Ann N Y Acad Sci. 2006;1071:137-166. (Pubitemid 44126726)
47. Lemieux A.M., Coe C.L. Abuse-related posttraumatic stress disorder: Evidence for chronic neuroendocrine activation in women. Psychosom Med. 1995;57(2): 105-115.
48. Yehuda R. Status of glucocorticoid alterations in post-traumatic stress disorder. Ann N Y Acad Sci. 2009;1179:56-69.
49. Bachmann A.W., Sedgley T.L., Jackson R.V., Gibson J.N., Young R.M., Torpy D.J. Glucocorticoid receptor polymorphisms and post-traumatic stress disorder. Psychoneuroendocrinology. 2005;30(3):297-306. (Pubitemid 39423363)
50. Vermeer H., Hendriks-Stegeman B.I., Van Suylekom D., Rijkers G.T., Van Buul-Offers S.C., Jansen M. An in vitro bioassay to determine individual sensitivity to glucocorticoids: Induction of FKBP51 mRNA in peripheral blood mononuclear cells. Mol Cell Endocrinol. 2004;218(1-2):49-55. (Pubitemid 38578427)
51. Woodruff P.G., Boushey H.A., Dolganov G.M., Barker C.S., Yang Y.H., Donnelly S., Ellwanger A., Sidhu S.S., Dao-Pick T.P., Pantoja C., Erle D.J., Yamamoto K.R., Fahy J.V. Genome-wide profiling identifies epithelial cell genes associated with asthma and with treatment response to corticosteroids. Proc Natl Acad Sci U S A. 2007; 104(40):15858-15863. (Pubitemid 350035389)
52. Engelhard I.M., Arntz A., Van den Hout M.A. Low specificity of symptoms on the post-traumatic stress disorder (PTSD) symptom scale: A comparison of individuals with PTSD, individuals with other anxiety disorders and individuals without psychopathology. Br J Clin Psychol. 2007;46(pt 4):449-456. (Pubitemid 350225899)
53. Segman R.H., Shalev A.Y. Genetics of posttraumatic stress disorder. CNS Spectr. 2003;8(9):693-698. (Pubitemid 38418989)
54. Drago A., De Ronchi D., Serretti A. Incomplete coverage of candidate genes: A poorly considered bias. Curr Genomics. 2007;8(7):476-483. (Pubitemid 351486278)
55. Hu F.Y., Hu W.B., Liu L., Yu L.H., Xi J., He X.H., Zhu M.R., Liu Z.L., Xu Y.M. Lack of replication of a previously reported association between polymorphism in the 3'UTR of the alpha-synuclein gene and Parkinson's disease in Chinese subjects. Neurosci Lett. 2010;479(1):31-33.
56. Holsboer F. How can we realize the promise of personalized antidepressant medicines? Nat Rev Neurosci. 2008;9(8):638-646.