Sex dependent influence of a functional polymorphism in steroid 5-α-reductase type 2 (SRD5A2) on post-traumatic stress symptoms

American Journal of Medical Genetics, Part B: Neuropsychiatric Genetics

Volumn 162, Issue 3, 2013, Pages 283-292

  Gillespie, Charles F ^a   Almli, Lynn M ^a   Smith, Alicia K ^a   Bradley, Bekh ^a,b   Kerley, Kimberly ^c   Crain, Daniel F ^a   Mercer, Kristina B ^c   Weiss, Tamara ^a   Phifer, Justine ^a   Tang, Yilang ^a   Cubells, Joseph F ^a   Binder, Elisabeth B ^a,d   Conneely, Karen N ^a   Ressler, Kerry J ^a,c,e  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b ATLANTA VA MEDICAL CENTER   (United States)

^c HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^d MAX PLANCK INSTITUTE OF PSYCHIATRY   (Germany)

^e EMORY UNIVERSITY   (United States)

Author keywords

African American; Civilian; Cortisol; Genetic; Human; Male; PTSD; Testosterone; Trauma

Indexed keywords

ANDROSTANOLONE; HYDROCORTISONE; STEROID 5ALPHA REDUCTASE 2;

ADULT; AFRICAN AMERICAN; ARTICLE; DISEASE SEVERITY; FEMALE; GENE REPLICATION; GENETIC ASSOCIATION; GENETIC VARIABILITY; GENOTYPE; HORMONE METABOLISM; HUMAN; HYDROCORTISONE BLOOD LEVEL; MAJOR CLINICAL STUDY; MALE; POSTTRAUMATIC STRESS DISORDER; PRIORITY JOURNAL; SEX DIFFERENCE; SINGLE NUCLEOTIDE POLYMORPHISM; SOCIOECONOMICS;

3-OXO-5-ALPHA-STEROID 4-DEHYDROGENASE; ADULT; AFRICAN AMERICANS; DEPRESSION; FEMALE; GENETIC PREDISPOSITION TO DISEASE; GENOTYPE; HUMANS; HYDROCORTISONE; MALE; PHENOTYPE; POLYMORPHISM, GENETIC; QUESTIONNAIRES; SEX FACTORS; STRESS DISORDERS, POST-TRAUMATIC; TESTOSTERONE; WOUNDS AND INJURIES;

EID: 84875284885     PISSN: 15524841     EISSN: 1552485X     Source Type: Journal    
DOI: 10.1002/ajmg.b.32147     Document Type: Article

References (79)

1. Ahn J, Schumacher FR, et al. 2009. Quantitative trait loci predicting circulating sex steroid hormones in men from the NCI-Breast and Prostate Cancer Cohort Consortium (BPC3). Hum Mol Genet 18(19):3749-3757.
2. Aikey JL, Nyby JG, et al. 2002. Testosterone rapidly reduces anxiety in male house mice (Mus musculus). Horm Behav 42(4):448-460.
3. Alim TN, Graves E, et al. 2006. Trauma exposure, posttraumatic stress disorder and depression in an African-American primary care population. J Natl Med Assoc 98(10):1630-1636.
4. Allen NE, Forrest MS, et al. 2001. The association between polymorphisms in the CYP17 and 5alpha-reductase (SRD5A2) genes and serum androgen concentrations in men. Cancer Epidemiol Biomarkers Prev 10(3):185-189.
5. Anda RF, Felitti VJ, et al. 2006. The enduring effects of abuse and related adverse experiences in childhood. A convergence of evidence from neurobiology and epidemiology. Eur Arch Psychiatry Clin Neurosci 256(3):174-186.
6. Andersson S, Berman DM, et al. 1991. Deletion of steroid 5 alpha-reductase 2 gene in male pseudohermaphroditism. Nature 354(6349):159-161.
7. Archer J. 1976. Testosterone and fear behavior in male chicks. Physiol Behav 17(4):561-564.
8. Baker DG, Ekhator NN, et al. 2005. Higher levels of basal serial CSF cortisol in combat veterans with posttraumatic stress disorder. Am J Psychiatry 162(5):992-994.
9. Bauer M, Priebe S, et al. 1994. Psychological and endocrine abnormalities in refugees from East Germany: Part II. Serum levels of cortisol, prolactin, luteinizing hormone, follicle stimulating hormone, and testosterone. Psychiatry Res 51(1):75-85.
10. Beck AT, Ward CH, et al. 1961. An inventory for measuring depression. Arch Gen Psychiatry 4:561-571.
11. Beck AT, Steer RA, et al. 1988. Psychometric properties of the Beck Depression Inventory: Twenty-five years of evaluation. Clin Psychol Rev 8:77-100.
12. Bernstein DP, Fink L. 1998. Childhood trauma questionnaire manual. San Antonio, TX: Psychological Corporation.
13. Bernstein DP, Fink L, et al. 1994. Initial reliability and validity of a new retrospective measure of child abuse and neglect. Am J Psychiatry 151(8):1132-1136.
14. Bernstein DP, Ahluvalia T, et al. 1997. Validity of the Childhood Trauma Questionnaire in an adolescent psychiatric population. J Am Acad Child Adolesc Psychiatry 36(3):340-348.
15. Bernstein DP, Stein JA, et al. 2003. Development and validation of a brief screening version of the Childhood Trauma Questionnaire. Child Abuse Negl 27(2):169-190.
16. Bierer LM, Tischler L, et al. 2006. Clinical correlates of 24-h cortisol and norepinephrine excretion among subjects seeking treatment following the world trade center attacks on 9/11. Ann N Y Acad Sci 1071:514-520.
17. Binder EB, Bradley RG, et al. 2008. Association of FKBP5 polymorphisms and childhood abuse with risk of posttraumatic stress disorder symptoms in adults. JAMA 299(11):1291-1305.
18. Boissy A, Bouissou MF. 1994. Effects of androgen treatment on behavioral and physiological responses of heifers to fear-eliciting situations. Horm Behav 28(1):66-83.
19. Bradley RG, Binder EB, et al. 2008. Influence of child abuse on adult depression: moderation by the corticotropin-releasing hormone receptor gene. Arch Gen Psychiatry 65(2):190-200.
20. Coffey SF, Dansky BS, et al. 1998. Screening for PTSD in a substance abuse sample: psychometric properties of a modified version of the PTSD Symptom Scale Self-Report Posttraumatic stress disorder. J Trauma Stress 11(2):393-399.
21. Dohrenwind BP, Turner JB, Turse NA, Adams BG, Koenen KC. 2006. The psychological risks of Vietnam for U.S. veterans: A revisit with new data and methods. Science 313:979-982.
22. Edinger KL, Lee B, et al. 2004. Mnemonic effects of testosterone and its 5alpha-reduced metabolites in the conditioned fear and inhibitory avoidance tasks. Pharmacol Biochem Behav 78(3):559-568.
23. Ellis JA, Panagiotopoulos S, et al. 2005. Androgenic correlates of genetic variation in the gene encoding 5alpha-reductase type 1. J Hum Genet 50(10):534-537.
24. Falsetti SA, Resnick HS, et al. 1993. The Modified PTSD Symptom Scale: A brief self-report measure of posttraumatic stress disorder. Behav Ther 16:161-162.
25. Febbo PG, Kantoff PW, et al. 1999. The V89L polymorphism in the 5alpha-reductase type 2 gene and risk of prostate cancer. Cancer Res 59(23):5878-5881.
26. Finken MJ, Andrews RC, et al. 1999. Cortisol metabolism in healthy young adults: sexual dimorphism in activities of A-ring reductases, but not 11beta-hydroxysteroid dehydrogenases. J Clin Endocrinol Metab 84(9):3316-3321.
27. Foa EB, Tolin DF. 2000. Comparison of the PTSD Symptom Scale-Interview Version and the Clinician Administered PTSD Scale. J Traum Stress 13(2):181-191.
28. Frye CA, Van Keuren KR, et al. 1996a. Behavioral effects of 3 alpha-androstanediol. I: Modulation of sexual receptivity and promotion of GABA-stimulated chloride flux. Behav Brain Res 79(1-2):109-118.
29. Frye CA, Van Keuren KR, et al. 1996b. Analgesic effects of the neurosteroid 3 alpha-androstanediol. Brain Res 709(1):1-9.
30. Frye CA, Edinger KL. 2004. Testosterone's metabolism in the hippocampus may mediate its anti-anxiety effects in male rats. Pharmacol Biochem Behav 78(3):473-481.
31. Frye CA, Edinger K, et al. 2008. Androgen administration to aged male mice increases anti-anxiety behavior and enhances cognitive performance. Neuropsychopharmacology 33(5):1049-1061.
32. Gann PH, Hennekens CH, et al. 1996. Prospective study of sex hormone levels and risk of prostate cancer. J Natl Cancer Inst 88(16):1118-1126.
33. Gillespie CF, Bradley B, et al. 2009. Trauma exposure and stress-related disorders in inner city primary care patients. Gen Hosp Psychiatry 31(6):505-514.
34. Gisleskog PO, Hermann D, et al. 1998. A model for the turnover of dihydrotestosterone in the presence of the irreversible 5 alpha-reductase inhibitors GI198745 and finasteride. Clin Pharmacol Ther 64(6):636-647.
35. Griffin MG, Resick PA, et al. 2005. Enhanced cortisol suppression following dexamethasone administration in domestic violence survivors. Am J Psychiatry 162(6):1192-1199.
36. Hermans EJ, Putman P, et al. 2006. A single administration of testosterone reduces fear-potentiated startle in humans. Biol Psychiatry 59(9):872-874.
37. Hoge CW, Castro CA, et al. 2004. Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care. N Engl J Med 351(1):13-22.
38. Hsing AW, Chen C, et al. 2001. Polymorphic markers in the SRD5A2 gene and prostate cancer risk: A population-based case-control study. Cancer Epidemiol Biomarkers Prev 10(10):1077-1082.
39. Inslicht SS, Marmar CR, et al. 2006. Increased cortisol in women with intimate partner violence-related posttraumatic stress disorder. Psychoneuroendocrinology 31(7):825-838.
40. Kessler RC, Sonnega A, et al. 1995. Posttraumatic stress disorder in the National Comorbidity Survey. Arch Gen Psychiatry 52(12):1048-1060.
41. Li J, Coates RJ, et al. 2010a. Steroid 5-{alpha}-reductase Type 2 (SRD5a2) gene polymorphisms and risk of prostate cancer: A HuGE review. Am J Epidemiol 171(1):1-13.
42. Li X, Huang Y, et al. 2010b. Meta-analysis of three polymorphisms in the steroid-5-alpha-reductase, alpha polypeptide 2 gene (SRD5A2) and risk of prostate cancer. Mutagenesis 26(3):371-383.
43. Makridakis N, Ross RK, et al. 1997. A prevalent missense substitution that modulates activity of prostatic steroid 5alpha-reductase. Cancer Res 57(6):1020-1022.
44. Makridakis NM, di Salle E, et al. 2000. Biochemical and pharmacogenetic dissection of human steroid 5 alpha-reductase type II. Pharmacogenetics 10(5):407-413.
45. McInnes KJ, Kenyon CJ, et al. 2004. 5alpha-reduced glucocorticoids, novel endogenous activators of the glucocorticoid receptor. J Biol Chem 279(22):22908-22912.
46. Milad MR, Zeidan MA, et al. 2010. The influence of gonadal hormones on conditioned fear extinction in healthy humans. Neuroscience 168(3):652-658.
47. Morgan CA III, Wang S, et al. 2000. Hormone profiles in humans experiencing military survival training. Biol Psychiatry 47(10):891-901.
48. Mulchahey JJ, Ekhator NN, et al. 2001. Cerebrospinal fluid and plasma testosterone levels in post-traumatic stress disorder and tobacco dependence. Psychoneuroendocrinology 26(3):273-285.
49. Newport DJ, Heim C, et al. 2004. Pituitary-adrenal responses to standard and low-dose dexamethasone suppression tests in adult survivors of child abuse. Biol Psychiatry 55(1):10-20.
50. Paterson JM, Holmes MC, et al. 2007. Liver-selective transgene rescue of hypothalamic-pituitary-adrenal axis dysfunction in 11beta-hydroxysteroid dehydrogenase type 1-deficient mice. Endocrinology 148(3):961-966.
51. Patterson N, Price AL, et al. 2006. Population structure and eigenanalysis. PLoS Genet 2(12):e190.
52. Peterson RE, Imperato-McGinley J, et al. 1985. Urinary steroid metabolites in subjects with male pseudohermaphroditism due to 5 alpha-reductase deficiency. Clin Endocrinol (Oxf) 23(1):43-53.
53. Pinna G. 2010. In a mouse model relevant for post-traumatic stress disorder, selective brain steroidogenic stimulants (SBSS) improve behavioral deficits by normalizing allopregnanolone biosynthesis. Behav Pharmacol 21(5-6):438-450.
54. Pinna G, Agis-Balboa RC, et al. 2008. Neurosteroid biosynthesis regulates sexually dimorphic fear and aggressive behavior in mice. Neurochem Res 33(10):1990-2007.
55. Purcell S, Neale B, et al. 2007. PLINK: A tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81(3):559-575.
56. Rahe RH, Karson S, et al. 1990. Psychological and physiological assessments on American hostages freed from captivity in Iran. Psychosom Med 52(1):1-16.
57. Rasmusson AM, Vasek J, et al. 2004. An increased capacity for adrenal DHEA release is associated with decreased avoidance and negative mood symptoms in women with PTSD. Neuropsychopharmacology 29(8):1546-1557.
58. Rasmusson AM, Pinna G, et al. 2006. Decreased cerebrospinal fluid allopregnanolone levels in women with posttraumatic stress disorder. Biol Psychiatry 60(7):704-713.
59. Ressler KJ, Mercer KB, et al. 2011. Post-traumatic stress disorder is associated with PACAP and the PAC1 receptor. Nature 470(7335):492-497.
60. Ross RK, Bernstein L, et al. 1992. 5-alpha-reductase activity and risk of prostate cancer among Japanese and US white and black males. Lancet 339(8798):887-889.
61. Russell DW, Wilson JD. 1994. Steroid 5 alpha-reductase: Two genes/two enzymes. Annu Rev Biochem 63:25-61.
62. Schwartz A, Bradley RG, et al. 2005a. Posttraumatic stress disorder among African Americans in an inner city mental health clinic. Psychiatr Serv 56(2):212-215.
63. Schwartz AC, Bradley R, et al. 2006. Pain medication use among patients with posttraumatic stress disorder. Psychosomatics 47(2):136-142.
64. Spivak B, Maayan R, et al. 2003. Plasma testosterone levels in patients with combat-related posttraumatic stress disorder. Neuropsychobiology 47(2):57-60.
65. Steen NE, Tesli M, et al. 2010. SRD5A2 is associated with increased cortisol metabolism in schizophrenia spectrum disorders. Prog Neuropsychopharmacol Biol Psychiatry 34(8):1500-1506.
66. Stoffel-Wagner B. 2003. Neurosteroid biosynthesis in the human brain and its clinical implications. Ann N Y Acad Sci 1007:64-78.
67. Stoffel-Wagner B, Watzka M, et al. 1998. Expression of 5alpha-reductase in the human temporal lobe of children and adults. J Clin Endocrinol Metab 83(10):3636-3642.
68. Stoffel-Wagner B, Beyenburg S, et al. 2000. Expression of 5alpha-reductase and 3alpha-hydroxisteroid oxidoreductase in the hippocampus of patients with chronic temporal lobe epilepsy. Epilepsia 41(2):140-147.
69. Thigpen AE, Silver RI, et al. 1993. Tissue distribution and ontogeny of steroid 5 alpha-reductase isozyme expression. J Clin Invest 92(2):903-910.
70. Tian C, Hinds DA, et al. 2006. A genomewide single-nucleotide-polymorphism panel with high ancestry information for African American admixture mapping. Am J Hum Genet 79(4):640-649.
71. van Honk J, Peper JS, et al. 2005. Testosterone reduces unconscious fear but not consciously experienced anxiety: Implications for the disorders of fear and anxiety. Biol Psychiatry 58(3):218-225.
72. Vandenheede M, Bouissou MF. 1993. Effect of androgen treatment on fear reactions in ewes. Horm Behav 27(4):435-448.
73. Wheler GH, Brandon D, et al. 2006. Cortisol production rate in posttraumatic stress disorder. J Clin Endocrinol Metab 91(9):3486-3489.
74. Wilson JD. 2001. The role of 5alpha-reduction in steroid hormone physiology. Reprod Fertil Dev 13(7-8):673-678.
75. Wong IL, Morris RS, et al. 1995. A prospective randomized trial comparing finasteride to spironolactone in the treatment of hirsute women. J Clin Endocrinol Metab 80(1):233-238.
76. Yehuda R, Southwick SM, et al. 1993. Enhanced suppression of cortisol following dexamethasone administration in posttraumatic stress disorder. Am J Psychiatry 150(1):83-86.
77. Yehuda R, Kahana B, et al. 1995. Low urinary cortisol excretion in Holocaust survivors with posttraumatic stress disorder. Am J Psychiatry 152(7):982-986.
78. Yehuda R, Yang RK, et al. 2006. Alterations in cortisol negative feedback inhibition as examined using the ACTH response to cortisol administration in PTSD. Psychoneuroendocrinology 31(4):447-451.
79. Yehuda R, Bierer LM, et al. 2009. Enduring effects of severe developmental adversity, including nutritional deprivation, on cortisol metabolism in aging Holocaust survivors. J Psychiatr Res 43(9):877-883.