High-dose testosterone treatment increases serotonin transporter binding in transgender people

Biological Psychiatry

Volumn 78, Issue 8, 2015, Pages 525-533

  Kranz, Georg S ^a   Wadsak, Wolfgang ^b   Kaufmann, Ulrike ^c   Savli, Markus ^a   Baldinger, Pia ^a   Gryglewski, Gregor ^a   Haeusler, Daniela ^b   Spies, Marie ^a   Mitterhauser, Markus ^b   Kasper, Siegfried ^a   Lanzenberger, Rupert ^a  

^a MEDICAL UNIVERSITY OF VIENNA   (Austria)

^b Division of Nuclear Medicine   (Austria)

^c UNIV KLIN FÜR FRAUENHEILKUNDE   (Austria)

Author keywords

Estradiol; Hormone treatment; Positron emission tomography; Serotonin transporter; Testosterone; Transsexual

Indexed keywords

CYPROTERONE ACETATE; ESTRADIOL; FINASTERIDE; GLYCERYL TRINITRATE; LYNESTRENOL; PROGESTERONE; SEROTONIN TRANSPORTER; TESTOSTERONE; TESTOSTERONE UNDECANOATE; TRIPTORELIN; ANDROGEN; ESTROGEN;

AMYGDALOID NUCLEUS; ANDROGEN THERAPY; ANTERIOR CINGULATE; ARTICLE; BLOOD SAMPLING; BRAIN REGION; CAUDATE NUCLEUS; CELL SURFACE; CINGULATE GYRUS; CLINICAL ARTICLE; CONTROLLED STUDY; DORSAL RAPHE NUCLEUS; DRUG DOSE INCREASE; DRUG MEGADOSE; ESTROGEN THERAPY; FEMALE; FEMALE TO MALE TRANSGENDER; HAIR LOSS; HIPPOCAMPUS; HORMONAL THERAPY; HORMONE BLOOD LEVEL; HUMAN; HYPOTHALAMUS; LONGITUDINAL STUDY; MALE; MALE TO FEMALE TRANSGENDER; MEDIAN RAPHE NUCLEUS; OUTCOME ASSESSMENT; POSITRON EMISSION TOMOGRAPHY; POSTERIOR CINGULATE; PRIORITY JOURNAL; PROGESTERONE BLOOD LEVEL; PROTEIN BINDING; PROTEIN EXPRESSION; PUTAMEN; SEX REASSIGNMENT; TESTOSTERONE BLOOD LEVEL; THALAMUS; ADULT; CASE CONTROL STUDY; CLASSIFICATION; DRUG EFFECTS; MIDDLE AGED; RAPHE NUCLEUS; STATISTICAL MODEL; TRANSGENDER; YOUNG ADULT;

ADULT; ANDROGENS; CASE-CONTROL STUDIES; ESTRADIOL; ESTROGENS; FEMALE; HUMANS; LINEAR MODELS; MALE; MIDDLE AGED; POSITRON-EMISSION TOMOGRAPHY; PUTAMEN; RAPHE NUCLEI; SEROTONIN PLASMA MEMBRANE TRANSPORT PROTEINS; TESTOSTERONE; TRANSGENDER PERSONS; YOUNG ADULT;

EID: 84941809419     PISSN: 00063223     EISSN: 18732402     Source Type: Journal    
DOI: 10.1016/j.biopsych.2014.09.010     Document Type: Article

References (66)

1. R.C. Kessler Epidemiology of women and depression J Affect Disord 74 2003 5 13
2. M.H. Bekker, and J. van Mens-Verhulst Anxiety disorders: Sex differences in prevalence, degree, and background, but gender-neutral treatment Gend Med 4 suppl B 2007 S178 S193
3. D.J. Smith, S. Kyle, L. Forty, C. Cooper, J. Walters, E. Russell, and et al. Differences in depressive symptom profile between males and females J Affect Disord 108 2008 279 284
4. T.M. McGuinness, J.G. Dyer, and E.H. Wade Gender differences in adolescent depression J Psychosoc Nurs Ment Health Serv 50 2012 17 20
5. R.J. Valentino, B. Reyes, E. Van Bockstaele, and D. Bangasser Molecular and cellular sex differences at the intersection of stress and arousal Neuropharmacology 62 2012 13 20
6. M.M. Weissman, and M. Olfson Depression in women: Implications for health care research Science 269 1995 799 801
7. H.A. Bennett, A. Einarson, A. Taddio, G. Koren, and T.R. Einarson Prevalence of depression during pregnancy: Systematic review Obstet Gynecol 103 2004 698 709
8. P. Llaneza, M.P. Garcia-Portilla, D. Llaneza-Suarez, B. Armott, and F.R. Perez-Lopez Depressive disorders and the menopause transition Maturitas 71 2012 120 130
9. D.F. Smith, and S. Jakobsen Molecular tools for assessing human depression by positron emission tomography Eur Neuropsychopharmacol 19 2009 611 628
10. J.B. Savitz, and W.C. Drevets Neuroreceptor imaging in depression Neurobiol Dis 52 2013 49 65
11. N. Hesselgrave, and R.V. Parsey Imaging the serotonin 1A receptor using [11C]WAY100635 in healthy controls and major depression Philos Trans R Soc Lond B Biol Sci 368 2013 20120004
12. G. Gryglewski, R. Lanzenberger, G.S. Kranz, and P. Cumming Meta-analysis of molecular imaging of serotonin transporters in major depression J Cereb Blood Flow Metab 34 2014 1096 1103
13. D.M. Cannon, J.M. Klaver, S.A. Klug, P.J. Carlson, D.A. Luckenbaugh, M. Ichise, and W.C. Drevets Gender-specific abnormalities in the serotonin transporter system in panic disorder Int J Neuropsychopharmacol 16 2013 733 743
14. E. Maron, I. Toru, J. Hirvonen, L. Tuominen, V. Lumme, V. Vasar, and et al. Gender differences in brain serotonin transporter availability in panic disorder J Psychopharmacol 25 2011 952 959
15. J.K. Staley, G. Sanacora, G. Tamagnan, P.K. Maciejewski, R.T. Malison, R.M. Berman, and et al. Sex differences in diencephalon serotonin transporter availability in major depression Biol Psychiatry 59 2006 40 47
16. H.G. Ruhe, J. Booij, J.B. Reitsma, and A.H. Schene Serotonin transporter binding with [123I]beta-CIT SPECT in major depressive disorder versus controls: Effect of season and gender Eur J Nucl Med Mol Imaging 36 2009 841 849
17. G.M. Sullivan, R.T. Ogden, M.A. Oquendo, J.S. Kumar, N. Simpson, Y.Y. Huang, and et al. Positron emission tomography quantification of serotonin-1A receptor binding in medication-free bipolar depression Biol Psychiatry 66 2009 223 230
18. B. Szewczyk, P.R. Albert, A.M. Burns, M. Czesak, J.C. Overholser, G.J. Jurjus, and et al. Gender-specific decrease in NUDR and 5-HT1A receptor proteins in the prefrontal cortex of subjects with major depressive disorder Int J Neuropsychopharmacol 12 2009 155 168
19. H. Jovanovic, J. Lundberg, P. Karlsson, A. Cerin, T. Saijo, A. Varrone, and et al. Sex differences in the serotonin 1A receptor and serotonin transporter binding in the human brain measured by PET Neuroimage 39 2008 1408 1419
20. D. Erritzoe, V.G. Frokjaer, M.T. Haahr, J. Kalbitzer, C. Svarer, K.K. Holst, and et al. Cerebral serotonin transporter binding is inversely related to body mass index Neuroimage 52 2010 284 289
21. E.L. Moses-Kolko, J.C. Price, N. Shah, S. Berga, S.M. Sereika, P.M. Fisher, and et al. Age, sex, and reproductive hormone effects on brain serotonin-1A and serotonin-2A receptor binding in a healthy population Neuropsychopharmacology 36 2011 2729 2740
22. K. Madsen, M.T. Haahr, L. Marner, S.H. Keller, W.F. Baare, C. Svarer, and et al. Age and sex effects on 5-HT(4) receptors in the human brain: A [(11)C]SB207145 PET study J Cereb Blood Flow Metab 31 2011 1475 1481
23. 18F]MPPF binding potential in healthy subjects: A PET study Behav Brain Funct 6 2010 37
24. G.S. Kranz, A. Hahn, P. Baldinger, D. Haeusler, C. Philippe, U. Kaufmann, and et al. Cerebral serotonin transporter asymmetry in females, males and male-to-female transsexuals measured by PET in vivo Brain Struct Funct 219 2014 171 183
25. 11C]WAY-100635 Eur J Nucl Med Mol Imaging 35 2008 2159 2168
26. R. Lanzenberger, M. Mitterhauser, G.S. Kranz, C. Spindelegger, W. Wadsak, P. Stein, and et al. Progesterone level predicts serotonin-1a receptor binding in the male human brain Neuroendocrinology 94 2011 84 88
27. U. Moser, W. Wadsak, C. Spindelegger, M. Mitterhauser, L.K. Mien, C. Bieglmayer, and et al. Hypothalamic serotonin-1A receptor binding measured by PET predicts the plasma level of dehydroepiandrosterone sulfate in healthy women Neurosci Lett 476 2010 161 165
28. H. Jovanovic, A. Cerin, P. Karlsson, J. Lundberg, C. Halldin, and A.L. Nordstrom A PET study of 5-HT1A receptors at different phases of the menstrual cycle in women with premenstrual dysphoria Psychiatry Res 148 2006 185 193
29. H. Jovanovic, P. Karlsson, A. Cerin, C. Halldin, and A.L. Nordstrom 5-HT(1A) receptor and 5-HTT binding during the menstrual cycle in healthy women examined with [(11)C] WAY100635 and [(11)C] MADAM PET Psychiatry Res 172 2009 31 37
30. H.M. Rivera, D.R. Oberbeck, B. Kwon, T.A. Houpt, and L.A. Eckel Estradiol increases Pet-1 and serotonin transporter mRNA in the midbrain raphe nuclei of ovariectomized rats Brain Res 1259 2009 51 58
31. C.L. Bethea, N.Z. Lu, C. Gundlah, and J.M. Streicher Diverse actions of ovarian steroids in the serotonin neural system Front Neuroendocrinol 23 2002 41 100
32. P.P. Bertrand, U.T. Paranavitane, C. Chavez, A. Gogos, M. Jones, and M. van den Buuse The effect of low estrogen state on serotonin transporter function in mouse hippocampus: A behavioral and electrochemical study Brain Res 1064 2005 10 20
33. M. Pecins-Thompson, N.A. Brown, and C.L. Bethea Regulation of serotonin re-uptake transporter mRNA expression by ovarian steroids in rhesus macaques Brain Res Mol Brain Res 53 1998 120 129
34. B.E. Sumner, K.E. Grant, R. Rosie, C. Hegele-Hartung, K.H. Fritzemeier, and G. Fink Raloxifene blocks estradiol induction of the serotonin transporter and 5-hydroxytryptamine2A receptor in female rat brain Neurosci Lett 417 2007 95 99
35. N. Koldzic-Zivanovic, P.K. Seitz, C.S. Watson, K.A. Cunningham, and M.L. Thomas Intracellular signaling involved in estrogen regulation of serotonin reuptake Mol Cell Endocrinol 226 2004 33 42
36. Austrian Government (2014): Recommendations for the Treatment of Gender Dysphoria and Transsexualism. Federal Ministry of Health. Available at: http://www.bmg.gv.at/home/Schwerpunkte/Psychische-Gesundheit/Transsexualismus-Geschlechtsdysphorie/. Accessed October 14, 2014.
37. R.R. Lanzenberger, A. Hahn, C. Windischberger, W. Wadsak, A. Holik, F. Gerstl, and et al. Serotonin-1A receptor binding and reward-dependent activation are associated within the human dorsal raphe nucleus as revealed by PET-fMRI Neuroimage 47 2009 S1 S286
38. R. Lanzenberger, G.S. Kranz, D. Haeusler, E. Akimova, M. Savli, A. Hahn, and et al. Prediction of SSRI treatment response in major depression based on serotonin transporter interplay between median raphe nucleus and projection areas Neuroimage 63 2012 874 881
39. D. Haeusler, L.K. Mien, L. Nics, J. Ungersboeck, C. Philippe, R.R. Lanzenberger, and et al. Simple and rapid preparation of [11C]DASB with high quality and reliability for routine applications Appl Radiat Isot 67 2009 1654 1660
40. R.B. Innis, V.J. Cunningham, J. Delforge, M. Fujita, A. Gjedde, R.N. Gunn, and et al. Consensus nomenclature for in vivo imaging of reversibly binding radioligands J Cereb Blood Flow Metab 27 2007 1533 1539
41. M. Ichise, J.S. Liow, J.Q. Lu, A. Takano, K. Model, H. Toyama, and et al. Linearized reference tissue parametric imaging methods: Application to [11C]DASB positron emission tomography studies of the serotonin transporter in human brain J Cereb Blood Flow Metab 23 2003 1096 1112
42. R.V. Parsey, J.M. Kent, M.A. Oquendo, M.C. Richards, M. Pratap, T.B. Cooper, and et al. Acute occupancy of brain serotonin transporter by sertraline as measured by [11C]DASB and positron emission tomography Biol Psychiatry 59 2006 821 828
43. S.J. Kish, Y. Furukawa, L.J. Chang, J. Tong, N. Ginovart, A. Wilson, and et al. Regional distribution of serotonin transporter protein in postmortem human brain: Is the cerebellum a SERT-free brain region? Nucl Med Biol 32 2005 123 128
44. N. Tzourio-Mazoyer, B. Landeau, D. Papathanassiou, F. Crivello, O. Etard, N. Delcroix, and et al. Automated anatomical labeling of activations in SPM using a macroscopic anatomical parcellation of the MNI MRI single-subject brain Neuroimage 15 2002 273 289
45. G.S. Kranz, A. Hahn, M. Savli, and R. Lanzenberger Challenges in the differentiation of midbrain raphe nuclei in neuroimaging research Proc Natl Acad Sci U S A 109 2012 E2000
46. M. Savli, A. Bauer, M. Mitterhauser, Y.S. Ding, A. Hahn, T. Kroll, and et al. Normative database of the serotonergic system in healthy subjects using multi-tracer PET Neuroimage 63 2012 447 459
47. K. Varnas, C. Halldin, and H. Hall Autoradiographic distribution of serotonin transporters and receptor subtypes in human brain Hum Brain Mapp 22 2004 246 260
48. M.K. Osterlund, J.A. Gustafsson, E. Keller, and Y.L. Hurd Estrogen receptor beta (ERbeta) messenger ribonucleic acid (mRNA) expression within the human forebrain: Distinct distribution pattern to ERalpha mRNA J Clin Endocrinol Metab 85 2000 3840 3846
49. M.K. Osterlund, E. Keller, and Y.L. Hurd The human forebrain has discrete estrogen receptor alpha messenger RNA expression: High levels in the amygdaloid complex Neuroscience 95 2000 333 342
50. J.K. McQueen, H. Wilson, B.E. Sumner, and G. Fink Serotonin transporter (SERT) mRNA and binding site densities in male rat brain affected by sex steroids Brain Res Mol Brain Res 63 1999 241 247
51. C.H. Phoenix, R.W. Goy, A.A. Gerall, and W.C. Young Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig Endocrinology 65 1959 369 382
52. J.H. Meyer Imaging the serotonin transporter during major depressive disorder and antidepressant treatment J Psychiatry Neurosci 32 2007 86 102
53. D.M. Cannon, M. Ichise, D. Rollis, J.M. Klaver, S.K. Gandhi, D.S. Charney, and et al. Elevated serotonin transporter binding in major depressive disorder assessed using positron emission tomography and [11C]DASB; comparison with bipolar disorder Biol Psychiatry 62 2007 870 877
54. B.B. Sherwin, and M.M. Gelfand Differential symptom response to parenteral estrogen and/or androgen administration in the surgical menopause Am J Obstet Gynecol 151 1985 153 160
55. M. Khera Patients with testosterone deficit syndrome and depression Arch Esp Urol 66 2013 729 736
56. L.S. Cohen, C.N. Soares, J.R. Poitras, J. Prouty, A.B. Alexander, and J.L. Shifren Short-term use of estradiol for depression in perimenopausal and postmenopausal women: A preliminary report Am J Psychiatry 160 2003 1519 1522
57. C.L. Bethea, A.P. Reddy, N. Robertson, and K. Coleman Effects of aromatase inhibition and androgen activity on serotonin and behavior in male macaques Behav Neurosci 127 2013 400 414
58. C. Gundlah, N.Z. Lu, S.J. Mirkes, and C.L. Bethea Estrogen receptor beta (ERbeta) mRNA and protein in serotonin neurons of macaques Brain Res Mol Brain Res 91 2001 14 22
59. S. Ramamoorthy, and R.D. Blakely Phosphorylation and sequestration of serotonin transporters differentially modulated by psychostimulants Science 285 1999 763 766
60. D.F. Swaab, and A. Garcia-Falgueras Sexual differentiation of the human brain in relation to gender identity and sexual orientation Funct Neurol 24 2009 17 28
61. G. Rametti, B. Carrillo, E. Gomez-Gil, C. Junque, S. Segovia, A. Gomez, and et al. White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study J Psychiatr Res 45 2011 199 204
62. G. Rametti, B. Carrillo, E. Gomez-Gil, C. Junque, L. Zubiarre-Elorza, S. Segovia, and et al. The microstructure of white matter in male to female transsexuals before cross-sex hormonal treatment. A DTI study J Psychiatr Res 45 2011 949 954
63. J.N. Zhou, M.A. Hofman, L.J. Gooren, and D.F. Swaab A sex difference in the human brain and its relation to transsexuality Nature 378 1995 68 70
64. E. Luders, F.J. Sanchez, C. Gaser, A.W. Toga, K.L. Narr, L.S. Hamilton, and E. Vilain Regional gray matter variation in male-to-female transsexualism Neuroimage 46 2009 904 907
65. S. Schoning, A. Engelien, C. Bauer, H. Kugel, A. Kersting, C. Roestel, and et al. Neuroimaging differences in spatial cognition between men and male-to-female transsexuals before and during hormone therapy J Sex Med 7 2010 1858 1867
66. L. Simon, U. Zsolt, D. Fogd, and P. Czobor Dysfunctional core beliefs, perceived parenting behavior and psychopathology in gender identity disorder: A comparison of male-to-female, female-to-male transsexual and nontranssexual control subjects J Behav Ther Exp Psychiatry 42 2011 38 45