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Brain Structure and Function

, Volume 219, Issue 1, pp 171–183 | Cite as

Cerebral serotonin transporter asymmetry in females, males and male-to-female transsexuals measured by PET in vivo

  • Georg S. Kranz
  • Andreas Hahn
  • Pia Baldinger
  • Daniela Haeusler
  • Cecile Philippe
  • Ulrike Kaufmann
  • Wolfgang Wadsak
  • Markus Savli
  • Anna Hoeflich
  • Christoph Kraus
  • Thomas Vanicek
  • Markus Mitterhauser
  • Siegfried Kasper
  • Rupert LanzenbergerEmail author
Original Article

Abstract

The serotonergic system modulates brain functions that are considered to underlie affective states, emotion and cognition. Several lines of evidence point towards a strong lateralization of these mental processes, which indicates similar asymmetries in associated neurotransmitter systems. Here, our aim was to investigate a potential asymmetry of the serotonin transporter distribution using positron emission tomography and the radioligand [11C]DASB in vivo. As brain asymmetries may differ between sexes, we further aimed to compare serotonin transporter asymmetry between females, males and male-to-female (MtF) transsexuals whose brains are considered to be partly feminized. Voxel-wise analysis of serotonin transporter binding in all groups showed both strong left and rightward asymmetries in several cortical and subcortical structures including temporal and frontal cortices, anterior cingulate, hippocampus, caudate and thalamus. Further, male controls showed a rightward asymmetry in the midcingulate cortex, which was absent in females and MtF transsexuals. The present data support the notion of a lateralized serotonergic system, which is in line with previous findings of asymmetric serotonin-1A receptor distributions, extracellular serotonin concentrations, serotonin turnover and uptake. The absence of serotonin transporter asymmetry in the midcingulate in MtF transsexuals may be attributed to an absence of brain masculinization in this region.

Keywords

Serotonin transporter Cerebral asymmetry Lateralization Gender dysphoria Transsexual 

Notes

Acknowledgments

This research was funded by Austrian National Bank Grant P 13214 (to R. L.) and P 13675 (to M.M.). A. Hahn is a recipient of a DOC fellowship of the Austrian Academy of Sciences at the Department of Psychiatry and Psychotherapy. The authors are especially grateful to all transsexual subjects for participating in this study and to the clinical staff at the PET centre, the Department of Psychiatry and Psychotherapy for their technical and medical support and to Marie Spies for linguistic support.

Conflict of interest

The authors declare no conflict of interest related to this work.

References

  1. Alves NT, Fukusima SS, Aznar-Casanova JA (2008) Models of brain asymmetry in emotional processing. Psychol Neurosci 1(1):63–66Google Scholar
  2. American Psychiatric Association (2000) Diagnostic and statistical manual of mental disorders DSM-IV-TR, 4th edn (text revision), 4th edn. American Psychiatric Press, WashingtonGoogle Scholar
  3. Amunts VV (2008) Individual variability in the structural asymmetry of the dorsomedial nucleus of the thalamus in men and women. Neurosci Behav Physiol 38(7):715–720PubMedGoogle Scholar
  4. Amunts K, Armstrong E, Malikovic A, Homke L, Mohlberg H, Schleicher A, Zilles K (2007) Gender-specific left-right asymmetries in human visual cortex. J Neurosci 27(6):1356–1364PubMedGoogle Scholar
  5. Andersen SL, Teicher MH (1999) Serotonin laterality in amygdala predicts performance in the elevated plus maze in rats. NeuroReport 10(17):3497–3500PubMedGoogle Scholar
  6. Asthana HS, Mandal MK (2001) Visual-field bias in the judgment of facial expression of emotion. J Gen Psychol 128(1):21–29PubMedGoogle Scholar
  7. Bakker J, Brock O (2010) Early oestrogens in shaping reproductive networks: evidence for a potential organisational role of oestradiol in female brain development. J Neuroendocrinol 22(7):728–735PubMedGoogle Scholar
  8. Bar KJ, Greiner W, Letsch A, Kobele R, Sauer H (2003) Influence of gender and hemispheric lateralization on heat pain perception in major depression. J Psychiatr Res 37(4):345–353PubMedGoogle Scholar
  9. Belcheva I, Tashev R, Belcheva S (2007) Hippocampal asymmetry in serotonergic modulation of learning and memory in rats. Laterality 12(6):475–486PubMedGoogle Scholar
  10. Benmansour S, Weaver RS, Barton AK, Adeniji OS, Frazer A (2012) Comparison of the effects of estradiol and progesterone on serotonergic function. Biol Psychiatry 71(7):633–641PubMedCentralPubMedGoogle Scholar
  11. Bethea CL, Lu NZ, Gundlah C, Streicher JM (2002) Diverse actions of ovarian steroids in the serotonin neural system. Front Neuroendocrinol 23(1):41–100PubMedGoogle Scholar
  12. Biondi M, Parise P, Venturi P, Riccio L, Brunetti G, Pancheri P (1993) Frontal hemisphere lateralization and depressive personality traits. Percept Mot Skills 77(3 Pt 1):1035–1042PubMedGoogle Scholar
  13. Chandramouli R, Kanchan BR, Ambadevi B (1993) Right-left asymmetry in tonic pain perception and its modification by simultaneous contralateral noxious stimulation. Neuropsychologia 31(7):687–694PubMedGoogle Scholar
  14. Chua EF, Schacter DL, Rand-Giovannetti E, Sperling RA (2007) Evidence for a specific role of the anterior hippocampal region in successful associative encoding. Hippocampus 17(11):1071–1080PubMedGoogle Scholar
  15. Clarke HF, Dalley JW, Crofts HS, Robbins TW, Roberts AC (2004) Cognitive inflexibility after prefrontal serotonin depletion. Science 304(5672):878–880PubMedGoogle Scholar
  16. Clarke HF, Walker SC, Crofts HS, Dalley JW, Robbins TW, Roberts AC (2005) Prefrontal serotonin depletion affects reversal learning but not attentional set shifting. J Neurosci 25(2):532–538PubMedGoogle Scholar
  17. Clarke HF, Walker SC, Dalley JW, Robbins TW, Roberts AC (2007) Cognitive inflexibility after prefrontal serotonin depletion is behaviorally and neurochemically specific. Cereb Cortex 17(1):18–27PubMedGoogle Scholar
  18. Coles P (2008) Statistical errors and asymmetry indices. Proc Natl Acad Sci USA 105(45):E82 (author reply E83)Google Scholar
  19. Dakin CL, Wilson CA, Kallo I, Coen CW, Davies DC (2008) Neonatal stimulation of 5-HT(2) receptors reduces androgen receptor expression in the rat anteroventral periventricular nucleus and sexually dimorphic preoptic area. Eur J Neurosci 27(9):2473–2480PubMedGoogle Scholar
  20. Diamond MC (1991) Hormonal effects on the development or cerebral lateralization. Psychoneuroendocrinology 16(1–3):121–129PubMedGoogle Scholar
  21. Didelot A, Mauguière F, Redouté J, Bouvard S, Lothe A, Reilhac A, Hammers A, Costes N, Ryvlin P (2010) Voxel-based analysis of asymmetry index maps increases the specificity of 18F-MPPF PET abnormalities for localizing the epileptogenic zone in temporal lobe epilepsies. J Nucl Med 51(11):1732–1739PubMedGoogle Scholar
  22. Draca S (2010) Gender-specific functional cerebral asymmetries and unilateral cerebral lesion sequelae. Rev Neurosci 21(6):421–425PubMedGoogle Scholar
  23. Dunlap WP, Cortina JM, Vaslow JB, Burke MJ (1996) Meta-analysis of experiments with matched groups or repeated measures designs. Psychol Methods 1(2):170–177Google Scholar
  24. Fink M, Wadsak W, Savli M, Stein P, Moser U, Hahn A, Mien LK, Kletter K, Mitterhauser M, Kasper S, Lanzenberger R (2009) Lateralization of the serotonin-1A receptor distribution in language areas revealed by PET. Neuroimage 45(2):598–605PubMedGoogle Scholar
  25. Fitzgerald PJ (2012) Whose side are you on: does serotonin preferentially activate the right hemisphere and norepinephrine the left? Med Hypotheses 79(2):250–254PubMedGoogle Scholar
  26. Garcia-Falgueras A, Swaab DF (2008) A sex difference in the hypothalamic uncinate nucleus: relationship to gender identity. Brain 131(Pt 12):3132–3146PubMedGoogle Scholar
  27. Garcia-Falgueras A, Ligtenberg L, Kruijver FP, Swaab DF (2011) Galanin neurons in the intermediate nucleus (InM) of the human hypothalamus in relation to sex, age, and gender identity. J Comp Neurol 519(15):3061–3084PubMedGoogle Scholar
  28. Good CD, Johnsrude I, Ashburner J, Henson RN, Friston KJ, Frackowiak RS (2001) Cerebral asymmetry and the effects of sex and handedness on brain structure: a voxel-based morphometric analysis of 465 normal adult human brains. Neuroimage 14(3):685–700PubMedGoogle Scholar
  29. Gur RC, Turetsky BI, Matsui M, Yan M, Bilker W, Hughett P, Gur RE (1999) Sex differences in brain gray and white matter in healthy young adults: correlations with cognitive performance. J Neurosci 19(10):4065–4072PubMedGoogle Scholar
  30. Haeusler D, Mien LK, Nics L, Ungersboeck J, Philippe C, Lanzenberger RR, Kletter K, Dudczak R, Mitterhauser M, Wadsak W (2009) Simple and rapid preparation of [11C]DASB with high quality and reliability for routine applications. Appl Radiat Isot 67(9):1654–1660PubMedGoogle Scholar
  31. Hahn A, Wadsak W, Windischberger C, Baldinger P, Hoflich AS, Losak J, Nics L, Philippe C, Kranz GS, Kraus C, Mitterhauser M, Karanikas G, Kasper S, Lanzenberger R (2012) Differential modulation of the default mode network via serotonin-1A receptors. Proc Natl Acad Sci USA 109(7):2619–2624PubMedGoogle Scholar
  32. Hausmann M, Gunturkun O (2000) Steroid fluctuations modify functional cerebral asymmetries: the hypothesis of progesterone-mediated interhemispheric decoupling. Neuropsychologia 38(10):1362–1374PubMedGoogle Scholar
  33. Hayes SM, Baena E, Truong TK, Cabeza R (2010) Neural mechanisms of context effects on face recognition: automatic binding and context shift decrements. J Cogn Neurosci 22(11):2541–2554PubMedCentralPubMedGoogle Scholar
  34. Hummerich R, Reischl G, Ehrlichmann W, Machulla HJ, Heinz A, Schloss P (2004) DASB -in vitro binding characteristics on human recombinant monoamine transporters with regard to its potential as positron emission tomography (PET) tracer. J Neurochem 90(5):1218–1226PubMedGoogle Scholar
  35. Huster RJ, Westerhausen R, Herrmann CS (2011) Sex differences in cognitive control are associated with midcingulate and callosal morphology. Brain Struct Funct 215(3–4):225–235PubMedGoogle Scholar
  36. Ichise M, Liow JS, Lu JQ, Takano A, Model K, Toyama H, Suhara T, Suzuki K, Innis RB, Carson RE (2003) 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(9):1096–1112PubMedGoogle Scholar
  37. Innis RB, Cunningham VJ, Delforge J, Fujita M, Gjedde A, Gunn RN, Holden J, Houle S, Huang SC, Ichise M, Iida H, Ito H, Kimura Y, Koeppe RA, Knudsen GM, Knuuti J, Lammertsma AA, Laruelle M, Logan J, Maguire RP, Mintun MA, Morris ED, Parsey R, Price JC, Slifstein M, Sossi V, Suhara T, Votaw JR, Wong DF, Carson RE (2007) Consensus nomenclature for in vivo imaging of reversibly binding radioligands. J Cereb Blood Flow Metab 27(9):1533–1539PubMedGoogle Scholar
  38. Johnson MD, Ojemann GA (2000) The role of the human thalamus in language and memory: evidence from electrophysiological studies. Brain Cogn 42(2):218–230PubMedGoogle Scholar
  39. Kahkonen S, Ahveninen J, Pennanen S, Liesivuori J, Ilmoniemi RJ, Jaaskelainen IP (2002) Serotonin modulates early cortical auditory processing in healthy subjects: evidence from MEG with acute tryptophan depletion. Neuropsychopharmacology 27(5):862–868PubMedGoogle Scholar
  40. Klein F, Sepekoff B, Wolf TJ (1985) Sexual orientation: a multi-variable dynamic process. J Homosex 11(1–2):35–49PubMedGoogle Scholar
  41. Kruijver FPM, Zhou JN, Pool CW, Hofman MA, Gooren LJG, Swaab DF (2000) Male-to-female transsexuals have female neuron numbers in a limbic nucleus. J Clin Endocrinol Metab 85(5):2034–2041PubMedGoogle Scholar
  42. Lanzenberger RR, Hahn A, Windischberger C, Wadsak W, Holik A, Gerstl F, Savli M, Moser U, Mien LK, Akimova E, Mitterhauser M, Kletter K, Moser E, Kasper S (2009) Serotonin-1A receptor binding and Reward-dependent Activation are associated within the Human Dorsal Raphe Nucleus as revealed by PET-fMRI. NeuroImage 47(Supplement 1):S1–S286Google Scholar
  43. Lanzenberger R, Mitterhauser M, Kranz GS, Spindelegger C, Wadsak W, Stein P, Moser U, Savli M, Kletter K, Kasper S (2011) Progesterone level predicts serotonin-1a receptor binding in the male human brain. Neuroendocrinology 94(1):84–88PubMedGoogle Scholar
  44. Lanzenberger R, Kranz GS, Haeusler J, Akimova E, Savli M, Hahn A, Mitterhauser M, Spindelegger C, Philippe C, Fink M, Wadsak W, Karanikas G, Kasper S (2012) Prediction of SSRI treatment response in major depression based on serotonin transporter interplay between median raphe nucleus and projection areas. NeuroImage 63(3):1091–1098PubMedGoogle Scholar
  45. Ley RG, Bryden MP (1979) Hemispheric differences in processing emotions and faces. Brain Lang 7(1):127–138PubMedGoogle Scholar
  46. Lugo M, Isturiz G, Lara C, Garcia N, Eblen-Zaijur A (2002) Sensory lateralization in pain subjective perception for noxious heat stimulus. Somatosens Mot Res 19(3):207–212PubMedGoogle Scholar
  47. Martin-Soelch C, Szczepanik J, Nugent A, Barhaghi K, Rallis D, Herscovitch P, Carson RE, Drevets WC (2011) Lateralization and gender differences in the dopaminergic response to unpredictable reward in the human ventral striatum. Eur J Neurosci 33(9):1706–1715PubMedCentralPubMedGoogle Scholar
  48. McCarthy MM (2008) Estradiol and the developing brain. Physiol Rev 88(1):91–124PubMedCentralPubMedGoogle Scholar
  49. McEwen BS (1992) Steroid hormones: effect on brain development and function. Horm Res 37(Suppl 3):1–10PubMedGoogle Scholar
  50. McQueen JK, Wilson H, Fink G (1997) Estradiol-17 beta increases serotonin transporter (SERT) mRNA levels and the density of SERT-binding sites in female rat brain. Brain Res Mol Brain Res 45(1):13–23PubMedGoogle Scholar
  51. Meyer JH (2007) Imaging the serotonin transporter during major depressive disorder and antidepressant treatment. J Psychiatry Neurosci 32(2):86–102PubMedCentralPubMedGoogle Scholar
  52. Meyer JH, Gunn RN, Myers R, Grasby PM (1999) Assessment of spatial normalization of PET ligand images using ligand-specific templates. Neuroimage 9(5):545–553PubMedGoogle Scholar
  53. Moser MB, Moser EI (1998) Functional differentiation in the hippocampus. Hippocampus 8(6):608–619PubMedGoogle Scholar
  54. Nielsen K, Brask D, Knudsen GM, Aznar S (2006) Immunodetection of the serotonin transporter protein is a more valid marker for serotonergic fibers than serotonin. Synapse 59(5):270–276PubMedGoogle Scholar
  55. Nijboer TC, Jellema T (2012) Unequal impairment in the recognition of positive and negative emotions after right hemisphere lesions: a left hemisphere bias for happy faces. J Neuropsychol 6(1):79–93PubMedGoogle Scholar
  56. Ocklenburg S, Gunturkun O, Beste C (2012) Hemispheric asymmetries and cognitive flexibility: an ERP and sLORETA study. Brain Cogn 78(2):148–155PubMedGoogle Scholar
  57. Oke A, Keller R, Mefford I, Adams RN (1978) Lateralization of norepinephrine in human thalamus. Science 200(4348):1411–1413PubMedGoogle Scholar
  58. Oldfield RC (1971) The assessment and analysis of handedness: the Edinburgh inventory. Neuropsychologia 9(1):97–113PubMedGoogle Scholar
  59. Otto MW, Dougher MJ, Yeo RA (1989) Depression, pain, and hemispheric activation. J Nerv Ment Dis 177(4):210–218PubMedGoogle Scholar
  60. Parsey RV, Kent JM, Oquendo MA, Richards MC, Pratap M, Cooper TB, Arango V, Mann JJ (2006) Acute occupancy of brain serotonin transporter by sertraline as measured by [11C]DASB and positron emission tomography. Biol Psychiatry 59(9):821–828PubMedGoogle Scholar
  61. Paus T (2010) Sex differences in the human brain: a developmental perspective. In: Savic I (ed) Sex differences in the human brain, their underpinnings and implications, vol 186. Elsevier, Amsterdam, pp 13–28Google Scholar
  62. Pedraza O, Bowers D, Gilmore R (2004) Asymmetry of the hippocampus and amygdala in MRI volumetric measurements of normal adults. J Int Neuropsy Soc 10(5):664–678Google Scholar
  63. Phoenix CH, Goy RW, Gerall AA, Young WC (1959) Organizing action of prenatally administered testosterone propionate on the tissues mediating mating behavior in the female guinea pig. Endocrinology 65:369–382PubMedGoogle Scholar
  64. Riccio O, Potter G, Walzer C, Vallet P, Szabo G, Vutskits L, Kiss JZ, Dayer AG (2009) Excess of serotonin affects embryonic interneuron migration through activation of the serotonin receptor 6. Mol Psychiatry 14(3):280–290PubMedGoogle Scholar
  65. Robichaud M, Debonnel G (2005) Oestrogen and testosterone modulate the firing activity of dorsal raphe nucleus serotonergic neurones in both male and female rats. J Neuroendocrinol 17(3):179–185PubMedGoogle Scholar
  66. Rosen GD, Finklestein S, Stoll AL, Yutzey DA, Denenberg VH (1984) Neurochemical asymmetries in the albino rat’s cortex, striatum, and nucleus accumbens. Life Sci 34(12):1143–1148PubMedGoogle Scholar
  67. Rubinow DR, Schmidt PJ, Roca CA (1998) Estrogen-serotonin interactions: implications for affective regulation. Biol Psychiatry 44(9):839–850PubMedGoogle Scholar
  68. Sapir A, Rafal R, Henik A (2002) Attending to the thalamus: inhibition of return and nasal-temporal asymmetry in the pulvinar. NeuroReport 13(5):693–697PubMedGoogle Scholar
  69. Sarlani E, Farooq N, Greenspan JD (2003) Gender and laterality differences in thermosensation throughout the perceptible range. Pain 106(1–2):9–18PubMedGoogle Scholar
  70. Savic I, Garcia-Falgueras A, Swaab DF (2010) Sexual differentiation of the human brain in relation to gender identity and sexual orientation. In: Savic I (ed) Sex differences in the human brain, their underpinnings and implications, vol 186. Elsevier, Amsterdam, pp 41–61Google Scholar
  71. Schwier C, Kliem A, Boettger MK, Bar KJ (2010) Increased cold-pain thresholds in major depression. J Pain 11(3):287–290PubMedGoogle Scholar
  72. Shackman AJ, Salomons TV, Slagter HA, Fox AS, Winter JJ, Davidson RJ (2011) The integration of negative affect, pain and cognitive control in the cingulate cortex. Nat Rev Neurosci 12(3):154–167PubMedCentralPubMedGoogle Scholar
  73. Shi F, Liu B, Zhou Y, Yu C, Jiang T (2009) Hippocampal volume and asymmetry in mild cognitive impairment and Alzheimer’s disease: meta-analyses of MRI studies. Hippocampus 19(11):1055–1064PubMedGoogle Scholar
  74. Shinohara Y, Hosoya A, Yamasaki N, Ahmed H, Hattori S, Eguchi M, Yamaguchi S, Miyakawa T, Hirase H, Shigemoto R (2012) Right-hemispheric dominance of spatial memory in split-brain mice. Hippocampus 22(2):117–121PubMedGoogle Scholar
  75. Simerly RB, Swanson LW, Gorski RA (1985) Reversal of the sexually dimorphic distribution of serotonin-immunoreactive fibers in the medial preoptic nucleus by treatment with perinatal androgen. Brain Res 340(1):91–98PubMedGoogle Scholar
  76. Soma T, Momose T, Takahashi M, Koyama K, Kawai K, Murase K, Ohtomo K (2012) Usefulness of extent analysis for statistical parametric mapping with asymmetry index using inter-ictal FGD-PET in mesial temporal lobe epilepsy. Ann Nucl Med 26(4):319–326PubMedGoogle Scholar
  77. Sommer IE, Aleman A, Somers M, Boks MP, Kahn RS (2008) Sex differences in handedness, asymmetry of the planum temporale and functional language lateralization. Brain Res 1206:76–88PubMedGoogle Scholar
  78. Spernal J, Krieg JC, Lautenbacher S (2003) Pain thresholds as a putative functional test for cerebral laterality in major depressive disorder and panic disorder. Neuropsychobiology 48(3):146–151PubMedGoogle Scholar
  79. Stefanics G, Csukly G, Komlosi S, Czobor P, Czigler I (2012) Processing of unattended facial emotions: a visual mismatch negativity study. Neuroimage 59(3):3042–3049PubMedGoogle Scholar
  80. Stein P, Savli M, Wadsak W, Mitterhauser M, Fink M, Spindelegger C, Mien LK, Moser U, Dudczak R, Kletter K, Kasper S, Lanzenberger R (2008) The serotonin-1A receptor distribution in healthy men and women measured by PET and [carbonyl-11C]WAY-100635. Eur J Nucl Med Mol Imaging 35(12):2159–2168PubMedGoogle Scholar
  81. Stern CE, Hasselmo ME (1999) Bridging the gap: integrating cellular and functional magnetic resonance imaging studies of the hippocampus. Hippocampus 9(1):45–53PubMedGoogle Scholar
  82. Swaab DF, Garcia-Falgueras A (2009) Sexual differentiation of the human brain in relation to gender identity and sexual orientation. Funct Neurol 24(1):17–28PubMedGoogle Scholar
  83. Takao H, Abe O, Yamasue H, Aoki S, Sasaki H, Kasai K, Yoshioka N, Ohtomo K (2011) Gray and white matter asymmetries in healthy individuals aged 21–29 years: a voxel-based morphometry and diffusion tensor imaging study. Hum Brain Mapp 32(10):1762–1773PubMedGoogle Scholar
  84. Tellez R, Rocha L, Castillo C, Meneses A (2010) Autoradiographic study of serotonin transporter during memory formation. Behav Brain Res 212(1):12–26PubMedGoogle Scholar
  85. Tomer R, Slagter HA, Christian BT, Fox AS, King CR, Murali D, Davidson RJ (2012) Dopamine asymmetries predict orienting bias in healthy individuals. Cereb Cortex. doi: 10.1093/cercor/bhs277 PubMedGoogle Scholar
  86. Underwood MD, Kassir SA, Bakalian MJ, Galfalvy H, Mann JJ, Arango V (2012) Neuron density and serotonin receptor binding in prefrontal cortex in suicide. Int J Neuropsychopharmacol 15(4):435–447PubMedGoogle Scholar
  87. Valdes JJ, Mactutus CF, Cory RN, Cameron WR (1981) Lateralization of norepinephrine, serotonin and choline uptake into hippocampal synaptosomes of sinistral rats. Physiol Behav 27(2):381–383PubMedGoogle Scholar
  88. Varnas K, Halldin C, Hall H (2004) Autoradiographic distribution of serotonin transporters and receptor subtypes in human brain. Hum Brain Mapp 22(3):246–260PubMedGoogle Scholar
  89. Vernaleken I, Weibrich C, Siessmeier T, Buchholz HG, Rosch F, Heinz A, Cumming P, Stoeter P, Bartenstein P, Grunder G (2007) Asymmetry in dopamine D(2/3) receptors of caudate nucleus is lost with age. Neuroimage 34(3):870–878PubMedGoogle Scholar
  90. Verney C, Lebrand C, Gaspar P (2002) Changing distribution of monoaminergic markers in the developing human cerebral cortex with special emphasis on the serotonin transporter. Anat Rec 267(2):87–93PubMedGoogle Scholar
  91. Vertes RP (1991) A PHA-L analysis of ascending projections of the dorsal raphe nucleus in the rat. J Comp Neurol 313(4):643–668PubMedGoogle Scholar
  92. Vertes RP, Linley SB, Hoover WB (2010) Pattern of distribution of serotonergic fibers to the thalamus of the rat. Brain Struct Funct 215(1):1–28PubMedGoogle Scholar
  93. Vitalis T, Cases O, Passemard S, Callebert J, Parnavelas JG (2007) Embryonic depletion of serotonin affects cortical development. Eur J Neurosci 26(2):331–344PubMedGoogle Scholar
  94. Walsh A, McDowall J, Grimshaw GM (2010) Hemispheric specialization for emotional word processing is a function of SSRI responsiveness. Brain Cogn 74(3):332–340PubMedGoogle Scholar
  95. Watkins KE, Paus T, Lerch JP, Zijdenbos A, Collins DL, Neelin P, Taylor J, Worsley KJ, Evans AC (2001) Structural asymmetries in the human brain: a voxel-based statistical analysis of 142 MRI scans. Cereb Cortex 11(9):868–877PubMedGoogle Scholar
  96. Westergaard GC, Chavanne TJ, Lussier ID, Houser L, Cleveland A, Suomi SJ, Higley JD (2003) Left-handedness is correlated with CSF monoamine metabolite and plasma cortisol concentrations, and with impaired sociality, in free-ranging adult male rhesus macaques (Macaca mulatta). Laterality 8(2):169–187PubMedGoogle Scholar
  97. Wilson CA, Davies DC (2007) The control of sexual differentiation of the reproductive system and brain. Reproduction 133(2):331–359PubMedGoogle Scholar
  98. Wisniewski AB (1998) Sexually-dimorphic patterns of cortical asymmetry, and the role for sex steroid hormones in determining cortical patterns of lateralization. Psychoneuroendocrinology 23(5):519–547PubMedGoogle Scholar
  99. Witte AV, Floel A, Stein P, Savli M, Mien LK, Wadsak W, Spindelegger C, Moser U, Fink M, Hahn A, Mitterhauser M, Kletter K, Kasper S, Lanzenberger R (2009) Aggression is related to frontal serotonin-1A receptor distribution as revealed by PET in healthy subjects. Hum Brain Mapp 30(8):2558–2570PubMedGoogle Scholar
  100. Woolard AA, Heckers S (2012) Anatomical and functional correlates of human hippocampal volume asymmetry. Psychiatry Res 201(1):48–53PubMedCentralPubMedGoogle Scholar
  101. Young EJ, Williams CL (2010) Valence dependent asymmetric release of norepinephrine in the basolateral amygdala. Behav Neurosci 124(5):633–644PubMedGoogle Scholar
  102. Zhou JN, Hofman MA, Gooren LJ, Swaab DF (1995) A sex difference in the human brain and its relation to transsexuality. Nature 378(6552):68–70PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Georg S. Kranz
    • 1
  • Andreas Hahn
    • 1
  • Pia Baldinger
    • 1
  • Daniela Haeusler
    • 2
  • Cecile Philippe
    • 2
  • Ulrike Kaufmann
    • 3
  • Wolfgang Wadsak
    • 2
  • Markus Savli
    • 1
  • Anna Hoeflich
    • 1
  • Christoph Kraus
    • 1
  • Thomas Vanicek
    • 1
  • Markus Mitterhauser
    • 2
  • Siegfried Kasper
    • 1
  • Rupert Lanzenberger
    • 1
    Email author
  1. 1.Functional, Molecular and Translational Neuroimaging Lab, Department of Psychiatry and PsychotherapyMedical University of ViennaViennaAustria
  2. 2.Department of Nuclear MedicineMedical University of ViennaViennaAustria
  3. 3.Department of Obstetrics and GynecologyMedical University of ViennaViennaAustria

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