Adolescent; Diagnostic and Statistical Manual of Mental Disorders; Executive Function; Female; Functional Laterality/physiology; Gender Dysphoria/pathology/physiopathology/psychology; Gonadotropin-Releasing Hormone/therapeutic use; Humans; Magnetic Resonance Imaging; Male; Neuropsychological Tests; Prefrontal Cortex/physiopathology; Psychomotor Performance; Puberty/psychology; Reaction Time/physiology; Sex Differentiation; Adolescents; Gender dysphoria; Gonadotropin releasing hormone analog; Sex difference; Tower of London; fMRI
Abstract :
[en] Adolescents with gender dysphoria (GD) may be treated with gonadotropin releasing hormone analogs (GnRHa) to suppress puberty and, thus, the development of (unwanted) secondary sex characteristics. Since adolescence marks an important period for the development of executive functioning (EF), we determined whether the performance on the Tower of London task (ToL), a commonly used EF task, was altered in adolescents with GD when treated with GnRHa. Furthermore, since GD has been proposed to result from an atypical sexual differentiation of the brain, we determined whether untreated adolescents with GD showed sex-atypical brain activations during ToL performance. We found no significant effect of GnRHa on ToL performance scores (reaction times and accuracy) when comparing GnRHa treated male-to-females (suppressed MFs, n=8) with untreated MFs (n=10) or when comparing GnRHa treated female-to-males (suppressed FMs, n=12) with untreated FMs (n=10). However, the suppressed MFs had significantly lower accuracy scores than the control groups and the untreated FMs. Region-of-interest (ROI) analyses showed significantly greater activation in control boys (n=21) than control girls (n=24) during high task load ToL items in the bilateral precuneus and a trend (p<0.1) for greater activation in the right DLPFC. In contrast, untreated adolescents with GD did not show significant sex differences in task load-related activation and had intermediate activation levels compared to the two control groups. GnRHa treated adolescents with GD showed sex differences in neural activation similar to their natal sex control groups. Furthermore, activation in the other ROIs (left DLPFC and bilateral RLPFC) was also significantly greater in GnRHa treated MFs compared to GnRHa treated FMs. These findings suggest that (1) GnRHa treatment had no effect on ToL performance in adolescents with GD, and (2) pubertal hormones may induce sex-atypical brain activations during EF in adolescents with GD.
Disciplines :
Neurosciences & behavior
Author, co-author :
Staphorsius, Annemieke S.
Kreukels, Baudewijntje P. C.
Cohen-Kettenis, Peggy T.
Veltman, Dick J.
Burke, Sarah M.
Schagen, Sebastian E. E.
Wouters, Femke M.
Delemarre-van de Waal, Henriette A.
Bakker, Julie ; Université de Liège > Département des sciences biomédicales et précliniques > Biologie de la différenciation sexuelle du cerveau
Language :
English
Title :
Puberty suppression and executive functioning: An fMRI-study in adolescents with gender dysphoria.
Publication date :
2015
Journal title :
Psychoneuroendocrinology
ISSN :
0306-4530
eISSN :
1873-3360
Publisher :
Elsevier, United Kingdom
Volume :
56
Pages :
190-9
Peer reviewed :
Peer Reviewed verified by ORBi
Commentary :
Copyright (c) 2015 Elsevier Ltd. All rights reserved.
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Bibliography
Achenbach T.M., Edelbrock C.S. Manual for the Child Behavior Checklist and Revised Child Behavior Profile 1983, University of Vermont, Department of Psychiatry, Burlington, VT.
Albert D., Steinberg L. Age differences in strategic planning as indexed by the Tower of London. Child Dev. 2011, 82:1501-1517. 10.1111/j.1467-8624.2011.01613.x.
American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders 2000, American Psychiatry Association, Washington, DC. fourth ed.
American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders 2013, American Psychiatric Publishing, Arlington, VA. fifth ed.
Asato M.R., Sweeney J.A., Luna B. Cognitive processes in the development of TOL performance. Neuropsychologia 2006, 44:2259-2269. 10.1016/j.neuropsychologia.2006.05.010.
Ashburner J. A fast diffeomorphic image registration algorithm. Neuroimage 2007, 38:95-113. 10.1016/j.neuroimage.2007.07.007.
Baker S.C., Rogers R.D., Owen A.M., Frith C.D., Dolan R.J., Frackowiak R.S., Robbins T.W. Neural systems engaged by planning: a PET study of the Tower of London task. Neuropsychologia 1996, 34:515-526.
Berglund H., Lindström P., Dhejne-Helmy C., Savic I. Male-to-female transsexuals show sex-atypical hypothalamus activation when smelling odorous steroids. Cereb. Cortex 2008, 18:1900-1908. 10.1093/cercor/bhm216.
Boghi A., Rasetti R., Avidano F., Manzone C., Orsi L., D'Agata F., Caroppo P., Bergui M., Rocca P., Pulvirenti L., Bradac G.B., Bogetto F., Mutani R., Mortara P. The effect of gender on planning: an fMRI study using the Tower of London task. Neuroimage 2006, 33:999-1010. 10.1016/j.neuroimage.2006.07.022.
Bourgeois J.P., Goldman-Rakic P.S., Rakic P. Synaptogenesis in the prefrontal cortex of rhesus monkeys. Cereb. Cortex 1994, 4:78-96.
Casey B.J., Trainor R.J., Orendi J.L., Schubert A.B., Nystrom L.E., Giedd J.N., Castellanos F.X., Haxby J.V., Noll D.C., Cohen J.D., Forman S.D., Dahl R.E., Rapoport J.L. A developmental functional MRI study of prefrontal activation during performance of a Go-No-Go task. J. Cognit. Neurosci. 1997, 9:835-847. 10.1162/jocn.1997.9.6.835.
Cohen-Kettenis P.T., Gooren L.J. Transsexualism: a review of etiology, diagnosis and treatment. J. Psychosom. Res. 1999, 46:315-333.
Dagher A., Owen A.M., Boecker H., Brooks D.J. Mapping the network for planning: a correlational PET activation study with the Tower of London task. Brain 1999, 122(Pt. 1):1973-1987.
De Luca C.R., Wood S.J., Anderson V., Buchanan J.A., Proffitt T.M., Mahony K., Pantelis C. Normative data from the CANTAB. I: development of executive function over the lifespan. J. Clin. Exp. Neuropsychol. 2003, 25:242-254. 10.1076/jcen.25.2.242.13639.
Giedd J.N. The teen brain: insights from neuroimaging. J. Adolesc. Health 2008, 42:335-343. 10.1016/j.jadohealth.2008.01.007.
Gizewski E.R., Krause E., Schlamann M., Happich F., Ladd M.E., Forsting M., Senf W. Specific cerebral activation due to visual erotic stimuli in male-to-female transsexuals compared with male and female controls: an fMRI study. J. Sex. Med. 2009, 6:440-448. 10.1111/j.1743-6109.2008.00981.x.
Gooren L., Delemarre-van de Waal H. The feasibility of endocrine interventions in juvenile transsexuals. J. Psychol. Hum. Sex. 1996, 8:69-74. 10.1300/J056v08n04_05.
Hoekzema E., Schagen S., Kreukels B., Veltman D.J., Cohen-Kettenis P., de Waal H.D., Bakker J. Regional volumes and spatial volumetric distribution of grey matter in the gender dysphoric brain. Psychoneuroendocrinology 2015, 55:59-71. 10.1016/j.psyneuen.2015.01.016.
Houk C.P., Lee P.A. The diagnosis and care of transsexual children and adolescents: a pediatric endocrinologists' perspective. J. Pediatr. Endocrinol. Metab. 2006, 19:103-109.
Huizinga M., Dolan C.V., van der Molen M.W. Age-related change in executive function: developmental trends and a latent variable analysis. Neuropsychologia 2006, 44:2017-2036. 10.1016/j.neuropsychologia.2006.01.010.
Huttenlocher P.R. Synaptic density in human frontal cortex - developmental changes and effects of aging. Brain Res. 1979, 163:195-205.
Juraska J.M., Sisk C.L., DonCarlos L.L. Sexual differentiation of the adolescent rodent brain: hormonal influences and developmental mechanisms. Horm. Behav. 2013, 64:203-210. 10.1016/j.yhbeh.2013.05.010.
Korte A., Lehmkuhl U., Goecker D., Beier K.M., Krude H., Grüters-Kieslich A. Gender identity disorders in childhood and adolescence: currently debated concepts and treatment strategies. Dtsch. Arztebl. Int. 2008, 105:834-841. 10.3238/arztebl.2008.0834.
Kranz G.S., Hahn A., Kaufmann U., Küblböck M., Hummer A., Ganger S., Seiger R., Winkler D., Swaab D.F., Windischberger C., Kasper S., Lanzenberger R. White matter microstructure in transsexuals and controls investigated by diffusion tensor imaging. J. Neurosci. 2014, 34:15466-15475. 10.1523/JNEUROSCI.2488-14.2014.
Kreukels B.P.C., Cohen-Kettenis P.T. Puberty suppression in gender identity disorder: the Amsterdam experience. Nat. Rev. Endocrinol. 2011, 7:466-472. 10.1038/nrendo.2011.78.
Lazeron R.H., Rombouts S.A., Machielsen W.C., Scheltens P., Witter M.P., Uylings H.B., Barkhof F. Visualizing brain activation during planning: the tower of London test adapted for functional MR imaging. AJNR Am. J. Neuroradiol. 2000, 21:1407-1414.
Lemieux L., Salek-Haddadi A., Lund T.E., Laufs H., Carmichael D. Modelling large motion events in fMRI studies of patients with epilepsy. Magn. Reson. Imaging 2007, 25:894-901. 10.1016/j.mri.2007.03.009.
Luders E., Sánchez F.J., Gaser C., Toga A.W., Narr K.L., Hamilton L.S., Vilain E. Regional gray matter variation in male-to-female transsexualism. Neuroimage 2009, 46:904-907. 10.1016/j.neuroimage.2009.03.048.
Luders E., Sánchez F.J., Tosun D., Shattuck D.W., Gaser C., Vilain E., Toga A.W. Increased cortical thickness in male-to-female transsexualism. J. Behav. Brain Sci. 2012, 2:357-362. 10.4236/jbbs.2012.23040.
Maldjian J.A., Laurienti P.J., Kraft R.A., Burdette J.H. An automated method for neuroanatomic and cytoarchitectonic atlas-based interrogation of fMRI data sets. Neuroimage 2003, 19:1233-1239.
Marshall W.A., Tanner J.M. Variations in pattern of pubertal changes in girls. Arch. Dis. Child. 1969, 44:291-303.
Marshall W.A., Tanner J.M. Variations in the pattern of pubertal changes in boys. Arch. Dis. Child. 1970, 45:13-23.
Newman S.D., Carpenter P.A., Varma S., Just M.A. Frontal and parietal participation in problem solving in the Tower of London: fMRI and computational modeling of planning and high-level perception. Neuropsychologia 2003, 41:1668-1682. 10.1016/S0028-3932(03)00091-5.
Nielsen F.A., Hansen L.K. Automatic anatomical labeling of Talairach coordinates and generation of volumes of interest via the BrainMap database. Neuroimage 2002, 16.
Ogawa S., Lee T.M., Kay A.R., Tank D.W. Brain magnetic resonance imaging with contrast dependent on blood oxygenation. Proc. Natl. Acad. Sci. U. S. A. 1990, 87:9868-9872.
Owen A.M., Doyon J., Petrides M., Evans A.C. Planning and spatial working memory: a positron emission tomography study in humans. Eur. J. Neurosci. 1996, 8:353-364.
Rametti G., Carrillo B., Gómez-Gil E., Junque C., Segovia S., Gomez Á., Guillamon A. White matter microstructure in female to male transsexuals before cross-sex hormonal treatment. A diffusion tensor imaging study. J. Psychiatr. Res. 2011, 45:199-204. 10.1016/j.jpsychires.2010.05.006.
Rametti G., Carrillo B., Gómez-Gil E., Junque C., Zubiarre-Elorza L., Segovia S., Gomez Á., Guillamon A. The microstructure of white matter in male to female transsexuals before cross-sex hormonal treatment. A DTI study. J. Psychiatr. Res. 2011, 45:949-954. 10.1016/j.jpsychires.2010.11.007.
Romeo R.D. Puberty: a period of both organizational and activational effects of steroid hormones on neurobehavioural development. J. Neuroendocrinol. 2003, 15:1185-1192.
Rowe J.B., Owen A.M., Johnsrude I.S., Passingham R.E. Imaging the mental components of a planning task. Neuropsychologia 2001, 39:315-327.
Savic I., Arver S. Sex dimorphism of the brain in male-to-female transsexuals. Cereb. Cortex 2011, 21:2525-2533. 10.1093/cercor/bhr032.
Schall U., Johnston P., Lagopoulos J., Jüptner M., Jentzen W., Thienel R., Dittmann-Balçar A., Bender S., Ward P.B. Functional brain maps of Tower of London performance: a positron emission tomography and functional magnetic resonance imaging study. Neuroimage 2003, 20:1154-1161. 10.1016/S1053-8119(03)00338-0.
Schöning S., Engelien A., Bauer C., Kugel H., Kersting A., Roestel C., Zwitserlood P., Pyka M., Dannlowski U., Lehmann W., Heindel W., Arolt V., Konrad C. Neuroimaging differences in spatial cognition between men and male-to-female transsexuals before and during hormone therapy. J. Sex. Med. 2010, 7:1858-1867. 10.1111/j.1743-6109.2009.01484.x.
Simon L., Kozák L.R., Simon V., Czobor P., Unoka Z., Szabó Á., Csukly G. Regional grey matter structure differences between transsexuals and healthy controls - a voxel based morphometry study. PLOS ONE 2013, 8:e83947. 10.1371/journal.pone.0083947.
Sisk C.L., Zehr J.L. Pubertal hormones organize the adolescent brain and behavior. Front. Neuroendocrinol. 2005, 26:163-174. 10.1016/j.yfrne.2005.10.003.
Soleman R.S., Schagen S.E.E., Veltman D.J., Kreukels B.P.C., Cohen-Kettenis P.T., Lambalk C.B., Wouters F., Delemarre-van de Waal H.A. Sex differences in verbal fluency during adolescence: a functional magnetic resonance imaging study in gender dysphoric and control boys and girls. J. Sex. Med. 2013, 10:1969-1977. 10.1111/jsm.12083.
Spriggs M.P. Ethics and the proposed treatment for a 13-year-old with atypical gender identity. Med. J. Aust. 2004, 181:319-321.
Steensma T.D., Kreukels B.P.C., de Vries A.L.C., Cohen-Kettenis P.T. Gender identity development in adolescence. Horm. Behav. 2013, 64:288-297. 10.1016/j.yhbeh.2013.02.020.
Swaab D.F. Sexual differentiation of the human brain: relevance for gender identity, transsexualism and sexual orientation. Gynecol. Endocrinol. 2004, 19:301-312.
Van den Heuvel O.A., Groenewegen H.J., Barkhof F., Lazeron R.H.C., van Dyck R., Veltman D.J. Frontostriatal system in planning complexity: a parametric functional magnetic resonance version of Tower of London task. Neuroimage 2003, 18:367-374.
Van Goozen S.H.M., Slabbekoorn D., Gooren L.J.G., Sanders G., Cohen-Kettenis P.T. Organizing and activating effects of sex hormones in homosexual transsexuals. Behav. Neurosci. 2002, 116:982-988.
Van Strien J.W. Classificatie van links- en rechtshandige proefpersonen. Ned. Tijdschr. Psychol. 1992, 47:88-92.
Verhulst F.C., van der Ende J., Koot H.M. Handleiding voor de CBCL/4-18 1996, Erasmus University, Department of Child and Adolescent Psychiatry, Sophia Children's Hospital, Rotterdam, The Netherlands.
Viner R. Sex on the brain: dilemmas in the endocrine management of children and adolescents with gender identity disorder. Arch. Dis. Child. 2005, 90(Sup.2):A77-A81.
Wagner G., Koch K., Reichenbach J.R., Sauer H., Schlösser R.G.M. The special involvement of the rostrolateral prefrontal cortex in planning abilities: an event-related fMRI study with the Tower of London paradigm. Neuropsychologia 2006, 44:2337-2347. 10.1016/j.neuropsychologia.2006.05.014.
Wechsler D. Wechsler Intelligence Scale for Children 1991, The Psychological Corporation, San Antonio. third ed.
Wechsler D. Wechsler Adult Intelligence Scale 1997, The Psychological Corporation, San Antonio. third ed.
Wojniusz S., Vögele C., Ropstad E., Evans N., Robinson J., Sütterlin S., Erhard H.W., Solbakk A.-K., Endestad T., Olberg D.E., Haraldsen I.R.H. Prepubertal gonadotropin-releasing hormone analog leads to exaggerated behavioral and emotional sex differences in sheep. Horm. Behav. 2011, 59:22-27. 10.1016/j.yhbeh.2010.09.010.
Woo T.U., Pucak M.L., Kye C.H., Matus C.V., Lewis D.A. Peripubertal refinement of the intrinsic and associational circuitry in monkey prefrontal cortex. Neuroscience 1997, 80:1149-1158.
Zubiaurre-Elorza L., Junque C., Gómez-Gil E., Segovia S., Carrillo B., Rametti G., Guillamon A. Cortical thickness in untreated transsexuals. Cereb. Cortex 2013, 23:2855-2862. 10.1093/cercor/bhs267.
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