[en] Various previous studies have reported that brains of people diagnosed with gender dysphoria (GD) show sex-atypical features. In addition, recent functional magnetic resonance imaging studies found that several brain resting-state networks (RSNs) in adults with GD show functional connectivity (FC) patterns that are not sex-atypical, but specific for GD. In the current study we examined whether FC patterns are also altered in prepubertal children and adolescents with GD in comparison with non-gender dysphoric peers. We investigated FC patterns within RSNs that were previously examined in adults: visual networks (VNs), sensorimotor networks (SMNs), default mode network (DMN) and salience network. Thirty-one children (18 birth assigned males; 13 birth assigned females) and 40 adolescents with GD (19 birth assigned males or transgirls; 21 birth assigned females or transboys), and 39 cisgender children (21 boys; 18 girls) and 41 cisgender adolescents (20 boys; 21 girls) participated. We used independent component analysis to obtain the network maps of interest and compared these across groups. Within one of the three VNs (VN-I), adolescent transgirls showed stronger FC in the right cerebellum compared with all other adolescent groups. Sex differences in FC between the cisgender adolescent groups were observed in the right supplementary motor area within one of the two SMNs (SMN-II; girls>boys) and the right posterior cingulate gyrus within the posterior DMN (boys>girls). Within these networks adolescent transgirls showed FC patterns similar to their experienced gender (female). Also adolescent transboys showed a FC pattern similar to their experienced gender (male), but within the SMN-II only. The prepubertal children did not show any group differences in FC, suggesting that these emerge with aging and during puberty. Our findings provide evidence for the existence of both GD-specific and sex-atypical FC patterns in adolescents with GD.
Disciplines :
Neurosciences & comportement
Auteur, co-auteur :
Nota, Nienke M.
Kreukels, Baudewijntje P. C.
den Heijer, Martin
Veltman, Dick J.
Cohen-Kettenis, Peggy T.
Burke, Sarah M.
Bakker, Julie ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques > Biologie de la différenciation sexuelle du cerveau
Langue du document :
Anglais
Titre :
Brain functional connectivity patterns in children and adolescents with gender dysphoria: Sex-atypical or not?
Date de publication/diffusion :
2017
Titre du périodique :
Psychoneuroendocrinology
ISSN :
0306-4530
eISSN :
1873-3360
Maison d'édition :
Elsevier, Royaume-Uni
Volume/Tome :
86
Pagination :
187-195
Peer reviewed :
Peer reviewed vérifié par ORBi
Commentaire :
Copyright (c) 2017 Elsevier Ltd. All rights reserved.
Allen, E.A., Erhardt, E.B., Damaraju, E., Gruner, W., Segall, J.M., Silva, R.F., A baseline for the multivariate comparison of resting-state networks. Front. Syst. Neurosci. 5 (2011), 1–23, 10.3389/fnsys.2011.00002.
American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders. fourth ed., text revision, 2000, American Psychiatric Association, Washington, DC.
American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders. fifth ed., 2013, American Psychiatric Publishing, Arlington, VA.
Bell, A.J., Sejnowski, T.J., An information maximisation approach to blind separation and blind deconvolution. Neural. Comput. 7 (1995), 1129–1159.
Bui, H.N., Schagen, S.E., Klink, D.T., Delemarre-van de Waal, H.A., Blankenstein, M.A., Heijboer, A.C., Salivary testosterone in female-to-male transgender adolescents during treatment with intra-muscular injectable testosterone esters. Steroids 78 (2013), 91–95, 10.1016/j.steroids.2012.10.006.
Burke, S.M., Cohen-kettenis, P.T., Veltman, D.J., Klink, D.T., Bakker, J., Hypothalamic response to the chemo-signal androstadienone in gender dysphoric children and adolescents. Front. Endocrinol. (Lausanne) 5 (2014), 1–10, 10.3389/fendo.2014.00060.
Burke, S.M., Manzouri, A.H., Dhejne, C., Bergström, K., Arver, S., Feusner, J.D., Savic-Berglund, I., Testosterone effects on the brain in transgender men. Cereb. Cortex, 2017, 1–15.
De Bie, H.M.A., Boersma, M., Wattjes, M.P., Adriaanse, S., Vermeulen, R.J., Oostrom, K.J., Huisman, J., Veltman, D.J., Delemarre-Van de Waal, H.A., Preparing children with a mock scanner training protocol results in high quality structural and functional MRI scans. Eur. J. Pediatr. 169 (2010), 1079–1085, 10.1007/s00431-010-1181-z.
De Bie, H.M., Boersma, M., Adriaanse, S., Veltman, D.J., Wink, A.M., Roosendaal, S.D., Barkhof, F., Stam, C.J., Oostrom, K.J., Delemarre-van de Waal, H.A., Sanz-Arigita, E.J., Resting-state networks in awake five- to eight-year old children. Hum. Brain Mapp. 33 (2012), 1189–1201, 10.1002/hbm.21280.
De Vries, A.L.C., McGuire, J.K., Steensma, T.D., Wagenaar, E.C.F., Doreleijers, T.A.H., Cohen-Kettenis, P.T., Young adult psychological outcome after puberty suppression and gender reassignment. Pediatrics 134 (2014), 696–704, 10.1542/peds.2013-2958.
Fair, D.A., Cohen, A.L., Dosenbach, N.U.F., Church, J.A., Miezin, F.M., Barch, D.M., Raichle, M.E., Petersen, S.E., Schlaggar, B.L., The maturing architecture of the brain's default network. Proc. Natl. Acad. Sci. U. S. A. 105 (2008), 4028–4032, 10.1073/pnas.0800376105.
Ferri, F., Frassinetti, F., Ardizzi, M., Costantini, M., Gallese, V., A sensorimotor network for the bodily self. J. Cogn. Neurosci. 24 (2012), 1584–1595, 10.1162/jocn_a_00230.
Feusner, J.D., Lidström, A., Moody, T.D., Dhejne, C., Bookheimer, S.Y., Savic, I., Intrinsic network connectivity and own body perception in gender dysphoria. Brain Imaging Behav., 2016, 10.1007/s11682-016-9578-6 Epub ahead of print.
Filippi, M., Valsasina, P., Misci, P., Falini, A., Comi, G., Rocca, M.A., The organization of intrinsic brain activity differs between genders: a resting-state FMRI study in a large cohort of young healthy subjects. Hum. Brain Mapp. 34 (2013), 1330–1343, 10.1002/hbm.21514.
Fuss, J., Auer, M.K., Briken, P., Gender dysphoria in children and adolescents: a review of recent research. Curr. Opin. Psychiatry 28 (2015), 430–434, 10.1097/YCO.0000000000000203.
Gong, Q., He, Y., Depression, neuroimaging and connectomics: a selective overview. Biol. Psychiatry, 2015, 223–235, 10.1016/j.biopsych.2014.08.009.
Guerrieri, G.M., Wakim, P.G., Keenan, P.A., Schenkel, L.A., Berlin, K., Gibson, C.J., Rubinow, D.R., Schmidt, P.J., Sex differences in visuospatial abilities persist during induced hypogonadism. Neuropsychologia 81 (2016), 219–229, 10.1016/j.neuropsychologia.2015.12.021.
Halpern, D.F., Benbow, C.P., Geary, D.C., Gur, R.C., Hyde, J.S., Gernsbacher, M.A., The science of sex differences in science and mathematics. Psychol. Sci. Public Interest 8 (2007), 1–51, 10.1111/j.1529-1006.2007.00032.x.
Hembree, W.C., Cohen-kettenis, P., Delemarre-van de Waal, H.A., Gooren, L.J., Meyer, W.J.M., Spack, N.P., Tangpricha, V., Montori, V.M., Endocrine treatment of transsexual persons: an endocrine society clinical practice guideline. J. Clin. Endocrinol. Metab. 94 (2009), 3132–3154, 10.1210/jc.2009-0345.
Himberg, J., Hyvärinen, A., Esposito, F., Validating the independent components of neuroimaging time series via clustering and visualization. Neuroimage 22 (2004), 1214–1222, 10.1016/j.neuroimage.2004.03.027.
Hupfeld, K.E., Ketcham, C.J., Schneider, H.D., Transcranial direct current stimulation (tDCS) to the supplementary motor area (SMA) influences performance on motor tasks. Exp. Brain Res. 235 (2016), 851–859, 10.1007/s00221-016-4848-5.
Koenig, K.A., Lowe, M.J., Lin, J., Sakaie, K.E., Stone, L., Bermel, R.A., Beall, E.B., Rao, S.M., Trapp, B.D., Phillips, M.D., Sex differences in resting-state functional connectivity in multiple sclerosis. AJNR. Am. J. Neuroradiol. 34 (2013), 2304–2311, 10.3174/ajnr.A3630.
Kreukels, B.P.C., Cohen-Kettenis, P.T., Puberty suppression in gender identity disorder: the Amsterdam experience. Nat. Rev. Endocrinol. 7 (2011), 466–472, 10.1038/nrendo.2011.78.
Ku, H.-L., Lin, C.-S., Chao, H.-T., Tu, P.-C., Li, C.-T., Cheng, C.-M., Su, T.-P., Lee, Y.-C., Hsieh, J.-C., Brain signature characterizing the body-brain-mind axis of transsexuals. PLoS One, 8, 2013, e70808.
Lee, M., Smyser, C., Shimony, J., Resting-state fMRI: a review of methods and clinical applications. AJNR Am. J. Neuroradiol. 34 (2013), 1866–1872.
Li, Y.-O., Adali, T.A., Calhoun, V.D., Estimating the number of independent components for functional magnetic resonance imaging data. Hum. Brain Mapp. 28 (2007), 1251–1266, 10.1002/hbm.20359.
Lin, C.-S., Ku, H.-L., Chao, H.-T., Tu, P.-C., Li, C.-T., Cheng, C.-M., Su, T.-P., Lee, Y.-C., Hsieh, J.-C., Neural network of body representation differs between transsexuals and cissexuals. PLoS One, 9, 2014, e85914, 10.1371/journal.pone.0085914.
Manzouri, A., Kosidou, K., Savic, I., Anatomical and functional findings in female-to-male transsexuals: testing a new hypothesis. Cereb. Cortex, 2015, 10.1093/cercor/bhv278 Epub ahead of print.
Marshall, W.A., Tanner, J.M., Variations in pattern of pubertal changes in girls. Arch. Dis. Child. 44 (1969), 291–303, 10.1136/adc.44.235.291.
Marshall, W.A., Tanner, J.M., Variations in the pattern of pubertal changes in boys. Arch. Dis. Child. 45 (1970), 13–23, 10.1136/adc.45.239.13.
Moreno-Briseño, P., Díaz, R., Campos-Romo, A., Fernandez-Ruiz, J., Sex-related differences in motor learning and performance. Behav. Brain Funct., 6, 2010, 10.1186/1744-9081-6-74.
Morris, N.M., Udry, J.R., Validation of a self-administered instrument to assess stage of adolescent development. J. Youth Adolesc. 9 (1980), 271–280, 10.1007/BF02088471.
Mueller, S.C., Wierckx, K., Jackson, K., Sjoen, G.T., Psychoneuroendocrinology Circulating androgens correlate with resting-state MRI in transgender men. Psychoneuroendocrinology 73 (2016), 91–98, 10.1016/j.psyneuen.2016.07.212.
Nieder, T.O., Herff, M., Cerwenka, S., Preuss, W.F., Cohen-Kettenis, P.T., De Cuypere, G., Haraldsen, I.R.H., Richter-Appelt, H., Age of onset and sexual orientation in transsexual males and females. J. Sex. Med. 8 (2011), 783–791, 10.1111/j. 1743-6109.2010.02142. x.
Pickett, T.C., Lewis, R.J., Cash, T.F., Men, muscles, and body image: comparisons of competitive bodybuilders, weight trainers, and athletically active controls. Br. J. Sports Med. 39 (2005), 217–222, 10.1136/bjsm.2004.012013.
Rubia, K., Functional brain imaging across development. Eur. Child Adolesc. Psychiatry 22 (2013), 719–731, 10.1007/s00787-012-0291-8.
Savic, I., Arver, S., Sex dimorphism of the brain in male-to-female transsexuals. Cereb. Cortex 21 (2011), 2525–2533, 10.1093/cercor/bhr032.
Scheinost, D., Finn, E.S., Tokoglu, F., Shen, X., Papademetris, X., Hampson, M., Constable, R.T., Sex differences in normal age trajectories of functional brain networks. Hum. Brain Mapp. 36 (2015), 1524–1535, 10.1002/hbm.22720.
Schraa-Tam, C.K.L., Rietdijk, W.J.R., Verbeke, W.J.M.I., Dietvorst, R.C., van den Berg, W.E., Bagozzi, R.P., De Zeeuw, C.I., fMRI activities in the emotional cerebellum: a preference for negative stimuli and hoal-directed behavior. Cerebellum 11 (2012), 233–245, 10.1007/s12311-011-0301-2.
Smith, E.S., Junger, J., Derntl, B., Habel, U., The transsexual brain—a review of findings on the neural basis of transsexualism. Neurosci. Biobehav. Rev. 59 (2015), 251–266.
Solé-Padullés, C., Castro-Fornieles, J., Sde la Serna, E., Calvo, R., Baeza, I., Moya, J., Lázaro, L., Rosa, M., Bargalló, N., Sugranyes, G., Intrinsic connectivity networks from childhood to late adolescence: effects of age and sex. Dev. Cogn. Neurosci. 17 (2016), 35–44, 10.1016/j.dcn.2015.11.004.
Staphorsius, A.S., Kreukels, B.P.C., Cohen-Kettenis, P.T., Veltman, D.J., Burke, S.M., Schagen, S.E.E., Wouters, F.M., Delemarre-van de Waal, H.A., Bakker, J., Puberty suppression and executive functioning: an fMRI-study in adolescents with gender dysphoria. Psychoneuroendocrinology 56 (2015), 190–199, 10.1016/j.psyneuen.2015.03.007.
Steensma, T.D., Biemond, R., de Boer, F., Cohen-Kettenis, P.T., Desisting and persisting gender dysphoria after childhood: a qualitative follow-up study. Clin. Child Psychol. Psychiatry 16 (2011), 499–516.
Swaab, D.F., Sexual differentiation of the brain and behavior. Best Pract. Res. Clin. Endocrinol. Metab. 21 (2007), 431–444, 10.1016/j.beem.2007.04.003.
Van Dijk, K.R.A., Sabuncu, M.R., Buckner, R.L., The influence of head motion on intrinsic functional connectivity MRI. Neuroimage 59 (2012), 431–438, 10.1016/j.neuroimage.2011.07.044.
Whitfield-Gabrieli, S., Moran, J.M., Nieto-Castañón, A., Triantafyllou, C., Saxe, R., Gabrieli, J.D.E., Associations and dissociations between default and self-reference networks in the human brain. Neuroimage 55 (2011), 225–232, 10.1016/j.neuroimage.2010.11.048.
Zhang, S., Li, C.R., Functional networks for cognitive control in a stop signal task: independent component analysis. Hum. Brain Mapp. 33 (2012), 89–104, 10.1002/hbm.21197.
Zhang, C., Cahill, N.D., Arbabshirani, M.R., White, T., Baum, S.A., Michael, A.M., Sex and age effects of functional connectivity in early adulthood. Brain Connect. 6 (2016), 700–713, 10.1089/brain.2016.0429.
Zuo, X.-N., Kelly, C., Di Martino, A., Mennes, M., Margulies, D.S., Bangaru, S., Grzadzinski, R., Evans, A.C., Zang, Y.-F., Castellanos, F.X., Milham, M.P., Growing together and growing apart: regional and sex differences in the lifespan developmental trajectories of functional homotopy. J. Neurosci. 30 (2011), 15034–15043, 10.1523/JNEUROSCI.2612-10.2010.
