Spurny-Dworak B, Handschuh P, Spies M, Kaufmann U, Seiger R, Klöbl M, Konadu M E, Reed M B, Ritter V, Baldinger-Melich P, Bogner W, Kranz G S, Lanzenberger R
Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria.
Department of Obstetrics and Gynecology, Medical University of Vienna, Austria.
Psychoneuroendocrinology. 2022 Apr;138:105683. doi: 10.1016/j.psyneuen.2022.105683. Epub 2022 Feb 1.
Sex hormones affect the GABAergic and glutamatergic neurotransmitter system as demonstrated in animal studies. However, human research has mostly been correlational in nature. Here, we aimed at substantiating causal interpretations of the interaction between sex hormones and neurotransmitter function by using magnetic resonance spectroscopy imaging (MRSI) to study the effect of gender-affirming hormone treatment (GHT) in transgender individuals. Fifteen trans men (TM) with a DSM-5 diagnosis of gender dysphoria, undergoing GHT, and 15 age-matched cisgender women (CW), receiving no therapy, underwent MRSI before and after at least 12 weeks. Additionally, sex differences in neurotransmitter levels were evaluated in an independent sample of 80 cisgender men and 79 cisgender women. Mean GABA+ (combination of GABA and macromolecules) and Glx (combination of glutamate and glutamine) ratios to total creatine (GABA+/tCr, Glx/tCr) were calculated in five predefined regions-of-interest (hippocampus, insula, pallidum, putamen and thalamus). Linear mixed models analysis revealed a significant measurement by gender identity effect (p = 0.048) for GABA+/tCr ratios in the hippocampus, with the TM cohort showing decreased GABA+/tCr levels after GHT compared to CW. Moreover, analysis of covariance showed a significant sex difference in insula GABA+/tCr ratios (p = 0.049), indicating elevated GABA levels in cisgender women compared to cisgender men. Our study demonstrates GHT treatment-induced GABA+/tCr reductions in the hippocampus, indicating hormone receptor activation on GABAergic cells and testosterone-induced neuroplastic processes within the hippocampus. Moreover, elevated GABA levels in the female compared to the male insula highlight the importance of including sex as factor in future MRS studies. DATA AVAILABILITY STATEMENT: Due to data protection laws processed data is available from the authors upon reasonable request. Please contact rupert.lanzenberger@meduniwien.ac.at with any questions or requests.
如动物研究所示，性激素会影响γ-氨基丁酸（GABA）能和谷氨酸能神经递质系统。然而，人体研究大多具有相关性。在此，我们旨在通过使用磁共振波谱成像（MRSI）研究跨性别者的性别确认激素治疗（GHT）的效果，以证实性激素与神经递质功能之间相互作用的因果解释。15名被诊断为性别焦虑症（DSM-5）且正在接受GHT治疗的跨性别男性（TM）和15名年龄匹配的未接受治疗的顺性别女性（CW）在至少12周前后接受了MRSI检查。此外，在一个由80名顺性别男性和79名顺性别女性组成的独立样本中评估了神经递质水平的性别差异。在五个预先定义的感兴趣区域（海马体、脑岛、苍白球、壳核和丘脑）计算平均GABA +（GABA与大分子的组合）和Glx（谷氨酸与谷氨酰胺的组合）与总肌酸的比率（GABA +/tCr，Glx/tCr）。线性混合模型分析显示，海马体中GABA +/tCr比率存在显著的性别认同测量效应（p = 0.048），与CW相比，TM队列在GHT后GABA +/tCr水平降低。此外，协方差分析显示脑岛GABA +/tCr比率存在显著的性别差异（p = 0.049），表明顺性别女性的GABA水平高于顺性别男性。我们的研究表明，GHT治疗可导致海马体中GABA +/tCr降低，表明GABA能细胞上的激素受体激活以及睾酮诱导的海马体内神经可塑性过程。此外，与男性脑岛相比，女性脑岛中GABA水平升高凸显了在未来的MRS研究中将性别作为一个因素的重要性。数据可用性声明：由于数据保护法，经处理的数据可在合理请求时向作者获取。如有任何问题或请求，请联系rupert.lanzenberger@meduniwien.ac.at。
