THE IMPACT OF PUBERTAL SUPPRESSION ON ADOLESCENT NEURAL AND MENTAL HEALTH TRAJECTORIES - Resubmission - 1

项目摘要 这项拟议的项目考察了青春期抑制疗法对青少年心理健康的影响。 随着时间的推移，变性青少年。青春期带来的生理变化往往会放大性别焦虑症。 变性人青年。应用促性腺激素释放激素激动剂(GnRHa)是一种有效的手段 抑制青春期，为变性人青年、他们的家人和卫生保健团队提供更多时间考虑 是否指示进行部分和/或完全不可逆的治疗。抑制青春期是世界认可的 变性人健康专业协会和内分泌协会作为护理的标准。初步 报告表明，使用GnRHa治疗可能会为变性人青年带来心理健康益处。然而， GnRHa还可能以破坏心理健康成果的方式扰乱青春期信号的神经成熟 随着时间的推移，还会在其他方面影响生活质量。GnRHa治疗的总体影响尚未得到 对其进行了系统研究。为了探索这些影响，本项目侧重于维度的评估 心理健康和映射到NIMH RDoC矩阵的三个神经系统：认知/情绪控制、社会 认知和奖励反应。在这些系统中，现有的文献文件标志着成熟 正常的青春期发育和性腺激素被认为有助于这种成熟。我们会 采取多模式的方法，其中自我和父母报告，标准化的神经心理评估， 神经成像方法被用来评估GnRHa治疗在两年的研究期间的效果。 我们将在三个地点招收132名变性青少年：全国儿童医院；儿童医院 国立医院和鲁里儿童医院。一半人将接受GnRHa和GnRHa青春期抑制 另一半将是没有接受治疗的变性人青年。评价促性腺激素释放激素受体α治疗对高血压患者的影响 心理健康功能以及与青春期相关的RDoC系统的成熟将阐明其潜在的保护作用 和风险效应，以支持治疗方案的优化和个性化。

Project Summary The proposed project examines the effects of pubertal suppression treatment on the mental health of transgender adolescents over time. The physical changes brought on by puberty often amplify gender dysphoria in transgender youth. Administering gonadotropin releasing hormone agonists (GnRHa) is an effective means of suppressing puberty to provide transgender youth, their families, and health care teams more time to consider whether partially and/or fully irreversible treatments are indicated. Pubertal suppression is endorsed by the World Professional Association for Transgender Health and the Endocrine Society as standard of care. Preliminary reports suggest that treatment with GnRHa may confer mental health benefits for transgender youth. However, GnRHa may also disrupt puberty-signaled neural maturation in ways that can undermine mental health gains over time and impact quality of life in other ways. The overall impacts of GnRHa treatment have not been systematically studied. In order to probe these effects, this project focuses on the assessment of dimensional mental health and three neural systems that map onto the NIMH RDoC matrix: cognitive/emotional control, social cognition, and reward responsiveness. Existing literature documents marked maturation in these systems during normative adolescent development, and gonadal hormones are thought to contribute to this maturation. We will take a multimodal approach, in which self- and parent-report, standardized neuropsychological assessments, and neuroimaging methods are used to assess the effects of GnRHa treatment over a two-year study period. We will enroll 132 transgender adolescents across three sites: Nationwide Children’s Hospital; Children’s National Hospital; and Lurie Children’s Hospital. Half will be undergoing pubertal suppression with GnRHa and the other half will be transgender youth not undergoing treatment. Evaluating the impact of GnRHa treatment on mental health functioning as well as puberty-linked RDoC system maturation will clarify its potential protective and risk effects to support optimization and personalization of treatment protocols.