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

项目摘要 拟议的项目审查青春期抑制治疗对精神健康的影响， 跨性别青少年青春期带来的身体变化往往会放大性别焦虑 在变性青年中。给予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，为跨性别青少年、他们的家人和医疗保健团队提供更多考虑时间 是否指示部分和/或完全不可逆的治疗。青春期抑制得到世界的认可 跨性别健康专业协会和内分泌学会作为护理标准。初步 报告表明，GnRHa治疗可能会为跨性别青年带来心理健康益处。然而，在这方面， GnRHa也可能以破坏心理健康收益的方式破坏青春期信号神经成熟 并以其他方式影响生活质量。GnRHa治疗的总体影响尚未得到证实。 系统地研究。为了探索这些影响，本项目着重于评估维度 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，社交 认知和奖励反应。现有的文献文件标志着这些系统的成熟， 正常的青春期发育和性腺激素被认为有助于这种成熟。我们将 采取多模式方法，其中自我和父母报告，标准化的神经心理评估， 和神经影像学方法用于评估GnRHa治疗在两年研究期内的效果。 我们将在三个地点招募132名变性青少年：全国儿童医院;儿童医院; 国立医院和Lurie儿童医院。一半将接受GnRHa的青春期抑制， 另一半将是未接受治疗的变性青年。评价GnRHa治疗对 心理健康功能以及与青春期相关的RDoC系统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.