Thurston Lindsey T, Skorska Malvina N, Lobaugh Nancy J, Zucker Kenneth J, Chakravarty M Mallar, Lai Meng-Chuan, Chavez Sofia, VanderLaan Doug P
Department of Psychology, University of Toronto Mississauga, Mississauga, Ontario, Canada.
Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
PLoS One. 2024 Mar 12;19(3):e0300139. doi: 10.1371/journal.pone.0300139. eCollection 2024.
Adolescence is a sensitive developmental period for neural sex/gender differentiation. The present study used multiparametric mapping to better characterize adolescent white matter (WM) microstructure. WM microstructure was investigated using diffusion tensor indices (fractional anisotropy; mean, radial, and axial diffusivity [AD]) and quantitative T1 relaxometry (T1) in hormone therapy naïve adolescent cisgender girls, cisgender boys, and transgender boys (i.e., assigned female at birth and diagnosed with gender dysphoria). Diffusion indices were first analyzed for group differences using tract-based spatial statistics, which revealed a group difference in AD. Thus, two multiparametric and multivariate analyses assessed AD in conjunction with T1 relaxation time, and with respect to developmental proxy variables (i.e., age, serum estradiol, pubertal development, sexual attraction) thought to be relevant to adolescent brain development. The multivariate analyses showed a shared pattern between AD and T1 such that higher AD was associated with longer T1, and AD and T1 strongly related to all five developmental variables in cisgender boys (10 significant correlations, r range: 0.21-0.73). There were fewer significant correlations between the brain and developmental variables in cisgender girls (three correlations, r range: -0.54-0.54) and transgender boys (two correlations, r range: -0.59-0.77). Specifically, AD related to direction of sexual attraction (i.e., gynephilia, androphilia) in all groups, and T1 related to estradiol inversely in cisgender boys compared with transgender boys. These brain patterns may be indicative of less myelination and tissue density in cisgender boys, which corroborates other reports of protracted WM development in cisgender boys. Further, these findings highlight the importance of considering developmental trajectory when assessing the subtleties of neural structure associated with variations in sex, gender, and sexual attraction.
青春期是神经性别分化的敏感发育时期。本研究使用多参数映射来更好地表征青少年白质（WM）微观结构。在未接受激素治疗的青春期顺性别女孩、顺性别男孩和跨性别男孩（即出生时被指定为女性并被诊断为性别焦虑症）中，使用扩散张量指数（分数各向异性；平均、径向和轴向扩散率[AD]）和定量T1弛豫测量法（T1）研究WM微观结构。首先使用基于束的空间统计学分析扩散指数的组间差异，结果显示AD存在组间差异。因此，进行了两项多参数和多变量分析，将AD与T1弛豫时间以及与被认为与青少年大脑发育相关的发育代理变量（即年龄、血清雌二醇、青春期发育、性吸引力）相结合来评估AD。多变量分析显示AD和T1之间存在共同模式，即较高的AD与较长的T1相关，并且AD和T1与顺性别男孩的所有五个发育变量密切相关（10个显著相关性，r范围：0.21 - 0.73）。在顺性别女孩（三个相关性，r范围：-0.54 - 0.54）和跨性别男孩（两个相关性，r范围：-0.59 - 0.77）中，大脑与发育变量之间的显著相关性较少。具体而言，AD在所有组中都与性吸引力方向（即异性恋、同性恋）相关，与跨性别男孩相比，顺性别男孩中T1与雌二醇呈负相关。这些大脑模式可能表明顺性别男孩的髓鞘形成和组织密度较低，这与其他关于顺性别男孩白质发育延长的报道一致。此外，这些发现强调了在评估与性别、性取向和性吸引力变化相关的神经结构细微差异时考虑发育轨迹的重要性。
