Previous studies demonstrate profound sex-specific patterns of white matter microstructural neurodevelopment (i.e. fractional anisotropy; FA, and mean diffusivity; MD) during adolescence. While alcohol use has been associated with alterations in FA and MD, no studies have addressed the potential for sex-specific, alcohol-dose-dependent effects, during development. This prospective longitudinal study (2-4 visits, 310 total scans) used voxel-wise multilevel modeling, in 132 (68 female) adolescents (ages 12-21), to assess the sex-specific effects of lifetime alcohol use on FA and MD, during development. Follow-up analyses tested the role of sex hormones, testosterone and estradiol, in explaining the effects of alcohol use on FA and MD. In the splenium of the corpus callosum and posterior thalamic radiation, male adolescents demonstrated lower FA and greater MD as a function of more lifetime alcohol use, while female adolescents demonstrated the opposite. Further, significant associations between sex hormones and FA/MD partially explained the effect of alcohol use on FA and MD in male adolescents. These results provide evidence for sex-specific and dose-related effects of alcohol use on white matter microstructure, which are partially explained by sex hormones, and highlight the importance of studying sex and hormones when investigating the effects of alcohol use on the adolescent brain.

中文翻译：

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性激素部分解释了终生饮酒对青少年白质微结构的性别依赖性影响

以前的研究表明青春期白质微结构神经发育（即分数各向异性；FA 和平均扩散率；MD）具有深刻的性别特异性模式。虽然酒精使用与 FA 和 MD 的改变有关，但没有研究解决发育过程中性别特异性、酒精剂量依赖性影响的可能性。这项前瞻性纵向研究（2-4 次访问，310 次总扫描）在 132 名（68 名女性）青少年（12-21 岁）中使用体素多层次建模来评估终生饮酒对 FA 和 MD 的性别特异性影响, 在开发过程中。后续分析测试了性激素、睾酮和雌二醇在解释酒精使用对 FA 和 MD 的影响方面的作用。在胼胝体压部和丘脑后放射区，男性青少年表现出较低的 FA 和较高的 MD 作为终生饮酒量的函数，而女性青少年则表现出相反的情况。此外，性激素与 FA/MD 之间的显着关联部分解释了酒精使用对男性青少年 FA 和 MD 的影响。这些结果为酒精使用对白质微观结构的性别特异性和剂量相关影响提供了证据，这部分由性激素解释，并强调了在研究酒精使用对青少年大脑的影响时研究性和激素的重要性。