Center for Multimodal Imaging and Genetics, University of California, San Diego, La Jolla, CA 92093.
Medical Scientist Training Program, University of California, San Diego, La Jolla, CA 92093.
Proc Natl Acad Sci U S A. 2024 Jul 30;121(31):e2403212121. doi: 10.1073/pnas.2403212121. Epub 2024 Jul 23.
Some mental health problems such as depression and anxiety are more common in females, while others such as autism and attention deficit/hyperactivity (AD/H) are more common in males. However, the neurobiological origins of these sex differences are poorly understood. Animal studies have shown substantial sex differences in neuronal and glial cell structure, while human brain imaging studies have shown only small differences, which largely reflect overall body and brain size. Advanced diffusion MRI techniques can be used to examine intracellular, extracellular, and free water signal contributions and provide unique insights into microscopic cellular structure. However, the extent to which sex differences exist in these metrics of subcortical gray matter structures implicated in psychiatric disorders is not known. Here, we show large sex-related differences in microstructure in subcortical regions, including the hippocampus, thalamus, and nucleus accumbens in a large sample of young adults. Unlike conventional T1-weighted structural imaging, large sex differences remained after adjustment for age and brain volume. Further, diffusion metrics in the thalamus and amygdala were associated with depression, anxiety, AD/H, and antisocial personality problems. Diffusion MRI may provide mechanistic insights into the origin of sex differences in behavior and mental health over the life course and help to bridge the gap between findings from experimental, epidemiological, and clinical mental health research.
一些心理健康问题，如抑郁症和焦虑症，在女性中更为常见，而另一些如自闭症和注意力缺陷/多动障碍（AD/H）则在男性中更为常见。然而，这些性别差异的神经生物学起源还知之甚少。动物研究表明，神经元和神经胶质细胞结构存在显著的性别差异，而人类大脑成像研究仅显示出很小的差异，这些差异在很大程度上反映了整体身体和大脑的大小。先进的扩散 MRI 技术可用于检查细胞内、细胞外和游离水信号的贡献，并提供对微观细胞结构的独特见解。然而，在这些与精神障碍相关的皮质下灰质结构的指标中，性别差异的程度尚不清楚。在这里，我们在一大群年轻成年人中显示了皮质下区域（包括海马体、丘脑和伏隔核）微观结构的大的性别相关差异。与传统的 T1 加权结构成像不同，在调整年龄和脑容量后，仍存在较大的性别差异。此外，丘脑和杏仁核的扩散指标与抑郁、焦虑、AD/H 和反社会人格问题有关。扩散 MRI 可能为行为和心理健康的性别差异在整个生命周期中的起源提供机制上的见解，并有助于弥合实验、流行病学和临床心理健康研究之间的差距。
