Department of Psychiatry, University of California, San Diego, La Jolla, CA 92093, USA.
Neuroimage. 2010 Nov 15;53(3):1093-102. doi: 10.1016/j.neuroimage.2010.02.026. Epub 2010 Feb 13.
Although glucocorticoid receptors are highly expressed in the prefrontal cortex, the hippocampus remains the predominant focus in the literature examining relationships between cortisol and brain. We examined phenotypic and genetic associations of cortisol levels with the thickness of prefrontal and anterior cingulate cortex regions, and with hippocampal volume in a sample of 388 middle-aged male twins who were 51-59 years old. Small but significant negative phenotypic associations were found between cortisol levels and the thickness of left dorsolateral (superior frontal gyrus, left rostral middle frontal gyrus) and ventrolateral (pars opercularis, pars triangularis, pars orbitalis) prefrontal regions, and right dorsolateral (superior frontal gyrus) and medial orbital frontal cortex. Most of the associations remained significant after adjusting for general cognitive ability, cardiovascular risk factors, and depression. Bivariate genetic analyses suggested that some of the associations were primarily accounted for by shared genetic influences; that is, some of the genes that tend to result in increased cortisol levels also tend to result in reduced prefrontal cortical thickness. Aging has been associated with reduced efficiency of hypothalamic-pituitary-adrenal function, frontal lobe shrinkage, and increases in health problems, but our present data do not allow us to determine the direction of effects. Moreover, the degree or the direction of the observed associations and the extent of their shared genetic underpinnings may well change as these individuals age. Longitudinal assessments are underway to elucidate the direction of the associations and the genetic underpinnings of longitudinal phenotypes for changes in cortisol and brain morphology.
尽管糖皮质激素受体在前额叶皮质中高度表达，但在研究皮质醇与大脑之间关系的文献中，海马体仍然是主要关注点。我们在 388 名 51-59 岁的中年男性双胞胎样本中，检查了皮质醇水平与前额叶和前扣带回皮质区域厚度以及海马体体积之间的表型和遗传关联。我们发现，皮质醇水平与左侧背外侧（额上回、左侧额中回额极）和腹外侧（额下回眶部、三角部、眶部）前额叶区域以及右侧背外侧（额上回）和内侧眶额皮质的厚度之间存在着小但显著的负相关。在调整了一般认知能力、心血管危险因素和抑郁之后，大多数关联仍然显著。双变量遗传分析表明，一些关联主要是由共同的遗传影响造成的；也就是说，一些导致皮质醇水平升高的基因也倾向于导致前额皮质厚度降低。衰老与下丘脑-垂体-肾上腺功能效率降低、额叶缩小以及健康问题增加有关，但我们目前的数据还不能确定这些关联的影响方向。此外，随着这些个体年龄的增长，观察到的关联的程度或方向及其遗传基础的共享程度可能会发生变化。正在进行纵向评估，以阐明皮质醇和大脑形态变化的关联方向以及纵向表型的遗传基础。
