Department of Theoretical and Clinical Psychobiology, University of Trier, Trier, Germany.
Neuropsychobiology. 2010;61(1):49-56. doi: 10.1159/000262180. Epub 2009 Nov 26.
Cortisol has a modulatory influence on cognitive functions in humans. Both impairing and enhancing effects of cortisol administration have been shown for hippocampus-dependent declarative memory, and impairing effects have been shown for prefrontal-cortex-dependent working memory function. Given the high density of glucocorticoid (GC) receptors in the prefrontal cortex, we investigated whether common polymorphisms of the GC receptor (GR) gene (ER22/23EK, N363S, BclI, 9 beta A3669G) modulate the influence of cortisol administration on working memory. Working memory performance was investigated in 169 subjects on 10 mg hydrocortisone (cortisol) and placebo using an item recognition task. No impairing effect of hydrocortisone treatment became evident. However, a sex x genotype interaction on general working memory performance was revealed (p = 0.02). While female heterozygous carriers of the 9 beta G allele displayed faster reaction times than the other genotype groups, 9 beta G heterozygous men were relatively slower. Heritability estimates for memory are roughly 50%, indicating that common genetic polymorphisms have an important impact on cognitive performance. Our results suggest that variants of the GR gene might explain some of the variance attributable to genetic factors. Furthermore, it can be speculated that they modulate the individual vulnerability for memory impairments related to stress-related psychiatric disorders.
皮质醇对人类的认知功能具有调节作用。皮质醇给药对海马体依赖的陈述性记忆具有改善和损害作用，对前额叶皮层依赖的工作记忆功能具有损害作用。鉴于皮质醇（GC）受体在前额叶皮层中的高密度，我们研究了 GC 受体（GR）基因的常见多态性（ER22/23EK、N363S、BclI、9βA3669G）是否调节皮质醇给药对工作记忆的影响。使用项目识别任务，我们在 169 名受试者中研究了 10mg 氢化可的松（皮质醇）和安慰剂对工作记忆的影响。皮质醇治疗没有明显的损害作用。然而，在一般工作记忆表现方面发现了性别与基因型的相互作用（p=0.02）。虽然 9βG 等位基因的女性杂合子携带者的反应时间比其他基因型组快，但 9βG 杂合子男性则相对较慢。记忆的遗传率估计约为 50%，这表明常见的遗传多态性对认知表现有重要影响。我们的结果表明，GR 基因的变异可能解释了与应激相关的精神障碍相关的记忆损伤归因于遗传因素的部分差异。此外，可以推测它们调节与应激相关的精神障碍相关的记忆损伤的个体易感性。
