Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Wuerzburg, Wuerzburg, Germany.
Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany.
Nitric Oxide. 2019 Jul 1;88:45-49. doi: 10.1016/j.niox.2019.04.003. Epub 2019 Apr 16.
The neuronal isoform of the nitric oxide synthase (NOS-I) encoded by NOS1 is the main source of nitric oxide (NO) in the brain. Reduced NO signaling in the prefrontal cortex has been linked to schizophrenia and cognitive processes while reduced striatal NOS1 expression has been associated with impulsive behavior.
To evaluate the effect of two functional polymorphisms in alternative first exons of NOS1, ex1f-VNTR and ex1c-SNP rs41279104, on the HPA stress axis and neurocognitive abilities, 280 healthy subjects were genotyped, had their salivary cortisol levels measured and were assessed in verbal memory, verbal fluency, working memory and verbal IQ by using the California Verbal Learning Test (CVLT), the Regensburger test of verbal fluency (RWT), a n-back task and subscales of the Wechsler Adult Intelligence Scale III (WAIS-III).
Schizophrenia risk (A)-allele carriers of NOS1 ex1c-SNP rs41279104 displayed significantly lower baseline cortisol levels (p = 0.004). NOS1 ex1f-VNTR genotype carriers showed differences in working memory performance (p = 0.05) in a gene-dose effect manner, with homozygous carriers of the short impulsivity-risk allele committing most commission errors. Finally, A-allele carriers of the NOS1 ex1c-SNP rs41279104 tended to react faster during the working memory task (p = 0.065).
For the first time, we demonstrated an influence of the NOS1 ex1c-SNP rs41279104 on salivary cortisol levels and additionally implicate the A-allele in an enhanced reaction time during a working memory task. Regarding the NOS1 ex1f-VNTR our study supports the previously reported influence on impulsivity, lending further support to the hypothesis that this genetic variant underlies impulsive behavior.
一氧化氮合酶（NOS-I）的神经元同工型由 NOS1 编码，是大脑中一氧化氮（NO）的主要来源。前额叶皮质中一氧化氮信号的减少与精神分裂症和认知过程有关，而纹状体中 NOS1 表达的减少与冲动行为有关。
为了评估 NOS1 两个替代第一外显子中的两个功能多态性（ex1f-VNTR 和 ex1c-SNP rs41279104）对 HPA 应激轴和神经认知能力的影响，对 280 名健康受试者进行了基因分型，测量了唾液皮质醇水平，并通过使用加利福尼亚语言学习测试 (CVLT)、雷根斯堡语言流畅性测试 (RWT)、n-back 任务和韦氏成人智力量表 III (WAIS-III) 的子量表评估了他们的言语记忆、言语流畅性、工作记忆和言语智商。
NOS1 ex1c-SNP rs41279104 的精神分裂症风险（A）-等位基因携带者的皮质醇基础水平明显较低（p=0.004）。NOS1 ex1f-VNTR 基因型携带者以基因剂量效应的方式表现出工作记忆表现的差异（p=0.05），短冲动风险等位基因的纯合携带者犯的错误最多。最后，NOS1 ex1c-SNP rs41279104 的 A-等位基因携带者在工作记忆任务中反应速度更快（p=0.065）。
我们首次证明了 NOS1 ex1c-SNP rs41279104 对唾液皮质醇水平的影响，并进一步表明 A-等位基因在工作记忆任务中的反应时间加快。关于 NOS1 ex1f-VNTR，我们的研究支持了先前关于冲动性的影响，进一步支持了这样的假设，即这种遗传变异是冲动行为的基础。
