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5-HT3A受体基因多态性与童年期性创伤对中枢5-羟色胺活性的影响

Influence of the 5-HT3A Receptor Gene Polymorphism and Childhood Sexual Trauma on Central Serotonin Activity.

作者信息

Jang Kuk-In, Lee Seung-Hwan, Huh Hyu Jung, Chae Jeong-Ho

机构信息

Department of Biomedicine & Health Sciences, The Catholic University of Korea, College of Medicine, Seoul, Korea.

Clinical Emotion and Cognition Research Laboratory, Inje University, Goyang, Korea.

出版信息

PLoS One. 2015 Dec 23;10(12):e0145269. doi: 10.1371/journal.pone.0145269. eCollection 2015.

DOI:10.1371/journal.pone.0145269
PMID:26701104
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4689356/
Abstract

BACKGROUND

Gene-environment interactions are important for understanding alterations in human brain function. The loudness dependence of auditory evoked potential (LDAEP) is known to reflect central serotonergic activity. Single nucleotide polymorphisms (SNPs) in the 5-HT3A serotonin receptor gene are associated with psychiatric disorders. This study aimed to investigate the effect between 5-HT3A receptor gene polymorphisms and childhood sexual trauma on the LDAEP as an electrophysiological marker in healthy subjects.

METHODS

A total of 206 healthy subjects were recruited and evaluated using the childhood trauma questionnaire (CTQ) and hospital anxiety and depression scale (HADS). Peak-to-peak N1/P2 was measured at five stimulus intensities, and the LDAEP was calculated as the linear-regression slope. In addition, the rs1062613 SNPs of 5-HT3A (CC, CT, and TT) were analyzed in healthy subjects.

RESULTS

There was a significant interaction between scores on the CTQ-sexual abuse subscale and 5-HT3A genotype on the LDAEP. Subjects with the CC polymorphism had a significantly higher LDEAP than T carriers in the sexually abused group. In addition, CC genotype subjects in the sexually abused group showed a significantly higher LDAEP compared with CC genotype subjects in the non-sexually abused group.

CONCLUSIONS

Our findings suggest that people with the CC polymorphism of the 5-HT3A gene have a greater risk of developing mental health problems if they have experienced childhood sexual abuse, possibly due to low central serotonin activity. Conversely, the T polymorphism may be protective against any central serotonergic changes following childhood sexual trauma.

摘要

背景

基因-环境相互作用对于理解人类大脑功能的改变至关重要。已知听觉诱发电位的响度依赖性(LDAEP)反映中枢5-羟色胺能活性。5-HT3A血清素受体基因中的单核苷酸多态性(SNP)与精神疾病相关。本研究旨在调查5-HT3A受体基因多态性与童年期性创伤之间对LDAEP的影响,LDAEP作为健康受试者的一种电生理标志物。

方法

共招募206名健康受试者,并使用儿童创伤问卷(CTQ)和医院焦虑抑郁量表(HADS)进行评估。在五种刺激强度下测量峰峰值N1/P2,并将LDAEP计算为线性回归斜率。此外,对健康受试者的5-HT3A的rs1062613 SNP(CC、CT和TT)进行分析。

结果

CTQ性虐待分量表得分与5-HT3A基因型在LDAEP上存在显著交互作用。在性虐待组中,具有CC多态性的受试者的LDEAP显著高于T等位基因携带者。此外,性虐待组中的CC基因型受试者与非性虐待组中的CC基因型受试者相比,LDAEP显著更高。

结论

我们的研究结果表明,5-HT3A基因CC多态性的人如果经历过童年期性虐待,患心理健康问题的风险更大,这可能是由于中枢5-羟色胺活性较低所致。相反,T多态性可能对童年期性创伤后任何中枢5-羟色胺能变化具有保护作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce1/4689356/0a200b66e600/pone.0145269.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce1/4689356/308302bdd69b/pone.0145269.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce1/4689356/0a200b66e600/pone.0145269.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce1/4689356/308302bdd69b/pone.0145269.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ce1/4689356/0a200b66e600/pone.0145269.g002.jpg

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