催产素受体多态性的多效效应:影响双相情感障碍的纹状皮质连通性。

IF 3.5 2区 医学 Q2 PSYCHIATRY
Shyh-Yuh Wei, Huai-Hsuan Tseng, Hui Hua Chang, Po See Chen
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引用次数: 0

摘要

背景:催产素(OXT)是一种参与社会行为和情绪的神经肽,根据积极或消极的环境表现出双向作用。我们之前的报告强调了OXT对双相情感障碍(BD)患者纹状皮质功能连接(FC)的失调。我们假设:(1)在健康对照(HC)中,“敏感”OXTR等位基因的携带者会显示出FC的改变,特别是与儿童创伤相关的FC;(2)在BD患者中,这种基因-脑关系将从根本上改变或逆转,反映出基因-疾病的相互作用。方法:对39例BD患者和32例年龄匹配的HC患者进行静息状态功能MRI检查,并采血进行基因分型和血浆OXT水平评估。结果:与HC相比,BD患者表现出血浆OXT水平升高,儿童创伤评分更高。在纹状皮质回路中观察到OXTR rss53576和rs2228485的基因-疾病相互作用,其中rs2228485的鲁棒性更强。在HC中,rs2228485 AA纯合子表现出纹状皮质FC、感觉关联区和边缘区增强,这与儿童创伤相关。相反,BD患者腹侧纹状皮质FC的改变是逆转的,AA纯合子的FC低,g等位基因携带者的FC高。结论:这些发现强调了基因与疾病的相互作用,表明携带“敏感”等位基因的个体可能在显著性相关的大脑网络中表现出上下文依赖性的改变。我们的研究结果确定了一种潜在的神经机制,通过该机制,OXTR多态性调节环境敏感性,在HC和BD中具有不同的作用。儿童创伤可能以OXTR基因型依赖的方式塑造纹状皮质FC。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Pleiotropic effects of oxytocin receptor polymorphisms: influencing striatocortical connectivity in bipolar disorder.

Pleiotropic effects of oxytocin receptor polymorphisms: influencing striatocortical connectivity in bipolar disorder.

Background: Oxytocin (OXT), a neuropeptide involved in social behaviors and emotions, exhibits bidirectional effects depending upon positive or negative environments. Our previous report highlighted dysregulation of OXT on striatocortical functional connectivity (FC) in bipolar disorder (BD) patients. We hypothesized that: (1) in healthy controls (HC), carriers of a "sensitive" OXTR allele would show altered FC, particularly in association with childhood trauma; and (2) this gene-brain relationship would be fundamentally altered or reversed in BD patients, reflecting a gene-disease interaction.

Method: Thirty-nine BD patients and 32 age-matched HC underwent resting-state functional MRI and blood sampling for genotyping and plasma OXT level assessment.

Results: BD patients, compared to HC, demonstrated elevated plasma OXT levels and higher scores in childhood trauma. Gene-disease interactions were observed in the striatocortical circuitry with OXTR rs53576 and rs2228485, with greater robustness in rs2228485. In HC, the rs2228485 AA homozygotes showed enhanced striatocortical FC with the sensory association and limbic areas, which were correlated with the childhood trauma. Conversely, alterations in ventral striatocortical FC were reversed among BD patients, with hypo-FC in AA homozygotes and hyper-FC in G-allele carriers.

Conclusions: These findings highlight a gene-disease interplay, suggesting that individuals carrying the "sensitive" allele may exhibit context-dependent alterations in salience-related brain networks. Our results identify a potential neural mechanism through which the OXTR polymorphism modulates environmental sensitivity, with distinct effects in HC and BD. Childhood trauma may shape striatocortical FC in an OXTR genotype-dependent manner.

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来源期刊
International Journal of Bipolar Disorders
International Journal of Bipolar Disorders Medicine-Psychiatry and Mental Health
CiteScore
6.70
自引率
5.00%
发文量
26
审稿时长
13 weeks
期刊介绍: The International Journal of Bipolar Disorders is a peer-reviewed, open access online journal published under the SpringerOpen brand. It publishes contributions from the broad range of clinical, psychological and biological research in bipolar disorders. It is the official journal of the ECNP-ENBREC (European Network of Bipolar Research Expert Centres ) Bipolar Disorders Network, the International Group for the study of Lithium Treated Patients (IGSLi) and the Deutsche Gesellschaft für Bipolare Störungen (DGBS) and invites clinicians and researchers from around the globe to submit original research papers, short research communications, reviews, guidelines, case reports and letters to the editor that help to enhance understanding of bipolar disorders.
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