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早期生活应激对幼年恒河猴 5-羟色胺 1A 受体的影响:正电子发射断层扫描研究。

Effects of early-life stress on serotonin(1A) receptors in juvenile Rhesus monkeys measured by positron emission tomography.

机构信息

National Institute on Alcohol Abuse and Alcoholism, Poolesville, MD, USA.

出版信息

Biol Psychiatry. 2010 Jun 15;67(12):1146-53. doi: 10.1016/j.biopsych.2009.12.030. Epub 2010 Feb 20.

Abstract

BACKGROUND

Traumatic experiences in early childhood are associated with increased risk for developing mood and anxiety disorders later in life. Low serotonin(1A) receptor (5-HT(1A)R) density during development has been proposed as a trait-like characteristic leading to increased vulnerability of stress-related neuropsychiatric disorders.

METHODS

To assess the relationship between early-life stress and alterations in the serotonin system during development, we used positron emission tomography to measure in vivo 5-HT(1A)R density and apparent dissociation constant (K(D)(app)) in the brain of juvenile Rhesus monkeys exposed to the early-life stress of peer-rearing.

RESULTS

In general, 5-HT(1A)R density and K(D)(app) were decreased in peer-reared compared with control mother-reared animals. However, increase in receptor density was found in the dorsomedial prefrontal cortex of peer-reared females.

CONCLUSIONS

These findings suggest that exposure to an adverse early-life environment during infancy is associated with long-term alterations in the serotonin system and support previous studies suggesting that reduced 5-HT(1A)R density during development might be a factor increasing vulnerability to stress-related neuropsychiatric disorders. Furthermore, alterations in the serotonin system seemed to be gender- and region-specific, providing a biological basis for the higher prevalence of affective disorders in women.

摘要

背景

儿童早期的创伤经历与成年后患情绪和焦虑障碍的风险增加有关。发育过程中低血清素(1A)受体(5-HT(1A)R)密度被认为是导致与压力相关的神经精神障碍易感性增加的特质特征。

方法

为了评估早期生活应激与发育过程中血清素系统改变之间的关系,我们使用正电子发射断层扫描来测量暴露于同伴养育的早期生活应激的幼年恒河猴大脑中的 5-HT(1A)R 密度和表观离解常数(K(D)(app))。

结果

一般来说,与对照母养动物相比,同伴养育的 5-HT(1A)R 密度和 K(D)(app)降低。然而,在同伴养育的雌性的背内侧前额叶皮层中发现了受体密度的增加。

结论

这些发现表明,婴儿期暴露于不良的早期生活环境与长期的血清素系统改变有关,并支持先前的研究表明,发育过程中 5-HT(1A)R 密度降低可能是增加与压力相关的神经精神障碍易感性的一个因素。此外,血清素系统的改变似乎具有性别和区域特异性,为女性中情感障碍的更高患病率提供了生物学基础。

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