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首页> 美国卫生研究院文献>The Journal of Neuroscience >Variation in the Corticotropin-Releasing Hormone Receptor 1 (CRHR1) Gene Influences fMRI Signal Responses during Emotional Stimulus Processing
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Variation in the Corticotropin-Releasing Hormone Receptor 1 (CRHR1) Gene Influences fMRI Signal Responses during Emotional Stimulus Processing

机译：促肾上腺皮质激素释放激素受体1（CRHR1）基因的变异影响情绪刺激过程中的fMRI信号反应。

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The corticotropin-releasing hormone (CRH) system coordinates neuroendocrine and behavioral responses to stress and has been implicated in the development of major depressive disorder (MDD). Recent reports suggest that GG-homozygous individuals of a single nucleotide polymorphism (rs110402) in the CRH receptor 1 (CRHR1) gene show behavioral and neuroendocrine evidence of stress vulnerability. The present study explores whether those observations extend to the neuronal processing of emotional stimuli in humans. CRHR1 was genotyped in 83 controls and a preliminary sample of 16 unmedicated patients with MDD who completed a functional magnetic resonance imaging scan while viewing blocks of positive, negative, and neutral words. In addition, potential mediating factors such as early life stress, sex, personality traits, and negative memory bias were examined. Robust differences in blood oxygenation level-dependent (BOLD) signal were found in healthy controls (A allele carriers > GG-homozygotes) in the right middle temporal/angular gyrus while subjects were viewing negative versus neutral words. Among GG-homozygotes, BOLD signal in the subgenual cingulate was greater in MDD participants (n = 9) compared with controls (n = 33). Conversely, among A-carriers, BOLD signal was smaller in MDD (n = 7) compared with controls (n = 50) in the hypothalamus, bilateral amygdala, and left nucleus accumbens. Early life stress, personality traits, and levels of negative memory bias were associated with brain activity depending on genotype. Results from healthy controls and a preliminary sample of MDD participants show that CRHR1 single nucleotide polymorphism rs110402 moderates neural responses to emotional stimuli, suggesting a potential mechanism of vulnerability for the development of MDD.
机译：促肾上腺皮质激素释放激素（CRH）系统协调神经内分泌和行为对压力的反应，并与主要抑郁症（MDD）的发生有关。最近的报告表明，CRH受体1（CRHR1）基因中的单核苷酸多态性（rs110402）的GG杂合子个体表现出压力和脆弱性的行为和神经内分泌证据。本研究探讨了这些观察是否扩展到人类情绪刺激的神经元处理。 CRHR1在83例对照和16例未经药物治疗的MDD患者的初步样本中进行了基因分型，他们完成了功能性磁共振成像扫描，同时查看了正，负和中性词的块。此外，还检查了潜在的中介因素，例如早期生活压力，性别，人格特质和负面记忆偏见。在受试者右中颞/角回中的健康对照（等位基因携带者> GG-纯合子）中发现血液氧合水平依赖性（BOLD）信号存在明显差异，而受试者观察的是负面词还是中性词。在GG-纯合子中，MDD参与者（n = 9）与对照组（n = 33）相比，亚舌状扣带中的BOLD信号更大。相反，在下丘脑，双侧杏仁核和伏隔核中，在A型携带者中，MDD中的BOLD信号（n = 7）比对照组（n = 50）小。根据基因型，早期生活压力，人格特质和负记忆偏向水平与大脑活动有关。来自健康对照组和MDD参与者的初步样本的结果表明，CRHR1单核苷酸多态性rs110402会调节对情绪刺激的神经反应，这提示了开发MDD的潜在脆弱性机制。

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