Center for Integrated Molecular Brain Imaging, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen O, Denmark.
Neuroimage. 2012 Aug 1;62(1):130-6. doi: 10.1016/j.neuroimage.2012.05.013. Epub 2012 May 11.
Serotonin (5-HT) is a neuromodulator affecting myriad aspects of personality and behavior and has been implicated in the pathophysiology of affective disorders including depression and anxiety. The 5-HTTLPR is a common genetic polymorphism within the promoter region of the gene coding for the serotonin transporter such that the S allele is associated with reduced transcriptional efficacy compared to the L allele, potentially contributing to increased serotonin levels. In humans, this genetic variant has been linked to inter-individual variability in risk for affective disorders, related aspects of personality and brain function including response to threat. However, its effects on aspects of serotonin signaling in humans are not fully understood. Studies in animals suggest that the 5-HT 4 receptor (5-HT(4)) shows a monotonic inverse association with long-term changes in serotonin levels indicating that it may be a useful measure for identifying differences in serotonergic neurotransmission. In 47 healthy adults we evaluated the association between 5-HTTLPR status and in vivo 5-HT(4) receptor binding assessed with [(11)C]SB207145 positron emission tomography (PET). We observed a significant association within the neocortex where [(11)C]SB207145 binding was 9% lower in S carriers compared to LL homozygotes. We did not find evidence for an effect of season or a season-by-5-HTTLPR interaction effect on regional [(11)C]SB207145 binding. Our findings are consistent with a model wherein the 5-HTTLPR S allele is associated with relatively increased serotonin levels. These findings provide novel evidence supporting an effect of 5-HTTLPR status on serotonergic neurotransmission in adult humans. There were no indications of seasonal effects on serotonergic neurotransmission.
血清素（5-HT）是一种影响人格和行为诸多方面的神经调质，它与包括抑郁和焦虑在内的情感障碍的病理生理学有关。5-HTTLPR 是编码血清素转运体的基因启动子区域中的常见遗传多态性，与 L 等位基因相比，S 等位基因与转录效率降低有关，可能导致血清素水平升高。在人类中，这种遗传变异与情感障碍、人格和大脑功能的相关方面的个体间易感性有关，包括对威胁的反应。然而，其对人类血清素信号转导方面的影响尚不完全清楚。动物研究表明，5-HT4 受体（5-HT4）与血清素水平的长期变化呈单调负相关，表明它可能是识别血清素能神经传递差异的有用指标。在 47 名健康成年人中，我们评估了 5-HTTLPR 状态与使用 [(11)C]SB207145 正电子发射断层扫描（PET）评估的体内 5-HT4 受体结合之间的关联。我们在大脑皮层中观察到了显著的关联，与 LL 纯合子相比，S 携带者的 [(11)C]SB207145 结合降低了 9%。我们没有发现季节或季节-5-HTTLPR 相互作用对区域 [(11)C]SB207145 结合有影响的证据。我们的研究结果与以下模型一致，即 5-HTTLPR S 等位基因与相对较高的血清素水平有关。这些发现为 5-HTTLPR 状态对成年人类中血清素能神经传递的影响提供了新的证据。没有迹象表明季节对血清素能神经传递有影响。
