Beversdorf David Q, Carpenter Allen L, Alexander Jessica K, Jenkins Neil T, Tilley Michael R, White Catherine A, Hillier Ashleigh J, Smith Ryan M, Gu Howard H
Departments of Radiology, Neurology, and Psychological Sciences and The Thompson Center, William and Nancy Thompson Endowed Chair in Radiology, University of Missouri, Columbia, Missouri.
Department of Neuroscience.
Cogn Behav Neurol. 2018 Jun;31(2):79-85. doi: 10.1097/WNN.0000000000000153.
Previous research has shown an effect of various psychosocial stressors on unconstrained cognitive flexibility, such as searching through a large set of potential solutions in the lexical-semantic network during verbal problem-solving. Functional magnetic resonance imaging has shown that the presence of the short (S) allele (lacking a 43-base pair repeat) of the promoter region of the gene (SLC6A4) encoding the serotonin transporter (5-HTT) protein is associated with a greater amygdalar response to emotional stimuli and a greater response to stressors. Therefore, we hypothesized that the presence of the S-allele is associated with greater stress-associated impairment in performance on an unconstrained cognitive flexibility task, anagrams.
In this exploratory pilot study, 28 healthy young adults were genotyped for long (L)-allele versus S-allele promoter region polymorphism of the 5-HTT gene, SLC6A4. Participants solved anagrams during the Trier Social Stress Test, which included public speaking and mental arithmetic stressors. We compared the participants' cognitive response to stress across genotypes.
A Gene×Stress interaction effect was observed in this small sample. Comparisons revealed that participants with at least one S-allele performed worse during the Stress condition.
Genetic susceptibility to stress conferred by SLC6A4 appeared to modulate unconstrained cognitive flexibility during psychosocial stress in this exploratory sample. If confirmed, this finding may have implications for conditions associated with increased stress response, including performance anxiety and cocaine withdrawal. Future work is needed both to confirm our findings with a larger sample and to explore the mechanisms of this proposed effect.
先前的研究表明，各种心理社会应激源会对无约束的认知灵活性产生影响，比如在言语问题解决过程中，在词汇语义网络中搜索大量潜在解决方案时。功能磁共振成像显示，编码血清素转运蛋白（5-HTT）的基因（SLC6A4）启动子区域的短（S）等位基因（缺少一个43碱基对重复序列）的存在，与杏仁核对情绪刺激的更大反应以及对应激源的更大反应相关。因此，我们假设S等位基因的存在与在无约束认知灵活性任务（变位词任务）中与应激相关的表现受损程度更大有关。
在这项探索性初步研究中，对28名健康年轻成年人进行了SLC6A4基因5-HTT基因启动子区域长（L）等位基因与S等位基因多态性的基因分型。参与者在特里尔社会应激测试期间解决变位词问题，该测试包括公开演讲和心算应激源。我们比较了不同基因型参与者对应激的认知反应。
在这个小样本中观察到了基因×应激交互效应。比较结果显示，至少有一个S等位基因的参与者在应激条件下表现更差。
在这个探索性样本中，SLC6A4赋予的对应激的遗传易感性似乎在心理社会应激期间调节了无约束的认知灵活性。如果得到证实，这一发现可能对与应激反应增加相关的病症有影响，包括表演焦虑和可卡因戒断。未来需要开展工作，用更大的样本证实我们的发现，并探索这种假定效应的机制。
