Faulkner Paul, Mancinelli Federico, Lockwood Patricia L, Matarin Mar, Dolan Raymond J, Wood Nick W, Dayan Peter, Roiser Jonathan P
Institute of Cognitive Neuroscience, University College London, London, United Kingdom; Psychiatry and Biobehavioral Sciences, Semel Institute, University of California, Los Angeles, California.
Gatsby Computational Neuroscience Unit, and CoMPLEX Centre for Mathematics, Physics and Engineering in the Life Sciences and Experimental Biology, University College London, London, United Kingdom; Experimental Psychology, University of Oxford, Oxford, United Kingdom; Clinical and Experimental Epilepsy, Institute of Neurology, and Wellcome Trust Centre for Neuroimaging, University College London, London, United Kingdom; Molecular Neuroscience, UCL Institute of Neurology, Queen Square, London, United Kingdom.
Int J Neuropsychopharmacol. 2017 Jan 1;20(1):58-66. doi: 10.1093/ijnp/pyw075.
The effects of acute tryptophan depletion on human decision-making suggest that serotonin modulates the processing of rewards and punishments. However, few studies have assessed which of the many types of serotonin receptors are responsible.
Using a within-subject, double-blind, sham-controlled design in 26 subjects, we examined whether individual differences in serotonin system gene transcription, measured in peripheral blood, predicted the effect of acute tryptophan depletion on decision-making. Participants performed a task in which they chose between successive pairs of fixed, lower-stakes (control) and variable, higher-stakes (experimental) gambles, each involving wins or losses. In 21 participants, mRNA from 9 serotonin system genes was measured in whole blood prior to acute tryptophan depletion: 5-HT1B, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT3A, 5-HT3E, 5-HT7 (serotonin receptors), 5-HTT (the serotonin transporter), and tryptophan hydroxylase 1.
Acute tryptophan depletion did not significantly influence participants' sensitivity to probability, wins, or losses, although there was a trend for a lower tendency to choose experimental gambles overall following depletion. Significant positive correlations, which survived correction for multiple comparisons, were detected between baseline 5-HT1B mRNA levels and acute tryptophan depletion-induced increases in both the overall tendency to choose the experimental gamble and sensitivity to wins. No significant relationship was observed with any other peripheral serotonin system markers. Computational analyses of decision-making data provided results consistent with these findings.
These results suggest that the 5-HT1B receptor may modulate the effects of acute tryptophan depletion on risky decision-making. Peripheral levels of serotonin markers may predict response to treatments that act upon the serotonin system, such as selective serotonin reuptake inhibitors.
急性色氨酸耗竭对人类决策的影响表明，血清素调节奖励和惩罚的处理过程。然而，很少有研究评估众多类型的血清素受体中哪一种起作用。
我们采用受试者内、双盲、假手术对照设计，对26名受试者进行研究，以检验外周血中测量的血清素系统基因转录的个体差异是否能预测急性色氨酸耗竭对决策的影响。参与者执行一项任务，在连续的固定低风险（对照）和可变高风险（实验）赌博对之间进行选择，每次赌博都涉及赢或输。在21名参与者中，在急性色氨酸耗竭前测量全血中9种血清素系统基因的mRNA：5-HT1B、5-HT1F、5-HT2A、5-HT2B、5-HT3A、5-HT3E、5-HT7（血清素受体）、5-HTT（血清素转运体）和色氨酸羟化酶1。
急性色氨酸耗竭并未显著影响参与者对概率、赢或输的敏感性，尽管在耗竭后总体上选择实验性赌博的倾向有降低趋势。在基线5-HT1B mRNA水平与急性色氨酸耗竭诱导的选择实验性赌博的总体倾向和对赢的敏感性增加之间，检测到显著的正相关，这些相关性在多重比较校正后仍然存在。未观察到与任何其他外周血清素系统标志物有显著关系。决策数据的计算分析提供了与这些发现一致的结果。
这些结果表明，5-HT1B受体可能调节急性色氨酸耗竭对风险决策的影响。血清素标志物的外周水平可能预测对作用于血清素系统的治疗（如选择性血清素再摄取抑制剂）的反应。
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