Agorastos Agorastos, Kellner Michael, Stiedl Oliver, Muhtz Christoph, Wiedemann Klaus, Demiralay Cüneyt
Department of Psychiatry and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Drs Agorastos, Kellner, Muhtz, Wiedemann, and Demiralay); Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus, VU University, Amsterdam, Netherlands (Dr Stiedl); Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognitive Research, Neuroscience Campus, VU University, Amsterdam, Netherlands (Dr Stiedl); Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany (Dr Muhtz).
Int J Neuropsychopharmacol. 2014 Dec 11;18(5):pyu053. doi: 10.1093/ijnp/pyu053.
Central serotonergic pathways influence brain areas involved in vagal cardiovascular regulation and, thereby, influence sympathetic efferent activity. Selective serotonin reuptake inhibitors (SSRIs) affect multiple serotonergic pathways, including central autonomic pathways. However, only a few studies have assessed SSRI-mediated effects on autonomic reactivity in healthy individuals using heart rate variability (HRV).
The present study assessed the influence of long-term treatment with escitalopram (ESC) on autonomic reactivity to an intravenous application of 50 µg cholecystokinin tetrapeptide (CCK-4) in 30 healthy young men using a double-blind, placebo (PLA)-controlled, randomized, within-subject cross-over design. Main outcome measures were time- and frequency-domain HRV parameters, assessed at both baseline and immediately after CCK-4 application.
Results showed substantial effects for the treatment × CCK-4 challenge interaction with respect to heart rate (p < 0.001; pη(2) = 0.499), SDNN (p < 0.001; pη(2) = 576), RMSSD (p = 0.015; pη(2) = 194), NN50% (p = 0.008; pη(2) = 0.224), and LF% (p = 0.014; pη(2) = 0.196), and moderate effects with respect HF% (p = 0.099; pη(2) = 0.094), with PLA subjects showing a higher increase in HR and SDNN and a higher decrease in RMSSD, NN50, LF and HF than subjects in the ESC condition. Thus, ESC treatment significantly blunted the autonomic reactivity to CCK-4. Secondary analysis indicated no effect of the 5-HTTLPR polymorphism on CCK-4-induced autonomic response.
Our results support findings suggesting an effect of SSRI treatment on autonomic regulation and provide evidence that ESC treatment is associated with blunted autonomic reactivity in healthy men.
中枢5-羟色胺能通路影响参与迷走神经心血管调节的脑区,从而影响交感神经传出活动。选择性5-羟色胺再摄取抑制剂(SSRI)影响多种5-羟色胺能通路,包括中枢自主神经通路。然而,仅有少数研究使用心率变异性(HRV)评估了SSRI对健康个体自主反应性的影响。
本研究采用双盲、安慰剂(PLA)对照、随机、受试者内交叉设计,评估了30名健康青年男性长期使用艾司西酞普兰(ESC)治疗对静脉注射50μg四肽胆囊收缩素(CCK-4)后自主反应性的影响。主要观察指标为基线时和注射CCK-4后即刻评估的时域和频域HRV参数。
结果显示,治疗×CCK-4激发相互作用对心率(p<0.001;偏η²=0.499)、标准差(SDNN)(p<0.001;偏η²=0.576)、平方根连续差值的均值(RMSSD)(p=0.015;偏η²=0.194)、NN50%(p=0.008;偏η²=0.224)和低频功率百分比(LF%)(p=0.014;偏η²=0.196)有显著影响,对高频功率百分比(HF%)有中度影响(p=0.099;偏η²=0.094),PLA组受试者的心率和SDNN升高幅度更大,RMSSD、NN50、LF和HF降低幅度比ESC组受试者更大。因此,ESC治疗显著减弱了对CCK-4的自主反应性。二次分析表明,5-羟色胺转运体基因相关多态性(5-HTTLPR)对CCK-4诱导的自主反应无影响。
我们的结果支持了SSRI治疗对自主调节有影响的研究结果,并提供了证据表明ESC治疗与健康男性自主反应性减弱有关。