Guaraldi Pietro, Sancisi Elisa, La Morgia Chiara, Calandra-Buonaura Giovanna, Carelli Valerio, Cameli Olivia, Battistini Alberto, Cortelli Pietro, Piperno Roberto
IRCCS Istituto delle Scienze Neurologiche di Bologna , Bologna , Italy .
Chronobiol Int. 2014 Jun;31(5):741-5. doi: 10.3109/07420528.2014.901972. Epub 2014 Mar 28.
Circadian rhythms were recently proposed as a measure of physiological state and prognosis in disorders of consciousness (DOC). So far, melatonin regulation was never assessed in vegetative state (VS). Aim of our research was to investigate the nocturnal melatonin levels and light-induced melatonin suppression in a cohort of VS patients. We assessed six consecutive patients (four men, age 33.3 ± 9.3 years) with post-traumatic VS and nine age-matched healthy volunteers (five men, age 34.3 ± 8.9 years) on two consecutive nights: one baseline and one light exposure night. During baseline, night subjects were in bed in a dim (<5 lux) room from 10 pm to 8 am. Blood samples were collected hourly 00:30-3:30 am (00:30 = MLT1; 1:30 = MLT2; 2:30 = MLT3; and 3:30 = MLT4). Identical setting was used for melatonin suppression test night, except for the exposure to monochromatic (470 nm) light from 1:30 to 3:30 am. Plasma melatonin levels were evaluated by radioimmunoassay. Magnitude of melatonin suppression was assessed by melatonin suppression score (caMSS) and suppression rate. We searched for group differences in melatonin levels, differences between repeated samples melatonin concentrations during baseline night and light exposure night, and light-induced suppression of melatonin secretion. During baseline night, controls showed an increase of melatonin (MLT4 vs MLT1, p = 0.037), while no significant changes were observed in VS melatonin levels (p = 0.172). Baseline night MLT4 was significantly lower in VS vs controls (p = 0.036). During light-exposure night, controls displayed a significant suppression of melatonin (MLT3 and MLT4 vs MLT2, p = 0.016 and 0.002, respectively), while VS patients displayed no significant changes. The magnitude of light-induced suppression of melatonin levels was statistically different between groups considering control adjusted caMSS (p = 0.000), suppression rate (p = 0.002) and absolute percentage difference (p = 0.012). These results demonstrate for the first time that VS patients present an alteration in night melatonin secretion and reduced light-induced melatonin suppression. These findings confirm previous studies demonstrating a disruption of the circadian system in DOC and suggest a possible benefit from melatonin supplementation in VS.
昼夜节律最近被提议作为意识障碍（DOC）患者生理状态和预后的一项指标。到目前为止，从未对植物状态（VS）患者的褪黑素调节情况进行过评估。我们研究的目的是调查一组VS患者夜间的褪黑素水平以及光诱导的褪黑素抑制情况。我们连续两晚评估了6例创伤后VS患者（4例男性，年龄33.3±9.3岁）和9例年龄匹配的健康志愿者（5例男性，年龄34.3±8.9岁）：一晚为基线期，另一晚为光照期。在基线期，受试者于晚上10点至次日上午8点在昏暗（<5勒克斯）的房间卧床休息。在凌晨00:30至3:30每小时采集血样（00:30 = MLT1；1:30 = MLT2；2:30 = MLT3；3:30 = MLT4）。褪黑素抑制试验当晚采用相同设置，只是在凌晨1:30至3:30暴露于单色（470纳米）光下。通过放射免疫分析法评估血浆褪黑素水平。通过褪黑素抑制评分（caMSS）和抑制率评估褪黑素抑制的程度。我们研究了褪黑素水平的组间差异、基线期夜晚和光照期夜晚重复采样的褪黑素浓度差异以及光诱导的褪黑素分泌抑制情况。在基线期夜晚，对照组的褪黑素水平升高（MLT4对比MLT1，p = 0.037），而VS患者的褪黑素水平未观察到显著变化（p = 0.172）。VS患者的基线期夜晚MLT4显著低于对照组（p = 0.036）。在光照期夜晚，对照组的褪黑素显著受到抑制（MLT3和MLT4对比MLT2，p分别为0.016和0.002），而VS患者未出现显著变化。考虑到对照组校正后的caMSS（p = 0.000）、抑制率（p = 0.002）和绝对百分比差异（p = 0.012），两组间光诱导的褪黑素水平抑制程度存在统计学差异。这些结果首次表明VS患者夜间褪黑素分泌存在改变且光诱导的褪黑素抑制减弱。这些发现证实了先前关于DOC患者昼夜节律系统紊乱的研究，并提示VS患者补充褪黑素可能有益。
