Hanish Alyson E, Butman John A, Thomas Francine, Yao Jianhua, Han Joan C
J Sleep Res. 2016 Feb;25(1):16-22. doi: 10.1111/jsr.12345.
In rodent studies, paired box 6 (PAX6) appears to play an important role in the development of the pineal, the primary source of the circadian regulating hormone, melatonin. Pineal hypoplasia has been previously reported in patients with PAX6 haploinsufficiency (+/−); however, pineal measurement, melatonin concentrations and sleep quality have not been reported. This cross-sectional descriptive study examined pineal volume, melatonin secretion and sleep disturbance in 37 patients with PAX6+/− (age 15.3 ± 9.9 years) and 17 healthy controls (16.0 ± 7.2 years), within an inpatient setting at the Clinical Research Center of the National Institutes of Health, Bethesda, Maryland, USA. Pineal volume was evaluated by magnetic resonance imaging. Diurnal serum cortisol, serum melatonin and urine 6-sulphatoxymelatonin concentrations were measured by enzyme-linked immunosorbent assay. The Child Sleep Habits Questionnaire was administered for patients <13 years old. Pineal volume was fivefold lower in PAX6+/− versus controls (mean ± SD: 25 ± 15 versus 129 ± 50 μL, P < 0.001). Midnight serum cortisol was similar in PAX6+/− versus controls (P = 0.14). Midnight serum melatonin was > twofold lower in PAX6+/− versus controls [median (25th-75 th): 28 (22-42) versus 71 (46-88) pg mL-(1), P < 0.001]. First morning void urinary 6-sulphatoxymelatonin was fourfold lower in PAX6+/− versus controls [11 (6-26) versus 45 (34-61) ng mg(-1) Cr, P = 0.001]. Child Sleep Habits Questionnaire score was higher in PAX6+/− versus controls (48 ± 6 versus 41 ± 5, P = 0.03). The current findings suggest that PAX6+/− is associated with smaller pineal size, lower melatonin secretion and greater parental report of sleep disturbances in children. Further studies are needed to explore the potential use of melatonin replacement for improving sleep quality in patients with PAX6+/−.
在啮齿动物研究中，配对盒基因6（PAX6）似乎在松果体的发育中发挥重要作用，松果体是昼夜节律调节激素褪黑素的主要来源。先前已有报道，PAX6单倍剂量不足（+/−）的患者存在松果体发育不全；然而，尚未有关于松果体测量、褪黑素浓度和睡眠质量的报道。这项横断面描述性研究，在美国马里兰州贝塞斯达国立卫生研究院临床研究中心的住院环境中，对37例PAX6+/−患者（年龄15.3±9.9岁）和17名健康对照者（16.0±7.2岁）的松果体体积、褪黑素分泌和睡眠障碍进行了检查。通过磁共振成像评估松果体体积；采用酶联免疫吸附测定法测量日间血清皮质醇、血清褪黑素和尿6-硫酸氧褪黑素浓度；对13岁以下患者发放儿童睡眠习惯问卷。PAX6+/−患者的松果体体积比对照组低五倍（平均值±标准差：25±15与129±50μL，P<0.001）。PAX6+/−患者与对照组的午夜血清皮质醇水平相似（P=0.14）。PAX6+/−患者的午夜血清褪黑素比对照组低两倍以上[中位数（第25-75百分位数）：28（22-42）与71（46-88）pg mL-1，P<0.001]。PAX6+/−患者晨尿中6-硫酸氧褪黑素比对照组低四倍[11（6-26）与45（34-61）ng mg-1 Cr，P=0.001]。PAX6+/−患者的儿童睡眠习惯问卷得分高于对照组（48±6与41±5，P=0.03）。目前的研究结果表明，PAX6+/−与儿童松果体体积较小、褪黑素分泌减少以及父母报告的睡眠障碍增加有关。需要进一步研究探索褪黑素替代疗法在改善PAX6+/−患者睡眠质量方面的潜在应用。
