Zhou J N, Riemersma R F, Unmehopa U A, Hoogendijk W J, van Heerikhuize J J, Hofman M A, Swaab D F
Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam, The Netherlands.
Arch Gen Psychiatry. 2001 Jul;58(7):655-62. doi: 10.1001/archpsyc.58.7.655.
Circadian rhythm disturbances are frequently found in depressed subjects. Although it has been presumed that these disturbances may reflect a disorder of the circadian pacemaker, this has never been established. The suprachiasmatic nucleus (SCN) is the pacemaker of the circadian timing system in mammals, and arginine vasopressin (AVP) is one of its major neuropeptides. As peptide content is often taken as a measure for activity, we hypothesized that a decreased number of AVP-immunoreactive (AVP-IR) neurons and amount of AVP-messenger RNA (mRNA) would be present in the SCN of depressed subjects.
Brains of 11 subjects suffering from major depression (8 cases) and bipolar disorder (3 cases), and of 11 controls, matched for sex, age, and clock time at death, were collected. The number of AVP-IR neurons in the SCN was determined by means of a digitizer (CalComp Inc, Reading, England). The amount of AVP-mRNA expression in the SCN was quantified with the Interaktive Bild Analyse System image analysis system (Kontron, Munich, Germany).
In depressed subjects, the number of AVP-IR neurons in the SCN was more than one and a half times higher than in controls, while the total masked area of silver grains, as an estimate of the amount of AVP-mRNA, was about one half that of controls.
Contrary to our hypothesis, an increase in the number of AVP-IR neurons in the SCN in depression was found, together with an expected decrease in AVP-mRNA. These findings suggest that, in depressed patients, both the synthesis and release of AVP in the SCN is reduced, resulting in an impaired functional ability. A disbalance between AVP production and transport needs further investigation in future studies.
昼夜节律紊乱在抑郁症患者中很常见。尽管人们推测这些紊乱可能反映了昼夜节律起搏器的功能失调，但这一点从未得到证实。视交叉上核（SCN）是哺乳动物昼夜节律系统的起搏器，精氨酸加压素（AVP）是其主要神经肽之一。由于肽含量常被用作活性的衡量指标，我们假设抑郁症患者的SCN中AVP免疫反应性（AVP-IR）神经元数量减少，且AVP信使核糖核酸（mRNA）含量降低。
收集了11例患有重度抑郁症（8例）和双相情感障碍（3例）的受试者以及11例对照者的大脑，这些对照者在性别、年龄和死亡时间上相匹配。通过数字转换器（CalComp公司，英国雷丁）确定SCN中AVP-IR神经元的数量。用交互式图像分析系统（Kontron公司，德国慕尼黑）对SCN中AVP-mRNA的表达量进行定量分析。
在抑郁症患者中，SCN中AVP-IR神经元的数量比对照组高出一倍半以上，而作为AVP-mRNA含量估计值的银颗粒总遮盖面积约为对照组的一半。
与我们的假设相反，抑郁症患者的SCN中AVP-IR神经元数量增加，同时AVP-mRNA如预期那样减少。这些发现表明，抑郁症患者SCN中AVP的合成和释放均减少，导致功能受损。AVP产生与转运之间的失衡在未来研究中需要进一步探究。
