Steiner M, Werstiuk E S, Seggie J
Prog Neuropsychopharmacol Biol Psychiatry. 1987;11(2-3):267-78. doi: 10.1016/0278-5846(87)90070-4.
The pathophysiology of depression and the mechanism of action of lithium and other antidepressant drugs involve alterations in circadian rhythms. These include changes in both the intrinsic rhythm of circadian oscillators and in the sensitivity of the retina to LIGHT. The retina in humans is the only photoreceptor for circadian entrainment. The retinal-hypothalamic-pineal axis is the essential pathway for neuronal entrainment of rhythms which use light as a phase cue. A common substance throughout this axis in many species is MELATONIN. Retinal melatonin has been implicated in regulation of the sensitivity of the retina to light. The hypothalamus, at THE NEUROENDOCRINE CROSSROADS, has a central role in the integration of neurotransmitters and hormones in circadian rhythms. DYSREGULATION of the hypothalamic-pituitary-adrenal, as well as -gonadal, axes has been documented in depressed patients. Abnormalities in circulating melatonin have also been found in patients with affective disorders. It is speculated that the availability of melatonin along the retinal-hypothalamic-pineal axis may have important implications in the genesis of affective disorders. More specifically--is there a latent biochemical defect which causes a phase shift and change in circadian rhythms of melatonin and/or other neurotransmitters in the retina which then alters the sensitivity of the retina to light (for the visible spectrum) which in turn desynchronizes all other biological rhythms thus disrupting mental well-being? We suggest that variations of retinal photosensitivity in humans can be measured by using a visual testing system, and that depressed patients might show changes in photosensitivity which could be corrected when treated with lithium and/or antidepressants. It is our working hypothesis that the primary defect in depression may be a change in retinal function, and that behavioural and neuroendocrine concomitants of this disorder are secondary events.
抑郁症的病理生理学以及锂盐和其他抗抑郁药物的作用机制涉及昼夜节律的改变。这些改变包括昼夜节律振荡器的内在节律变化以及视网膜对光的敏感性变化。人类视网膜是昼夜节律同步的唯一光感受器。视网膜 - 下丘脑 - 松果体轴是利用光作为相位线索的节律神经元同步的重要途径。在许多物种中，贯穿该轴的一种常见物质是褪黑素。视网膜褪黑素与视网膜对光的敏感性调节有关。下丘脑处于神经内分泌的交叉路口，在昼夜节律中神经递质和激素的整合中起核心作用。抑郁症患者下丘脑 - 垂体 - 肾上腺轴以及性腺轴的调节失调已有文献记载。情感障碍患者也发现了循环褪黑素的异常。据推测，沿着视网膜 - 下丘脑 - 松果体轴的褪黑素可用性可能在情感障碍的发生中具有重要意义。更具体地说，是否存在潜在的生化缺陷，导致视网膜中褪黑素和/或其他神经递质的昼夜节律发生相移和变化，进而改变视网膜对光（可见光谱）的敏感性，这反过来又使所有其他生物节律不同步，从而破坏心理健康？我们建议可以使用视觉测试系统测量人类视网膜光敏性的变化，并且抑郁症患者可能表现出光敏性变化，在用锂盐和/或抗抑郁药治疗时这些变化可能会得到纠正。我们的工作假设是，抑郁症的主要缺陷可能是视网膜功能的改变，而该疾病的行为和神经内分泌伴随症状是继发事件。
