Parry B L, Udell C, Elliott J A, Berga S L, Klauber M R, Mostofi N, LeVeau B, Gillin J C
Department of Psychiatry, University of California, San Diego, La Jolla 92093-0804, USA.
J Biol Rhythms. 1997 Oct;12(5):443-56. doi: 10.1177/074873049701200506.
Patients with premenstrual dysphoric disorder (PMDD) respond therapeutically to sleep deprivation and light therapy. They have blunted circadian rhythms of melatonin. The authors sought to test the hypothesis that these disturbances are a reflection of a disturbance in the underlying circadian pacemaker or, alternatively, that they reflect a disturbance in the input pathways to the clock. To test these hypotheses, after a 2-month diagnostic evaluation, 8 patients who met DSM-IV criteria for PMDD and 5 normal control (NC) subjects underwent two studies to determine whether PMDD subjects showed (1) altered melatonin sensitivity to light suppression (Study 1) and (2) altered phase-shift responses to morning light as a measure of the functional capacity of the underlying pacemaker (Study 2). In both studies, measurements were made during asymptomatic follicular and symptomatic luteal menstrual cycle phases in PMDD patients. The results of Study 1 showed no significant effect of group or menstrual cycle phase on the amount or percentage of suppression of melatonin by light. The results of Study 2 showed that with respect to the variable of offset time, PMDD subjects, when symptomatic, showed a reduced and directionally altered melatonin phase-shift response to a morning bright light stimulus; in 4 of 5 NC subjects, melatonin offset was advanced by bright morning light, whereas in PMDD subjects, it was delayed (3 subjects) or not shifted (5 subjects) (group effect, p = .045). Study 2 also revealed that area under the curve also changed differentially in PMDD versus NC subjects. In summary, the primary findings from this pilot study suggest that in PMDD there is a maladaptive (directionally altered and blunted) response to light in the symptomatic luteal phase. Because the suppressive effects of light were similar in PMDD and NC subjects, the previously observed low melatonin levels in this disorder do not likely represent a disturbance in pineal reactivity to suprachiasmatic nucleus efferents. Instead, the findings support a possible disturbance in PMDD in the clock itself or its coupling mechanisms.
经前烦躁障碍（PMDD）患者对睡眠剥夺和光照疗法有治疗反应。他们的褪黑素昼夜节律减弱。作者试图检验以下假设：这些紊乱反映了潜在昼夜节律起搏器的紊乱，或者相反，它们反映了时钟输入通路的紊乱。为了检验这些假设，在进行2个月的诊断评估后，8名符合DSM-IV标准的PMDD患者和5名正常对照（NC）受试者进行了两项研究，以确定PMDD受试者是否表现出（1）褪黑素对光抑制的敏感性改变（研究1），以及（2）作为潜在起搏器功能能力指标的对早晨光照的相移反应改变（研究2）。在两项研究中，均在PMDD患者无症状的卵泡期和有症状的黄体期进行测量。研究1的结果表明，组或月经周期阶段对光抑制褪黑素的量或百分比没有显著影响。研究2的结果表明，就偏移时间变量而言，PMDD受试者在有症状时，对早晨强光刺激的褪黑素相移反应降低且方向改变；在5名NC受试者中有4名，早晨强光使褪黑素偏移提前，而在PMDD受试者中，它被延迟（3名受试者）或未发生偏移（5名受试者）（组效应，p = 0.045）。研究2还表明，PMDD患者与NC受试者的曲线下面积变化也存在差异。总之，这项初步研究的主要发现表明，在PMDD中，有症状的黄体期对光存在适应不良（方向改变且减弱）的反应。由于PMDD患者和NC受试者对光的抑制作用相似，因此该疾病中先前观察到的低褪黑素水平不太可能代表松果体对视交叉上核传出神经反应性的紊乱。相反，这些发现支持了PMDD中时钟本身或其耦合机制可能存在紊乱的观点。
