背景:经前烦躁不安症(PMDD)的特征是在月经周期的黄体期出现严重的情感症状。有一些证据表明PMDD中下丘脑垂体性腺(HPG)和下丘脑垂体肾上腺(HPA)轴之间的相互作用发生了变化。还有证据表明,类似的情感障碍,如重度抑郁症和围产期抑郁症与免疫因子失调有关,但这在PMDD中没有特征。
目的:这项探索性研究的目的是确定1)在整个月经周期中,PMDD患者和对照组之间HPA-HPG轴相互作用和免疫标志物是否不同;2)黄体期舍曲林治疗如何影响应激和炎症标志物。
方法:参与者为18-50岁女性,月经周期规律,不使用精神药物或荷尔蒙药物,根据前瞻性每日症状评分和临床访视将患者分为对照组或PMDD组.在卵泡和黄体期抽血,在涉及轻度压力任务的实验室会议期间。在第二个黄体期,PMDD参与者从排卵到月经接受开放标签的舍曲林(50mg/d)。通过ELISA测量血清皮质醇和ACTH,并操作为相对于地面的曲线下面积(AUCg),和实验室任务后的峰值水平。血清TNF-α,使用多重试剂盒测量IL-6、CXCL-8和IL-1β。通过气相色谱/质谱法测量血清别孕烯醇酮(ALLO)。为了表征PMDD参与者和对照者整个月经周期的HPA-HPG轴相互作用,多级线性模型从周期阶段(控制舍曲林治疗)的相互作用中预测皮质醇和ACTH,ALLO,和团体。为了确定舍曲林治疗对炎症标记物的影响,以及各组在每种标记物的周期性变化方面可能存在的差异,多水平线性模型从周期期(舍曲林治疗对照)和组预测炎症标志物。最后一组探索性模型测试了炎症标志物是否可以预测经前症状评分的严重程度。
结果:样本包括n=77名参与者(41名对照,36PMDD);28名PMDD参与者完成了舍曲林治疗。组x相xALLO相互作用表明,较高的ALLO水平预测治疗黄体期的皮质醇峰较低(相和ALLO之间的相互作用,p=0.042),并且在处理过的黄体期中存在比未处理的黄体期更高的皮质醇峰(p=0.038)。CXCL-8与控制组和周期后的经前期症状严重程度显着相关(p=0.011)。没有组的主要影响,阶段,或者皮质醇AUCg的ALLO,ACTHAUCg,IL-6,CXCL-8,IL-1β,肿瘤坏死因子-α(p>0.05)。
结论:HPA轴和免疫功能的血清标志物没有因月经周期阶段或PMDD状态而变化。然而,黄体期舍曲林治疗与较高的ALLO水平相关,预测轻度实验室应激时皮质醇峰值降低,提示舍曲林治疗可以使PMDD患者之间的HPG-HPA轴相互作用正常化。更高的经前症状与更高水平的炎症标志物CXCL-8相关,但需要进一步研究炎症在PMDD中的潜在作用。
BACKGROUND: Premenstrual dysphoric disorder (PMDD) is characterized by severe affective symptoms during the luteal phase of the menstrual cycle. There is some evidence of altered interactions between the hypothalamic pituitary gonadal (HPG) and hypothalamic pituitary adrenal (HPA) axes in PMDD. There is also evidence that similar affective disorders such as major depression and perinatal depression are associated with dysregulation in immune factors, but this has not been characterized in PMDD.
OBJECTIVE: The goals of this exploratory study were to identify 1) whether HPA-HPG axis interactions and immune markers differ between PMDD patients and controls across the menstrual cycle; 2) how luteal phase sertraline treatment impacts stress and inflammatory markers.
METHODS: Participants were females age 18-50 with regular menstrual cycles, not using psychotropic or hormonal medications, and were assigned to a control group or PMDD group based on prospective daily symptom ratings and clinical interview. Blood was drawn in the follicular and luteal phases, during laboratory sessions involving a mildly stressful task. In a second luteal phase, PMDD participants received open-label sertraline (50 mg/d) from ovulation to menses. Serum cortisol and ACTH were measured via ELISA and operationalized as area under the curve with respect to ground (AUCg), and peak level following laboratory task. Serum TNF-α, IL-6, CXCL-8, and IL-1β were measured using multiplex kits. Serum allopregnanolone (ALLO) was measured by gas chromatography/mass spectroscopy. To characterize HPA-HPG axis interactions across the menstrual cycle in PMDD participants and controls, multilevel linear models predicted cortisol and ACTH from the interaction of cycle phase (controlling for sertraline treatment), ALLO, and group. To determine the effects of sertraline treatment on inflammatory markers and how groups might differ in cyclical change on each marker, multilevel linear models predicted inflammatory markers from cycle phase (controlling for sertraline treatment) and group. A final set of exploratory models tested whether inflammatory markers predict premenstrual symptom score severity.
RESULTS: The sample included n=77 participants (41 controls, 36 PMDD); 28 participants with PMDD completed sertraline treatment. Group x phase x ALLO interactions showed that higher ALLO levels predicted lower cortisol peak in the treated luteal phase (interaction between phase and ALLO, p=0.042), and there was a higher cortisol peak in the treated luteal phase than the untreated luteal phase (p=0.038). CXCL-8 was significantly associated with premenstrual symptom severity after controlling for group and cycle phase (p=0.011). There were no main effects of group, phase, or ALLO on cortisol AUCg, ACTH AUCg, IL-6, CXCL-8, IL-1β, nor TNF-α (p\'s>0.05).
CONCLUSIONS: Serum markers of HPA axis and immune function did not vary by menstrual cycle phase nor PMDD status. However, sertraline treatment in the luteal phase was associated with higher ALLO levels predicting lower cortisol peak in response to mild laboratory stress, suggesting that sertraline treatment may normalize HPG-HPA axis interactions among individuals with PMDD. Greater premenstrual symptomatology was associated with higher levels of the inflammatory marker CXCL-8, but further research is needed into the potential role of inflammation in PMDD.