Emotion and Neuroimaging Lab, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; Clinic for Cognitive Neurology, University of Leipzig Medical Center, Leipzig, Germany; Zentrum für Seelische Gesundheit, Helios Park-Klinikum, Leipzig, Germany.
Emotion and Neuroimaging Lab, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
Biol Psychiatry. 2023 Jun 15;93(12):1081-1088. doi: 10.1016/j.biopsych.2022.12.023. Epub 2023 Jan 18.
Premenstrual dysphoric disorder (PMDD) disrupts the lives of millions of people each month. The timing of symptoms suggests that hormonal fluctuations play a role in the pathogenesis. Here, we tested whether a heightened sensitivity of the serotonin system to menstrual cycle phase underlies PMDD, assessing the relationship of serotonin transporter (5-HTT) changes with symptom severity across the menstrual cycle.
In this longitudinal case-control study, we acquired 118 [C]DASB positron emission tomography scans measuring 5-HTT nondisplaceable binding potential (BP) in 30 patients with PMDD and 29 controls during 2 menstrual cycle phases (periovulatory, premenstrual). The primary outcome was midbrain and prefrontal cortex 5-HTT BP. We tested whether BP changes correlated with depressed mood.
Linear mixed effects modeling (significant group × time × region interaction) showed a mean increase of 18% in midbrain 5-HTT BP (mean [SD] periovulatory = 1.64 [0.40], premenstrual = 1.93 [0.40], delta = 0.29 [0.47]: t = -3.43, p = .0002) in patients with PMDD, whereas controls displayed a mean 10% decrease in midbrain 5-HTT BP (periovulatory = 1.65 [0.24] > premenstrual = 1.49 [0.41], delta = -0.17 [0.33]: t = -2.73, p = .01). In patients, increased midbrain 5-HTT BP correlated with depressive symptom severity (R = 0.41, p < .0015) across the menstrual cycle.
These data suggest cycle-specific dynamics with increased central serotonergic uptake followed by extracellular serotonin loss underlying the premenstrual onset of depressed mood in patients with PMDD. These neurochemical findings argue for systematic testing of pre-symptom-onset dosing of selective serotonin reuptake inhibitors or nonpharmacological strategies to augment extracellular serotonin in people with PMDD.
经前烦躁障碍（PMDD）每月扰乱数百万人的生活。症状出现的时间表明激素波动在发病机制中起作用。在这里，我们测试了月经周期阶段下 5-羟色胺系统敏感性的增加是否是 PMDD 的基础，评估了 5-羟色胺转运蛋白（5-HTT）变化与整个月经周期中症状严重程度的关系。
在这项纵向病例对照研究中，我们在 30 名 PMDD 患者和 29 名对照者的 2 个月经周期阶段（排卵前、经前期）中获得了 118 个 [C]DASB 正电子发射断层扫描，测量 5-HTT 不可置换结合潜能（BP）。主要结局是中脑和前额叶皮质 5-HTT BP。我们测试了 BP 变化是否与抑郁情绪相关。
线性混合效应模型（显著的组×时间×区域相互作用）显示，PMDD 患者的中脑 5-HTT BP 平均增加 18%（排卵前平均[标准差] = 1.64[0.40]，经前期 = 1.93[0.40]，差值 = 0.29[0.47]：t = -3.43，p =.0002），而对照组中脑 5-HTT BP 平均降低 10%（排卵前 = 1.65[0.24]>经前期 = 1.49[0.41]，差值 = -0.17[0.33]：t = -2.73，p =.01）。在患者中，中脑 5-HTT BP 的增加与月经周期中抑郁症状的严重程度相关（R = 0.41，p <.0015）。
这些数据表明，在 PMDD 患者中，经前期抑郁发作的背后存在与月经周期相关的动态变化，即中枢 5-羟色胺摄取增加，随后细胞外 5-羟色胺丢失。这些神经化学发现表明，对于 PMDD 患者，应该系统地测试选择性 5-羟色胺再摄取抑制剂的症状前给药或非药物策略，以增加细胞外 5-羟色胺。
