Larsen Søren Vinther, Ozenne Brice, Köhler-Forsberg Kristin, Poulsen Asbjørn Seenithamby, Dam Vibeke Høyrup, Svarer Claus, Knudsen Gitte Moos, Jørgensen Martin Balslev, Frokjaer Vibe Gedso
Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.
Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Front Endocrinol (Lausanne). 2022 Mar 11;13:799675. doi: 10.3389/fendo.2022.799675. eCollection 2022.
Hormonal contraceptive (HC) use has been associated with an increased risk of developing a depressive episode. This might be related to HC's effect on the serotonergic brain system as suggested by recent cross-sectional data from our group, which show that healthy oral contraceptive (OC) users relative to non-users have lower cerebral serotonin 4 receptor (5-HT4R) levels. Here, we determine if cerebral 5-HT4R binding differs between HC non-users, OC users, and hormonal intrauterine device (HIUD) users among women with an untreated depressive episode. Also, we test if antidepressant drug treatment response and its association with pre-treatment 5-HT4R binding depends on HC status.
[C]-SB207145 Positron Emission Tomography imaging data from the NeuroPharm-NP1 Study (NCT02869035) were available from 59 depressed premenopausal women, of which 26 used OCs and 10 used HIUDs. The participants were treated with escitalopram. Treatment response was measured as the relative change in the Hamilton Depression Rating Scale 6 items (rΔHAMD) from baseline to week eight. Latent variable models were used to evaluate the association between global 5-HT4R binding and OC and HIUD use as well as rΔHAMD.
We found no evidence of a difference in global 5-HT4R binding between depressed HC users and non-users (p≥0.51). A significant crossover interaction (p=0.02) was observed between non-users and OC users in the association between baseline global 5-HT4R binding and week eight rΔHAMD; OC users had 3-4% lower binding compared to non-users for every 10% percent less improvement in HAMD. Within the groups, we observed a trend towards a positive association in non-users (p=0.10) and a negative association in OC users (p=0.07). We found no strong evidence of a difference in treatment response between the groups (p=0.13).
We found no difference in 5-HT4R binding between HC users . non-users in depressed women, however, it seemed that 5-HT4R settings differed qualitatively in their relation to antidepressant drug treatment response between OC users and non-users. From this we speculate that depressed OC users constitutes a special serotonin subtype of depression, which might have implications for antidepressant drug treatment response.
使用激素避孕（HC）与发生抑郁发作的风险增加有关。这可能与HC对血清素能脑系统的影响有关，正如我们团队最近的横断面数据所表明的，该数据显示，与未使用者相比，健康的口服避孕药（OC）使用者脑内血清素4受体（5-HT4R）水平较低。在此，我们确定在未接受治疗的抑郁发作女性中，HC非使用者、OC使用者和激素宫内节育器（HIUD）使用者之间脑内5-HT4R结合是否存在差异。此外，我们测试抗抑郁药物治疗反应及其与治疗前5-HT4R结合的关联是否取决于HC状态。
可从NeuroPharm-NP1研究（NCT02869035）获得59名绝经前抑郁女性的[C]-SB207145正电子发射断层扫描成像数据，其中26人使用OC，10人使用HIUD。参与者接受艾司西酞普兰治疗。治疗反应以汉密尔顿抑郁量表6项（rΔHAMD）从基线到第8周的相对变化来衡量。使用潜在变量模型来评估整体5-HT4R结合与OC和HIUD使用以及rΔHAMD之间的关联。
我们没有发现抑郁的HC使用者和非使用者之间整体5-HT4R结合存在差异的证据（p≥0.51）。在基线整体5-HT4R结合与第8周rΔHAMD之间的关联中，非使用者和OC使用者之间观察到显著的交叉相互作用（p=0.02）；HAMD每改善10%，OC使用者的结合比非使用者低3 - 4%。在各亚组中，我们在非使用者中观察到正相关趋势（p=0.10），在OC使用者中观察到负相关趋势（p=0.07）。我们没有发现各亚组之间治疗反应存在差异的有力证据（p=0.13）。
我们发现抑郁女性中HC使用者和非使用者之间5-HT4R结合没有差异，然而，似乎5-HT4R状态在OC使用者和非使用者与抗抑郁药物治疗反应的关系上存在质的差异。由此我们推测，抑郁的OC使用者构成了一种特殊的血清素亚型抑郁症，这可能对抗抑郁药物治疗反应有影响。
