PDF(Sci-hub)
Abstract：
Sex steroid hormones potently shape brain functions, including those critical to maintain mental health such as serotonin signaling. Use of oral contraceptives (OCs) profoundly changes endogenous sex steroid hormone levels and dynamics. Recent register-based studies show that starting an OC is associated with increased risk of developing depression. Here, we investigate whether use of OCs in healthy women is associated with a marker of the serotonin system in terms of serotonin 4 receptor (5-HT4R) brain imaging.
[11C]SB207145-PET imaging data on 53 healthy women, of whom 16 used OCs, were available from the Cimbi database. We evaluated global effects of OC use on 5-HT4R binding in a latent variable model based on 5-HT4R binding across cortical and subcortical regions.
We demonstrate that OC users have 9-12% lower global brain 5-HT4R binding potential compared to non-users. Univariate region-based analyses (pallidostriatum, caudate, hippocampus, amygdala, anterior cingulate cortex, and neocortex) supported the global effect of OC use with the largest difference present in the hippocampus (-12.8% (95% CI [-21.0; -3.9], Pcorrected = 0.03).
We show that women who use OCs have markedly lower brain 5-HT4R binding relative to non-users, which constitutes a plausible molecular link between OC use and increased risk of depressive episodes. We propose that this reflects a reduced 5-HT4R gene expression, possibly related to a blunted ovarian hormone state among OC users.
[11C]SB207145-PET imaging data on 53 healthy women, of whom 16 used OCs, were available from the Cimbi database. We evaluated global effects of OC use on 5-HT4R binding in a latent variable model based on 5-HT4R binding across cortical and subcortical regions.
We demonstrate that OC users have 9-12% lower global brain 5-HT4R binding potential compared to non-users. Univariate region-based analyses (pallidostriatum, caudate, hippocampus, amygdala, anterior cingulate cortex, and neocortex) supported the global effect of OC use with the largest difference present in the hippocampus (-12.8% (95% CI [-21.0; -3.9], Pcorrected = 0.03).
We show that women who use OCs have markedly lower brain 5-HT4R binding relative to non-users, which constitutes a plausible molecular link between OC use and increased risk of depressive episodes. We propose that this reflects a reduced 5-HT4R gene expression, possibly related to a blunted ovarian hormone state among OC users.
摘要：
性类固醇激素能有效地塑造大脑功能，包括那些对维持心理健康至关重要的人，如血清素信号。口服避孕药（OCs）的使用会深刻地改变内源性类固醇激素的水平和动力学。最近基于注册的研究表明，开始OC与患抑郁症的风险增加有关。这里,我们在5-羟色胺4受体(5-HT4R)脑成像方面,调查健康女性使用OCs是否与5-羟色胺系统标志物相关.
[11C]53名健康女性的SB207145-PET成像数据，其中16人使用OCs，可从Cimbi数据库获得。我们在基于皮层和皮层下区域的5-HT4R结合的潜在变量模型中评估了OC使用对5-HT4R结合的总体影响。
我们证明，与非使用者相比，OC使用者的全脑5-HT4R结合潜能低9-12%。基于区域的单变量分析(苍白条，尾状,海马体,杏仁核,前扣带皮质,和新皮质）支持OC使用的整体效应，海马中存在最大差异（-12.8%（95%CI[-21.0;-3.9]，P校正=0.03)。
我们表明，使用OCs的女性相对于非使用者的大脑5-HT4R结合明显较低，这构成了OC使用与抑郁发作风险增加之间的合理分子联系。我们认为这反映了5-HT4R基因表达的减少，可能与OC使用者的卵巢激素状态钝化有关。
[11C]53名健康女性的SB207145-PET成像数据，其中16人使用OCs，可从Cimbi数据库获得。我们在基于皮层和皮层下区域的5-HT4R结合的潜在变量模型中评估了OC使用对5-HT4R结合的总体影响。
我们证明，与非使用者相比，OC使用者的全脑5-HT4R结合潜能低9-12%。基于区域的单变量分析(苍白条，尾状,海马体,杏仁核,前扣带皮质,和新皮质）支持OC使用的整体效应，海马中存在最大差异（-12.8%（95%CI[-21.0;-3.9]，P校正=0.03)。
我们表明，使用OCs的女性相对于非使用者的大脑5-HT4R结合明显较低，这构成了OC使用与抑郁发作风险增加之间的合理分子联系。我们认为这反映了5-HT4R基因表达的减少，可能与OC使用者的卵巢激素状态钝化有关。
