A history of depression in women is associated with an altered GABAergic neuroactive steroid profile.
A history of depression in women is associated with an altered GABAergic neuroactive steroid profile.
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DOI：
10.1016/j.psyneuen.2011.08.004
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发表时间：
2012-04
影响因子：
3.7
通讯作者：
Morrow, A. Leslie
中科院分区：
文献类型：
--
作者：
Girdler, Susan S.;Lindgren, Monica;Porcu, Patrizia;Rubinow, David R.;Johnson, Jacqueline L.;Morrow, A. Leslie
孕酮、脱氧皮质酮和脱氢表雄酮（DHEA）的3α，5 α-和3α，5 β-还原代谢产物对GABAA受体介导的神经传递具有强效作用，这些受体的失调与抑郁症有关。使用气相色谱-质谱法，我们比较了神经活性类固醇浓度的妇女与抑郁症的历史，但谁是在测试时完全缓解（n=11），从来没有抑郁的妇女（n=17）之前和之后的挑战与口服微粉化孕酮（300毫克）。获得以下血清浓度：四种甾体衍生的GABA能神经活性类固醇、前体双烯醇酮、雄烯二酮衍生的神经活性类固醇和前体DHEA。作为孕酮向神经活性类固醇转化的指标，我们还检查了口服孕酮激发后神经活性类固醇与孕酮的比率。结果表明，口服黄体酮前后，有抑郁症病史的女性比从未抑郁的女性显示出更低的GABA能神经活性类固醇浓度。那些有抑郁史的人也倾向于有较低的皮质醇浓度。由于血清神经活性类固醇主要在肾上腺合成，我们推测抑郁症病史可能与持续的肾上腺抑制有关。孕激素激发后，在有抑郁症病史的女性中，孕酮衍生的神经活性类固醇与血浆孕酮浓度的比值升高，这表明可能存在孕酮代谢的适应性转变，以补偿较低的循环神经活性类固醇浓度。
The 3α,5α- and 3α,5β-reduced metabolites of progesterone, deoxycorticosterone, and dehydroepiandrosterone (DHEA) have potent effects on neurotransmission mediated by GABAA receptors, and dysregulation of these receptors has been implicated in depression. Using gas chromatography-mass spectrometry, we compared neuroactive steroid concentrations in women with a history of depressive disorders, but who were in full remission at the time of testing (n=11) to never depressed women (n=17) both before and after a challenge with oral micronized progesterone (300 mg). Serum concentrations of the following were obtained: four progesterone-derived GABAergic neuroactive steroids, the precursor pregnenolone, androstenedione-derived neuroactive steroids, and the precursor DHEA. As an index of conversion of progesterone to neuroactive steroids, we also examined ratios of neuroactive steroids to progesterone following the oral progesterone challenge. Results indicated that both before and after oral progesterone, women with histories of depression showed lower concentrations of all GABAergic neuroactive steroids than never depressed women. Those with a history of depression also tended to have lower cortisol concentrations. Because serum neuroactive steroids are mainly synthesized in the adrenals, we hypothesize that histories of depression may be associated with persistent adrenal suppression. Following the progesterone challenge, ratios of the progesterone-derived neuroactive steroids to plasma progesterone concentrations were elevated in women with depression histories, suggesting there may be an adaptive shift in the metabolism of progesterone that compensates for lower circulating neuroactive steroid concentrations.
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影响因子：
3.3
作者：
Eser, D;Romeo, E;Rupprecht, R
通讯作者：
Rupprecht, R
影响因子：
2
作者：
Evans, SEG;Ross, LE;Romach, MK
通讯作者：
Romach, MK
影响因子：
3.2
作者：
KIRSCHBAUM, C;PIRKE, KM;HELLHAMMER, DH
通讯作者：
HELLHAMMER, DH
影响因子：
6.1
作者：
De Geyter, C;De Geyter, M;Holzgreve, W
通讯作者：
Holzgreve, W
影响因子：
56.9
作者：
MAJEWSKA, MD;HARRISON, NL;PAUL, SM
通讯作者：
PAUL, SM