Total and ionized calcium and magnesium are significantly lowered in drug-naive depressed patients: effects of antidepressants and associations with immune activation
Total and ionized calcium and magnesium are significantly lowered in drug-naive depressed patients: effects of antidepressants and associations with immune activation
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DOI：
10.1007/s11011-019-00458-5
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发表时间：
2019-10-01
影响因子：
3.6
通讯作者：
Maes, Michael
中科院分区：
文献类型：
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作者：
Al-Dujaili, Arafat Hussein;Al-Hakeim, Hussein Kadhem;Maes, Michael
严重抑郁障碍(MDD)与钙(Ca)和镁(Mg)以及循环中的促炎和抗炎细胞因子的变化有关。抗炎药通常被用作MDD的辅助治疗。然而，没有研究考察舍曲林和消炎药酮洛芬联合治疗对MDD患者钙和镁水平的影响。本研究检测了未用药的MDD患者和对照组两种阳离子的差异，以及舍曲林和酮洛芬对钙和镁(包括总钙和镁离子)的影响。在相同的患者中，我们还检测了这两种阳离子与IL-1β、IL-4、IL-6、IL-18、干扰素-γ、转化生长因子-β1、锌和吲哚胺2，3-双加氧酶(IDO)的关系。在基线和随访2个月后，使用Beck抑郁量表(BDI-II)评估临床改善情况。MDD患者血清钙和镁(总钙和离子镁)显著低于对照组，而治疗后钙显著升高，镁显著下降。从基线到终点的BDI-II评分与钙(总钙和离子钙)水平之间存在显著的负相关，但与镁水平之间没有相关性。在考虑了锌、IDO和基于所有细胞因子总和的免疫激活z单位加权综合评分的影响后，钙对BDI-II评分的影响仍然显著。从基线到终点，这一免疫激活指数与钙水平之间存在显著的负相关。总而言之，这两种阳离子水平的降低在抑郁症的病理生理学中起着一定的作用。抗抑郁药诱导的钙升高与临床疗效和免疫反应的减弱有关。抗抑郁药对镁水平的抑制作用可能是这些药物的副作用。应该开发新的抗抑郁药物来提高钙和镁的水平。
Major depressive disorder (MDD) is associated with alterations in calcium (Ca) and magnesium (Mg), as well as circulating pro- and anti-inflammatory cytokines. Anti-inflammatory drugs are commonly used as adjuvant treatments for MDD. However, no studies examined the effects of a combinatorial treatment with sertraline and ketoprofen, an anti-inflammatory drug, on Ca and Mg levels in MDD. The present study examined a) differences in both cations between drug-naive MDD patients and controls, and b) the effects of sertraline and ketoprofen on Ca and Mg (both total and ionized). In the same patients, we also examined the associations between both cations and IL-1 beta, IL-4, IL-6, IL-18, IFN-gamma, TGF-beta 1, zinc, and indoleamine 2,3-dioxygenase (IDO). Clinical improvement was assessed using the Beck Depression Inventory-II (BDI-II) at baseline and after follow up for 2 months. Serum Ca and Mg (total and ionized) were significantly lower in MDD patients as compared with controls, while treatment significantly increased calcium but decreased magnesium levels. There were significant and inverse correlations between the BDI-II scores from baseline to endpoint and Ca (both total and ionized), but not Mg, levels. The effects of calcium on the BDI-II score remained significant after considering the effects of zinc, IDO and an immune activation z unit-weighted composite score based on the sum of all cytokines. There was a significant and inverse association between this immune activation index and calcium levels from baseline to endpoint. In conclusion, lowered levels of both cations play a role in the pathophysiology of major depression. Antidepressant-induced increases in Ca are associated with clinical efficacy and attenuation of the immune response. The suppressant effect of antidepressants on Mg levels is probably a side effect of those drugs. New antidepressant treatments should be developed that increase the levels both Ca and Mg.