Faculty of Medicine, University of Kufa, Kufa, Iraq.
Department of Chemistry, College of Science, University of Kufa, Kufa, Iraq.
Metab Brain Dis. 2019 Oct;34(5):1493-1503. doi: 10.1007/s11011-019-00458-5. Epub 2019 Jul 10.
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-naïve 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-1β, IL-4, IL-6, IL-18, IFN-γ, TGF-β1, 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. Graphical abstract.
重度抑郁症（MDD）与钙（Ca）和镁（Mg）的变化有关，以及循环中的促炎和抗炎细胞因子。抗炎药通常被用作 MDD 的辅助治疗。然而，没有研究检查过舍曲林和酮洛芬（一种抗炎药）联合治疗对 MDD 患者 Ca 和 Mg 水平的影响。本研究检查了 a）未经药物治疗的 MDD 患者和对照组之间两种阳离子的差异，以及 b）舍曲林和酮洛芬对 Ca 和 Mg（总离子和游离离子）的影响。在相同的患者中，我们还检查了两种阳离子与白细胞介素-1β、白细胞介素-4、白细胞介素-6、白细胞介素-18、干扰素-γ、转化生长因子-β1、锌和吲哚胺 2,3-双加氧酶（IDO）之间的关系。使用贝克抑郁量表二（BDI-II）在基线和随访 2 个月后评估临床改善情况。与对照组相比，MDD 患者的血清 Ca 和 Mg（总离子和游离离子）明显降低，而治疗后 Ca 显著升高，Mg 水平降低。从基线到终点的 BDI-II 评分与 Ca（总离子和游离离子）呈显著负相关，但与 Mg 无关。在考虑锌、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，该免疫激活指数与 Ca 水平呈显著负相关。总之，两种阳离子水平的降低在重度抑郁症的病理生理学中起作用。抗抑郁药诱导的 Ca 增加与临床疗效和免疫反应的衰减有关。抗抑郁药对 Mg 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治疗方法，以增加 Ca 和 Mg 的水平。
