Abstract：
OBJECTIVE: Elevated bilirubin levels have been associated with major depressive disorder (MDD); however, the exact impact of bilirubin on MDD and the underlying molecular mechanisms remain unclear. Here, we explored the influence of bilirubin on MDD and sought to identify the mechanisms via which bilirubin induces depressive-like behavior.
METHODS: Forty patients who were diagnosed with MDD and received treatment with selective serotonin reuptake inhibitors (SSRIs) were included, with 43 healthy volunteers serving as controls. Clinical symptoms were evaluated using Hamilton depression rating scale-24 (HAMD-24) and the Hamilton anxiety rating scale. Serum concentrations of total bilirubin (TBIL) and indirect bilirubin (IBIL) were measured at baseline and after treatment using an automated biochemical analyzer. The connection between clinical symptoms and TBIL or IBIL was examined using Pearson correlation. Chronic restraint stress (CRS) was employed to generate a rat model of depression. TBIL, IBIL in rat serum were measured by ELISA. Reactive oxygen species (ROS) contents in rat hippocampal tissues were quantified by flow cytometry. The levels of microglial markers and the extent of neuronal damage in the rat hippocampus were assessed by immunofluorescence and transmission electron microscopy, respectively.
RESULTS: Serum TBIL and IBIL levels were higher in patients with MDD than in the healthy controls. After treatment with SSRIs, the serum levels of TBIL and IBIL in MDD patients were significantly reduced. The levels of TBIL and IBIL were associated with HAMD-24 in MDD patients. Compared with the controls, the serum levels of TBIL, IBIL and the hippocampal ROS contents were elevated in CRS-exposed rats. Fluoxetine lowered inflammatory factor levels, mitigated oxidative stress.
CONCLUSIONS: Our findings indicate a possible correlation between elevated serum bilirubin and depressive symptoms. Increases in ROS levels, along with neuronal damage, may represent pathological mechanisms underlying MDD.
METHODS: Forty patients who were diagnosed with MDD and received treatment with selective serotonin reuptake inhibitors (SSRIs) were included, with 43 healthy volunteers serving as controls. Clinical symptoms were evaluated using Hamilton depression rating scale-24 (HAMD-24) and the Hamilton anxiety rating scale. Serum concentrations of total bilirubin (TBIL) and indirect bilirubin (IBIL) were measured at baseline and after treatment using an automated biochemical analyzer. The connection between clinical symptoms and TBIL or IBIL was examined using Pearson correlation. Chronic restraint stress (CRS) was employed to generate a rat model of depression. TBIL, IBIL in rat serum were measured by ELISA. Reactive oxygen species (ROS) contents in rat hippocampal tissues were quantified by flow cytometry. The levels of microglial markers and the extent of neuronal damage in the rat hippocampus were assessed by immunofluorescence and transmission electron microscopy, respectively.
RESULTS: Serum TBIL and IBIL levels were higher in patients with MDD than in the healthy controls. After treatment with SSRIs, the serum levels of TBIL and IBIL in MDD patients were significantly reduced. The levels of TBIL and IBIL were associated with HAMD-24 in MDD patients. Compared with the controls, the serum levels of TBIL, IBIL and the hippocampal ROS contents were elevated in CRS-exposed rats. Fluoxetine lowered inflammatory factor levels, mitigated oxidative stress.
CONCLUSIONS: Our findings indicate a possible correlation between elevated serum bilirubin and depressive symptoms. Increases in ROS levels, along with neuronal damage, may represent pathological mechanisms underlying MDD.
摘要：
目的：胆红素水平升高与重度抑郁症（MDD）有关；然而，胆红素对MDD的确切影响和潜在的分子机制尚不清楚.这里,我们探讨了胆红素对MDD的影响,并试图确定胆红素诱导抑郁样行为的机制.
方法：纳入40例诊断为MDD并接受选择性5-羟色胺再摄取抑制剂（SSRIs）治疗的患者，43名健康志愿者作为对照。采用汉密尔顿抑郁量表（HAMD-24）和汉密尔顿焦虑量表对临床症状进行评估。使用自动生化分析仪在基线和治疗后测量血清总胆红素（TBIL）和间接胆红素（IBIL）的浓度。使用Pearson相关性检查临床症状与TBIL或IBIL之间的联系。采用慢性束缚应激（CRS）制备抑郁症大鼠模型。TBIL,ELISA法测定大鼠血清中IBIL。通过流式细胞术对大鼠海马组织中的活性氧（ROS）含量进行定量。免疫荧光和透射电镜观察大鼠海马小胶质细胞标志物水平和神经元损伤程度,分别。
结果：MDD患者血清TBIL和IBIL水平高于健康对照组。用SSRIs治疗后，MDD患者血清TBIL和IBIL水平显著降低。MDD患者TBIL和IBIL水平与HAMD-24相关。与对照组相比，血清TBIL水平，CRS暴露大鼠的IBIL和海马ROS含量升高。氟西汀降低炎症因子水平,减轻氧化应激。
结论：我们的研究结果表明血清胆红素升高与抑郁症状之间可能存在相关性。ROS水平增加，伴随着神经元损伤，可能代表MDD的病理机制。
方法：纳入40例诊断为MDD并接受选择性5-羟色胺再摄取抑制剂（SSRIs）治疗的患者，43名健康志愿者作为对照。采用汉密尔顿抑郁量表（HAMD-24）和汉密尔顿焦虑量表对临床症状进行评估。使用自动生化分析仪在基线和治疗后测量血清总胆红素（TBIL）和间接胆红素（IBIL）的浓度。使用Pearson相关性检查临床症状与TBIL或IBIL之间的联系。采用慢性束缚应激（CRS）制备抑郁症大鼠模型。TBIL,ELISA法测定大鼠血清中IBIL。通过流式细胞术对大鼠海马组织中的活性氧（ROS）含量进行定量。免疫荧光和透射电镜观察大鼠海马小胶质细胞标志物水平和神经元损伤程度,分别。
结果：MDD患者血清TBIL和IBIL水平高于健康对照组。用SSRIs治疗后，MDD患者血清TBIL和IBIL水平显著降低。MDD患者TBIL和IBIL水平与HAMD-24相关。与对照组相比，血清TBIL水平，CRS暴露大鼠的IBIL和海马ROS含量升高。氟西汀降低炎症因子水平,减轻氧化应激。
结论：我们的研究结果表明血清胆红素升高与抑郁症状之间可能存在相关性。ROS水平增加，伴随着神经元损伤，可能代表MDD的病理机制。
