BACKGROUND Altered nitric oxide (NO) signaling has been associated with the pathophysiology of Bipolar Disorder (BD), directly affecting neurotransmitter release and synaptic plasticity cascades. Lithium has shown to regulate NO levels in preclinical models. However, no study has addressed peripheral NO levels in unmedicated BD. Also, lithium's effects on NO levels have not been studied in humans. METHODS Plasma NO was evaluated in subjects with BD I and II during a depressive episode (n = 26). Subjects had a score of ≥18 in the 21-item Hamilton Depression Rating Scale and were followed-up during a 6-week trial with lithium. Plasma NO levels were also compared to matched healthy controls (n = 28). NO was determined by chemiluminescence method. RESULTS Lithium treatment significantly increased plasma NO levels after 6 weeks of treatment in comparison to baseline levels in bipolar depression (p = 0.016). Baseline NO levels during depressive episodes showed no difference when matching up to healthy controls (p = 0.66). CONCLUSION The present findings suggest that lithium upregulates NO signaling in unmedicated BD with short illness duration. Further studies with larger samples are needed to confirm the effects of lithium on NO pathway and its association with synaptic plasticity and therapeutics of BD.

中文翻译：

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在抑郁发作期间，锂会增加双相情感障碍患者的一氧化氮水平。

背景改变的一氧化氮 (NO) 信号与双相情感障碍 (BD) 的病理生理学相关，直接影响神经递质释放和突触可塑性级联。锂已显示在临床前模型中调节 NO 水平。然而，没有研究解决未用药的 BD 中的外周 NO 水平。此外，尚未在人体中研究锂对 NO 水平的影响。方法 在抑郁发作期间评估 BD I 和 II 受试者的血浆 NO（n = 26）。受试者在 21 项汉密尔顿抑郁量表中得分≥18 分，并在为期 6 周的锂试验中进行了随访。血浆 NO 水平也与匹配的健康对照 (n = 28) 进行了比较。NO采用化学发光法测定。结果 与双相抑郁症的基线水平相比，锂治疗 6 周后血浆 NO 水平显着增加（p = 0.016）。当与健康对照匹配时，抑郁发作期间的基线 NO 水平显示没有差异（p = 0.66）。结论 目前的研究结果表明，锂可以上调疾病持续时间较短的未用药 BD 中的 NO 信号。需要更大样本的进一步研究来证实锂对 NO 通路的影响及其与突触可塑性和 BD 治疗的关联。结论 目前的研究结果表明，锂可以上调疾病持续时间较短的未用药 BD 中的 NO 信号。需要更大样本的进一步研究来证实锂对 NO 通路的影响及其与突触可塑性和 BD 治疗的关联。结论 目前的研究结果表明，锂可以上调疾病持续时间较短的未用药 BD 中的 NO 信号传导。需要更大样本的进一步研究来证实锂对 NO 通路的影响及其与突触可塑性和 BD 治疗的关联。