Calcium signalling has long been implicated in bipolar disorder, especially by reports of altered intracellular calcium ion concentrations ([Ca²⁺]). However, the evidence has not been appraised critically. We carried out a systematic review and meta-analysis of studies of cellular calcium indices in bipolar disorder. 2281 records were identified and 117 screened, of which 32 were eligible and 21 were suitable for meta-analyses. The latter each involved up to 642 patients and 404 control subjects. We found that basal free intracellular [Ca²⁺] is increased in bipolar disorder, both in platelets and in lymphocytes. The effect size is 0.55, with an estimated elevation of 29%. It is observed in medication-free patients. It is present in mania and bipolar depression, but data are equivocal for euthymia. Cells from bipolar disorder individuals also show an enhanced [Ca²⁺] response to stimulation with 5-HT or thrombin, by an estimated 25%, with an effect size of 0.63. In studies which included other diagnoses, intracellular basal [Ca²⁺] was higher in bipolar disorder than in unipolar depression, but not significantly different from schizophrenia. Functional parameters of cellular Ca²⁺ (e.g. calcium transients), and neuronal [Ca²⁺], have been much less investigated, and no firm conclusions can be drawn. In summary, there is a robust, medium effect size elevation of basal and stimulated free intracellular [Ca²⁺] in bipolar disorder. The results suggest altered calcium functioning in the disorder, and encourage further investigations into the underlying mechanisms, and the implications for pathophysiology and therapeutics.

长期以来，钙信号与双相情感障碍有关，尤其是细胞内钙离子浓度 ([Ca ²⁺ ]) 改变的报道。然而，这些证据还没有经过批判性的评估。我们对双相情感障碍中细胞钙指数的研究进行了系统回顾和荟萃分析。确定了 2281 条记录并筛选了 117 条记录，其中 32 条符合条件，21 条适合进行荟萃分析。后者各涉及多达 642 名患者和 404 名对照受试者。我们发现基底游离细胞内 [Ca ²⁺] 在双相情感障碍中，血小板和淋巴细胞均增加。效应大小为 0.55，估计提升为 29%。在未服用药物的患者中观察到。它存在于躁狂症和双相抑郁症中，但关于情绪愉悦的数据是模棱两可的。来自双相情感障碍个体的细胞也显示出对 5-HT 或凝血酶刺激的 [Ca ²⁺ ] 反应增强，估计提高了 25%，效应大小为 0.63。在包括其他诊断的研究中，双相情感障碍的细胞内基础 [Ca ²⁺ ] 高于单相抑郁症，但与精神分裂症没有显着差异。细胞 Ca ²⁺的功能参数（例如钙瞬变）和神经元 [Ca ²⁺]，调查得少得多，也不能得出肯定的结论。总之，双相情感障碍中基础和受刺激的游离细胞内 [Ca ^{2+ ] 存在稳健的中等效应量升高。}结果表明该疾病中的钙功能发生了改变，并鼓励进一步研究其潜在机制以及对病理生理学和治疗学的影响。