Background Lysophosphatidic acid (LPA) is involved in numerous biological processes, including neurodevelopment, chronic inflammation, and immunologic response in the central nervous system. Autotaxin (ATX) is a secreted enzyme that produces LPA from lysophosphatidylcholine (LPC). Previous studies have demonstrated decreased protein levels of ATX in cerebrospinal fluid (CSF) of patients with major depressive disorder (MDD). Based on those studies, the current study investigated the levels of lysophospholipids species including LPA and related metabolic enzymes, in CSF of patients with MDD and schizophrenia (SCZ). Methods The levels of lysophospholipids species and related metabolic enzymes were measured with either liquid chromatography-tandem mass spectrometry or enzyme-linked immunosorbent assay. Japanese patients were diagnosed with DSM-IV-TR. CSF was obtained from age- and sex-matched healthy controls (n = 27) and patients with MDD (n = 26) and SCZ (n = 27). Results Of all lysophospholipids species, the levels of LPA 22:6 (LPA - docosahexaenoic acid) were significantly lower in patients with MDD and SCZ than in healthy controls. These levels were negatively correlated with several clinical symptomatic scores of MDD, but not those of SCZ. In addition, the levels of LPA 22:6 were significantly correlated with the levels of LPC 22:6 among all 3 groups. On the other hand, the levels of LPA 22:6 were not correlated with ATX activity in patients with MDD and SCZ. Conclusion The lower levels of LPA 22:6 in patients with MDD and SCZ suggest an abnormality of LPA 22:6 metabolism. In addition, several depressive symptoms in patients with MDD were significantly associated with the lower levels of LPA 22:6, suggesting an involvement of LPA 22:6 in the pathophysiology of MDD.

中文翻译：

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重度抑郁症和精神分裂症患者脑脊液中溶血磷脂酸二十二碳六烯酸水平降低

背景溶血磷脂酸 (LPA) 涉及许多生物过程，包括神经发育、慢性炎症和中枢神经系统的免疫反应。Autotaxin (ATX) 是一种从溶血磷脂酰胆碱 (LPC) 产生 LPA 的分泌酶。先前的研究表明，重度抑郁症 (MDD) 患者脑脊液 (CSF) 中 ATX 的蛋白质水平降低。基于这些研究，本研究调查了 MDD 和精神分裂症 (SCZ) 患者脑脊液中溶血磷脂种类的水平，包括 LPA 和相关代谢酶。方法采用液相色谱-串联质谱法或酶联免疫吸附法测定溶血磷脂种类和相关代谢酶的水平。日本患者被诊断出患有 DSM-IV-TR。CSF 来自年龄和性别匹配的健康对照 (n = 27) 以及 MDD (n = 26) 和 SCZ (n = 27) 患者。结果 在所有溶血磷脂种类中，MDD 和 SCZ 患者的 LPA 22:6（LPA - 二十二碳六烯酸）水平显着低于健康对照组。这些水平与 MDD 的几种临床症状评分呈负相关，但与 SCZ 的评分无关。此外，3组中LPA 22:6水平与LPC 22:6水平显着相关。另一方面，LPA 22:6 的水平与 MDD 和 SCZ 患者的 ATX 活性无关。结论 MDD 和 SCZ 患者 LPA 22:6 水平较低提示 LPA 22:6 代谢异常。此外，