Department of Psychiatry, Psychotherapy and Psychosomatic Medicine, Goethe University Hospital Frankfurt, Frankfurt, Germany.
Institute of Clinical Pharmacology, Goethe-University Hospital Frankfurt, Germany.
Metabolism. 2019 Jun;95:65-76. doi: 10.1016/j.metabol.2019.04.002. Epub 2019 Apr 5.
Changes of sphingolipid metabolism were suggested to contribute to the patho-etiology of major depression (MD) and bipolar disorder (BD). In a pilot study we assessed if lipid allostasis manifested in pathological plasma concentrations of bioactive lipids i.e. endocannabinoids, sphingolipids, ceramides, and lysophosphatidic acids.
Targeted and untargeted lipidomic analyses were performed according to GLP guidelines in 67 patients with unipolar or bipolar disorders (20-67 years, 36 male, 31 female) and 405 healthy controls (18-79 years, 142 m, 263 f), who were matched according to gender, age and body mass index. Multivariate analyses were used to identify major components, which accounted for the variance between groups and were able to predict group membership.
Differences between MD and BP patients versus controls mainly originated from ceramides and their hexosyl-metabolites (C16Cer, C18Cer, C20Cer, C22Cer, C24Cer and C24:1Cer; C24:1GluCer, C24LacCer), which were strongly increased, particularly in male patients. Ceramide levels were neither associated with the current episode, nor with the therapeutic improvement of the Montgomery Åsberg Depression Rating Scale (MARDS). However, long-chain ceramides were linearly associated with age, stronger in patients than controls, and with high plasma levels of diacyl- and triacylglycerols. Patients receiving antidepressants had higher ceramide levels than patients not taking these drugs. There was no such association with lithium or antipsychotics except for olanzapine.
Our data suggest that high plasma ceramides in patients with major depression and bipolar disorder are indicative of a high metabolic burden, likely aggravated by certain medications.
改变神经酰胺代谢被认为有助于重度抑郁症（MD）和双相情感障碍（BD）的发病机制。在一项初步研究中，我们评估了脂质的稳定性是否表现为生物活性脂质即内源性大麻素、神经酰胺、神经酰胺、鞘氨醇、溶血磷脂酸的病理性血浆浓度。
根据 GLP 指南，对 67 名单相或双相情感障碍患者（20-67 岁，36 名男性，31 名女性）和 405 名健康对照者（18-79 岁，142 名男性，263 名女性）进行靶向和非靶向脂质组学分析。采用多元分析方法确定主要成分，这些成分解释了组间差异，并能够预测组间差异。
MD 和 BP 患者与对照组之间的差异主要来源于神经酰胺及其己糖代谢物（C16Cer、C18Cer、C20Cer、C22Cer、C24Cer 和 C24：1Cer；C24：1GluCer、C24LacCer），这些物质明显增加，尤其是男性患者。神经酰胺水平与当前发作无关，也与蒙哥马利抑郁评定量表（MARDS）的治疗改善无关。然而，长链神经酰胺与年龄呈线性相关，在患者中比在对照组中更强，与二酰基和三酰基甘油的血浆水平呈正相关。服用抗抑郁药的患者神经酰胺水平高于未服用这些药物的患者。除了奥氮平外，锂或抗精神病药物与神经酰胺水平无相关性。
我们的数据表明，重度抑郁症和双相情感障碍患者的高血浆神经酰胺表明代谢负担较高，可能因某些药物而加重。
