Targeted lipidomics reveal derangement of ceramides in major depression and bipolar disorder

Metabolism. 2019 Jun;95:65-76. doi: 10.1016/j.metabol.2019.04.002. Epub 2019 Apr 5.

Abstract

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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Bipolar disorder; Ceramides; Lipidome; Major depression; Tandem mass spectrometry.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Antidepressive Agents / adverse effects
  • Antidepressive Agents / therapeutic use
  • Antimanic Agents / adverse effects
  • Antimanic Agents / therapeutic use
  • Antipsychotic Agents / adverse effects
  • Antipsychotic Agents / therapeutic use
  • Bipolar Disorder / drug therapy
  • Bipolar Disorder / metabolism*
  • Bipolar Disorder / psychology
  • Body Mass Index
  • Ceramides / metabolism*
  • Depressive Disorder, Major / drug therapy
  • Depressive Disorder, Major / metabolism*
  • Depressive Disorder, Major / psychology
  • Diglycerides / metabolism
  • Female
  • Humans
  • Lipid Metabolism / genetics*
  • Lithium / adverse effects
  • Lithium / therapeutic use
  • Male
  • Middle Aged
  • Pilot Projects
  • Psychiatric Status Rating Scales
  • Sex Characteristics
  • Triglycerides / metabolism
  • Young Adult

Substances

  • Antidepressive Agents
  • Antimanic Agents
  • Antipsychotic Agents
  • Ceramides
  • Diglycerides
  • Triglycerides
  • Lithium