Plasma lipidomics reveals potential lipid markers of major depressive disorder

Abstract

Major depressive disorder (MDD) is a grave debilitating mental disease with a high incidence and severely impairs quality of life. Therefore, its physiopathological basis study and diagnostic biomarker discovery are extremely valuable. In this study, a non-targeted lipidomics strategy using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was performed to reveal differential lipids between MDD (n = 60) and healthy controls (HCs, n = 60). Validation of changed lipid species was performed in an independent batch including 75 MDD and 52 HC using the same lipidomic method. Pronouncedly changed lipid species in MDD were discovered, which mainly were lysophosphatidylcholine (LPC), lysophosphatidylethanolamine (LPE), phosphatidylcholine (PC), phosphatidylethanolamine (PE), phosphatidylinositol (PI), 1-O-alkyl-2-acyl-PE (PE O), 1-O-alkyl-2-acyl-PC (PC O), sphingomyelin (SM), diacylglycerol (DG), and triacylglycerol (TG). Among these lipid species, LPC, LPE, PC, PE, PI, TG, etc. remarkably increased in MDD and showed pronounced positive relationships with depression severity, while 1-O-alkyl-2-acyl-PE and SM with odd summed carbon number significantly decreased in MDD and demonstrated negative relationships with depression severity. A combinational lipid panel including LPE 20:4, PC 34:1, PI 40:4, SM 39:1, 2, and TG 44:2 was defined as potential diagnostic biomarker with a good sensitivity and specificity for distinguishing MDD from HCs. Our study brings insights into lipid metabolism disorder in MDD and provides a specific potential biomarker for MDD diagnose.

The Relationship between Fatty Acids and Different Depression-Related Brain Regions, and Their Potential Role as Biomarkers of Response to Antidepressants

“…Further, plasma levels of total free fatty acids and glycerophospholipids were reduced in these patients and inversely associated with the severity of depression. Collectively, this suggests that plasma lipid profiles could be used to diagnose individuals with this mental disorder [110]. In addition, the evidence presented in the current review suggests that blood levels of specific fatty acids (e.g., n -3 PUFAs) and fatty acid metabolites (e.g., endocannabinoids) may serve as promising markers to assess a person’s risk and vulnerability for depression.…”

“…In support of this idea, significant differences in the plasma lipid profile of young adults (27–33 years of age) with major depressive disorder compared to age-matched healthy controls have been observed. Specifically, plasma levels of specific phospholipids, lysophospholipids and triacylglycerols were increased in depressed individuals and positively associated with severity of depression [110]. Further, plasma levels of total free fatty acids and glycerophospholipids were reduced in these patients and inversely associated with the severity of depression.…”

Plasma sphingolipids and depressive symptoms in coronary artery disease

“…Altered sphingolipid concentrations have recently been reported in depression (Demirkan et al., 2013; Gracia‐Garcia et al., 2011; Liu et al., 2016). Elevations in ceramide concentrations have been reported in those with depression (Gracia‐Garcia et al., 2011), while sphingolipid concentrations have been observed to be associated with depressive symptoms in some populations (Demirkan et al., 2013; Liu et al., 2016; Xing et al., 2016).…”

“…Elevations in ceramide concentrations have been reported in those with depression (Gracia‐Garcia et al., 2011), while sphingolipid concentrations have been observed to be associated with depressive symptoms in some populations (Demirkan et al., 2013; Liu et al., 2016; Xing et al., 2016). To our knowledge, no study to date has assessed plasma sphingolipids as correlates of depressive symptoms in a CAD population.…”

Biomarkers for Depression: Recent Insights, Current Challenges and Future Prospects

“…90 Lipid profiles, including HDL-cholesterol, appear altered in many patients with depression, including those without comorbid physical illness, though this relationship is complex and requires further elucidation. 91 Additionally, hyperglycemia 92 and hypoalbuminemia 93 in depression have been reported in reviews.…”