Plasma sphingolipids and depressive symptoms in coronary artery disease

Abstract

BackgroundDepression is highly prevalent in individuals with coronary artery disease (CAD) and increases the risk of future cardiac events and mortality. Sphingolipids have been implicated in the pathophysiology of both CAD and depression. This study assessed the association between plasma sphingolipid concentrations and depressive symptoms in CAD subjects.MethodsDepressive symptoms were measured using the depression subscale of the self‐reported Hospital Anxiety and Depression Scale (HADS). Sphingolipid concentrations were measured from fasting plasma samples using high‐performance liquid chromatography‐coupled electrospray ionization tandem mass spectrometry (LC/MS/MS). Linear regression models were used to assess associations between log‐transformed concentrations of plasma sphingolipids and depressive symptoms.ResultsA total of 111 CAD patients (mean (SD) age = 63.6 ± 6.4, 84.7% male) were included. In linear regression analyses, higher plasma concentrations of ceramides C16:0 (β = 0.204, p = .026) and C18:0 (β = 0.209, p = .023) and sphingomyelin SM18:1 (β = 0.210, p = .024) were significantly associated with higher HADS depression subscale score after adjusting for covariates.ConclusionSphingolipids, in particular the ceramide species C16:0 and C18:0 and the sphingomyelin species SM18:1, may be implicated in the pathophysiology of depression in CAD. The association between plasma sphingolipid concentrations and depression should be further examined in CAD patients and in other populations.

Association Between Sphingolipids and Cardiopulmonary Fitness in Coronary Artery Disease Patients Undertaking Cardiac Rehabilitation

“…These sphingolipids have been consistently associated with metabolic disease ( 35 ), psychiatric disorders ( 36 ), and neurodegenerative diseases ( 37 ). Our own studies have previously shown associations between these sphingolipids and depressive symptoms ( 38 ) and cognitive response to exercise in patient with CAD ( 17 ). As such, sphingolipids may be important markers of early pathophysiological changes in at-risk populations such as those with CAD.…”

Plasma metabolomic profiling of a ketamine and placebo crossover trial of major depressive disorder and healthy control subjects

“…For the PCs, “aa” indicates that both moieties at the sn-1 and sn2 positions are fatty acids and bound to the glycerol backbone via ester bonds—”ae” denotes that one of the moieties, either in the sn-1 or at sn-2 position, is a fatty alcohol and bound via an ether bond. Sphingolipids contain a sphingoid base attached to an acyl group such as a fatty acid (Dinoff et al 2017) and are the most common form of lipid in brain cell membranes.…”

“…The balance between these two sphingolipids is referred to as the “sphingolipid-rheostat” as increased ceramide levels can initiate apoptosis and increased S1P concentrations generally promote cell survival and proliferation (van Brocklyn and Williams 2012). Previous studies have suggested that sphingolipid metabolism may be a potential novel therapeutic target in depression (Kornhuber et al 2005; Dinoff et al 2017), as higher circulating levels of ceramides C16:0, C18:0, C20:0, C24:1, and C26:1 (Gracia-Garcia et al 2011) and lower circulating levels of SMs have been reported in patients with MDD. In our study, ketamine induced a significant increase in circulating concentration of SMs in MDD patients relative to placebo, suggesting that ketamine may be having an effect on acid sphingomyelinase activity, and as a result decreasing circulating ceramide levels; however, further studies in this pathway are needed to confirm these findings.…”

The Forebrain-Specific Overexpression of Acid Sphingomyelinase Induces Depressive-Like Symptoms in Mice

“…Similarly, plasma levels of several ceramide species, including Cer16:0, Cer18:0, Cer20:0, Cer24:1, and Cer26:1 but not Cer22:0 or Cer24:0, were increased in patients experiencing a major depressive episode during the past 2 years [9]. Higher plasma ceramide Cer16:0, Cer18:0, Cer20:0, Cer22:0, Cer24:0, and Cer24:1 levels were also observed in patients with MDD and bipolar disorder [10], and higher plasma levels of ceramide Cer16:0 and Cer18:0 and sphingomyelin SM18:1 were associated with the increased severity of depression symptoms in patients with coronary artery disease [11]. In contrast, plasma sphingomyelin SM26:1 [12], SM21:0 and SM21:1 [13] levels were decreased in MDD patients, and the SM23:1/SM16:0 ratio was negatively correlated with the severity of depressive symptoms in a Dutch family [14].…”