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      Evaluation of Serum Lysophosphatidic Acid and Lysophosphatidylcholine Levels in Major Depressive Disorder Patients

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          Abstract

          Background

          Major depressive disorder (MDD) is a heterogeneous condition featured with a continuous low mood, feeling of sadness, lack of interest to perform daily activities. Genetic, physiological, biological, social, and environmental factors are associated with the pathophysiology of depression. Though several human studies failed to identify the suitable biological markers for depression, some animal studies showed phospholipids play a vital role in the alteration of emotion. Thus, the current study aimed to measure the serum levels of lysophosphatidic acid (LPA) and lysophosphatidylcholine (LPC) in MDD patients and healthy controls (HCs) to explore their roles and relationship with depression.

          Methods

          This case-control study enrolled 53 MDD patients and 50 HCs matched by age, gender, and body mass index. Based on the diagnostic and statistical manual of mental disorders, 5 th edition, a qualified psychiatrist diagnosed patients and assessed HCs. We applied the Hamilton depression rating scale (Ham-D) to measure the severity of depression. We used enzyme-linked immunosorbent assay kits to measure serum lysophosphatidic acid and lysophosphatidylcholine levels.

          Results

          We found no alterations of these parameters in serum levels of MDD patients compared to HCs. We also observed a significant positive correlation between LPA and LPC levels in MDD patients. Moreover, the present study showed no significant associations between target markers and either diagnosis of depression or Ham-D scores, or management of depression.

          Conclusion

          The present study suggests that LPA and LPC levels probably would not serve as potential biomarkers of MDD. Thus, we recommend further studies with large and more homogeneous populations to explore the exact relationship between serum lipids and MDD.

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          Most cited references30

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          An Updated Review of Lysophosphatidylcholine Metabolism in Human Diseases

          Lysophosphatidylcholine (LPC) is increasingly recognized as a key marker/factor positively associated with cardiovascular and neurodegenerative diseases. However, findings from recent clinical lipidomic studies of LPC have been controversial. A key issue is the complexity of the enzymatic cascade involved in LPC metabolism. Here, we address the coordination of these enzymes and the derangement that may disrupt LPC homeostasis, leading to metabolic disorders. LPC is mainly derived from the turnover of phosphatidylcholine (PC) in the circulation by phospholipase A2 (PLA2). In the presence of Acyl-CoA, lysophosphatidylcholine acyltransferase (LPCAT) converts LPC to PC, which rapidly gets recycled by the Lands cycle. However, overexpression or enhanced activity of PLA2 increases the LPC content in modified low-density lipoprotein (LDL) and oxidized LDL, which play significant roles in the development of atherosclerotic plaques and endothelial dysfunction. The intracellular enzyme LPCAT cannot directly remove LPC from circulation. Hydrolysis of LPC by autotaxin, an enzyme with lysophospholipase D activity, generates lysophosphatidic acid, which is highly associated with cancers. Although enzymes with lysophospholipase A1 activity could theoretically degrade LPC into harmless metabolites, they have not been found in the circulation. In conclusion, understanding enzyme kinetics and LPC metabolism may help identify novel therapeutic targets in LPC-associated diseases.
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            Lysophosphatidic Acid signaling in the nervous system.

            The brain is composed of many lipids with varied forms that serve not only as structural components but also as essential signaling molecules. Lysophosphatidic acid (LPA) is an important bioactive lipid species that is part of the lysophospholipid (LP) family. LPA is primarily derived from membrane phospholipids and signals through six cognate G protein-coupled receptors (GPCRs), LPA1-6. These receptors are expressed on most cell types within central and peripheral nervous tissues and have been functionally linked to many neural processes and pathways. This Review covers a current understanding of LPA signaling in the nervous system, with particular focus on the relevance of LPA to both physiological and diseased states.
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              Brain membrane lipids in major depression and anxiety disorders.

              Major depression and anxiety disorders have high prevalence rates and are frequently comorbid. The neurobiological bases for these disorders are not fully understood, and available treatments are not always effective. Current models assume that dysfunctions in neuronal proteins and peptide activities are the primary causes of these disorders. Brain lipids determine the localization and function of proteins in the cell membrane and in doing so regulate synaptic throughput in neurons. Lipids may also leave the membrane as transmitters and relay signals from the membrane to intracellular compartments or to other cells. Here we review how membrane lipids, which play roles in the membrane's function as a barrier and a signaling medium for classical transmitter signaling, contribute to depression and anxiety disorders and how this role may provide targets for lipid-based treatment approaches. Preclinical findings have suggested a crucial role for the membrane-forming n-3 polyunsaturated fatty acids, glycerolipids, glycerophospholipids, and sphingolipids in the induction of depression- and anxiety-related behaviors. These polyunsaturated fatty acids also offer new treatment options such as targeted dietary supplementation or pharmacological interference with lipid-regulating enzymes. While clinical trials support this view, effective lipid-based therapies may need more individualized approaches. Altogether, accumulating evidence suggests a crucial role for membrane lipids in the pathogenesis of depression and anxiety disorders; these lipids could be exploited for improved prevention and treatment. This article is part of a Special Issue entitled Brain Lipids.
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                Author and article information

                Journal
                Cureus
                Cureus
                2168-8184
                Cureus
                Cureus (Palo Alto (CA) )
                2168-8184
                30 December 2020
                December 2020
                : 12
                : 12
                : e12388
                Affiliations
                [1 ] Department of Pharmacy, University of Asia Pacific, Dhaka, BGD
                Author notes
                Article
                10.7759/cureus.12388
                7849208
                33542861
                0f10e7c8-2144-4312-a4d7-96fda0fcf914
                Copyright © 2020, Riya et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 30 December 2020
                Categories
                Neurology
                Pathology
                Psychiatry

                lysophosphatidic acid,lpa,lysophosphatidylcholine,lpc,major depressive disorder,mdd

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