Phospholipid, arachidonate and eicosanoid signaling in schizophrenia

Messamore, Erik; Yao, Jeffrey

doi:10.1051/ocl/2015054

Cited by 11 publications

(12 citation statements)

References 79 publications

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“…Messamore and Yao (Messamore and Yao, 2016) propose a model relating abnormal levels of phospholipid signalling to neurochemical abnormalities observed in schizophrenia. The model links the low levels of phospholipids, high levels of LPC and low levels of arachidonic acid found in schizophrenia patients with levels of neuroactive molecules, including dopamine and glutamate, and several neuronal signalling pathways.…”

Section: Membrane Phospholipid Hypothesismentioning

confidence: 99%

A systematic review of metabolite biomarkers of schizophrenia

Davison

O’Gorman

Brennan

et al. 2018

Schizophrenia Research

116

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Current diagnosis of schizophrenia relies exclusively on the potentially subjective interpretation of clinical symptoms and social functioning as more objective biological measurement and medical diagnostic tests are not presently available. The use of metabolomics in the discovery of disease biomarkers has grown in recent years. Metabolomic methods could aid in the discovery of diagnostic biomarkers of schizophrenia. This systematic review focuses on biofluid metabolites associated with schizophrenia. A systematic search of Web of Science and Ovid Medline databases was conducted and 63 studies investigating metabolite biomarkers of schizophrenia were included. A review of these studies revealed several potential metabolite signatures of schizophrenia including reduced levels of essential polyunsaturated fatty acids (EPUFAs), vitamin E and creatinine; and elevated levels of lipid peroxidation metabolites and glutamate. Further research is needed to validate these biomarkers and would benefit from large cohort studies and more homogeneous and well-defined subject groups.

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Section: Membrane Phospholipid Hypothesismentioning

confidence: 99%

A systematic review of metabolite biomarkers of schizophrenia

Davison

O’Gorman

Brennan

et al. 2018

Schizophrenia Research

116

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“…The levels of AA have been consistently reported to be lower in patients with schizophrenia versus control individuals, and the alteration of AA is consistent in the literature 50 , 51 . Most recently, Messamore and Yao showed a link between altered AA and a sub-type of schizophrenia 52 . The reduced levels of PUFAs in schizophrenia therefore suggest the therapeutic potential of some PUFA species in the disease 53 ; (2) Phospholipids.…”

Section: Implications Perspectives and Challenges Of The Aberrant Lmentioning

confidence: 99%

Lipidomics of the brain, retina, and biofluids: from the biological landscape to potential clinical application in schizophrenia

et al. 2020

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Schizophrenia is a serious neuropsychiatric disorder, yet a clear pathophysiology has not been identified. To date, neither the objective biomarkers for diagnosis nor specific medications for the treatment of schizophrenia are clinically satisfactory. It is well accepted that lipids are essential to maintain the normal structure and function of neurons in the brain and that abnormalities in neuronal lipids are associated with abnormal neurodevelopment in schizophrenia. However, lipids and lipid-like molecules have been largely unexplored in contrast to proteins and their genes in schizophrenia. Compared with the gene- and protein-centric approaches, lipidomics is a recently emerged and rapidly evolving research field with particular importance for the study of neuropsychiatric disorders such as schizophrenia, in which even subtle aberrant alterations in the lipid composition and concentration of the neurons may disrupt brain functioning. In this review, we aimed to highlight the lipidomics of the brain, retina, and biofluids in both human and animal studies, discuss aberrant lipid alterations in correlation with schizophrenia, and propose future directions from the biological landscape towards potential clinical applications in schizophrenia. Recent studies are in support of the concept that aberrations in some lipid species [e.g. phospholipids, polyunsaturated fatty acids (PUFAs)] lead to structural alterations and, in turn, impairments in the biological function of membrane-bound proteins, the disruption of cell signaling molecule accessibility, and the dysfunction of neurotransmitter systems. In addition, abnormal lipidome alterations in biofluids are linked to schizophrenia, and thus they hold promise in the discovery of biomarkers for the diagnosis of schizophrenia.

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“…On the other hand, another plausible mechanism by which neurosteroids could exert neuroprotective effects involves their capacity to modulate polyunsaturated fatty acid (PUFA) metabolism. As a major component of neuron membranes in the brain, long-chain PUFAs play a key role in the maintenance of brain functions, and dysregulation of PUFAs has consistently been observed in SZ ( 27 , 29 , 32 ). Estradiol is able to enhance the synthesis of linolenic acid elongation products, including eicosapentaenoic acid, docosapentaenoic acid, and docosahexaenoic acid in neuroblastoma cells, thereby suggesting that neurosteroids may regulate PUFA synthesis ( 116 ).…”

Section: Mechanisms Underlying Neurosteroid Actionsmentioning

confidence: 99%

“…In addition, many other theories have been proposed in SZ over the years that aim to characterize the inherent pathological processes related to altered neurotransmission and signal transduction, including autoimmune dysfunction, membrane phospholipids deficits, etc. ( 27 – 32 ). However, many metabolic pathways which are likely modified by current treatment and of what relevance they are to clinical outcome remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Neurosteroids in Schizophrenia: Pathogenic and Therapeutic Implications

et al. 2018

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Neurosteroids are a group of important endogenous molecules affecting many neural functions in the brain. Increasing evidence suggests a possible role of these neurosteroids in the pathology and symptomatology of schizophrenia (SZ) and other mental disorders. The aim of this review is to summarize the current knowledge about the neural functions of neurosteroids in the brain, and to evaluate the role of the key neurosteroids as candidate modulators in the etiology and therapeutics of SZ. The present paper provides a brief introduction of neurosteroid metabolism and distribution, followed by a discussion of the mechanisms underlying neurosteroid actions in the brain. The content regarding the modulation of the GABAA receptor is elaborated, given the considerable knowledge of its interactions with other neurotransmitter and neuroprotective systems, as well as its ameliorating effects on stress that may play a role in the SZ pathophysiology. In addition, several preclinical and clinical studies suggested a therapeutic benefit of neurosteroids in SZ patients, even though the presence of altered neurosteroid pathways in the circulating blood and/or brain remains debatable. Following treatment of antipsychotic drugs in SZ, therapeutic benefits have also been linked to the regulation of neurosteroid signaling. Specifically, the neurosteroids such as pregnenolone and dehydroepiandrosterone affect a broad spectrum of behavioral functions through their unique molecular characteristics and may represent innovative therapeutic targets for SZ. Future investigations in larger cohorts with long-term follow-ups will be required to ascertain the neuropsychopharmacological role of this yet unexploited class of neurosteroid agents.

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Phospholipid, arachidonate and eicosanoid signaling in schizophrenia

Cited by 11 publications

References 79 publications

A systematic review of metabolite biomarkers of schizophrenia

A systematic review of metabolite biomarkers of schizophrenia

Lipidomics of the brain, retina, and biofluids: from the biological landscape to potential clinical application in schizophrenia

Neurosteroids in Schizophrenia: Pathogenic and Therapeutic Implications

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