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Phospholipids and insulin resistance in psychosis: a lipidomics study of twin pairs discordant for schizophrenia
Open accessAbstract
BACKGROUND: Several theories have been proposed to conceptualize the pathological processes inherent to schizophrenia. The 'prostaglandin deficiency' hypothesis postulates that defective enzyme systems converting essential fatty acids to prostaglandins lead to diminished levels of prostaglandins, which in turn affect synaptic transmission. METHODS: Here we sought to determine the lipidomic profiles associated with schizophrenia in twin pairs discordant for schizophrenia as well as unaffected twin pairs. The study included serum samples from 19 twin pairs discordant for schizophrenia (mean age 51 ± 10 years; 7 monozygotic pairs; 13 female pairs) and 34 age and gender matched healthy twins as controls. Neurocognitive assessment data and gray matter density measurements taken from high-resolution magnetic resonance images were also obtained. A lipidomics platform using ultra performance liquid chromatography coupled to time-of-flight mass spectrometry was applied for the analysis of serum samples. RESULTS: In comparison to their healthy co-twins, the patients had elevated triglycerides and were more insulin resistant. They had diminished lysophosphatidylcholine levels, which associated with decreased cognitive speed. CONCLUSIONS: Our findings may be of pathophysiological relevance since lysophosphatidylcholines, byproducts of phospholipase A2-catalyzed phospholipid hydrolysis, are preferred carriers of polyunsaturated fatty acids across the blood-brain barrier. Furthermore, diminishment of lysophosphatidylcholines suggests that subjects at risk of schizophrenia may be more susceptible to infections. Their association with cognitive speed supports the view that altered neurotransmission in schizophrenia may be in part mediated by reactive lipids such as prostaglandins.
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“Nine studies evaluated the broad panels of different lipid markers in patients with SCZ [31,34,40,41,42,43,44,45,46] and detected statistical differences in the following lipid classes: fatty acyls, sterols, glycerolipids, sphingolipids, glycerophospholipids, and products of lipid metabolism.”
From Lipids in Psychiatric Disorders: Functional and Potential Diagnostic Role as Blood Biomarkers (2024) · cites this paper as [43]
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Metadata
- Authors
- Orešič, M., Seppänen-Laakso, T., Sun, D., Tang, J., Therman, S., Viehman, R., Mustonen, U., van Erp, T. G., Hyötyläinen, T., Thompson, P., Toga, A. W., Huttunen, M. O., Suvisaari, J., Kaprio, J., Lönnqvist, J., & Cannon, T. D.
- Affiliations
- VTT Technical Research Centre of Finland (FI)
- University of California, Los Angeles (US)
- Finnish Institute for Health and Welfare (FI)
- University of Helsinki (FI)
- Helsinki University Hospital (FI)
- Corresponding author
- Orešič, Matej
- ORCID
- Venue
- Genome Medicine
- Published
- 2012-01-18
- Volume
- 4
- Issue
- 1
- Pages
- 1-1
- ISSN
- 1756-994X (ISSN-L)
- PMC
- PMC3334549
- OpenAlex
- W1272423043
- Cited by
- 5
- References
- 45
- Citations by year
- 2024: 1 · 2020: 3 · 2018: 1
- FWCI
- 0.00
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Genome Medicine (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Työväentutkimus Vuosikirja (submittedVersion)
- STM:n Hallinnonalan avoin julkaisuarkisto (Julkari) (submittedVersion)
- Funders
- European Commission (222720)
- Academy of Finland
- FP7 Food, Agriculture and Fisheries, Biotechnology
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Keywords
- schizophrenia, insulin resistance, phospholipids, lysophosphatidylcholine, serum lipidomics, twin discordance, triglycerides, cognitive speed, phospholipase A2, polyunsaturated fatty acids, blood-brain barrier, gray matter density, neurocognitive function
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