Phospholipids and insulin resistance in psychosis

A lipidomics study of twin pairs discordant for schizophrenia

Matej Orešič (Corresponding Author), Tuulikki Seppänen-Laakso, D. Sun, Jing Tang, S. Therman, R. Viehman, U. Mustonen, T.G.M. van Erp, Tuulia Hyötyläinen, P. Thompson, A.W. Toga, M.O. Huttunen, J. Suvisaari, J. Kaprio, J. Lönnqvist, T.D. Cannon

Research output: Contribution to journalArticleScientificpeer-review

53 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number1
Number of pages11
JournalGenome Medicine
Volume4
DOIs
Publication statusPublished - 2012
MoE publication typeA1 Journal article-refereed

Fingerprint

Twin Studies
Psychotic Disorders
Insulin Resistance
Phospholipids
Schizophrenia
Lysophosphatidylcholines
Prostaglandins
Synaptic Transmission
Essential Fatty Acids
Phospholipases A2
Pathologic Processes
Blood-Brain Barrier
Serum
Unsaturated Fatty Acids
Liquid Chromatography
Mass Spectrometry
Triglycerides
Hydrolysis
Magnetic Resonance Spectroscopy
Insulin

Cite this

Orešič, Matej ; Seppänen-Laakso, Tuulikki ; Sun, D. ; Tang, Jing ; Therman, S. ; Viehman, R. ; Mustonen, U. ; van Erp, T.G.M. ; Hyötyläinen, Tuulia ; Thompson, P. ; Toga, A.W. ; Huttunen, M.O. ; Suvisaari, J. ; Kaprio, J. ; Lönnqvist, J. ; Cannon, T.D. / Phospholipids and insulin resistance in psychosis : A lipidomics study of twin pairs discordant for schizophrenia. In: Genome Medicine. 2012 ; Vol. 4.
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title = "Phospholipids and insulin resistance in psychosis: A lipidomics study of twin pairs discordant for schizophrenia",
abstract = "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.",
author = "Matej Orešič and Tuulikki Sepp{\"a}nen-Laakso and D. Sun and Jing Tang and S. Therman and R. Viehman and U. Mustonen and {van Erp}, T.G.M. and Tuulia Hy{\"o}tyl{\"a}inen and P. Thompson and A.W. Toga and M.O. Huttunen and J. Suvisaari and J. Kaprio and J. L{\"o}nnqvist and T.D. Cannon",
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Orešič, M, Seppänen-Laakso, T, Sun, D, Tang, J, Therman, S, Viehman, R, Mustonen, U, van Erp, TGM, Hyötyläinen, T, Thompson, P, Toga, AW, Huttunen, MO, Suvisaari, J, Kaprio, J, Lönnqvist, J & Cannon, TD 2012, 'Phospholipids and insulin resistance in psychosis: A lipidomics study of twin pairs discordant for schizophrenia', Genome Medicine, vol. 4, 1. https://doi.org/10.1186/gm300

Phospholipids and insulin resistance in psychosis : A lipidomics study of twin pairs discordant for schizophrenia. / Orešič, Matej (Corresponding Author); Seppänen-Laakso, Tuulikki; Sun, D.; Tang, Jing; Therman, S.; Viehman, R.; Mustonen, U.; van Erp, T.G.M.; Hyötyläinen, Tuulia; Thompson, P.; Toga, A.W.; Huttunen, M.O.; Suvisaari, J.; Kaprio, J.; Lönnqvist, J.; Cannon, T.D.

In: Genome Medicine, Vol. 4, 1, 2012.

Research output: Contribution to journalArticleScientificpeer-review

TY - JOUR

T1 - Phospholipids and insulin resistance in psychosis

T2 - A lipidomics study of twin pairs discordant for schizophrenia

AU - Orešič, Matej

AU - Seppänen-Laakso, Tuulikki

AU - Sun, D.

AU - Tang, Jing

AU - Therman, S.

AU - Viehman, R.

AU - Mustonen, U.

AU - van Erp, T.G.M.

AU - Hyötyläinen, Tuulia

AU - Thompson, P.

AU - Toga, A.W.

AU - Huttunen, M.O.

AU - Suvisaari, J.

AU - Kaprio, J.

AU - Lönnqvist, J.

AU - Cannon, T.D.

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

U2 - 10.1186/gm300

DO - 10.1186/gm300

M3 - Article

VL - 4

JO - Genome Medicine

JF - Genome Medicine

SN - 1756-994X

M1 - 1

ER -