Phospholipids and insulin resistance in psychosis: A lipidomics study of twin pairs discordant for schizophrenia

Matej Orešič (Corresponding Author), Tuulikki Seppänen-Laakso, Daqiang Sun, Jing Tang, Sebastian Therman, Rachel Viehman, Ulla Mustonen, Theo G. van Erp, Tuulia Hyötyläinen, Paul Thompson, Arthur W. Toga, Matti O. Huttunen, Jaana Suvisaari, Jaakko Kaprio, Jouko Lönnqvist, Tyrone D. Cannon

    Research output: Contribution to journalArticleScientificpeer-review

    80 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

    Funding

    This work was in part supported by the EU-funded projects ETHERPATHS (FP7-KBBE-22263 to MO) and TORNADO (FP7-KBBE-222720 to MO) and the Academy of Finland Centre of Excellence in Complex Disease Genetics.

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