Phospholipids and insulin resistance in psychosis: a lipidomics study of twin pairs discordant for schizophrenia
1 VTT Technical Research Centre of Finland, Tietotie 2, Espoo, FI-02044 VTT, Finland
2 Department of Psychology, University of California Los Angeles, Los Angeles, 5586 Franz Hall, Los Angeles, CA 90089, USA
3 Department of Mental Health and Alcohol Research, National Institute for Health and Welfare, Lintulahdenkuja 4, Helsinki, FI-00271, Finland
4 Department of Psychiatry and Human Behavior, University of California Irvine, 5251 California Avenue, Irvine, CA 92697, USA
5 Department of Neurology and Laboratory of NeuroImaging, University of California Los Angeles, 635 Charles E. Young Drive South, Los Angeles, CA 90095-7332, USA
6 Department of Public Health, University of Helsinki, Haartmaninkatu 8, Helsinki, FI-00290, Finland
7 Department of Psychiatry, Helsinki University Hospital, Välskärinkatu 12, Helsinki, FI-00029, Finland
8 Department of Psychiatry and Biobehavioral Sciences, University of California Los Angeles, 760 Westwood Plaza, Los Angeles, CA 90095, USA
Genome Medicine 2012, 4:1 doi:10.1186/gm300Published: 18 January 2012
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.
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.
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.
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.