Background
Based upon the concept of a prodromal risk syndrome for first psychosis, intense efforts are being applied to define potential biomarkers of disease onset in schizophrenia. One such tentative biomarker may be plasmalogens, complex structural glycerophospholipids that serve multiple functions in all cells.
Methods
To further investigate this possibility, we undertook a lipidomics analysis of choline and ethanolamine plasmalogens in the plasma and platelets of 23 patients with schizophrenia and 27 age-matched controls.
Results
Plasma levels of both choline and ethanolamine plasmalogens were decreased by 23 to 45% in patients with schizophrenia. In platelets, from patients with schizophrenia, ethanolamine plasmalogens also were decreased while choline plasmalogen levels were increased. Levels of docosahexaenoic acid (DHA) were decreased by approximately 30% both in plasma and platelets.
Conclusions
Our results suggest that alterations in lipid transport or lipid remodeling/metabolism of plasmalogens are present in schizophrenia and that changes in the steady-state levels of these complex lipid pools may be involved in altered neuronal function.
Schizophrenia is a chronic debilitating mental illness that affects approximately 1% of the world's population (an der Heiden and Häfner, 2000 and Saha et al., 2007). Integration of current clinical research data has led to the concept that schizophrenia may be a neurodevelopmental disorder that results in abnormal neuronal circuits supporting sensory processing, cognition, and emotion (Lewis and Sweet, 2009 and Insel, 2009). Discovery of the underlying biochemical processes responsible for this dysfunction in the development of brain neuronal circuits has remained elusive despite intensive research efforts (Oertel-Knöchel et al., 2011). Furthermore, since early intervention has already been demonstrated to lead to increased clinical success in the treatment of young patients with schizophrenia (McFarlane et al., 2014), it is important to define biomarkers of the prodromal phase of the disease (Woods et al., 2009).
In this regard, decreased circulating plasmalogens have been demonstrated in first onset and recurrent schizophrenia patients (Kaddurah-Daouk et al., 2012). Plasmalogens are complex structural glycerophospholipids that possess a vinyl-ether linked fatty alcohol at the sn-1 position of the glycerol backbone and either phosphoethanolamine or phosphocholine at sn-3 (Wood, 2012). Plasmalogens also serve as reservoirs for fatty acid mediators such as arachidonic acid and docosahexaenoic acid (DHA) which are released from the sn-2 position of the glycerol backbone via phospholipases in a dynamic deacylation–reacylation cycle termed “lipid remodeling” (Wood, 2012). As major components of membranes, plasmalogens are essential for membrane fluidity, lipid raft formation, membrane fusion for neurotransmitter release, ion transport, and regulation of cholesterol efflux (Wood, 2012). Plasmalogens are also essential in brain development, both in white and gray matter (Niemoller and Bazan, 2010 and Aubourg and Wanders, 2013).
In this study, we undertook a validation of the findings of reduced circulating plasmalogens by Kaddurah-Daouk et al. (2012). Since circulating plasmalogens are derived mainly from the liver and gastrointestinal epithelium (Wood, 2012), we also evaluated cellular plasmalogens in platelets, which possess the cellular machinery required for plasmalogen synthesis.
