Membrane lipidomics in schizophrenia patients: a correlational study with clinical and cognitive manifestations

Abstract

Schizophrenia is a severe mental condition in which several lipid abnormalities—either structural or metabolic—have been described. We tested the hypothesis that an abnormality in membrane lipid composition may contribute to aberrant dopamine signaling, and thereby symptoms and cognitive impairment, in schizophrenia (SCZ) patients. Antipsychotic-medicated and clinically stable SCZ outpatients (n=74) were compared with matched healthy subjects (HC, n=40). A lipidomic analysis was performed in red blood cell (RBC) membranes examining the major phospholipid (PL) classes and their associated fatty acids (FAs). Clinical manifestations were examined using the positive and negative syndrome scale (PANSS). Cognitive function was assessed using the Continuous Performance Test, Salience Attribution Test and Wisconsin Card Sorting Test. Sphingomyelin (SM) percentage was the lipid abnormality most robustly associated with a schizophrenia diagnosis. Two groups of patients were defined. The first group (SCZ c/SM−) is characterized by a low SM membrane content. In this group, all other PL classes, plasmalogen and key polyunsaturated FAs known to be involved in brain function, were significantly modified, identifying a very specific membrane lipid cluster. The second patient group (SCZ c/SM+) was similar to HCs in terms of RBC membrane SM composition. Compared with SCZ c/SM+, SCZ c/SM− patients were characterized by significantly more severe PANSS total, positive, disorganized/cognitive and excited psychopathology. Cognitive performance was also significantly poorer in this subgroup. These data show that a specific RBC membrane lipid cluster is associated with clinical and cognitive manifestations of dopamine dysfunction in schizophrenia patients. We speculate that this membrane lipid abnormality influences presynaptic dopamine signaling.

Lipidome alterations in human prefrontal cortex during development, aging, and cognitive disorders

“…Lipid concentration changes were reported for specific lipid classes in many cognitive disorders, including SZ [21][22][23][24][25][26][27]62], ASD [19,20], DS [18], bipolar disorder [26,63], and Alzheimer's disease [64]. In our study, 27 SZ, 17 ASD and five DS patients samples were measured together with the control group in a random order.…”

“…These studies, however, focused on specific lipid classes and had limited sample and age representation. Alterations of lipid compositions were reported to be associated with cognitive disorders, including autism (ASD), schizophrenia (SZ), and Down syndrome (DS), by studies examining lipid concentrations in the blood [18][19][20][21][22][23][24][25] and brain [26,27].…”

Changes in the blood plasma lipidome associated with response to atypical antipsychotic treatments in schizophrenia

“…Study showed changes in the expression of genes associated with sphingolipid metabolism in the prefrontal cortex (Narayan et al, 2009) and skin (Smesny et al, 2013) from schizophrenia patients. In addition, a lipidomic study reported a decrease of SM in red blood cells (RBCs) membranes of schizophrenia patients compared to controls (Tessier et al, 2016). A postmortem study also found decreased SM in brain samples of schizophrenia patients (Schmitt et al, 2004).…”

A Perspective: Active Role of Lipids in Neurotransmitter Dynamics

“…Recent lipidomics studies have led to the vast and rapid expansion of the available data on various organs, tissues, cell types, and cell organelles [82,83]. Similarly, data concerning lipidome changes in pathological states, including neurological and mental disorders, provide new insight into the possible role of lipids in neuronal tissues [84][85][86][87][88][89]. Although no direct link has been established so far, it is easy to fathom how an imbalance in the strength of NT-membrane partitioning could contribute to, for example, major depressive disorder or Parkinson's disease.…”