M10. SERUM AND CLINICAL MARKERS ASSOCIATED WITH MEMBRANE PUFA CONTENT IN A POPULATION OF STABILISED AND TREATED SCHIZOPHRENIA OUTPATIENTS
Authors: Bosc Nicolas , Adrien Vladimir , Ferreri Florian , Mouchabac Stephane , Fumat Hugo , Lamaziere Antonin , Tareste David , Tessier Cedric , Nuss Philippe 
Published: May 2020

Abstract

Background
Various candidate biomarkers have been proposed in schizophrenia to better characterise the several forms of the disorder. Among these candidates, peripheral (e.g. immunological, inflammatory, microbial) and brain (structural and functional) factors have been suggested and could help subtyping schizophrenia. One other potential biomarker, the membrane polyunsaturated fatty acid (PUFA) content, has been described both in peripheral cells and brain membranes of patients. Increased symptom severity along with more severe cognitive impairment were shown to be associated with decrease in the red blood cell (RBC) membrane sphingomyelin and PUFA content. However, little is known regarding the association between this membrane biomarker and serum related ones.
The results presented here are preliminary and come from a study examining clinical and cognitive symptoms, RBC total membrane fatty-acid (FA) content, and serum biomarkers in a population of schizophrenia patients.
We hypothesised that the sub-group of patients with decreased membrane PUFA content will also exhibit a higher incidence of abnormalities in some other serum biomarkers in comparison with patients with normal membrane PUFA content.

Methods
A population of 33 chronic, medicated, and clinically stable patients with schizophrenia gave their informed consent for a study examining in particular their medical, psychiatric, and treatment history. The other measures assessed psychopathology (PANSS, CGI, Calgary scale), functioning and quality of life (GAF, SF36), and cognition (MOCA, MCST). Various biological biomarkers - in particular those related to inflammation, immunity, energy and hormone metabolism - were also examined. The total RBC membrane FA content was also measured using GC-FID (Gas Chromatography–Flame-Ionization Detection).

Results
Based on the standard values of the docosohexaenoic acid (DHA) (expressed as percentage of total fatty acids) in the RBC lipid membrane, a subgroup of 18 patients exhibited an abnormal decrease in DHA content (DHA-), while the remaining 15 individuals had DHA value within the normal range (DHAn). DHA- and DHAn groups were compared using univariate analysis in terms of other clinical and biological associated characteristics.
We could also demonstrate a decrease in total membrane PUFAs in the DHA- group (p=0.004). Of interest, serum IL-6 was significantly (p=0.02) increased in the DHA- population. There was also a trend in favour of an increase in serum TNF-alpha in DHA- (mean value 30.5 vs 21 in DHA- and DHAn, respectively). In addition, the DHA- group have had significantly (p=0.03) more hospitalisations since the beginning of the disorder. The duration of untreated psychosis was 4 years vs 1 year in the DHA- vs DHAn groups, respectively. The same applied for the mean duration of hospitalisations (45 vs 34 days in DHA- vs DHAn). These values could not be explained by a longer duration in disease treatment in the 2 subpopulations.

Discussion
The presented data are in accordance with repeated findings showing decreased RBC membrane DHA and total PUFA content in a subgroup of individuals meeting criteria for schizophrenia. The splitting of the studied population into 2 groups numerically comparable as a function of their RBC membrane DHA content was thus justified. Interestingly, patients with lower membrane DHA content also exhibited abnormalities in other known biomarkers described in schizophrenia such as increased inflammation and disease severity. The presented data also show for the first time a biomarker associated with the duration of untreated psychosis. Altogether, these results, despite preliminary, are paving the way towards the identification of schizophrenia subtypes.