Evaluation of the universality of NMR metabolic fingerprints of schizophrenia

Abstract

Schizophrenia (SCZ) is a very disabling mental disorder whose molecular basis is a combination of many factors still not completely understood, with a diagnosis based on observed behavior, the person's reported experiences and reports of others that are familiar with the person, with no objective test. Also, up to date, there are no reliable markers for monitoring the SCZ. NMR-metabolomics [1] reported in 2017 bring some of the possible markers from blood serum of SCZ individuals linked strongly with known dopamine, glutamate and GABA dysfunction in SCZ. As to verify if these findings are universal, we have compared the SCZ patients from geographically different environments and cited interesting SCZ characteristics. The first set of samples was collected in Belgrade, Serbia. 14 mental health patients (50% male) with 52.86 ± 7.27 years of age had a confirmed diagnosis of SCZ. The control group of 13 healthy individuals (69% male) had none of psychotic disorders, and individuals were 23.07 ± 2.79 years of age. Blood serum samples were collected and prepared for the analysis following the published methodology [1, 2]. NMR spectra were measured on a Bruker AVANCE III spectrometer (500.26 MHz for 1H). The spectra were acquired at 298 K with 128 scans and 32 k. The serum samples were prepared and measured as triplicates. On the other side, the group of individuals from Brazil that was matched in number, age, gender and history of mental illness with individuals from Serbia was previously described [1]. 1H NMR spectra were phase and baseline corrected using MestreNova and the lactate doublet was used as the chemical shift reference. The data were binned (0.005 ppm) in a spectral range 0.50 - 9.00 ppm, while the residual HDO peak (4.50-5.00 ppm) was excluded. Then, the data were normalized by the sum equal to 1000, the variables were mean centered and PCA and PLS-DA were performed using MATLAB. It was shown that the mental health patients have clearly different blood serum metabolites when compared to the healthy ones independently from where the samples were obtained with almost identical marker set. Also, it was shown that the samples are different metabolically when Brazilian and Serbian samples were compared. 1] L. Tasic et al., Schizophrenia Research 2017, 185, 182. [2] J. Pontes et al., Analytical Methods 2017, 9, 1078.