Plasma prolidase levels are high in schizophrenia but not in first-episode psychosis

Abstract

An increasing number of studies have focussed on the neurobiology of schizophrenia (SCH), contributing to a better understanding of this disorder. Prolidase is a metalloprotease found in various tissues, which has been associated with the concentrations of proline, a neurotransmitter, in the brain. There is evidence to suggest that elevated proline levels play a role in SCH. The aim of the present study was to compare plasma proline levels in patients with drug-naive first-episode psychosis (FEP) and in those with SCH. Patients diagnosed with FEP (n = 26) and SCH (n = 26) were recruited for this study, in addition to healthy control volunteers (n = 26). Plasma prolidase levels were found to be elevated in the SCH group compared to drug-naive FEP and healthy control groups. This finding indicates that prolidase levels are higher in SCH patients, while levels in patients with drug-naive FEP are similar to those of healthy control. Follow-up studies are needed to provide a better understanding of prolidase in the etiopathogenesis of SCH.

Clinical Utility of Fluid Biomarker in Depressive Disorder

“…Biomarker investigations spanned across a large range of possible targets. Peripheral biomarkers, which is mainly the topic of the present paper, mainly include analyses on blood samples, such as DNA variants and Polygenic Risk Scores, gene expression, mRNA, non coding RNA, DNA methylation, proteins/peptides (e.g., immunological and metabolic factors), but we should also mention analyses not on body fluids such as post mortem tissues, imaging, electroencephalogram, cognitive, neuropsychological and clinical features [11,[14][15][16][17][18][19][20]. Those are not discussed in the present review but will probably be used in combination with peripheral biomarkers, as will be shown later.…”

Assessing the relationship between antipsychotic drug use and prolidase enzyme activity and oxidative stress in schizophrenia patients: a case-control study

“…Although genetic and environmental factors are thought to play a role in the pathogenesis of this devastating disease, the etiopathology of schizophrenia remains unclear (Bai et al , 2018). The most common hypothesis on the pathogenesis of schizophrenia is the presence of abnormalities in glutamatergic synapses (Bolu et al , 2021). There is also growing evidence that oxidative stress plays an important role in the pathogenesis of schizophrenia (Guidara et al , 2020; Hurşitoğlu et al , 2021; Yang et al , 2022).…”

“…Prolidase enzyme is a member of the matrix metalloproteinase family and is present in many tissues including erythrocytes, leukocytes, fibroblasts, and plasma as well as brain, intestinal mucosa, liver, kidney, uterus, thymus, and heart (Zanaboni et al , 1994; Wilk et al , 2021; Abdullah et al , 2022). Prolidase enzyme in the brain takes part in the regulation of proline levels, which is considered a neurotransmitter in the central nervous system (Bolu et al , 2021). Defective proline metabolism was shown to be associated with various psychiatric pathologies including schizophrenia and behavioral disorders (Mitsubuchi et al , 2008; Wyse and Netto, 2011; Güneş et al , 2016a).…”

“…Defective proline metabolism was shown to be associated with various psychiatric pathologies including schizophrenia and behavioral disorders (Mitsubuchi et al , 2008; Wyse and Netto, 2011; Güneş et al , 2016a). The increase in proline levels caused by the increase in prolidase enzyme activity is believed to cause impairment in glutamatergic/N-methyl d -aspartate receptor/dopaminergic signaling pathways, which are thought to be involved in the etiology and pathophysiological mechanisms of schizophrenia (Javitt, 2007; Nagaoka et al , 2020; Bolu et al , 2021). It was also shown that elevated proline levels caused an increase in oxidative stress in the brain (Delwing et al , 2003; Bahceci et al , 2015), while decreasing acetylcholinesterase activity (Delwing et al , 2005).…”

“…Aldehyde dehydrogenase 4 family member A1 (ALDH4A1), an enzyme responsible for dehydrogenating glutamic-γ-semialdehyde, a metabolite involved in the conversion of proline to glutamate, has been found to be significantly elevated in the brains of patients with schizophrenia (Hirayama-Kurogi et al , 2017; Nagaoka et al , 2020). Several studies reported that serum prolidase enzyme activity (SPEA) in psychotic individuals were found to be higher than in healthy individuals (Selek et al , 2011; Güneş et al , 2016a; Bolu et al , 2021).…”