Disruption of the Prolidase–Proline–PRODH Axis and Oxidative Stress in Schizophrenia

INTRODUCTION: This study aimed to investigate serum levels of proline, prolidase, proline dehydrogenase (PRODH), and reactive oxygen species (ROS) in patients with schizophrenia and healthy controls, to evaluate potential differences between groups and to examine the interrelationships among these biomarkers that may be associated with the pathophysiology of schizophrenia. METHODS: A total of individuals aged 18–65 years were enrolled and divided into two groups. The patient group consisted of 85 individuals diagnosed with schizophrenia according to the DSM-5 criteria, while the control group included 74 healthy volunteers with no history of psychiatric disorders. Clinical assessments, including the Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression Scale (CGI), Sheehan Disability Scale, Calgary Depression Scale for Schizophrenia, and Hamilton Anxiety Rating Scale, were administered exclusively to the patient group. Serum levels of proline, prolidase, PRODH, and ROS were measured, and statistical analyses were performed using SPSS version 24.0. RESULTS: Patients with schizophrenia showed significantly lower serum proline, prolidase activity, PRODH, and ROS levels compared with healthy controls (all p ≤ 0.005). Biochemical parameters were strongly intercorrelated within both groups, but none were associated with clinical symptom severity or functional outcomes. DISCUSSION AND CONCLUSION: The significantly reduced serum prolidase levels observed in patients with schizophrenia, together with the strong positive correlations between prolidase and proline, PRODH, and ROS, suggest a dysregulation of prolidase activity in schizophrenia. This dysregulation may exert downstream effects on proline metabolism and oxidative stress pathways, thereby contributing to the underlying pathophysiological mechanisms of the disorder.