Correlation of Proline, Kynurenic Acid and Glutamate Levels with Cognitive Function: Insights from Digit Span, TMT and RAVLT in Schizophrenia

<b>Background and Objective:</b> Schizophrenia is a severe and chronic mental disorder which are characterized by delusions, hallucinations, disorganized speech, catatonic behavior, negative symptoms and cognitive symptoms. Several gene polymorphisms and neurotransmitters have been linked to schizophrenia. This study assessed the correlation between proline level, Kynurenic Acid (KYNA) and glutamate level with cognitive function among schizophrenia patients, contributing to understanding biochemical factors associated with cognitive impairments. <b>Materials and Methods:</b> The research was a cross-sectional observational analytic study of 99 patients diagnosed with schizophrenia. Schizophrenia was diagnosed by SCID-1 questionnaire and the patient's blood was taken to be analyzed in the Biochemical Laboratory of Medical Faculty Andalas University using Enzyme-Linked Immunosorbent Assay (ELISA) to characterize kynurenic acid level, glutamate level and proline level. Data were analyzed using Spearman Correlation in SPSS 25.0, with significance at p<0.05. <b>Results:</b> There were 99 schizophrenia patients; most of them were male (62.6%), age median 37 years old and not married (50.5%). The Microproline Level median among participants was 2.64 μg/mL, the median KYNA level was 14.6 nmol/L and the glutamate level was 10.5 μg/mL. Cognitive function was assessed by Rey Auditory Verbal Learning Test (RAVLT), Digit Span Test and Trail Making Test (TMT) with a score median of 4/5/5/5 (Trial 1/2/3/Recall), 6/2 (forward/backward), 68/37 sec (TMT A/B), respectively. Spearman Correlation showed that microproline has a negative correlation with RAVLT Trial 1 (r = -0.221, p = 0.014), Digit Span Backward (r = -0.181, p = 0.036), TMT A (r = 0.204, p = 0.021) and TMT B (r = 0.185, p = 0.034). In contrast, other neurotransmitters do not correlate with any cognitive tests. <b>Conclusion:</b> Proline may play a role in the pathophysiology of cognitive deficits in schizophrenia, highlighting its potential as a target for therapeutic interventions.