Reduced serum Klotho in chronic schizophrenia: diagnostic value and association with cognitive impairment

To investigate the correlation between serum Klotho levels and cognitive function in individuals with chronic Schizophrenia (SZ).

A total of 108 patients diagnosed with chronic SZ and 83 age-matched healthy controls were recruited from four psychiatric specialist hospitals in Lianyungang from January to December 2024. Serum Klotho levels were measured using an enzyme-linked immunosorbent assay. Psychopathology and cognitive function were assessed using the Positive and Negative Syndrome Scale and the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), respectively. Kendall's tau-b correlation analyses were conducted to assess the associations between serum Klotho levels and cognitive function.

Compared with healthy controls, patients with SZ had significantly lower serum Klotho levels (233.61 ± 50.35 pg/mL vs 347.11 ± 62.64 pg/mL, P < 0.001). They also showed significantly lower total scores in the overall cognitive performance and across the RBANS sub-domains (all P < 0.01). ROC curve analysis revealed that serum Klotho levels discriminated patients with schizophrenia from healthy controls with an AUC of 0.914 (95% CI: 0.876-0.951), with an optimal cutoff of 268.25 pg/mL (sensitivity 76.9%, specificity 89.2%). After Bonferroni correction, serum Klotho levels were positively correlated with immediate memory in patients (corrected P = 0.010). No significant associations between serum Klotho levels and cognitive measures were found in healthy controls.

Patients with chronic SZ have lower serum Klotho levels and show cognitive impairment, and Klotho levels are specifically associated with immediate memory in this population.