The relationship between cognitive function and inflammatory-nutritional status in schizophrenia: cognitive impairment is inversely related to PNI and CALLY indices

Cognitive impairment in patients with schizophrenia is one of the symptoms most closely associated with functional loss throughout the disease course. There is increasing evidence suggesting that inflammation and nutritional status may contribute to impaired cognitive functions. The C-reactive protein/albumin ratio (CRP/ALB), prognostic nutritional index (PNI), and C-reactive protein–albumin–lymphocyte index (CALLY index) are easily calculated composite biomarkers reflecting nutritional status and immune-inflammatory processes. This study investigated the associations of the CRP/ALB, PNI, and CALLY indices with cognitive impairment in patients with schizophrenia. A total of 131 individuals (88 schizophrenia patients and 43 healthy controls) were included. Cognitive assessment was performed via the Montreal Cognitive Assessment Scale (MoCA). On the basis of the MoCA, 26 patients had cognitive impairment (SCH-CI), and 62 were classified as schizophrenia patients with preserved cognitive function (SCH-R), and 43 constituted the healthy control (HC) group. Serum ALB, lymphocyte, and CRP levels were first measured. The CRP/ALB ratio, PNI, and CALLY indices were then calculated on the basis of these parameters. Group differences were assessed via statistical analyses. The CRP/ALB ratio was significantly higher in both schizophrenia groups than in the HC group (p2 < 0.001; p3 < 0.001), whereas no significant difference was observed between the SCH-CI and SCH-R groups (p1 = 1.000). The CALLY index was significantly lower in both schizophrenia groups than in the HC group (p2 < 0.001; p3 < 0.001), with no significant unadjusted difference between SCH-CI and SCH-R (p1 = 0.200). PNI values were significantly lower in the SCH-CI group than in both the SCH-R (p1 = 0.008) and HC groups (p2 = 0.013), whereas no significant difference was observed between the SCH-R and HC groups (p3 = 1.000). In multivariable logistic regression analyses adjusted for age, sex, body mass index, smoking status, education year, depot antipsychotic use, and treatment duration, the CALLY index remained independently associated with cognitive impairment (OR = 0.112, 95% CI: 0.013–0.943, p = 0.044), whereas the association for PNI was attenuated to borderline significance (OR = 0.895, 95% CI: 0.800–1.001, p = 0.052). The CRP/ALB ratio was not independently associated with cognitive impairment (OR = 13.363, 95% CI: 0.147–1212.867, p = 0.260). Cognitive impairment in schizophrenia may be associated with disturbances in inflammatory and immunonutritional status. Among the evaluated biomarkers, the CALLY index showed the most robust independent association with cognitive impairment after adjustment for relevant covariates, whereas the association for PNI was weaker. Although these markers are inexpensive and easily obtainable from routine laboratory parameters, their modest discriminatory performance suggests that they may be more useful as supportive or risk-stratification markers than as standalone diagnostic tools. Larger prospective studies are needed to validate their clinical utility.