Cognitive functions in schizophrenia: the interplay between blood viscosity, serum osmolarity, and symptom severity

Abstract

Objective Cognitive impairments-especially in executive function and attention-are core features of schizophrenia and major barriers to functional recovery. Although systemic physiological factors such as blood viscosity and serum osmolarity have been implicated in schizophrenia, their association with cognitive deficits remains largely unexplored. This study aimed to investigate these relationships in male patients with schizophrenia in remission. Methods A total of 247 male patients diagnosed with schizophrenia in remission were recruited. Cognitive performance was assessed using the Frontal Assessment Battery (FAB), Stroop Test, and Trail Making Test (TMT). Hemorheological parameters, including whole blood viscosity (WBV) at low and high shear rates (LSR and HSR), and serum osmolarity were calculated. Regression analyses were conducted to determine predictors of cognitive outcomes. Results In the multivariate analysis, higher WBV at HSR (beta = 0.122, beta = 0.037) was positively associated with executive function (FAB scores) and inversely associated with Stroop 5 time (beta = -0.134, p = 0.025), TMT-A (beta = -0.134, p = 0.032), and TMT-B (beta = -0.137, p = 0.028) completion times, reflecting better cognitive performance. While higher serum osmolarity showed a positive correlation with FAB scores in univariate analysis, it did not remain an independent predictor in the multivariate model. The multivariate regression identified WBV at HSR, depressive symptoms, negative symptoms, use of long-acting injectable antipsychotics (LAI), and living arrangements as significant predictors of FAB scores, collectively explaining 16.9% of the variance (F(8,238) = 7.252, p < 0.001). Conclusion This study highlights the potential contribution of systemic physiological factors to cognitive function in schizophrenia. Higher WBV, within a physiological range, may support cerebral perfusion and be associated with better executive performance. Although serum osmolarity showed a positive association with executive function in univariate analysis, it was not an independent predictor in multivariate models, and its cognitive relevance remains to be clarified. These findings point to a possible role of physiological parameters in cognitive variability, but further studies are needed before drawing firm clinical implications.