In the realm of psychiatric disorders, schizophrenia stands out as one of the most complex and debilitating conditions, marked not only by hallucinations and delusions but also by profound impairments in cognitive functions. Executive function and attention deficits, in particular, have long been recognized as core hurdles, interfering with patients’ recovery and quality of life. Despite decades of clinical and neuroscientific research, the physiological underpinnings that shape these cognitive impairments remain incompletely understood. A groundbreaking study published in BMC Psychiatry in 2025 sheds new light on the intricate biological interplay affecting cognition in schizophrenia, exploring the often-overlooked role of systemic blood properties—specifically blood viscosity and serum osmolarity—in executive functioning among male patients in remission.
Traditionally, research into schizophrenia’s cognitive deficits has primarily focused on neurochemical and neuroanatomical factors. However, recent advances have prompted scientists to examine systemic physiological contributors, highlighting that brain function does not operate in isolation but depends intimately on whole-body vascular health and blood characteristics. The study led by Özönder Ünal and colleagues investigated how hemorheological parameters—properties that determine blood flow dynamics—might influence cognitive performance in schizophrenia, a novel perspective that bridges neurology and hematology.
The study enrolled 247 male patients diagnosed with schizophrenia who were in remission, thereby isolating cognitive variability not confounded by acute psychotic episodes. Cognitive performance was rigorously evaluated using three established neuropsychological tools: the Frontal Assessment Battery (FAB), which assesses executive function; the Stroop Test, measuring cognitive inhibition and selective attention; and the Trail Making Test (TMT), which gauges cognitive flexibility and processing speed. These assessments provided a multidimensional profile of participants’ cognitive capacities.
A centerpiece of the research was the measurement of whole blood viscosity (WBV) at both low and high shear rates—conditions mimicking different blood flow states within cerebral vessels. Additionally, serum osmolarity was calculated to assess the concentration of solutes in the blood, which could affect fluid balance within the brain and impact neuronal function. This approach enabled the researchers to quantify the rheological environment in which neuronal networks operate.
Crucially, regression analyses revealed that elevated WBV at high shear rates was positively correlated with better executive function as indexed by FAB scores. Moreover, higher blood viscosity was inversely related to completion times on the Stroop 5 task and both parts of the Trail Making Test, indicating enhanced cognitive processing speed and attention. This surprising discovery suggests that, within physiological limits, increased blood viscosity may enhance cerebral perfusion, thereby supporting better cognitive outcomes.
In contrast, serum osmolarity presented a more complex picture. Although univariate analyses indicated a positive correlation between serum osmolarity and executive function, these associations failed to hold up in multivariate models controlling for symptomatic and environmental factors. This finding implies that while osmolarity may reflect some preliminary relationship with cognition, it does not independently drive cognitive performance in schizophrenia. These nuanced insights call for further investigation into how fluid regulation impacts brain function.
The multivariate regression models also unearthed additional, non-physiological predictors of cognitive performance. Depressive and negative symptoms—commonly persistent in schizophrenia remission—emerged as significant detractors of executive function. Furthermore, the use of long-acting injectable antipsychotics (LAIs) and living arrangements were influential, underscoring the multifaceted nature of cognitive variability where biological, clinical, and social variables interplay.
Mechanistically, these findings bolster the hypothesis that systemic physiological parameters, such as blood viscosity, may directly affect cerebral microcirculation. Efficient blood flow is critical for delivering oxygen and nutrients to cortical regions responsible for executive processes. Elevations in WBV seemingly promote optimal shear stress in cerebral vessels, enhancing endothelial function and facilitating neurovascular coupling—a process essential for cognitive agility.
However, the concept of higher blood viscosity being beneficial contrasts with traditional clinical concerns where elevated viscosity is linked to vascular risks. This paradox highlights the importance of thresholds and ranges within which physiological parameters may either hinder or help brain function. It also points to the possibility that interventions modifying hemorheological factors could represent novel therapeutic avenues in schizophrenia treatment.
While this study pioneers a fresh perspective, the authors caution against overgeneralizing these findings before replication and deeper exploration, particularly in diverse populations beyond males in remission. Moreover, the cross-sectional design limits causal inference, necessitating longitudinal studies to clarify whether changes in blood viscosity precede cognitive improvements or simply co-occur.
The investigation also raises compelling questions about the interface between systemic health and neuropsychiatric disorders. Could blood rheology serve as a biomarker for cognitive prognosis in schizophrenia? Might targeted therapies optimizing blood flow properties complement existing pharmacological and psychosocial approaches? Such possibilities herald an era where treating the brain involves a holistic view of vascular and systemic health.
In addition, the study’s methodology sets a precedent for integrating rheological assessments into psychiatric research. Traditional focus on neurotransmitters and brain imaging may be insufficient to capture the full biological complexity of cognitive deficits. Incorporating parameters like WBV and serum osmolarity invites a more comprehensive understanding and fosters interdisciplinary collaboration between hematology, neurology, and psychiatry.
In summary, the research by Özönder Ünal et al. represents a paradigm shift, illuminating how blood viscosity—a physiological variable often relegated to cardiovascular contexts—intersects with the cognitive landscape of schizophrenia. Its findings spotlight a delicate balance, where certain systemic characteristics could nurture executive function, thereby opening new investigative and therapeutic frontiers. Although serum osmolarity’s role remains elusive, the study underscores the necessity of embracing multifactorial models that consider both systemic and neuropsychiatric dimensions in unraveling schizophrenia’s cognitive mysteries.
Continued research building on these foundational insights has the potential to revolutionize approaches to cognitive rehabilitation and functional recovery in schizophrenia, moving beyond symptom control toward enhancing life quality through biological modulation. As science advances, such integrative perspectives may redefine the clinical management of schizophrenia and perhaps other neuropsychiatric disorders.
Subject of Research: Cognitive functions in schizophrenia and their relationship with blood viscosity, serum osmolarity, and symptom severity.
Article Title: Cognitive functions in schizophrenia: the interplay between blood viscosity, serum osmolarity, and symptom severity.
Article References:
Özönder Ünal, I., Pirincci Aytac, M., Adalı Aker, D. et al. Cognitive functions in schizophrenia: the interplay between blood viscosity, serum osmolarity, and symptom severity. BMC Psychiatry 25, 542 (2025). https://doi.org/10.1186/s12888-025-06970-6
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