Factors involved in working memory in patients with schizophrenia and bipolar disorder: The role of peripheral biomarkers

Cognitive impairment, especially working memory (WM) dysfunction, is a core feature of schizophrenia (SZ) and bipolar disorder (BD), influenced by various factors including lifestyle, psychopathology, pharmacological factors, inflammation, and metabolic dysfunction. This study aimed to investigate the role of metabolic, inflammatory, and intestinal permeability biomarkers in WM impairments in SZ and BD patients. A cross-sectional, observational study included 146 outpatients (SZ=96, BD=50). We assessed sociodemographic, clinical, metabolic, and inflammatory markers. Cognitive performance was evaluated using the Screen for Cognitive Impairment in Psychiatry. Biomarkers included glycohemoglobin, C-reactive protein, and lipopolysaccharide-binding protein/soluble CD14. Multivariate analyses identified factors associated with WM dysfunction and, secondarily, with other cognitive deficits. WM impairment was present in 56.3 % of SZ and 52 % of BD patients, without inter-group differences. Independent predictors of WM dysfunction were antipsychotic polypharmacy (OR=2.415, p = 0.011), abdominal obesity (OR=2.884, p = 0.016), and elevated glycohemoglobin (OR=1.126, p = 0.020). While inflammatory and intestinal permeability markers correlated with metabolic parameters, they were not independent predictors of WM impairment. WM deficits in SZ and BD are primarily associated with metabolic and pharmacological factors. Addressing modifiable metabolic factors, optimizing antipsychotic treatment, and exploring interventions such as metformin and lifestyle modifications may improve cognitive outcomes in these populations.