Inflammation and sarcopenia exhibit distinct associations with psychopathology and executive function in schizophrenia

Background: Immune dysregulation and premature physical aging have been implicated in schizophrenia; however, few studies have concurrently examined inflammation, sarcopenia, psychopathology, cognitive and physical functioning within the same cohort. We investigated whether inflammation and sarcopenia exhibit distinct associations with clinical and cognitive outcomes in schizophrenia. Methods: This cross-sectional study recruited inpatients with schizophrenia from Suao and YuanShan branches of Taipei Veterans General Hospital. Psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS). Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 criteria. Cognitive function was assessed with the Wisconsin Card Sorting Test (WCST), 2-back and Go/No-Go task. Circulating inflammatory markers (C-reactive protein [CRP], soluble interleukin-6 receptor, soluble interleukin-2 receptor [sIL-2R], and soluble tumor necrosis factor-α receptor type 1) were measured by ELISA. Multivariable general linear models were used to examine associations, adjusting for age, sex, education, body mass index, and medication use. Results: A total of 120 patients with schizophrenia aged 20 to 65 years were recruited; sarcopenia was present in 21 participants (17.5%), and low-grade systemic inflammation (CRP >3 mg/L) in 41 (34.2%). Patients with inflammation had higher PANSS scores and poorer walking speed, and performed worse on WCST perseverative response (all p < 0.05). Patients with sarcopenia had higher PANSS total scores (74.76 vs 63.75; p = 0.014) but did not differ in cognitive measures. In multivariable analyses, CRP was positively associated with PANSS positive symptoms (B = 1.94, unstandardized coefficient; p = 0.009). Higher sIL-2R was associated with worse executive function (failure to maintain set), but not after multiple comparison correction. No significant inflammation-sarcopenia interactions were observed. Conclusion: These findings suggest that systemic inflammation and sarcopenia are independently associated with greater symptom severity in schizophrenia, highlighting the potential value of integrated metabolic and inflammatory assessment in clinical care.