C-Reactive Protein Levels and Elevations in Schizophrenia: The Central Role of Body Mass Index

Elevated levels of C-reactive protein (CRP) are consistently observed in individuals with schizophrenia. However, the extent to which this elevation is attributable to body mass index (BMI), demographic differences, and comorbid medical conditions remains unclear.

CRP was measured in blood plasma from 772 individuals (479 schizophrenia, 293 controls). Group differences in log10-transformed and binary CRP (≥3 μg/mL) were examined across 5 sequentially adjusted regression models progressively incorporating sex, age, maternal education, cigarette smoking, race, and BMI. Within schizophrenia, 44 comorbidity, clinical, and medication variables were each tested against both CRP quantitative and categorical outcomes using the 5-model framework, with multiple comparison correction applied to fully adjusted models.

Compared to controls, schizophrenia was associated with significantly higher CRP in models incorporating sex, age, maternal education, race and smoking (all P < .001). The addition of BMI substantially attenuated these group differences, although associations remained statistically significant. Within schizophrenia, BMI was the dominant predictor of CRP levels, accounting for a substantial amount of the CRP variance (β = +0.031/unit, P < .001). Of 20 variables significant in unadjusted models, only 7 remained significant after full adjustment and multiple comparison correction: acne vulgaris, gastrointestinal reflux, urinary tract infections, migraine, autoimmune disorders, clozapine, and antidepressant use.

CRP elevation in schizophrenia is substantially attenuated by BMI adjustment but remains significantly different from unaffected controls across continuous and binary outcomes in fully adjusted models. BMI and other relevant covariates should be incorporated into schizophrenia studies employing CRP as an inflammatory indicator.