Increased serum interleukin-1β and interleukin-6 in elderly, chronic schizophrenic patients on stable antipsychotic medication

Andrea Schmitt^1,3, Thomas Bertsch^2,5, Heike Tost¹, Andrea Bergmann³, Uwe Henning⁴, Ansgar Klimke⁴, Peter Falkai³

¹Central Institute of Mental Health, Mannheim, Germany; ²Institute of Clinical Chemistry and Laboratory Medicine, Municipal Hospital Nuremberg, University Erlangen-Nuremberg, Germany; ³Department of Psychiatry, University of Saarland, Homburg, Germany; ⁴Neurobiochemical Research Unit, Department of Psychiatry, Heinrich-Heine University, Düsseldorf, Germany; ⁵Institute of Clinical Chemistry, University Hospital Mannheim, Germany

Abstract: In schizophrenia, alterations of proinflammatory cytokine levels have been reported and related to the disease and psychopathology. However, only limited conclusions can be drawn in view of confounding factors such as infection, age, sex, smoking, and antipsychotic medication. Chronic schizophrenic patients with a long-term disease process and medication period have not been investigated so far. We have measured serum levels of interleukin (IL)- 1β, IL-6, and tumor necrosis factor (TNF)α in 41 elderly, chronic schizophrenic patients and 23 age- and sex-matched controls using enzyme-linked immunosorbent assay (ELISA). We assessed detailed psychopathology and neuropsychological performance and determined serum levels of haloperidol, clozapine, and the two main clozapine metabolites, desmethylclozapine and clozapine metabolite N-oxide, by high-pressure liquid chromatography (HPLC). IL-1β and IL-6 levels were increased in treatment-resistant schizophrenic patients compared with healthy controls, whereas TNFα showed no difference. We did not find statistically significant differences of cytokine levels between medication groups and there was no correlation with serum levels of antipsychotics or psychopathological rating scores. Elevations of IL-1β and IL-6 in elderly chronic schizophrenic patients may be related to an active disease process lasting until old age. Despite missing correlations, long-term treatment effects in treatment-resistant patients may have affected TNFα, leading to control levels. Post-mortem and animal studies should clarify the presence of altered immune function in the brain as well as the effect of cytokine levels in relation to neurodevelopmental disturbances and schizophrenia-associated behavior.

Keywords: interleukin-1β, interleukin-6, TNFα, schizophrenia, haloperidol, clozapine