title: Cytokine alterations in first-episode schizophrenia patients before and after antipsychotic treatment.
abstract: Schizophrenia has been associated with central nervous system and peripheral immune system imbalances. However, most studies have not yielded conclusive results due to limitations such as small sample size, dissimilarities in the clinical status of patients and the high variability of cytokine levels within the normal human population. Here, we have attempted to account for these limitations by carrying out standardised multiplex immunoassay analyses of 9 cytokines in serum from 180 antipsychotic-naïve first-episode schizophrenia patients and 350 matched controls across 5 clinical cohorts. All subjects were matched for potential confounding factors including age, gender, smoking and body mass index. We found that the levels of interleukin (IL)-1RA, IL-10 and IL-15 were increased significantly in patients across the cohorts. We also found that the levels of IL-1RA and IL-10 were decreased in 32 patients who had been followed up and treated for 6 weeks with atypical antipsychotics. Interestingly, we found that the changes in IL-10 levels were significantly correlated with the improvements in negative, general and total symptom scores. These results indicate that mixed pro- and anti-inflammatory responses may be altered in first onset patients, suggesting a role in the aetiology of schizophrenia. The finding that only the anti-inflammatory cytokine IL-10 responded to treatment in parallel with symptom improvement suggests that this could be used as a potential treatment response biomarker in future studies of schizophrenia.
authors.affiliation: Department of Psychiatry, University of Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: l.d.dewitte@umcutrecht.nl.
authors.forename: Lot
authors.initials: L
authors.lastname: de Witte
authors.affiliation: Department of Chemical Engineering and Biotechnology, Tennis Court Road, Cambridge CB21QT, University of Cambridge, UK; Department of Neuroscience, Erasmus Medical Centre, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands. Electronic address: jt455@cam.ac.uk.
authors.forename: Jakub
authors.initials: J
authors.lastname: Tomasik
authors.affiliation: Department of Chemical Engineering and Biotechnology, Tennis Court Road, Cambridge CB21QT, University of Cambridge, UK. Electronic address: es404@cam.ac.uk.
authors.forename: Emanuel
authors.initials: E
authors.lastname: Schwarz
authors.affiliation: Department of Chemical Engineering and Biotechnology, Tennis Court Road, Cambridge CB21QT, University of Cambridge, UK. Electronic address: pg110@hermes.cam.ac.uk.
authors.forename: Paul C
authors.initials: PC
authors.lastname: Guest
authors.affiliation: Department of Chemical Engineering and Biotechnology, Tennis Court Road, Cambridge CB21QT, University of Cambridge, UK. Electronic address: hr288@cam.ac.uk.
authors.forename: Hassan
authors.initials: H
authors.lastname: Rahmoune
authors.affiliation: Department of Psychiatry, University of Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. Electronic address: r.kahn@umcutrecht.nl.
authors.forename: René S
authors.initials: RS
authors.lastname: Kahn
authors.affiliation: Department of Chemical Engineering and Biotechnology, Tennis Court Road, Cambridge CB21QT, University of Cambridge, UK; Department of Neuroscience, Erasmus Medical Centre, Dr. Molewaterplein 50, 3015 GE, Rotterdam, The Netherlands. Electronic address: sb209@cam.ac.uk.
authors.forename: Sabine
authors.initials: S
authors.lastname: Bahn
mesh_terms: D000328:Adult; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001569:Benzodiazepines / Q000494:pharmacology; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007118:Immunoassay; D053590:Interleukin 1 Receptor Antagonist Protein / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007378:Interleukins / Q000097:blood; D008297:Male; D015201:Meta-Analysis as Topic; D000077152:Olanzapine; D011569:Psychiatric Status Rating Scales; D018967:Risperidone / Q000627:therapeutic use; D012559:Schizophrenia / Q000097:blood* / Q000188:drug therapy*
chemical_list: D014150:Antipsychotic Agents; D016207:Cytokines; C508609:IL10 protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D007378:Interleukins; D001569:Benzodiazepines; D016753:Interleukin-10; D018967:Risperidone; D000077152:Olanzapine
keywords: Antipsychotics; Biomarkers; Cytokines; Immune system; Multiplex immunoassay; Schizophrenia