title: Soluble interleukin-2 receptor levels correlated with positive symptoms during quetiapine treatment in schizophrenia-spectrum disorders.
abstract: BACKGROUND
  Some but not all antipsychotics have been shown to modulate plasma cytokine levels in schizophrenia patients. Thus far, the most consistent finding has been the increase in plasma levels of soluble interleukin (IL)-2 receptor (sIL-2R) associated with clozapine treatment. Quetiapine is a second-generation antipsychotic with a pharmacological profile similar to that of clozapine, but its immunomodulatory effects have not been investigated in schizophrenia yet. The purpose of this exploratory study was to examine the changes in plasma levels of sIL-2R in schizophrenia during quetiapine treatment and association with psychopathology.
  
  
  METHODS
  Participants were 29 schizophrenia-spectrum disorder patients (DSM-IV criteria), and 28 healthy controls. Patients had a comorbid substance use disorder (cannabis>alcohol>cocaine), since quetiapine is increasingly used in this population of dual diagnosis. No participant suffered from infection or overt inflammatory diseases. On baseline, patients taking mostly second-generation antipsychotics were switched to quetiapine for a 12-week open-label trial. Five patients were drop-outs. Mean dose of quetiapine for trial completers (n=24) was 466.6mg±227.3. Psychiatric variables were evaluated with the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia. Plasma sIL-2R levels were assessed at baseline, weeks 6 and 12 in patients, and in healthy controls, using sandwich immunoassay. Plasma IL-6 and IL-1 receptor antagonist (IL-1RA) were measured for comparison purposes.
  
  
  RESULTS
  On baseline, plasma sIL-2R, IL-6 and IL-1RA levels were higher in dual-diagnosis patients, compared to controls. Plasma sIL-2R further increased after quetiapine treatment (p=0.037), while plasma IL-6 and IL-1RA did not change. Clinical improvements were observed in positive, negative and depressive symptoms, and substance abuse severity (all p<0.01). Interestingly, changes in sIL-2R levels during treatment were inversely correlated with changes in positive symptoms (r=-0.524; p=0.009). That is, increases in sIL-2R levels were associated with reductions in positive symptoms.
  
  
  CONCLUSIONS
  These data show that quetiapine elevates, like clozapine, sIL-2R levels in schizophrenia. Furthermore, the results suggest that sIL-2R alterations in schizophrenia rely on complex interplays between antipsychotics and the positive symptoms of the disorder. Future randomized controlled trials involving larger samples of schizophrenia patients are warranted to determine whether changes in plasma sIL-2R are quetiapine-related.
authors.affiliation: Maisonneuve-Rosemont Hospital Research Center, Canada.
authors.forename: Raouf
authors.initials: R
authors.lastname: Igue
authors.forename: Stéphane
authors.initials: S
authors.lastname: Potvin
authors.forename: Ramatoulaye
authors.initials: R
authors.lastname: Bah
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Stip
authors.forename: Roch-Hugo
authors.initials: RH
authors.lastname: Bouchard
authors.forename: Olivier
authors.initials: O
authors.lastname: Lipp
authors.forename: Alain
authors.initials: A
authors.lastname: Gendron
authors.forename: Edouard
authors.initials: E
authors.lastname: Kouassi
mesh_terms: D000328:Adult; D000342:Affective Symptoms / Q000175:diagnosis / Q000503:physiopathology / Q000523:psychology; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015897:Comorbidity; D016207:Cytokines / Q000097:blood / Q000276:immunology; D003987:Dibenzothiazepines / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D015850:Interleukin-6 / Q000097:blood / Q000276:immunology; D008297:Male; D011569:Psychiatric Status Rating Scales; D000069348:Quetiapine Fumarate; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000097:blood / Q000276:immunology; D015375:Receptors, Interleukin-2 / Q000097:blood* / Q000276:immunology; D012559:Schizophrenia / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology* / Q000276:immunology; D019966:Substance-Related Disorders / Q000188:drug therapy / Q000453:epidemiology / Q000276:immunology; D055815:Young Adult
chemical_list: D014150:Antipsychotic Agents; D016207:Cytokines; D003987:Dibenzothiazepines; D015850:Interleukin-6; D017472:Receptors, Interleukin-1; D015375:Receptors, Interleukin-2; D000069348:Quetiapine Fumarate