Association between the interleukin-1 receptor antagonist gene and negative symptom improvement during antipsychotic treatment

The contribution of immune system to schizophrenia has been an important area of focus in schizophrenia research. Several genetic variants in the cytokine system have been associated with the pathogenesis of schizophrenia. The purpose of this study was to determine whether a pharmacogenetic relationship exists between a variable number of tandem repeats (VNTR) polymorphism in the interleukin-1 receptor antagonist gene (IL-1RN) and clinical improvement during antipsychotic treatment in patients with a first non-affective psychotic episode. One hundred and fifty-four subjects presenting with a first nonaffective psychotic episode were randomly assigned to treatment with haloperidol, risperidone, or olanzapine and rated with the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment of Negative Symptoms (SANS) and the Scale for the Assessment of Positive Symptoms (SAPS) both at baseline and after 6 weeks of treatment. A control sample of 336 blood bank donors was also included. No differences in genotype or allele distributions were found between patients and controls. However, after controlling for baseline SANS scores, the genotype in the VNTR polymorphism in the IL-1RN gene significantly predicted negative symptom improvement, accounting for approximately 7% of the variance (F = 5.23, df = 2, P = 0.006). The mean decrease in SANS scores was 58% for the IL-1RN* 2/2, 44% for the IL-IRN* 1/2, and 14% for the IL-1RN* 1/1 subjects, respectively. These results suggest that the VNTR polymorphism in the IL-1RN gene may be a useful predictor of negative symptom improvement in schizophrenic patients treated with antipsychotic drugs. (c) 2006 Wiley-Liss, Inc.