Effects of olanzapine on cytokine profile and brain-derived neurotrophic factor in drug-naive subjects with first-episode psychosis

Immunological abnormalities have been implicated in schizophrenia. On the other hand, antipsychotics may exert immunomodulatory effects, by triggering pro-inflammatory and anti-inflammatory agents through complex homeostatic mechanisms, which seem to be implicated in medication responsiveness and in the presence or not of adverse effects. There is evidence that olanzapine, a second generation antipsychotic, may increase synapse formation and neurogenesis through alterations in the levels of cytokines and neurotrophic factors. In the present study, we recruited 14 drug-naive inpatients with first-episode schizophrenia (male:female ratio, 7:7) with a mean age of 26.5 years. The positive and negative syndrome scale (PANSS) scores and serum levels of a broad spectrum of cytokines and of brain-derived neurotrophic factor (BDNF) were recorded twice, once at baseline prior to the initiation of olanzapine treatment and 8 weeks later, once the dose of olanzapine had stabilized. Subsequently, the associations between the PANSS scores and the measured markers were examined. Correlation analyses revealed that follow-up PANSS(negative) positively correlated with baseline interleukin (IL)-6 (ρ=0.685, P=0.007) and baseline IL-27 levels (ρ=0.785, P=0.001). Furthermore, the percentage change in PANSS(negative) [(PANSS-(follow-up) - PANSS-(baseline))/PANSS-baseline; ΔPANSS(negative%))] positively correlated with baseline IL-27 (ρ=0.785, P=0.001) and baseline IL-6 levels (ρ=0.685, P=0.007). Finally, linear regression revealed that follow-up PANSS(negative) was associated with baseline IL-27 (R(2)=0.301, P=0.042), ΔPANSS(negative%) was associated with baseline IL-6 (R(2)=0.301, P=0.042) and baseline IL-27 levels (R(2)=0.446, P=0.009). Thus, these findings indicate that IL-27 and IL-6 may be trait markers in patients being administered olanzapine monotherapy at the onset of schizophrenia. However, further studies are warranted in order to replicate these associations and to confirm their potential use as biomarkers of treatment effectiveness and safety, as well as to explore novel immunomodulatory strategies for the treatment of schizophrenia.