The levels of S100B, RAGE, and Fas Ligand of drug-naive first episode psychosis patients with schizophrenia were significantly higher than that of the same medicated first episode psychosis patients, indicating that an increase of apoptotic signaling is present at the onset of schizophrenia and is also associated with treatment progress.
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 PANSSnegative 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 PANSSnegative [(PANSS-follow-up - PANSS-baseline)/PANSS-baseline; ΔPANSSnegative%)] 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 PANSSnegative was associated with baseline IL-27 (R2=0.301, P=0.042), ΔPANSSnegative% was associated with baseline IL-6 (R2=0.301, P=0.042) and baseline IL-27 levels (R2=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.
Clozapine is a second-generation antipsychotic drug used in treatment-resistant schizophrenia (1, 2). Despite its effectiveness, this drug is not without adverse effects, highgrade fever and cardiotoxicity being among them, through its immunomodulatory effects (3). Clozapine-induced fever has been reported by several studies and a number of plausible explanations for the induction of fever exist including the implication of the immune-modulating effect by increasing soluble tumor necrosis factor (TNF) receptor p55, p75 and soluble interleukin-2 (IL2) receptor (4, 5). IL6 has also been suggested to induce fever by elevating the set point of body core temperature via temperature-sensitive neurons in the preoptic area of the hypothalamus (6), for example as a result of pyrogenic cytokines (7). Likewise, drug-induced cardiotoxicity has many underlying mechanisms, affecting the heart directly and, in other cases, indirectly, including the enhancement of immunological reactions, cell apoptosis, formation of free radicals and alterations of hemodynamic flow. Several preclinical and clinical reports have shown the relation of a high incidence of clozapine-induced myocarditis (3,4,8) with immunological-mediated mechanisms.Here we present the case of a 31-year-old Caucasian male with refractory schizophrenia who developed benign fever, increase of C-reactive protein (CRP) and high sensitivity (Hs)-troponin levels, without presenting any other signs of myocarditis, on the 13th day under clozapine treatment, all of which declined progressively upon discontinuation of the drug.
Case ReportA 31-year-old Caucasian male with no significant past medical history, besides heavy smoking and abusing marijuana, was 141
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