RESUMO
Studies of cellular and cytokine profiles have contributed to the inflammation hypothesis of schizophrenia; however, precise markers of inflammatory dysfunction remain elusive. A number of proton magnetic resonance spectroscopy (1H-MRS) studies in patients with first-episode psychosis (FEP) have shown higher brain levels of metabolites such as glutamate, myo-inositol (mI) and choline-containing compounds (tCho), suggesting neuroinflammation. Here, we present peripheral inflammatory profiles in antipsychotic-naive FEP patients and age-and-sex matched healthy controls, as well as cortical glutamate, mI and tCho levels using 1H-MRS. Inflammatory profiles were analyzed using cytokine production by peripheral blood mononuclear cells, that were either spontaneous or stimulated, in 48 FEP patients and 23 controls. 1H-MRS of the medial prefrontal cortex was obtained in 29 FEP patients and 18 controls. Finally, 16 FEP patients were rescanned after 4 weeks of treatment (open-label) with Risperidone. FEP patients showed a higher proportion of proinflammatory Th1/Th17 subset, and an increased spontaneous production of Interleukin (IL)-6, IL-2 and IL-4 compared with the control group. Results obtained from 1H-MRS showed no significant difference in either glutamate, mI or tCho between FEP and control groups. At baseline, CD8% showed a negative correlation with glutamate in FEP patients; after 4 weeks of risperidone treatment, the FEP group exhibited a decrease in glutamate levels which positively correlated with CD4 + T cells. Nevertheless, these correlations did not survive correction for multiple comparisons. FEP patients show evidence of immune dysregulation, affecting both the innate and adaptive immune response, with a predominantly Th2 signature. These findings, along with the changes produced by antipsychotic treatment, could be associated with both systemic and central inflammatory processes in schizophrenia.
Assuntos
Antipsicóticos , Neuroquímica , Transtornos Psicóticos , Humanos , Risperidona/uso terapêutico , Antipsicóticos/uso terapêutico , Leucócitos Mononucleares/metabolismo , Ácido Glutâmico/metabolismo , Interleucina-6 , Inflamação/complicaçõesRESUMO
Event related potentials (ERP) associated with early sensory information processing have been proposed as possible vulnerability markers for psychosis. Compared to other ERPs reported in schizophrenia research, like Mismatch Negativity (MMN), little is known about P3a, an ERP related to novelty detection. The aim of this study was to analyze the MMN-P3a complex in 20 antipsychotic naïve first-episode psychosis patients (FEP), 23 antipsychotic naïve individuals at clinical high-risk for psychosis (CHR) and 24 healthy controls. The MMN-P3a amplitudes and latencies were obtained during a passive auditory mismatch frequency deviant ERP paradigm and analyzed in frontal and central scalp regions. There were no significant differences in MMN amplitude between groups. There was a significant group difference in P3a due to reduced amplitude (F[2,64] = 3.7, p = 0.03) in both CHR and FEP groups (Mean difference (MD) = 0.39, p = 0.04 and MD = 0.49, p = 0.02, respectively) compared to the control group and this effect was most prominent on the right side (Group × laterality effect: MD = 0.57, p < 0.01 and MD = 0.58, p < 0.01, respectively). No significant differences were observed for MMN or P3a latencies between groups. Although a P3a decrement in chronic schizophrenia and FEP has been previously reported, our results suggest that this novelty detection impairment is present even in pre-psychosis stages in antipsychotic naïve subjects. This study supports the evidence that P3a could represent a neurophysiological vulnerability marker for the development of psychosis.