[Study of adiponectin, IL-1ß, IL-6 and TNF-α in first episode drug naїve schizophrenia].

OBJECTIVE: To explore the levels of adiponectin (APN), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in first episode drug naїve schizophrenics and further examine the role of adipocytokines in schizophrenia. METHODS: Ninety-six normal weight schizophrenics and 22 overweight/obese ones from First Affiliated Hospital, Zhengzhou University and 60 healthy controls were enrolled. Serum levels of IL-1ß, IL-6, TNF-α and APN were measured with enzyme linked immunosorbent assay (ELISA). RESULTS: Serum levels of IL-1ß, IL-6 and TNF-α in normal weight schizophrenics (54 ± 13, 34 ± 12, 48 ± 18) pg/ml and overweight/obese schizophrenics (71 ± 21, 40 ± 12, 53 ± 18) pg/ml were significantly higher than those in the controls (23 ± 16, 16 ± 7, 32 ± 15) pg/ml (P < 0.05). Serum levels of IL-1ß and IL-6 in overweight/obese schizophrenics were significantly higher than those in normal weight schizophrenics (P < 0.05). Serum level of adiponectin in normal weight schizophrenics was significantly higher than that in control group [(12 ± 4) vs (9 ± 4) pg/ml, P < 0.05]. CONCLUSION: The serum levels of APN, IL-1ß, IL-6 and TNF-α increase in first episode drug naїve schizophrenics. It suggests that an inflammatory response mediated by adipocytokines. APN may play a pro-inflammatory role in schizophrenia.

[Proteomic analysis of novel serum markers in first-episode schizophrenics before versus after treatment of risperidone].

OBJECTIVE: To explore the changes in serum protein levels of schizophrenics before and after treatment of risperidone and identify the potential markers of diagnosis, treatment and drug side effects of schizophrenia. METHODS: Eighty first-episode schizophrenics without other concurrent diseases and with positive and negative symptom scale (PANSS) score greater than or equal to 60 were recruited. And 15 of them were measured by proteomics. Different serum levels of proteins were obtained from these patients and were separated by two-dimensional electrophoresis (2-DE) before and after a single risperidone treatment for 8 weeks. These proteins were then identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and peptide mass fingerprinting. Enzyme-linked immunosorbent assay (ELISA) was used to verify the results. RESULTS: Almost 1400 spots were detected by 2-DE in each gel. Of these proteins, 23 protein spots showed significant differences in abundance before and after risperidone treatment. After MALDI-TOF peptide mass fingerprinting, 9 up-regulated proteins and 8 down-regulated proteins were validated after treatment. Of these proteins, the schizophrenics showed a significantly higher content of apolipoprotein A-1 (APOA-1) than those before treatment and haptoglobin (HP) protein was down-regulated after treatment. The results of ELISA were parallel with those of proteomic (P < 0.01). CONCLUSION: The serum proteins correlated with blood glucose and lipid metabolism are altered in schizophrenia after treatment of risperidone. A clinician should monitor the side effects of antipsychotic drugs according to the changes of serum proteins.

The interaction of nuclear factor-kappa B and cytokines is associated with schizophrenia.

BACKGROUND: Many reports suggest that schizophrenia is associated with the inflammatory response mediated by cytokines, and nuclear factor-kappa B (NF-kappaB) regulates the expression of cytokines. However, it remains unclear whether the interaction between NF-kappaB and cytokines is implicated in schizophrenia and whether the effect of neuroleptics treatment for 4 weeks is associated with the alteration of cytokines. METHODS: Sixty-five healthy subjects and 83 first-episode schizophrenic patients who met DSM-IV criteria and who were never treated with neuroleptics previously were included. Serum levels of cytokines such as interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) were examined by using sandwich enzyme immunoassay (EIA). Peripheral blood mononuclear cell (PBMC) mRNA expressions of cytokines (IL-1beta, TNF-alpha) and NF-kappaB were detected by using semiquantitative reverse transcription polymerase chain reaction (RT-PCR). NF-kappaB activation was examined by using transcription factor assay kits. RESULTS: Schizophrenic patients showed significantly higher serum levels and PBMC mRNA expressions of IL-1beta and TNF-alpha compared with healthy subjects. However, treatment with the neuroleptic risperidone for 4 weeks significantly decreased serum levels and PBMC mRNA expressions of IL-1beta in schizophrenic patients. NF-kappaB activation and PBMC mRNA expression in patients were significantly higher than those in healthy subjects. Furthermore, PBMC mRNA expressions of IL-1beta and TNF-alpha were positively correlated to NF-kappaB activation in both schizophrenic patients and healthy control subjects. CONCLUSIONS: Schizophrenic patients showed activation of the cytokine system and immune disturbance. NF-kappaB activation may play a pivotal role in schizophrenia through interaction with cytokines.