[Effects of Topiramate for atypical antipsychotic-induced body weight gain and metabolic adversities: a systematic review and meta-analysis].

OBJECTIVE: To systematically determine the effectiveness of Topiramate to counteract atypical antipsychotic-induced body weight gain and metabolic adversities in patients with psychiatric disorders. METHODS: A literature search using MEDLINE, EMBASE, PsycINFO, The Cochrane Library, CNKI, CBM and WanFang Data for randomized, open and double-blind, placebo-controlled trials of Topiramate targeting atypical antipsychotic-induced weight gain was performed.Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, and assessed methodological quality of included studies.Then meta-analysis was performed using RevMan 5.2 software. RESULTS: A total of 10 RCTs was included, consisting of 453 subjects. The results of meta-analysis showed that: compared with placebo, Topiramate was moderate effective in reducing antipsychotics-related weight gain (WMD=-1.82 kg (95%CI: -2.65--0.99), P<0.000 1), BMI increase (WMD=-1.31 kg/m(2) (95%CI: -1.69--0.93), P<0.000 01) and fasting glucose increase (SMD=-1.15 (95%CI: -1.50--0.79), P<0.000 01); but can not regulate the lipid metabolic disorders (Cholesterol: SMD=-0.23 (95%CI: -0.81-0.35), P=0.44); Triglycerides: SMD=-0.28 (95%CI: -0.75-0.19), P=0.24; HDL: SMD= 0.01 (95%CI: -0.52-0.53), P=0.98); LDL: SMD=-0.39 (95%CI: -0.89-0.11), P=0.13). Meanwhile, when compared with placebo, Positive and Negative Syndrome Scale (PANSS) in patients with schizophrenia did not show obviously clinical improvement in concomitant Topiramate group. CONCLUSION: Topiramate can prevent and/or treat atypical antipsychotic induced weight gain and glucose disorder, but current evidence does not support the effect of Topiramate in lipid metabolic regulation and the clinical symptoms improvement assessed by PANSS.

[Association of gene polymorphisms with the susceptibility of schizophrenia in Han Chinese population].

OBJECTIVE: To investigate the potential association of carbonic anhydrase I (CA1) anterior pharynx-defective 1A ( APH1A), neurodevelopment protein 1-like 1 (NDEL1) and serine racemase (SRR) gene polymorphisms with the susceptibility of schizophrenia (SZ). METHODS: A case-control study was performed to identify polymorphisms of the CA1, APH1A, NDEL1 and SRR gene that may confer susceptibility to SZ in the Han Chinese population. Five single nucleotide polymorphisms (SNPs) were genotyped in 516 paranoid SZ patients and 516 control subjects by real time quantitative polymerase chain reaction. The association between genotypes and positive and negative symptoms scale was also explored. RESULTS: No significant differences in genotype or allele frequencies of five SNPs were observed between schizophrenic patients and healthy controls (P = 0.163, 0.322, 0.494, 0.338, 0.545; 0.259, 0.149, 0.417, 0.527, 0.720; respectively). However, the frequency of CA haplotypes in SZ group was higher than control group (P = 0.041). The scores of depression/anxiety, positive and excited/hostile factors in SZ patients with genotype of rs2298161 (AG), rs4523957 (CC) and rs8081273 (GG) were higher than other genotypes (P = 0.008, 0.001, 0.000, respectively). CONCLUSIONS: These data suggests that the CA1, APH1A, NDEL1 and SRR gene may not be association with susceptibility to SZ in the Han Chinese population. However, the haplotype of CA may be the susceptible factor of SZ. Rs2298161, rs4523957 and rs8081273 may be associated with some phenotypes of SZ.

[Analysis of the changes of serum high mobility group protein B1 and cytokines in first-episode schizophrenia patients].

OBJECTIVE: To measure serum levels of high mobility group protein B-1 (HMGB1), interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α ( TNF-α) before and after antipsychotic treatment, and further study the role of HMGB1 in schizophrenics. METHODS: Thirty first-episode schizophrenics who were never treated with neuroleptics from First Affiliated Hospital of Zhengzhou University and thirty healthy subjects were enrolled. Serum levels of cytokines such as HMGB1, IL-1ß, IL-6 and TNF-α were examined with enzyme linked immunosorbent assay (ELISA) before and after antipsychotic treatment. RESULTS: The serum levels of HMGB1, IL-10, IL-6 and TNF-α in schizophrenics [(80 zophµ8/L, (51 zo, 441 zo, 591 zopng/L] were significantly higher than those in the healthy subjects [(54 gni) µ4/L, (25 gni, 17 gn, 41 gni) ng/L] (P < 0.05). After treating the schizophrenics with the neuroleptic risperidone for 6 months, the serum levels of HMGB1, IL-1ß, TNF-α and IL-6 were decreased. The serum levels of HMGB1 were positively correlated to IL-1ß, IL-6, TNF-α and Negative Symptoms (r = 0.377, r = 0.426, r = 0.454, r = 0.558, P < 0.05). CONCLUSIONS: Schizophrenics show activation of the cytokine system and immune disturbance. HMGB1 may play a proinflammatory role in schizophrenia and the decrease of HMGB1 after neuroleptic risperidone treatment may be a marker of mental symptoms remission.

[Correlation between serum levels of homocysteine and folate and cognitive dysfunction in first-episode schizophrenics].

OBJECTIVE: To explore the correlation between serum levels of homocysteine (Hcy) and folate and cognitive function in first-episode drug-naїve schizophrenics. METHODS: A total of 60 first-episode schizophrenics (schizophrenia group) from our hospital and 60 healthy individuals (control group) were enrolled.Serum levels of folate and Hcy were measured with electrochemical luminescence method and enzymatic cycling assay respectively. Positive and Negative Syndrome Scale (PANSS) was used to evaluate the mental symptoms and Matrics Consensus Cognitive Battery (MCCB) was used to evaluate the cognitive function. RESULTS: Serum level of folate in schizophrenia group (4.1 ± 1.9 ng/ml) was lower than that in control group (7.5 ± 1.9 ng/ml) (P < 0.001). And serum level of Hcy in schizophrenia group (27 ± 9 µmol/L) was significantly higher than that in control group (18 ± 6 µmol/L) (P = 0.006). Serum level of folate in schizophrenia group had negative correlations with Hcy level (r = -0.38, P = 0.002) and negative symptoms (r = -0.25, P < 0.05) while Hcy level was negatively correlated with cognitive function scores (r = -0.38, r = -0.33, r = -0.30, r = -0.30, P < 0.05). CONCLUSION: Serum level of folate decreases while serum level of Hcy increases in first-episode schizophrenics. Both have some relevance with mental symptom and cognitive dysfunction.

[Association of serum folic acid and homocysteine levels and 5, 10-methylenetetrahydrofolate reductase gene polymorphism with schizophrenia].

OBJECTIVE: To explore the association between serum concentrations of folic acid and homocysteine (HCY), 5, 10-methylenetetrahydrofolate reductase (MTHFR) C667T polymorphism and schizophrenia. METHODS: A total of 130 schizophrenics (schizophrenia group) from our hospital and 80 healthy individuals (control group) were enrolled. The serum concentration of homocysteine was measured by the electrochemical luminescence method, the concentration of serum folic acid by enzymatic cycling assay and MTHFR C667T genotype by PCR-DNA microarray. And positive and negative syndrome scale (PANSS) was used to evaluate the mental symptoms. RESULTS: (1) Serum HCY level in schizophrenia group was higher than that in control group [(20 ± 10) vs (11 ± 3) µmol/L; P < 0.001] while serum folate level in schizophrenia group was lower than that in control group [(6 ± 4) vs (9 ± 3) ng/ml; P < 0.001]; (2) the frequencies of CC, CT and TT in MTHFR C677T alleles were 13.1%, 50.0% and 36.9% in schizophrenia group versus 30.0%, 47.5% and 22.5% in control group respectively. Statistical significant inter-group difference existed in the frequencies of genotypes (χ² = 36.806, P < 0.05) . The frequencies of T and C alleles were 61.9%, 38.1% in schizophrenia group versus 46.25%, 53.75% in control group respectively. Statistical significant inter-group difference existed in the frequency of T allele (χ² = 9.872, P < 0.05). The frequency of TT genotype in schizophrenia group was 61.9% versus 22.5% in control group. Statistically significant inter-group difference existed in the frequency of TT homozygous mutation (χ² = 4.780, P < 0.05); (3) correlation analysis showed that serum folate level in schizophrenia group had a negative correlation with HCY level (r = -0.418, P < 0.001) . Serum HCY level had a positive correlation with negative symptoms scores (r = 0.345, P < 0.001) and serum folate level was negatively correlated with negative symptoms scores (r = -0.386, P < 0.001); (4) the serum HCY level in schizophrenia group with TT genotype was significantly higher than those with CC and CT genotypes (P < 0.05). CONCLUSION: There is a certain correlation between the serum levels of folate and HCY and the symptoms of schizophrenia. And MTHFR C677T polymorphism is a possible risk factor for schizophrenia.

[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.

[Effect of pyrrolidinedithiocarbamate on neural developmental disorder of adult offspring with maternal systemic exposure to Poly(I:C) during pregnancy].

OBJECTIVE: To explore the correlation between the elevated expression of cytokines under the induction of Poly(I:C) (polycytidylic acid) in maternal hosts and the abnormal behaviors of adult offsprings and understand the intervening effects of nuclear factor NF-κB inhibitor pyrrolidinedithiocarbamate (PDTC). METHODS: Poly(I:C) or saline was administered to model the maternal infection during early pregnancy in rats. And the expression of cytokines was blocked with PDTC. The maternal levels of tumor necrosis factor alpha and interleukin-10 were determined by ELISA (enzyme-linked immunosorbent assay). The adult offsprings on different treatments were then compared with regards to prepulse inhibition (PPI), passive avoidance and active avoidance. RESULTS: After the administration of Poly(I:C), there was an elevated levels of serum cytokines as shown by the markedly increased serum levels of IL-10 and TNF-α. The serum levels of IL-10 and TNF-α in the model group were significantly higher than those in the control group [(18.26 ± 1.52) pg/ml, (119.64 ± 16.42) pg/ml vs. (0.16 ± 0.13) pg/ml and (11.21 ± 1.81) pg/ml]. The elevation was partly blocked by PDTC. The serum levels of IL-10 and TNF-α in the intervention group [(12.64 ± 2.04) pg/ml and (30.34 ± 2.19) pg/ml respectively] were lower than those in the model group, but still higher than those in the control group. The psychotic-like phenotypes including defects in PPI, passive avoidance and active avoidance were observed in Poly(I:C)-treated offsprings. Such an effect was blunted by the PDTC intervention. The PPI results demonstrated that the PP2 and PP8 difference between rats in 3 groups were statistically significant, with a lower PPI value in the model group than in the intervention group, in the intervention group than in the control group and much lower in the model group than in the control group. PP4 was lower in the model group than that in the intervention group, and also lower in the model group than in the control group. There was no significant difference between the control group and the intervention group. The passive avoidance results indicated that T1 was higher in the model group than in the control and intervention groups and there was no statistical difference between the control and intervention groups. T2 was lower in the model group than in the control and intervention groups and there was no statistical difference between the control and intervention groups. And the active avoidance test results showed that total conditioned reflex times of the control group was higher than those of the intervention and model groups. No statistical difference was found between the intervention and model groups. Total reflex rate of the control group was higher than that of the intervention and model groups. No statistical difference was found between the intervention and model groups. CONCLUSION: PDTC can interfere with neural developmental disorder of adult offsprings through blunting the cytokine-mediated maternal immune response.

[Effect of antipsychotic drugs on life quality of schizophrenic patients: one year follow-up study].

OBJECTIVE: To compare the effect of 7 antipsychotic drugs on the life quality of schizophrenia patients including chlorpromazine, sulpiride, clozapine, risperidone, olanzapine, quetiapine, and aripiprazole. METHODS: A total of 1,227 stable schizophrenic patients within 5 years onset who took 1 of the 7 study medications as maintenance treatment were followed up for 1 year at 10 China sites. Patients were evaluated by the short form-36 health survey (SF-36) at the baseline and at the end of 1 year. RESULTS: The life quality was improved obviously at the end of the follow-up. There was significant difference in body pain, vitality, and mental health (P<0.05) among these antipsychotic drugs. CONCLUSION: All 7 antipsychotic drugs can improve the life quality of schizophrenia patients. Atypical antipsychotic drugs, especially olazapine and quetiapine, are superior to typical antipsychotic drugs in improving life quality.

[Effect of clozapine and risperidone on serum cytokine levels in patients with first-episode paranoid schizophrenia].

OBJECTIVE: To study the effects of clozapine and risperidone on serum cytokine levels in patients with first-episode paranoid schizophrenia, and explore the role of the cytokines in the psychopathological basis of the illness. METHOD: Fifty-eight patients with first-episode paranoid schizophrenia were treated with either clozapine or risperidone, and before and at the end of the 4th, 8th weeks and 6th months after the medication respectively, the serum levels of interleukin (IL)-6, 2, 18,and tumor necrosis factor (TNF)alpha were measured with enzyme-linked immunosorbent assay (ELISA). The Positive and Negative Syndrome Scale (PANSS) was used to evaluate the psychotic symptoms. RESULT: In patients treated with risperidone, the levels of serum IL-6 and IL-2 after 4 weeks, TNFalpha after 8 weeks, and IL-18 after 6 months were all significantly lowered in comparison with the pretreatment levels (P<0.01 or 0.05). In clozapine group, the levels of IL-2 after 4 weeks and IL-6 and IL-18 after 6 months were lowered significantly (P<0.01 or 0.05). Before the medication, serum IL-6 level was positively correlated with Positive Syndrome scores (r=0.386, P<0.01), IL-2 with the total score and Positive Syndrome scores (r=0.338, 0.305; P<0.01, 0.05), and TNFalpha with the total score (r=0.283, P<0.05). The changes of IL-2 and IL-6 after 8 weeks was positively correlated with the change of Positive Syndrome scores (r=0.268, 0.375; P<0.05, 0.01). Six months after the medication, the change in IL-6 and TNFalpha levels was positively correlated with the change of total score (r=0.365, 0.362; P<0.05). Before treatment, IL-6 was positively correlated with IL-2 levels (r=0.356, P<0.01), and TNFalpha with IL-18 levels (r=0.291, P<0.05). TNFalpha was positively correlated with IL-6 levels (r=0.332, P<0.01) 8 weeks after the medication. The changes in IL-6 was positively correlated with the those in IL-2 levels 6 months after the medication (r=0.391, P< 0.05). CONCLUSION: Clozapine and risperidone have similar immunosuppression actions and may affect serum IL-6 levels in patients with paranoid schizophrenia, in the psychopathology of which the cytokines play their roles of various importance.

[The changes of soluble interleukin-2 receptor in serum and cerebrospinal fluid of patients with delayed encephalopathy after acute carbon monoxide poisoning].

OBJECTIVE: To explore the changes of soluble interleukin-2 receptor(sIL-2R) in serum and cerebrospinal fluid (CSF) of patients with delayed encephalopathy after acute carbon monoxide poisoning (DEACMP). METHODS: There were 31 patients with DEACMP, 32 patients with other encephalopathy and 31 controls in this study. The levels of sIL-2R in serum and CSF were detected by ELISA. RESULTS: Serum sIL-2R in patients with DEACMP[(329.21 +/- 160.99)U/ml] was significantly higher than that in control[(115.67 +/- 89.58) U/ml, P < 0.05)], but not significantly different from that in the other encephalopathy group[(367.50 +/- 123.14) U/ml, P > 0.05)]. CSF sIL-2R in patients with DEACMP[(54.48 +/- 43.04) U/ml] measured a little before discharge was significantly lower than that in patients with the other encephalopathy[(110.24 +/- 76.56) U/ml, P < 0.05)], but not significantly different from that in the control group[(34.96 +/- 22.70)U/ml, P > 0.05)]. At the pre-discharged period, CSF sIL-2R in patients with DEACMP[(100.26 +/- 93.65) U/ml] was significantly higher than that at the early stage of hospitalization[(52.28 +/- 43.31) U/ml, P < 0.05)]. No significant difference in serum sIL-2R was found between early stage of hospitalization[(338.34 +/- 161.53) U/ml] and pre-discharge [(351.31 +/- 175.93) U/ml, P > 0.05)]. CONCLUSION: The occurrence of DEACMP may be related with immunopathological damage. The sIL-2R levels in serum and CSF may give information about the state of immunological function of the patients with DEACMP and may contribute to determining the patient's condition and prognosis.