Changes in oxidative stress markers in patients with schizophrenia: The effect of antipsychotic drugs

The aim of this study was to investigate the serum levels or activities of oxidative stress markers in patients with schizophrenia in acute phase and evaluate the changes in superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH) and thiobarbituric acid-reactive substances (TBARS) after treatment. We consecutively enrolled 41 patients with schizophrenia in acute phase, and 27 patients were followed up with a 4-week antipsychotic treatment. Serum oxidative stress markers were measured with assay kits. We found that Positive and Negative Syndrome Scale (PANSS) total scores were significantly negatively correlated with serum GPx activity and GSH levels and positively correlated with serum SOD activity in patients with schizophrenia in acute phase. In addition, serum GPx activity had a positive correlation with GSH levels and negative correlation with SOD activity. We also found that serum SOD activity was significantly negatively correlated with TBARS levels in patients in acute phase. Furthermore, we found significantly increased changes only in GPx activity in female patients receiving the 4-week treatment (P=0.006). In conclusion, our results suggest that SOD, GPX and GSH might be indicators of schizophrenia severity in acute phase. Furthermore, antipsychotic drugs might affect serum GPx activity in female patients receiving the 4-week treatment.     

Homer-1 polymorphisms are associated with psychopathology and response to treatment in schizophrenic patients

The HOMER 1 protein plays a crucial role in mediating glutamatergic neurotransmission. It has previously shown to be a candidate gene for etiology and pathophysiology of different psychiatric diseases such as schizophrenia. To identify genes involved in response to antipsychotics, subgroups of animals were treated with haloperidol (1 mg/kg, n = 11) or saline (n = 12) for one week. By analyzing microarray data, we replicated the observed increase of Homer 1 gene expression. Furthermore, we genotyped 267 schizophrenic patients, who were treated monotherapeutically with different antipsychotics within randomized-controlled trials. Psychopathology was measured weekly using the PANSS for a minimum of four and a maximum of twelve weeks. Correlations between PANSS subscale scores at baseline and PANSS improvement scores after four weeks of treatment and genotypes were calculated by using a linear model for all investigated SNP’s.We found an association between two HOMER 1 polymorphisms (rs2290639 and rs4704560) and different PANSS subscales at baseline. Furthermore all seven investigated polymorphisms were found to be associated with therapy response in terms of a significant correlation with different PANSS improvement subscores after four weeks of antipsychotic treatment. Most significant associations have been shown between the rs2290639 HOMER 1 polymorphism and PANSS subscales both at baseline conditions and after four weeks of antipsychotic treatment.This is the first study which shows an association between HOMER 1 polymorphisms and psychopathology data at baseline and therapy response in a clinical sample of schizophrenic patients. Thus, these data might further help in detecting differential therapy response in individuals with schizophrenia.     

利培酮对慢性精神分裂症泌乳素的影响

目的探讨非典型抗精神病药利培酮对泌乳素的影响及其与临床疗效的关系。方法采用固定剂量利培酮（６ｍｇ／ｄ）治疗慢性、男性精神分裂症３０例,疗程１２周;在治疗前后评定ＰＡＮＳＳ量表,并用放射免疫法测查血浆中泌乳素（ＰＲＬ）浓度。以１６例健康人为对照。结果治疗后,患者ＰＡＮＳＳ总分及其分量表均显著降低;治疗前患者ＰＲＬ较对照组显著降低,治疗后显著性增高。治疗前后泌乳素差值与ＰＡＮＳＳ阳性症状分量表减分值、减分率显著相关。结论利培酮对精神分裂症血泌乳素水平有明显影响,而且泌乳素水平与临床疗效相关。     

Efficacy and Tolerability of Switching to Ziprasidone in Italian Patients with Acute Exacerbation of Schizophrenia: An Open-Label Trial

The long-term maintenance of a stable condition is an important aim of schizophrenia therapy, which frequently requires the switch between 2 antipsychotic agents. This 8-week multicenter study, conducted in Italy, evaluates the switch from a previous antipsychotic to ziprasidone.Adult acute schizophrenic patients requiring a change in antipsychotic for lack of efficacy or tolerability issues took ziprasidone 20?-?80?mg/bid. Dosages could be adjusted during the study. The primary efficacy outcomes were the differences in positive and negative syndrome scale (PANSS) and clinical global impression severity (CGI-S) scores from baseline to study end. Other efficacy variables were clinical global impression improvement, global assessment of functioning, patient preference scale and drug attitude inventory.189 patients were evaluated; the mean (±SD) ziprasidone dose was 95.9±34.5?mg/day. PANSS and CGI-S scores significantly decreased throughout the study. All secondary outcomes significantly improved at the end of the study vs. baseline values. Ziprasidone was well tolerated; 13 patients reported a QTc prolongation (mild in 12 patients).Notwithstanding the limitations of any non-comparative study, these results suggest that ziprasidone may be an effective and well-tolerated option in acute schizophrenia patients who discontinued a previous antipsychotic agent.     

抗精神病药致血糖改变与体重体脂指标关系

目的：分析首次治疗的精神分裂症患者抗精神病药(APS)急性期治疗期间血糖改变及其与体重体脂指标间的关系方法：测定46例患者(男27例，女19例)APS单药治疗10周前后空腹血糖和餐后2h血糖；观察治疗前后体重指数(BMI)和腰臀比率(WHR)，并采用磁共振测定其中40例患者治疗前后腹部脂肪分布结果：患者治疗10周后餐后2h血糖明显增高，葡萄糖耐量低减(IGT)发生率增加。治疗前餐后2h血糖水平与体重体脂指标呈正相关；治疗10周后，餐后2h血糖水平与体重体脂指标无相关。结论：APS急性期治疗可致精神分裂症患者血糖异常；血糖水平改变与体重增加及体脂沉积有关。     

Risperidone-induced increase in serum prolactin is correlated with positive symptom improvement in chronic schizophrenia

The elevation in serum prolactin (PRL) concentration in schizophrenic patients treated with typical antipsychotic drugs is well documented. Recently, increased prolactin levels have been reported in patients taking risperidone. The purpose of this study was to explore the effect of the atypical antipsychotic drug risperidone on serum prolactin, and to investigate the relationship between the change in PRL and the therapeutic outcome. In this study, 30 male inpatients with a diagnosis of chronic schizophrenia (DSM-III-R) were assigned to 12 weeks of treatment with risperidone after a 2-week washout period. The risperidone dose was fixed at 6 mg/day. Clinical efficacy was determined using the Positive and Negative Syndrome Scale (PANSS). Serum PRL was assayed in serum by radioimmunometric assay in schizophrenic patients before and after 12-week treatment, as compared to 30 age-matched normal male subjects. The results showed that risperidone treatment significantly increased the serum PRL. A significant and positive relationship between the change in PRL at pre- and post-treatment and the reduction rate of PANSS positive subscore was observed. Risperidone treatment significantly increased the serum PRL levels of schizophrenic patients. There was a close relationship between the improvement in positive symptoms and the change of serum PRL level before and after risperidone treatment. The serum PRL levels at baseline could be used to predict the responses of schizophrenic patients to risperidone.     

D-alanine added to antipsychotics for the treatment of schizophrenia.

BACKGROUND: Hypofunction of the N-methyl-d-aspartate (NMDA) subtype glutamate receptor had been implicated in the pathophysiology of schizophrenia. Treatment with D-serine, glycine, endogenous full agonists of the glycine site of the NMDA receptor (NMDA-glycine site), D-cycloserine, a partial agonist, or sarcosine, a glycine transporter-1 inhibitor, improves the symptoms of schizophrenia. D-alanine is another endogenous agonist of the NMDA-glycine site that might have beneficial effects on schizophrenia. METHODS: Thirty-two schizophrenic patients enrolled in a 6-week double-blind, placebo-controlled trial of D-alanine (100 mg/kg/day), which was added to their stable antipsychotic regimens. Measures of clinical efficacy and side effects were determined every other week. RESULTS: Patint who received D-alanine treatment revealed significant reductions in their Clinical Global Impression Scale and Positive and Negative Syndrome Scale (PANSS) total scores. The Scale for the Assessment of Negative Symptoms and PANSS subscores of positive and cognitive symptoms were improved. D-alanine was well tolerated, and no significant side effect was noted. CONCLUSIONS: The significant improvement with the D-alanine further supports the hypothesis of hypofunction of NMDA neurotransmission in schizophrenia and strengthens the proof of the principle that NMDA-enhancing treatment is a promising approach for the pharmacotherapy of schizophrenia.     

Serum brain-derived neurotrophic factors in Taiwanese patients with drug-naïve first-episode schizophrenia: Effects of antipsychotics

Objectives: Brain-derived neurotrophic factors (BDNF) are known to be related to the psychopathology of schizophrenia. However, studies focussing on drug-naïve first-episode schizophrenia are still rare.

Methods: Over a 5-year period, we investigated the serum BDNF levels in patients with first-episode drug-naïve schizophrenia and compared them to age- and sex-matched healthy controls. We also explored the association between antipsychotic doses, positive and negative syndrome scale (PANSS) scores, and serum BDNF levels before and after a 4-week antipsychotic treatment.

Results: The baseline serum BDNF levels of 34 patients were significantly lower than those of the controls (df?=?66, P?=?.001). Although the PANSS scores of 20 followed-up patients improved significantly after antipsychotic treatment, the elevation of the serum BDNF levels was not statistically significant (P?=?.386). In addition, Pearson’s correlation test showed significant correlations between pre-treatment negative scale scores and percentage changes in BDNF (P?=?.002).

Conclusions: The peripheral BDNF levels in Taiwanese patients with drug-naïve first-episode schizophrenia, compared with healthy controls, did not elevate after antipsychotic treatment, and pre-treatment negative symptoms played a pivotal role in trajectories of serum BDNF levels. Large samples will be needed in future studies to verify these results.     

Effect of risperidone on serum cytokines

A variety of cytokines are dysregulated in schizophrenia, and some antipsychotic drugs effect cytokines. In order to examine the effect of risperidone on plasma cytokines, we measured the serum level of IL-1b, IL-2, IL-6, IL-12, and INF-g during acute states of illness, and after 4 weeks of treatment with risperidone in 19 schizophrenic patients. The patients' psychopathology was assessed by PANSS. Plasma IL-12 levels increased significantly after 4 weeks of treatment (p = .002). Plasma IL-b, IL-2, IL-6, and INF-g levels were not significantly different before and after treatment. There were no significant correlations between the changes in cytokine levels and the changes in PANSS scores. Increased IL-12 may contribute to activation of immune responses during treatment with risperidone. IL-12 may play an important role in immune responses related to neuropsychiatry.     

Elevated plasma superoxide dismutase in first-episode and drug naive patients with schizophrenia: inverse association with positive symptoms

Excessive free radical production or oxidative stress may be involved in the pathophysiology of schizophrenia as evidenced by increased superoxide dismutase (SOD) activities, a critical enzyme in the detoxification of superoxide radicals. This study compared plasma SOD activities in 78 never-medicated first-episode and 100 medicated chronic schizophrenia patients to 100 healthy control subjects and correlated these SOD activities with the Positive and Negative Syndrome Scale (PANSS) among the schizophrenic patients. We found that both first-episode and chronic patients had significantly increased plasma SOD activities compared to controls, and that chronic schizophrenic patients on antipsychotic medication had significantly higher SOD activities than first episode schizophrenic patients. Plasma SOD activities were also negatively correlated with positive symptoms of schizophrenia, but only in first-episode patients. Thus, oxidative stress appears to be greater in first episode schizophrenic patients with fewer positive symptoms and may become greater as schizophrenia becomes more chronic, although we cannot exclude the possibility that chronic antipsychotic treatment may increase SOD activities and presumed oxidative stress in schizophrenia.