Clozapine is strongly associated with the risk of pneumonia and inflammation

Clinicians need to remember that(1)systemic inflammations can increase clozapine level;(2)clozapine,by itself,can cause inflammation,particularly during titration that is too rapid for that patient;(3)clozapine may increase the risk of infection;and(4)more specifically,clozapine may be particularly strongly associated with the risk of pneumonia.Pneumonia appears to be associated with high mortality in clozapine patients around the world.Clinicians who are alert to the risk of pneumonia in clozapine patients may significantly decrease mortality in clozapine patients.There is no data on COVID-19 infections in clozapine patients,but based on what we know about clozapine pharmacology,we can hypothesise that clozapine,possibly by impairing immunological mechanisms,may increase the risk of pneumonia in infected patients.More importantly,once fever and/or pneumonia develops,the clozapine dose should be cut in half to decrease the risk of clozapine intoxication.If there is any doubt that in spite of halving the dose there are still signs of clozapine intoxication,completely stopping clozapine may be indicated.Once the signs of inflammation and fever have disappeared,the clozapine dose can be increased to the prior dosage level.

中国精神分裂症患者失匹配负波特征的Meta分析（英文）

背景:国外对精神分裂症患者失匹配负波(mismatch negativity,MMN)波幅进行Meta分析发现其明显低于健康对照组,区分效应值(Cohen’s d,)d在1.00左右,使之可能成为精神分裂症早期诊断的生物标志物。但检索文献未发现纳入中国精神分裂症人群MMN研究的Meta分析报道,因此有必要对中国精神分裂症患者的MMN进行Meta分析。目的:通过Meta分析计算中国精神分裂症患者MMN的平均效应值,探讨其是否可作为中国精神分裂症患者的生物标志物。方法:计算机检索中国知网(China National Knowledge Infrastructure,CKNI)、万方数据库(WanF ang Data)、维普数据库(Vip Citation Databases,VIP)、PubM ed数据库,收集2017年5月8日前公开发表的关于中国汉族精神分裂症患者MMN研究的相关文献。MMN受损的影响通过计算精神分裂症患者组和健康对照组之间的标准平均差(SMDs)来评估MMN波幅。结果:共有11篇文献纳入分析。Newcastle-Ottawa Scale(NOS)评估所有研究的总体质量超过6。这些研究的meta分析数据包括精神分裂症患者432例,健康对照人群392例。Meta分析结果显示,精神分裂症组与健康对照组相比MMN受损显著(Cohen’s d=1.004)。剔除异质性大的文献2个,患者组和健康对照组之间MMN差异的效应值降为0.79(Cohen’s d=0.79)。亚组分析显示精神分裂症病程大于3年的患者MMN波幅缺失的效应值为0.95,而病程小于3年的效应值为0.77。通过Egger回归分析得出的发表偏移(t=1.83;p=0.101)提示没有发表偏移。结论:中国精神分裂症患者和健康对照者之间的MMN波幅效应值与其他关于该研究的meta分析结果是一致的,提示中国汉族精神分裂症患者也表现有MMN受损。

Why sex differences in schizophrenia？

Clinical observation shows that men and women are different in prevalence, symptoms, and responses to treatment of several psychiatric disorders, including schizophrenia. While the etiology of gender differences in schizophrenia is only partially understood, recent genetic studies suggest significant sex-specific pathways in the schizophrenia between men and women. More research is needed to understand the causal roles of sex differences in schizophrenia in order to ultimately develop sex-specific treatment of this serious mental illness. In the present review, we will out-line the current evidence on the sex-related factors interaction with disease onset, symptoms and treatment of schizophrenia, and discuss the potential molecular mechanisms that may mediate their cooperative actions in schizophrenia pathogenesis.

Prepulse inhibition deficits in antipsychotic-na-ve first-episode schizophrenia:a meta-analysis

Objective:Published studies have found prepulse inhibition(PPI)in schizophrenia is impaired,suggesting PPI may be a biomarker of schizophrenia.We aim to examine whether PPI deficits exist in antipsychotic-na-ve,first-episode schizophrenia,and evaluate the effect size of PPI deficits between patients and healthy controls.Methods:The effect size of PPI deficits was evaluated for PPI%by calculating standard mean differences(SMDs)between patients with antipsychotic-na-ve,first-episode schizophrenia and healthy controls.Results:Twelve studies met the inclusion criteria,consisting390antipsychotic-na-ve,first-episode schizophrenia and406healthy controls.The effect sizes of76dB PPI in60ms and120ms interstimulus interval(ISI)were-0.19and-0.41respectively,and the76dB PPI overall effect size was-0.30.The effect sizes of85/86dB PPI in30ms,60ms and120ms ISI were-0.25,-0.42and-0.59respectively,and the85/86dB PPI overall effect size was-0.46.One study were excluded due to heterogeneity in the85/86dB,120ms ISI group,the pooled effect size of the PPI differences between patient group and health control dropped to-0.42,and the overall effect size changed to-0.39.There were no statistical differences in startle magnitude(overall effect size=-0.18)and habituation%(overall effect size=-0.17)between patients and healthy controls.Conclusions:Antipsychotic-na-ve,first-episode schizophrenia patients exhibit robust and reliable deficits in PPI,85/86dB PPI deficit was more severe than76dB PPI,and85/86dB,60-ms ISI PPI was more likely to be a biomarker for schizophrenia,it suggested that the parameters of PPI are particularly significant to affect the effect size so that should be interpreted with cautions in the future studies.

The effect of lithium on resting-state brain networks in patients with bipolar depression

Objective： Although lithium has been a commonly prescribed neurotrophic/neuroprotective mood-stabilizing agents, its effect on spontaneous brain activity in patients with bipolar depression remains unclear. The aim of this study is to reveal the basic mechanism underlying the pathological influences of lithium on resting-state brain function of bipolar depression patients. Methods：97 subjects including 9 bipolar depression patients with lithium treatment, 19 bipolar depression patients without lithium treatment and 69 healthy controls, were recruited to participate in this study. Amplitude of low-frequency fluctuation （ ALFF ） and fractional amplitude of low-frequency fluctuation （ fALFF） were used to capture the changes of spontane-ous brain activity among different groups. In addition, further analysis in terms of Hamilton Depression Rating Scale, the number of depressive episodes, and illness duration in pooled bipolar depression patients were conducted, which combined FLEF and fALEF to identify the basic neural features of bipolar depression patients. Results： It was observed from the imaging results that both the bipolar depression patients receiving lithium treatment and healthy control subjects showed signifi-cantly decreased ALFF/fALFF values in the right anterior cingulate cortex and right middle frontal gyrus compared to that from the bipolar depression patients without lithium treatmetn. The ALFF values of the right＆amp;nbsp;middle temporal gyrus was also found to be negative related to the number of depressive episode and the total episodes. Conclusions：Our findings suggested that the bipolar depression subjects were identified to have ab-normal ALFF/ fALFF in the corticolimbic systems, in-cluding regions like right anterior cingulate cortex, bilateral middle frontal gyrus, right orbital frontal gyrus, and right middle temporal gyrus. In addition, it was also revealed that the decreased ALFF/fALFF in the right anterior cingulate cortex and right middle frontal gyrus might be a biomarker that is related to the lithium effects.

Testing the role of genetic variation of the MC4R gene in Chinese population in antipsychotic-induced metabolic disturbance

Antipsychotic-induced metabolic disturbance(AIMD) is a common adverse effect of antipsychotics with genetics partly underpinning variation in susceptibility among schizophrenia patients. Melanocortin4 receptor(MC4 R) gene, one of the candidate genes for AIMD, has been under-studied in the Chinese patients. We conducted a pharmacogenetic study in a large cohort of Chinese patients with schizophrenia. In this study, we investigated the genetic variation of MC4 R in Chinese population by genotyping two SNPs(rs489693 and rs17782313) in 1,991 Chinese patients and examined association of these variants with the metabolic effects that were often observed to be related to AIMD. Metabolic measures, including body mass index(BMI), waist circumference(WC), glucose, triglyceride, high-density lipoprotein(HDL), and low-density lipoprotein(LDL) levels were assessed at baseline and after 6-week antipsychotic treatment. We found that interaction of SNP×medication status(drug-na?ve/medicated) was significantly associated with BMI, WC, and HDL change %, respectively. Both SNPs were significantly associated with baseline BMI and WC in the medicated group. Moderate association of rs489693 with WC, Triglyceride, and HDL change % were observed in the whole sample. In the drug-na?ve group, we found recessive effects of rs489693 on BMI gain more than 7%, WC and Triglyceride change %, with AA incurring more metabolic adverse effects. In conclusion, the association between rs489693 and the metabolic measures is ubiquitous but moderate. Rs17782313 is less involved in AIMD. Two SNPs confer risk of AIMD to patients treated with different antipsychotics in a similar way.

Interaction Between Variations in Dopamine D2 and Serotonin 2A Receptor is Associated with Short-Term Response to Antipsychotics in Schizophrenia

Dear Editor,Schizophrenia is a chronic and debilitating brain disorder,which has a strong genetic component with heritability ranging from 66%to 85%[1,2].Currently,antipsychotic drugs remain the most effective treatment for the psychotic symptoms of schizophrenia[3].Because of the severe sideeffects of first-generation antipsychotics(FGAs),secondgeneration antipsychotics(SGAs)have become more widely used in the treatment of schizophrenia.