Anxiety symptom remission is associated with genetic variation of PTPRZ1 among patients with major depressive disorder treated with escitalopram.

OBJECTIVES: Genome-wide analyses of antidepressant response have suggested that genes initially associated with risk for schizophrenia may also serve as promising candidates for selective serotonin reuptake inhibitor (SSRI) efficacy. Protein tyrosine phosphatase, receptor-type, zeta-1 (PTPRZ1) has previously been shown to be associated with schizophrenia, but it has not been investigated as a predictor of antidepressant efficacy. The main objective of the study was to assess whether SSRI-mediated depressive and anxiety symptom remission in Chinese patients with major depressive disorder (MDD) are associated with specific PTPRZ1 variants. METHODS: Two independent cohorts were investigated, the first sample (N = 344) received an SSRI (i.e. fluoxetine, sertraline, citalopram, escitalopram, fluvoxamine, or paroxetine) for 8 weeks. The second sample (N = 160) only received escitalopram for 8 weeks. Hamilton Depression and Hamilton Anxiety Rating Scale scores at 8-weeks post-baseline in both cohorts were used to determine remission status. Five PTPRZ1 variants (rs12154537, rs6466810, rs6466808, rs6955395, and rs1918031) were genotyped in both cohorts. RESULTS: Anxiety symptom remission was robustly associated with PTPRZ1 rs12154537 (P = 0.004) and the G-G-G-G haplotype (rs12154537-rs6466810-rs6466808-rs6955395; P = 0.005) in cohort 2 but not cohort 1 (mixed SSRI use). Associations with depressive symptom remission did not survive correction for multiple testing. CONCLUSIONS: These findings suggest that PTPRZ1 variants may serve as a marker of escitalopram-mediated anxiety symptom remission in MDD.

Associations among serum markers of inflammation, life stress and suicide risk in patients with major depressive disorder.

BACKGROUND: Patients with major depressive disorder (MDD) are at high risk for suicide. As the worst outcome of MDD and common self-concealment in patients with suicide risk, studies of biomarkers may provide useful tools for suicide prevention and treatment. METHODS: This study recruited 168 patients with MDD from the Objective Diagnostic Markers and Personalized Intervention in MDD patients (ODMPIM), including 50 patients with suicide risk. Based on previous evidence and hypothesis, 23 targeted serum biomarkers involving immune-inflammation, neurotrophins, hypothalamic-pituitary-adrenal (HPA) axis and metabolism, were measured. We used path analysis and principal components analysis (PCA) to clarify the associations among serum biomarkers, childhood adversities, adulthood life events, severity of depression and suicide risk. RESULTS: We identified that patients with suicide risk had a higher level of inflammatory markers in serum than patients without suicide risk (P < 0.001), especially chemokine (C-X-C motif) ligand 1 (CXCL-1). After using the Bonferroni correction, there were no differences in biomarkers related to neurotrophins, HPA-axis and metabolism. In addition, a higher proportion of patients with suicide risk had adulthood adversity (assessed by Life Events Scale) (P = 0.003). Intriguingly, path analysis demonstrated that the association between adulthood adversity and suicide risk mainly depended on severity of depression and inflammatory index. CONCLUSION: This study highlights the possible role of inflammation involved in suicide risk of MDD patients. Inflammatory markers have the potential for early identification and then reducing suicidal behaviors or becoming novel treatment targets in suicide risk management.

Lack of association between genetic polymorphisms of CYP3A4, CYP2C9 and CYP2C19 and antituberculosis drug-induced liver injury in a community-based Chinese population.

The precise pathogenic mechanism of antituberculosis (anti-TB) drug-induced liver injury (ATLI) is poorly understood. It may be associated with drug-metabolizing enzymes, such as cytochrome P450 (CYP) 3A4, CYP2C9 and CYP2C19. The aim of the present study was to explore the role of tagging single nucleotide polymorphisms (tSNPs) of CYP3A4, CYP2C9 and CYP2C19 in the risk of ATLI in a population-based anti-TB treatment cohort. A nested case-control study was designed. Each ATLI case was matched 1 : 4 with controls on the basis of age, gender, treatment history, disease severity and drug dosage. The tSNPs were selected using Haploview 4.2 based on the HapMap database of Han Chinese in Beijing and genotyped by TaqMan allelic discrimination technology. Eighty-nine patients with ATLI and 356 controls were included in the study. One tSNP in CYP3A4 (rs12333983), two in CYP2C9 (rs4918758, rs9332098) and two in CYP2C19 (rs11568732, rs4986894) were selected and genotyped. The minor allele frequencies of rs12333983, rs4918758, rs9332098, rs11568732 and rs4986894 were 36.0%, 41.4%, 1.1%, 5.7% and 35.7%, respectively, in the patients, compared with 31.7%, 42.9%, 3.4%, 8.9% and 35.1%, respectively, in the controls. No significant differences were observed in genotypes or allele frequencies of the five tSNPs between the two groups and none of the CYP2C9 or CYP2C19 haplotypes was significantly associated with the development of ATLI. Based on the Chinese anti-TB treatment cohort, we did not find a significant association between the risk of ATLI and genetic polymorphisms of CYP3A4, CYP2C9 and CYP2C19. None of the haplotypes exhibited a significant association with the development of ATLI in a Chinese tuberculosis population.

Effectiveness and safety of methylphenidate and atomoxetine for attention deficit hyperactivity disorder: a systematic review.

OBJECTIVE: To assess and compare the effectiveness and safety of methylphenidate immediate-release tablets (IR-MPH), methylphenidate controlled-release tablets (OROS-MPH) and atomoxetine (AHC) for attention deficit hyperactivity disorder (ADHD) in Chinese children. METHODS: Randomized or clinical controlled trials on the effectiveness and safety of IR-MPH, OROS-MPH and AHC for ADHD were searched in electronic databases of CNKI, VIP, CBMDISC online, PubMed, Embase and MEDLINE. Two reviewers independently extracted the data and assessed the quality of the included literatures. RESULTS: Eight trials were finally included. IR-MPH, OROS-MPH and AHC were effective for ADHD. OROS-MPH was superior to IR-MPH in the improvement of peer relationship, CGI-I score, mother satisfaction and psychosomatic problems. There were no significant differences in the effectiveness between the AHC and IR-MPH groups. The adverse events related to the therapy with IR-MPH, OROS-MPH or AHC were mild and total incidence rates of adverse events was not significantly different among the three groups. CONCLUSIONS: The effectiveness of OROS-MPH for the treatment of ADHD is probably superior to IR-MPH, and the effectiveness of AHC and IR-MPH is similar. The three drugs have equivalent safety and good tolerance.

[Effectiveness and safety of methylphenidate and atomoxetine for attention deficit hyperactivity disorder: a systematic review].

OBJECTIVE: To assess and compare the effectiveness and safety of methylphenidate immediate-release tablets (IR-MPH), methylphenidate controlled release tablets (OROS-MPH) and atomoxetine (AHC) for attention deficit hyperactivity disorder (ADHD) in Chinese children. METHODS: Randomized or clinical controlled trials on the effectiveness and safety of IR-MPH, OROS-MPH and AHC for ADHD were searched in electronic databases of CNKI, VIP, CBMDISC online, PubMed, Embase and MEDLINE. Two reviewers independently extracted the data and assessed the quality of the included literatures. RESULTS: Eight trials were finally included. IR-MPH, OROS-MPH and AHC were effective for ADHD. OROS-MPH was superior to IR-MPH in the improvement of peer relationship, CGI-I score, mother satisfaction and psychosomatic problems. There were no significant differences in the effectiveness between the AHC and IR-MPH groups. The adverse events related to the therapy with IR-MPH, OROS-MPH or AHC were mild and the incidence rates of adverse events were not significantly different among the three groups. CONCLUSIONS: The effectiveness of OROS-MPH for the treatment of ADHD is probably superior to IR-MPH, and the effectiveness between AHC and IR-MPH is similar. The three drugs demonstrate the safety and well tolerance.

[Fatality and secular trend of bloodstream infections during hospitalization in China: a systematic review and meta-analysis].

OBJECTIVE: To get an overview of the fatality and secular trend of bloodstream infection (BSI) during hospitalization in China. METHODS: Papers published between 1990 and Aug. 2008 on the core journals included by Chinese Biomedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI) and VIP Chinese Periodical Database were systematically searched. Studies providing data of BSI fatality during hospitalization with a non-comparative, observational design were included. Meta-analysis was done using the generic inverse variance model. RESULTS: Overall, 72 studies were included for this analysis. The weighted BSI fatality in-hospital based on them was 28.7% (95%CI: 27.2%-30.3%), with substantial differences between study and heterogeneity. For BSI cases from across all departments of hospitals, the weighed fatality was 20.7% (95%CI: 17.8%-24.0%). In the departments of burn, hematology and/or malignant tumors, and ICU, BSI fatalities were even higher, but were relatively low among BSI cases from neonatal wards, and patients with liver diseases, or diabetes mellitus. Fatality of hospital acquired BSI (HA-BSIs, 26.8%, 95%CI: 22.4%-32.0%) was significantly higher than that of community acquired BSI (CA-BSIs). For the past decades, BSI fatality has declined in various kinds of inpatients. CONCLUSION: BSI fatality during hospitalization was at a high level in China, but with a downward trend over the past decades.

[Genetic polymorphism of glutathione-S-transferase M1 and T1: a systematic review in Chinese population and a pilot study in smear-positive pulmonary tuberculosis cases of Jilin province].

OBJECTIVE: To investigate the distribution of glutathione-S-transferase M1 (GSTM1) and T1 (GSTT1) genes polymorphisms in Chinese population and smear-positive pulmonary tuberculosis cases of Jilin province. METHODS: Articles about GSTM1 and GSTT1 genes polymorphisms published before 2009 in China were searched. The study population was obtained from fourteen counties (or districts) of Jilin province, which included all cases from November, 2007 to May, 2008, totally 1120. The genotypes of GSTM1 and GSTT1 were detected by multiplex PCR technique. RESULTS: The frequencies of GSTM1 and GSTT1 'null' genotypes and combination M1-T1 'null' genotype acquired from systematic review were 54.2%, 46.8% and 26.2%, respectively, in Chinese Hans they were 53.4%, 44.9% and 25.5%, and in our research they are 57.2%, 20.4% and 13.7%, respectively. No significant differences between the frequencies of males and females as well as among that of different age groups were observed (P > 0.05). The frequency of GSTM1 'null' genotype in our research is slightly higher than that in systematic review (P = 0.016) , and the frequencies of GSTT1 'null' genotype and combination M1-T1 'null' genotype and are significantly lower than those in systematic review (both P < 0.001). CONCLUSION: The frequencies of GSTM1 and GSTT1 'null' genotypes were different among ethnic. The statistical difference between systematic review and our research may due to our large sample size and mostly Southern people in previous studies.