Patients with schizophrenia are susceptible to low bone mineral density (BMD). Many risk factors have been suggested. However, it remains uncertain whether the risk factors differ between men and women. In addition, the study of bone density in men is neglected more often than that in women. This study aims to examine specific risk factors of low BMD in different sexes. Men (n=80) and women (n=115) with schizophrenia, similar in demographic and clinical characteristics, were enrolled in three centers. Clinical and laboratory variables (including blood levels of prolactin, sex and thyroid hormones, cortisol, calcium, and alkaline phosphatase) were collected. BMD was measured using a dual-energy X-ray absorptiometer. Men had lower BMD than women. Predictors for BMD in men included hyperprolactinemia (B=-0.821, P=0.009), body weight (B=0.024, P=0.046), and Global Assessment of Functioning score (B=0.027, P=0.043); in women, BMD was associated with menopause (B=-1.070, P<0.001), body weight (B=0.027, P=0.003), and positive symptoms (B=0.094, P<0.001). In terms of the effect of psychotic symptoms, positive symptoms were related positively to BMD in women, but not in men. The findings suggest that sex-specific risk factors should be considered for an individualized intervention of bone loss in patients with schizophrenia. Physicians should pay particular attention to bone density in men with hyperprolactinemia and postmenopausal women. Further prospective studies in other populations are warranted to confirm these findings.
Objectives Hypofunction of NMDA receptor is implicated in the pathophysiology, particularly cognitive impairment, of schizophrenia. Sarcosine, a glycine transporter I (GlyT-1) inhibitor, and sodium benzoate, a d-amino acid oxidase (DAAO) inhibitor, can both enhance NMDA receptor-mediated neurotransmission. We proposed simultaneously inhibiting DAAO and GlyT-1 may be more effective than inhibition of either in improving the cognitive and global functioning of schizophrenia patients. Methods This study compared add-on sarcosine (2 g/day) plus benzoate (1 g/day) vs. sarcosine (2 g/day) for the clinical symptoms, as well as the cognitive and global functioning, of chronic schizophrenia patients in a 12-week, double-blind, randomised, placebo-controlled trial. Participants were measured with the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale every 3 weeks. Seven cognitive domains, recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia Committee, were measured at weeks 0 and 12. Results Adjunctive sarcosine plus benzoate, but not sarcosine alone, improved the cognitive and global functioning of patients with schizophrenia, even when their clinical symptoms had not improved. Conclusions This finding suggests N-methyl-d-aspartate receptor-enhancement therapy can improve the cognitive function of patients with schizophrenia, further indicating this pro-cognitive effect can be primary without improvement in clinical symptoms.
Background The efficacy and safety of ticagrelor compared with clopidogrel in acute coronary syndrome has not previously been evaluated in an Eastern Asian population, which is recognized to have a different response to P2Y12 antagonists compared with the Caucasian population in real-life situations. Methods A multicenter retrospective pilot study was performed to evaluate 928 consecutive patients with acute coronary syndrome, receiving aspirin and one P2Y12 antagonist (324 ticagrelor or 604 clopidogrel). Using propensity score matching, 448 patients were selected and divided into two equal groups. Kaplan–Meier analysis was used to study patient survival and event-free status using the log-rank test. Independent covariates were identified using univariate in a multivariate Cox proportional hazard model. Results In the overall cohort, significant differences were observed for certain variables between the two groups. During the mean 164.3 (±116.4)-day follow-up in the overall cohort, ticagrelor treatment had no significant effect on the primary efficacy endpoint (myocardial infarction, stroke, or vascular death); however, in the matched cohort, ticagrelor showed a lower incidence of primary endpoint (hazard ratio: 0.56; 95% confidence interval: 0.30–1.04; p = 0.07) and stroke (hazard ratio: 0.15; 95% confidence interval: 0.02–1.24; p = 0.08) with marginal statistical significance, and a similar bleeding rate. The protective effect of ticagrelor treatment was consistent for all subgroups. More patients treated with ticagrelor experienced dyspnea (21.0% vs. 11.6%, p = 0.007), and P2Y12 antagonist treatment was consequently discontinued. Conclusion Ticagrelor treatment could provide a marginally favorable effect at the expense of an increased risk of dyspnea in real-life situations. This pilot study provides a scientific basis to call for a larger, suitably powered Phase 4 prospective or observational study in this ethnic population.
Dry mouth is a rather common unpleasant adverse drug reaction (ADR) to lithium treatment in bipolar disorders that often lead to poor adherence or early dropout. The aim of this study was to identify the genetic variants of dry mouth associated with lithium treatment in patients with bipolar I (BPI) disorder. In total, 1242 BPI patients who had ever received lithium treatment were identified by the Taiwan Bipolar Consortium for this study. The proportions of patients who experienced impaired drug compliance during lithium medication were comparable between those only with dry mouth and those with any other ADR (86% and 93%, respectively). Dry mouth appeared to be the most prevalent (47.3%) ADR induced by lithium treatment. From the study patients, 921 were included in a genome-wide association study (GWAS), and replication was conducted in the remaining 321 patients. The SNP rs10135918, located in the immunoglobulin heavy chain locus (IGH), showed the strongest associations in the GWAS (p = 2.12 × 10-37) and replication groups (p = 6.36 × 10-13) (dominant model) for dry mouth with a sensitivity of 84.9% in predicting dry mouth induced by lithium. Our results may be translated into clinical recommendation to help identify at-risk individuals for early identification and management of dry mouth, which will improve medication adherence.
Decreased bone mineral density (BMD) is common in patients with schizophrenia; however, the pathogenesis is unclear. Different classes of antipsychotic agents may affect BMD. This study systemically examined the effects of clozapine vs. other antipsychotics, and several hormonal and metabolic factors that may contribute to BMD in female patients with schizophrenia, who are more vulnerable than males. Forty-eight women with schizophrenia, treated with long-term antipsychotics of the prototype prolactin-sparing (PS) antipsychotic agent clozapine vs. prolactin-raising (PR) antipsychotics were enrolled. They were matched for demographic and clinical characteristics. Various factors, including blood levels of prolactin and sex hormones, psychopathological symptoms, global assessment of functioning, physical activity, and menopausal status, were determined to explore their contribution to low BMD (LBMD), defined as a dual-energy X-ray absorptiometer (DEXA) T score <−1. Overall, women receiving clozapine have better bone density than women receiving PR antipsychotics. Compared to PR antipsychotics, PS clozapine therapy is a protective factor (odds ratio 28.2, 95% confidence interval 2.37–336.10, p=0.008) for LBMD. Predictors for higher bone density in the clozapine group included higher clozapine dose (p<0.001), younger age (p<0.001), and higher thyroid-stimulating hormone level (p<0.001); in the PR group, higher body mass index (p=0.003) and lower alkaline phosphatase level (p=0.007) were associated with LBMD. This study suggests that clozapine treatment is beneficial for BMD compared to PR antipsychotic treatment in women with chronic schizophrenia, and clozapine's bone-density protecting effect is dose-related.
Obesity is a common health problem among patients with schizophrenia, but the precise mechanisms are not fully understood. There has been much interest in the relationship between gut microbiome and development of obesity. Gender-dependent microbial alteration has been reported in previous studies. However, the gender factor in gut microbiome composition of schizophrenia patients has been less investigated. Our study aimed to identify differences in gut microbiota between schizophrenia patients with normal weight and central obesity and investigate the gender specific features.Twenty participants (10 males, 10 females) with central obesity (CO) and 20 participants (10 males, 10 females) with normal weight (NW) were recruited from two rehabilitation wards in a psychiatric hospital in central Taiwan. Fecal samples from 40 participants were processed for microbiota analysis. The intestinal microbiota composition was analyzed using next-generation sequencing and QIIME software.Significantly higher richness of gut microbiota at the class level (measured by the number of observed OTUs) was observed in female NW subjects than in female CO subjects (P = 0.033). Furthermore, female NW subjects showed higher alpha diversity at both phylum and class levels (measured by the Shannon, Simpson, and Inverse-Simpson indexes) compared with female CO subjects. Males showed no significant difference in alpha diversity between groups. Taxonomic analysis showed that female CO subjects had significantly lower abundance of Verrucomicrobia (P = 0.004) at the phylum level, reduced abundance of Akkermansia (P = 0.003) and elevated level of Prevotella (P = 0.038) and Roseburia (P = 0.005) at the genus level.The present results evidenced altered microbiome composition in schizophrenia patients with central obesity and further suggested the role of the gender factor in the process of gut dysbiosis.
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