[Cardiovascular diseases burden attributed to low physical activity in China, 1990-2019].

Objective: To analyze the burden of cardiovascular disease (CVD) attributed to low physical activity (LPA) and its changing trends in China from 1990 to 2019. Methods: On the basis of the province results of the Study of Global Burden of Disease 2019 in China, we described the distribution of CVD death and disability-adjusted life year (DALY) attributed to LPA by sex, age and province. Joinpoint 4.9.1.0 was used to calculate the average annual percentage change. Results: In 2019, the number of CVD deaths and DALY attributed to LPA in people aged ≥25 years were 0.127 million and 1.863 million person-years in China, respectively, The age-standardized mortality rate (ASMR) and standardized DALY rate of CVD attributed to LPA were slightly higher in men than in women, and much higher in ischemic heart disease patients than in ischemic stroke patients. The ASMR (8.85/100 000) and the standardized DALY rate (112.34/100 000) of CVD attributed to LPA in China in 2019 showed no obvious change compared with 1990, while decreased in the last decade. The largest increases in the mortality rate and DALY rate were observed in people aged ≥75 years from 1990 to 2019 (26.89%, 15.61%), but the mortality rate and DALY rate in people aged 60-74 years showed a decreasing trend. The mortality rate and DALY rate in men aged 25- 44 years showed the largest increases (37.50%, 35.49%), while women aged ≥75 years had the largest increases (31.00%, 18.02%). In 2019, the highest ASMR and standardized DALY rate of CVD attributed to LPA were found in Jilin, Inner Mongolia and Hebei. The largest increases were found in Qinghai (182.41%, 154.70%), Gansu (181.29%, 152.77%), and Chongqing (132.01%, 102.79%) and the largest decreases were found in Beijing (59.11%, 62.09%), Macau (41.89%, 39.37%) and Guangdong (36.93%, 40.72%) from 1990 to 2019. Conclusion: The disease burden of CVD attributed to LPA in China was quite high and showed gender, age and area specific differences.

Associations of a family history of lupus with the risks of lupus and major psychiatric disorders in first-degree relatives.

BACKGROUND: Genetic factors link psychiatric disorders, particularly major depressive disorder (MDD), bipolar disorder, and obsessive-compulsive disorder (OCD), with systemic lupus erythematosus (SLE). Additionally, maternal SLE is a risk factor for long-term developmental problems, particularly learning disabilities, attention disorders, autism spectrum disorder (ASD) and speech disorders, in children. AIM: We aimed to determine whether first-degree relatives (FDRs) of patients with SLE have increased risks of SLE and major psychiatric disorders. DESIGN AND METHODS: Using the Taiwan National Health Insurance Research Database, we recruited 40 462 FDRs of patients with SLE as well as 161 848 matched controls. The risks of major psychiatric disorders, including schizophrenia, bipolar disorder, OCD, MDD, ASD and attention-deficit/hyperactivity disorder (ADHD), were assessed. RESULTS: The FDRs of patients with SLE had higher risks of SLE (reported as the adjusted relative risk and 95% confidence interval: 14.54; 12.19-17.34), MDD (1.23; 1.12-1.34), ADHD (1.60; 1.55-1.65), OCD (1.41; 1.14-1.74) and bipolar disorder (1.18; 1.01-1.38) compared with controls. Specifically, male FDRs of patients with SLE had higher risks of SLE and bipolar disorder, whereas female FDRs of patients with SLE had higher risks of MDD and OCD. Differences in the familial relationship (i.e. parents, children, siblings and twins) were consistently associated with higher risks of these disorders compared with controls. CONCLUSIONS: The FDRs of patients with SLE had higher risks of SLE, MDD, ADHD, OCD and bipolar disorder than the controls.

[24 hours urinary sodium and potassium excretion and association with blood pressure among people aged 18-75 years old in six Chinese provinces].

Objective: To analyze the level of sodium and potassium intake and their association with blood pressure among people aged 18 to 75 years old in six provinces. Methods: From October to December 2018, participants aged 18 to 75 years were selected from Hebei, Hunan, Sichuan, Jiangxi, Qinghai and Heilongjiang provinces by using cluster random sampling method. Demographic characteristics and lifestyle information were collected by using questionnaire survey. Physical measurement and 24-hour urine collection were also conducted. Results: A total of 2 636 subjects were finally included in the analysis. The average urine sodium, potassium and sodium-to-potassium molar ratio were(4 438.4±1 822.8)mg/d, (1 566.2±646.3)mg/d, and 5.2±2.2, respectively. According to World Health Organization standards, 94.5% and 98.7% of the respondents had excessive sodium intake and insufficient potassium intake. After adjusting for related factors, each 1 000 mg increase in sodium excretion was associated with increased systolic blood pressure (1.65 mmHg, 95%CI: 1.07, 2.22) and diastolic blood pressure (0.53 mmHg, 95%CI: 0.21, 0.84), and each 1 000 mg increase in potassium excretion was associated with decreased systolic blood pressure (3.02 mmHg, 95%CI:-4.25, -1.80) and diastolic blood pressure (1.27 mmHg, 95%CI:-2.05, -0.48). Conclusion: The sodium intake in Chinese population remains excessive and potassium intake is insufficient. Sodium and potassium could be associated with blood pressure and the intervention of reducing sodium and supplementing potassium should be conducted in the corresponding population.

Silencing of miR-330-5p stimulates osteogenesis in bone marrow mesenchymal stem cells and inhibits bone loss in osteoporosis by activating Bgn-mediated BMP/Smad pathway.

OBJECTIVE: To illustrate the role of micro ribonucleic acid (miR)-330-5p in regulating osteogenesis through biglycan (Bgn)-mediated bone morphogenetic protein (BMP)/Smad pathway. MATERIALS AND METHODS: A mouse model of osteoporosis (OP) was established by ovariectomy (OVX). BMD and miR-330-5p levels in mice undergoing sham operation or OVX were determined. BMD and BV/TV in OP mice with in vivo knockdown of miR-330-5p were measured by Micro-CT. After silencing of miR-330-5p in mouse primary bone marrow stromal cells (BMSCs), expression changes in osteogenesis-associated genes, ALP activity, and mineralization ability were assessed. Subsequently, the interaction between miR-330-5p and Bgn was examined by Dual-Luciferase reporter gene assay and Western blotting. Then, Bgn levels in BMSCs undergoing osteogenesis at different time points were measured. At last, the regulatory effects of miR-330-5p/Bgn axis on the BMP/Smad pathway, ALP activity, and mineralization ability in BMSCs were evaluated. RESULTS: BMD was decreased and miR-330-5p was upregulated in OP mice. OP mice with in vivo knockdown of miNA-330-5p presented higher BMD and BV/TV than controls. Transfection with miR-330-5p inhibitor upregulated osteogenesis-associated genes, ALP activity, and mineralization ability in BMSCs. Bgn was time-dependently upregulated in BMSCs undergoing osteogenesis, which was indicated to be the target gene of miR-330-5p. Besides, Bgn level was negatively regulated by miR-330-5p. Importantly, Bgn was able to reverse the regulatory effects of miR-330-5p on the BMP/Smad pathway, ALP activity, and mineralization ability in BMSCs. CONCLUSIONS: Knockdown of miR-330-5p facilitates osteogenesis in BMSCs through the Bgn-induced BMP/Smad pathway, thus alleviating the progression of OP.

[Feasibility evaluation of estimating the 24-hour urinary sodium excretion in Chinese population with three spot urine methods].

Objective: To evaluate the feasibility of three spot urine methods (Kawasaki, INTERSALT and Tanaka) for estimating the 24 h urinary sodium excretion in the Chinese population. Methods: In 2017, 1 499 participants aged 18 to 69 years old were selected from Yiwu City, Haining City, Taishun County, Yinzhou District of Ningbo City and Liandu District of Lishui City of Zhejiang Province by using the multistage random sampling method. Sociodemographic information of the subjects was collected with questionnaires and physical measurements were performed. 24 h urine was collected and urinary volume was recorded. The concentrations of urinary sodium, potassium and creatinine were also measured. Kawasaki, INTERSALT and Tanaka spot urine methods were applied to estimate the 24 h urinary sodium excretion and compared with actual values among 1 426 participants who passed urine integrity test. Results: The age of participants was (46.71±14.04) years old, including 700 males, accounting for 49.1%. The actual value of 24 h urinary sodium excretion was (167.10±74.70) mmol, but Kawasaki method overestimated it as (184.61±57.10) mmol, and INTERSALT and Tanaka methods underestimated it as(134.62±39.21) and (143.20±35.66) mmol. Estimated difference (95%CI) (mmol) from small to large was Kawasaki method [17.51 (13.54, 21.47)], Tanaka method [-23.90 (-27.60, -20.20)] and INTERSALT method [-32.48 (-36.29, -28.67)]. With the increase of 24 h sodium intake, all estimation methods changed from the overestimation to underestimation. In those with 24 h sodium intake <9.0 g, the estimated difference (95%CI) of the INTERSALT method was the smallest as 43.15 (37.73, 48.57) and 1.26 (-2.10, 4.63) mmol for <6.0 and 6.0-8.9 g groups, respectively. In those with 24 h sodium intake≥9.0 g, the Kawasaki method had the smallest estimated difference (95%CI) as -12.50 (-18.14, -6.86) and -53.73 (-61.25, -46.22) for 9.0-11.9 g and ≥ 12.0 g group, respectively. The consistency analysis of the Bland-Altman method showed that the Kawasaki method had the best consistency with actual measured value and it had the least number of points outside the range (69 points accounting for 4.84%). Conclusion: Among the three spot urine methods, the Kawasaki method has better applicability in predicting the excretion of 24 h urine sodium in the Chinese population.

[Prevalence, control of hypertension and intake of sodium and potassium among residents aged 50-69 years old in Zhejiang Province in 2017].

Objective: To understand prevalence, control of hypertension and intake of sodium and potassium among residents aged 50-69 years old in Zhejiang Province. Methods: A multi-stage random cluster sampling method was used to select 3 032 residents aged 50-69 years old in Zhejiang Province. The demographic characteristics, prevalence and control of hypertension were collected through a questionnaire survey, and physical measurement was also performed. The stratified random sampling method was used to detect the level of sodium and potassium in the 24 h urine of 676 subjects. The total amount of 24 h urinary sodium ≥102.55 mmol and the ratio of 24 h urinary sodium and potassium content ≥2 were defined as excessive. Results: The prevalence of hypertension (95%CI) was 56.89% (54.39%-59.40%), and the awareness, treatment and control rate of hypertension were 58.25% (55.01%-61.49%), 45.37% (42.10%-48.65%) and 19.75% (17.01%-22.50%), respectively. 78.99% (n=534) of residents had excessive 24 h urinary sodium, and 95.41% (n=360) of residents had excessive ratio of 24 h urinary sodium and potassium. Conclusion: The prevalence of hypertension in residents aged 50-69 years old in Zhejiang Province was at a high level, and the control of hypertension was not satisfactory in 2017. Most of residents have excessive level of sodium intake and the level of sodium and potassium intake was not balanced.

Burden of diabetes, hyperglycaemia in China from to 2016: Findings from the 1990 to 2016, global burden of disease study.

AIMS: The prevalence of diabetes in China is among the highest in the world. For this reason, findings from the 2016 Global Burden of Disease (GBD) study were used to calculate the burden of hyperglycaemia and diabetes in China. METHODS: Following the general analytical strategy used in GBD 2016, diabetes prevalence and mortality were analyzed by age and gender. Trends in disability-adjusted life years (DALYs) due to diabetes were assessed in 33 province-level administrative units from 1990 to 2016, and similar data were provided for chronic kidney disease (CKD) related to diabetes and, as an overall summarizing measure, for hyperglycaemia expressed as high fasting plasma glucose (HFPG). RESULTS: From 1990 to 2016, all-age prevalence of diabetes rose from 3.7% to 6.6%, and all-age diabetes and diabetes-related CKD mortality rates increased by 63.5% and 33.3%, respectively, with both rates increasing more rapidly in diabetes patients aged 15-49 years than in any other age groups. In 2016, HFPG became China's sixth leading cause of DALYs, and the attributable DALYs burden was 1802.3/100,000 population. Although the number of diabetes DALYs increased by 95% from 1990 to 2016, age-standardized diabetes DALYs rates increased by only 2.3%. Also, from 1990 to 2016, rates of age-standardized DALYs due to diabetes decreased in 14 provinces, but increased in 19 provinces. High BMI Scores and diets low in whole grains, nuts and seeds were the most important risk factors for diabetes in 2016. CONCLUSION: Diabetes and hyperglycaemia constitute a huge health burden in China. The substantial increase in diabetes-related burden represents an ongoing challenge, given the rapidly ageing Chinese population. Thus, a targeted control and preventative strategy needs to be developed at risk factor level to reduce this burden.

[Effect of lifestyle intervention among high risk group of chronic diseases in Shenzhen Futian district].

Objective: To evaluate the effect of lifestyle intervention among high risk group of chronic diseases in Shenzhen Futian district. Methods: 12 out of 115 communities were randomly selected in Futian district of Shenzhen city from October to November, 2013, and 1 923 cases were screened by multiple ways as high risk groups of chronic diseases. High risk groups of chronic diseases were divided into intervention group (1 338 cases, from five residential communities and three villages within city) and control group (585 cases, from four residential communities). The intervention group received group based health education activities as well as lifestyle intervention. The intervention group was provided with health management which was mainly lifestyle intervention. No intervention was implemented in the control group. All participants were followed up over two years. 1 563 participants (1 002 in intervention group and 561 in control group) were followed up from October to November, 2015. The changes of lifestyle related outcome indicators were analyzed to examine the effect of intervention. Results: In the intervention group, 21.8% (219 persons) in high risk groups of chronic diseases became healthy individuals and 15.2% (152 persons) became patients with chronic diseases. In the control group, 9.6% (54 persons) in high risk groups of chronic diseases became healthy individuals and 20.5% (115 persons) became patients with chronic diseases. The outcome of the intervention group was better than that of the control group and the difference was statistically significant (χ2=-5.67, P<0.001). The proportion of people who knew how to correctly use of oil control pot in the intervention group increased from 61.00% (61/100) to 80.00% (280/350). The proportion of people who took oil control measures in the intervention group increased from 36.43% (365/1 002) to 56.99%(571/1 002). The changes in the intervention group were statistically different (P<0.001), but there was no statistical difference in the control group over the years (P>0.05). The proportion of people who knew how to correctly use of the salt restriction spoon increased from 81.95% (109/133) to 97.99% (342/349). The proportion of people who took salt control measures increased from 45.61% (457/1 002) to 62.67% (628/1 002) in the intervention group. The changes in the intervention group were statistically different (P<0.001). There was no statistical difference in the control group over the years (P>0.05). Conclusion: The proportion of people who adopted healthy lifestyles has increased after 2 years intervention and the lifestyle intervention demonstrated good effect.

Co-aggregation of major psychiatric disorders in individuals with first-degree relatives with schizophrenia: a nationwide population-based study.

A previous genetic study has suggested that schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorder (ASD) and attention deficit hyperactivity disorder (ADHD) share common disease-associated genes. However, whether individuals with first-degree relatives (FDRs) with schizophrenia have a higher risk of these major psychiatric disorders requires further investigation. This study used Taiwan's National Health Insurance Research Database and identified 151 650 patients with schizophrenia and 227 967 individuals with FDRs with schizophrenia. The relative risks (RRs) of schizophrenia and other major psychiatric disorders were assessed in individuals with FDRs with schizophrenia. The individuals with FDRs with schizophrenia exhibited higher RRs (95% confidence interval) of major psychiatric disorders, namely schizophrenia (4.76, 4.65-4.88), bipolar disorder (3.23, 3.12-3.35), major depressive disorder (2.05, 2.00-2.10), ASD (2.55, 2.35-2.77) and ADHD (1.31, 1.25-1.37) than were found in the total population. Several sensitivity analyses were conducted to confirm these results. A dose-dependent relationship was observed between the risks of major psychiatric disorders and the numbers of FDRs with schizophrenia. The increased risks of major psychiatric disorders were consistent in different family relationships, namely among parents, offspring, siblings and twins. Our study supports the familial dose-dependent co-aggregation of schizophrenia, bipolar disorder, major depressive disorder, ASD and ADHD, and our results may prompt governmental public health departments and psychiatrists to focus on the mental health of individuals with FDRs with schizophrenia.

Risk of developing Parkinson's disease among patients with asthma: a nationwide longitudinal study.

BACKGROUND: A cross-sectional retrospective study suggested a link between allergic diseases and Parkinson's disease. However, the temporal association between asthma and Parkinson's disease remains unknown. METHODS: From the Taiwan National Health Insurance Research Database, 10 455 patients who were diagnosed with asthma between 1998 and 2008 and aged ≥45 years and 41 820 age- and sex-matched controls were selected for our study and observed until the end of 2011. Those who developed Parkinson's disease during the follow-up period were identified. We also examined the asthma severity, as indicated by the frequency of admission (times per year) for asthma exacerbation, and the risk of subsequent Parkinson's disease. RESULTS: Patients with asthma had an increased risk of developing Parkinson's disease (hazard ratio [HR]: 3.10, 95% confidence interval [CI]: 2.20-4.36) after we adjusted for demographic data, health system use, medical comorbidities, and medication use. Sensitivity tests yielded consistent findings after we excluded observations on the first year (HR: 2.90, 95% CI: 2.04-4.13) and first 3 years (HR: 2.46, 95% CI: 1.64-3.69). Patients with asthma who had more frequent admissions (times per year) during the follow-up period exhibited a greater risk of subsequent Parkinson's disease (>2: HR: 16.42, 95% CI: 5.88-45.91; 1-2: 12.69, 95% CI: 5.03-31.71; 0-1: HR: 2.92, 95% CI: 1.91-4.49). CONCLUSION: Patients with asthma had an elevated risk of developing Parkinson's disease later in life, and we observed a dose-dependent relationship between greater asthma severity and a higher risk of subsequent Parkinson's disease.

Gene-gene interactions of the INSIG1 and INSIG2 in metabolic syndrome in schizophrenic patients treated with atypical antipsychotics.

The use of atypical antipsychotics (AAPs) is associated with increasing the risk of the metabolic syndrome (MetS), which is an important risk factor for cardiovascular disease and diabetes. Two insulin-induced gene (INSIG) isoforms, designated INSIG-1 and INSIG-2 encode two proteins that mediate feedback control of lipid metabolism. In this genetic case-control study, we investigated whether the common variants in INSIG1 and INSIG2 genes were associated with MetS in schizophrenic patients treated with atypical antipsychctics. The study included 456 schizophrenia patients treated with clozapine (n=171), olanzapine (n=91) and risperidone (n=194), for an average of 45.5±27.6 months. The prevalence of MetS among all subjects was 22.8% (104/456). Two single-nucleotide polymorphisms (SNPs) of the INSIG1 gene and seven SNPs of the INSIG2 gene were chosen as haplotype-tagging SNPs. In single-marker-based analysis, the INSIG2 rs11123469-C homozygous genotype was found to be more frequent in the patients with MetS than those without MetS (P=0.001). In addition, haplotype analysis showed that the C-C-C haplotype of rs11123469-rs10185316- rs1559509 of the INSIG2 gene significantly increased the risk of MetS (P=0.0023). No significant associations were found between polymorphisms of INSIG1 gene and MetS, however, INSIG1 and INSIG2 interactions were found in the significant 3-locus and 4-locus gene-gene interaction models (P=0.003 and 0.012, respectively). The results suggest that the INSIG2 gene may be associated with MetS in patients treated with AAPs independently or in an interactive manner with INSIG1.

The coding-synonymous polymorphism rs1045280 (Ser280Ser) in beta-arrestin 2 (ARRB2) gene is associated with tardive dyskinesia in Chinese patients with schizophrenia.

BACKGROUND: Tardive dyskinesia (TD) is a severe and potentially irreversible adverse effect of long-term antipsychotic treatment. Typical antipsychotics are commonly binding to the dopamine receptor D2 (DRD2), but the occurrence of antipsychotic-induced TD is rather delayed; therefore, the development of TD may be associated with mediators or signalling complexes behind DRD2, such as beta-arrestin 2 (ARRB2), an important mediator between DRD2 and serine-threonine protein kinase (AKT) signal cascade. METHODS: A case-control study to evaluate the association between rs1045280 (Ser280Ser) and antipsychotic-induced TD was performed amongst 381 patients (TD/non-TD = 228/153). RESULTS: There was a significant difference in the genotype distribution between TD and non-TD groups (P = 0.025); furthermore, the allelic analysis indicated that patients with T allele had increased risk of TD occurrence (OR(T) = 1.58, 95% CI = 1.14-2.19, P = 0.007). CONCLUSIONS: To the best of our knowledge, this is the first study reporting a positive association between the SNP rs1045280 and TD in schizophrenic patients.

A comparative efficacy and safety study of long-acting risperidone injection and risperidone oral tablets among hospitalized patients: 12-week randomized, single-blind study.

OBJECTIVE: The superiority of risperidone long-acting injection (RLAI) over oral typical and atypical antipsychotics demonstrated in previous studies may be related to the improved drug compliance. The aim of the 12-week randomized, single-blind study was to test whether the superiority of RLAI remained among hospitalized patients that drug compliance could be optimally controlled. METHODS: Fifty hospitalized stable schizophrenic patients, who had maintained on oral risperidone for more than 3 months, were randomized to the RLAI and oral risperidone group. Finally 49 patients (98 %) completed the study, and no dose change of oral risperidone, or RLAI was noted among all patients. RESULTS: The RLAI group showed significantly increased positive score of Positive and Negative Syndrome Scale (PANSS) than the risperidone group (0.72 +/- 3.52 vs. -1.24 +/- 3.81, p = 0.022), but without significance difference for the PANSS total, negative and general psychopathology scores. The RLAI group also showed a significantly improved Udvalg for Kliniske Undersogelser (UKU) Scale (p = 0.037), social life domains of Short-Form Health Survey (SF-36) (p = 0.011), and reduced prolactin level (p = 0.001). CONCLUSION: The results indicated that with optimal controlling of drug compliance among hospitalized patients, RLAI showed no benefit of efficacy over oral risperidone, but with advantages of improved side-effect profiles, social life ratings, and reduced prolactin levels.

Polymorphism of the adrenergic receptor alpha 2a -1291C>G genetic variation and clozapine-induced weight gain.

Weight gain, leading to further morbidity and poor treatment compliance, is a common consequence of treatment with clozapine. The substantial interindividual and interracial differences in drug-induced weight gain suggest that genetic factors may be important. Several studies showed that alpha-2, adrenoceptor may related to feeding behavior with rat or lipolytic activity of human adipocyte tissue, they are related to body weight change. In the study, we try to test the possible relation of clozapine-induced weight gain and adrenergic receptor alpha 2a -1291C>G genetic polymorphism in a long term follow up (14.0 +/- 6.2 months). Our results show the genotype GG (8.45 +/- 7.2 Kg) with higher mean body weight gain than genotype CC (2.79 +/- 6.1 Kg) (p = 0.023). The finding identify a genetic factor associated with clozapine-induced weight gain in schizophrenic patients.

Negative association between catechol-O-methyltransferase (COMT) gene Val158Met polymorphism and persistent tardive dyskinesia in schizophrenia.

Chronic administration of typical antipsychotic agents, which mainly act on the dopamine receptors, implicates a role of dopamine system on the susceptibility of tardive dyskinesia (TD). In the present study, the association between a functional Val158Met polymorphism of Catechol-O-methyltransferase (COMT) gene and TD occurrence and TD severity was investigated in 299 Chinese schizophrenic patients with long-term antipsychotic treatment (TD: 166, non-TD: 133). After adjusting the effects of confounding factors, there was no significant association between COMT genotype and TD occurrence (p=0.367). Among TD patients, we found no significant correlation between COMT genotypes and the total scores of abnormal involuntary movement scale (AIMS) (p=0.629). We concluded that this COMT polymorphism might not play a major role in the susceptibility of TD nor on the severity of TD.

Association analysis of a neural nitric oxide synthase gene polymorphism and antipsychotics-induced tardive dyskinesia in Chinese schizophrenic patients.

Recent findings from rodent studies with chronic administration of antipsychotic drugs have indicated the role of neural nitric oxide synthase (NOS1) on the susceptibility of tardive dyskinesia (TD). In the present study, the association between a 3'-untranslated region C267T (3'-UTR C267T) polymorphism of the NOS1 gene and TD as well as TD severity was investigated in 251 Chinese schizophrenic patients with long-term antipsychotic treatment (TD: 128, non-TD: 123). After adjusting the effects of confounding factors, there was no significant association between NOS1 3'-UTR C276T genotypes and TD occurrence (p=0.758). With in the TD group, we could not discover a significant correlation between NOS1 3'-UTR C276T genotypes and the scores of abnormal involuntary movement scale (AIMS) (p=0.219 and 0.774). We concluded that the NOS1 3'-UTR C276T polymorphism might not play a major role in the susceptibility of TD development, or on the severity of TD.

Therapeutic effect of pirenzepine for clozapine-induced hypersalivation: a randomized, double-blind, placebo-controlled, cross-over study.

The objective of this study was to investigate the efficacy of pirenzepine in the treatment of clozapine-induced hypersalivation. Pirenzepine is reported to counteract hypersalivation by its selective antagonistic activity on the M4-muscarinic receptor, which is stimulated by clozapine. Twenty patients with clozapine-induced hypersalivation underwent a random-order, double-blind, placebo-controlled, cross-over trial which lasted 8 weeks each for the pirenzepine and placebo investigations, with a 4-week washout period in between. The severity of hypersalivation was assessed using an objective measure: saliva production monitored through the diameter of wetted surface on tissue paper placed over the patient's pillow. Our study showed that pirenzepine had no significant therapeutic effect on hypersalivation compared with placebo, suggesting that hypersalivation induced by clozapine might have a neurobiological basis other than the M4-muscarinic receptor.