Patient-centered and integrated outreach care for chronic hepatitis C patients with serious mental illness in Taiwan.

Patients with serious mental illness have a higher risk of hepatitis C virus (HCV) infection but suboptimal HCV care. The current study aimed to facilitate HCV treatment uptake by implementing an integrated outreach care model. Multidisciplinary outreach screening followed by HCV reflex testing and onsite treatment for schizophrenia patients was accomplished through the coordination of nongovernmental organizations, remote specialists, and local care providers. The objective was microelimination effectiveness, defined as the multiplication of the rates of anti-HCV antibodies screening, accurate HCV RNA diagnosis, treatment allocation, treatment completion, and sustained virological response (SVR12; no detectable HCV RNA throughout 12 weeks in the post-treatment follow-up period). A total of 1478 of the 2300 (64.3%) psychiatric patients received HCV mass screening. Seventy-three (4.9%) individuals were seropositive for anti-HCV antibodies. Of the 73 anti-HCV seropositive patients, all (100%) received HCV reflex testing, and 29 (37.7%) patients had HCV viremia. Eight patients (34.8%) had advanced liver disease, including 3 with liver cirrhosis and 2 with newly diagnosed hepatocellular carcinoma. Twenty-three of the 24 (95.8%) patients who stayed in the healthcare system received and completed 8 weeks of glecaprevir/pibrentasvir treatment and post-treatment follow-up without significant DDIs or adverse events. The SVR12 rate was 100%. The microelimination effectiveness in the current study was 61.6%. Individuals with serious mental illness are underserved and suffer from diagnostic delays. This patient-centered and integrated outreach program facilitated HCV care in this marginalized population.

The Alpha-2A Adrenergic Receptor Gene -1291C/G Single Nucleotide Polymorphism is Associated with the Efficacy of Methylphenidate in Treating Taiwanese Children and Adolescents with Attention-Deficit Hyperactivity Disorder.

OBJECTIVE: The therapeutic effect of methylphenidate (MPH) in treating attention-deficit/hyperactivity disorder (ADHD) has been related to the alpha-2A adrenergic receptor (ADRA2A) gene -1291C/G single nucleotide polymorphism (SNP). We investigated the effect of MPH in treating Taiwanese children and adolescent with ADHD and its relation to the ADRA2A gene -1291C/G SNP. METHODS: The subjects with DSM-IV ADHD diagnosis underwent a titration period to find out the dose of MPH for maintenance treatment. After 4 weeks maintenance treatment, the effect of MPH was evaluated by the Swanson, Nolan and Pelham version IV total scores. The subjects with more than 25% score reduction were referred to responders and those with ≥50% improvement were considered as better responders. The -1291C/G variant of the ADRA2A gene was identified by DNA sequencing and what relevance it has to the MPH response was examined by binary logistic regression analysis. RESULTS: Of the 59 subjects, 44 (74.6%) were responsive to MPH treatment and the responsiveness was not shown to be associated with the ADRA2A gene -1291C/G SNP. As the responsive subjects were categorized as moderate responders and better responders and subjected to statistical analysis, the GG homozygotes showed a greater chance to have a better response to MPH treatment than CC homozygotes (p=0.02), with an odds ratio of 32.14 (95% CI=1.64-627.80). CONCLUSION: The ADRA2A gene -1291C/G SNP is associated with the efficacy of MPH for the treatment of ADHD in Taiwanese children and adolescents. The responsive subjects bearing homozygous -1291G allele are more likely to have a better response to MPH treatment.

Yokukansan and its ingredients as possible treatment options for schizophrenia.

Schizophrenia is a debilitating psychotic mental disorder that affects almost the entire range of human mental function. The devastating effect of the illness is usually long-lasting and requires lifelong treatment. Despite an evolved psychopharmacological understanding, the overall therapeutic effect of antipsychotics is still not satisfactory. The choice of proper medication presents a clinical dilemma between efficacy and safety. As a result, searching for comparable treatment options with safer profiles is very important. Yokukansan (TJ-54), also called yi-gan san in Chinese, is a traditional herbal medicine with evident therapeutic effect for neuropsychiatric disorders. There are several open-label clinical studies upholding the possibility of using yokukansan to treat schizophrenia or schizophrenia-like psychosis. Evidence from animal studies and neurobiology also sheds light on the antipsychotic implications of yokukansan and its ingredients. Nevertheless, correlations between the experimental environment and clinical settings may be complicated by a number of confounders. Clinical trials with more sophisticated designs are required to fill the gap between the experimental environment and clinical settings.

Effects of group music intervention on psychiatric symptoms and depression in patient with schizophrenia.

OBJECTIVES: To examine the effects of a group music therapy on psychiatric symptoms and depression for patient with schizophrenia in a psychiatric nursing home. SUBJECTS AND METHODS: Eighty patients with schizophrenia were randomly assigned to a music intervention group (MIG) or usual care group (UCG). Both groups received similar medical and routine care. The MIG received a 60-min group music therapy twice a week, a total of ten sessions. The UAG only received the usual care with no music therapy. Psychiatric symptoms and depression assessments were conducted using the positive and negative syndrome scale and the depression scale for schizophrenia at baseline, the posttest, and at a 3-month follow-up. RESULTS: Thirty-eight patients in the MIG and 42 in the UCG completed the study. After 10 sessions of group music therapy, the groups showed statistically significant differences in psychiatric symptoms (p<.05) and depression status (p<.05). CONCLUSION: Group music therapy is an economical and easily implemented method of improving depression and psychiatric symptoms in patients with schizophrenia.

Measurement of waist circumference at different sites affects the detection of abdominal obesity and metabolic syndrome among psychiatric patients.

There is a lack of understanding about the impact of different waist circumference (WC) measurements on the detection of abdominal obesity and metabolic syndrome in psychiatric patients. This cross-sectional study included a total of 382 inpatients with schizophrenia-related disorders to assess each component of metabolic syndrome. WC was measured at the lowest rib, midpoint between the iliac crest and lowest rib, iliac crest, minimal waist, and umbilicus. Logistic regression analysis was performed to examine the ability of WC at each site to predict the presence of metabolic risk clustering. The mean WC values for all sites were significantly different from each other. The measurement site had an influence on the prevalence of abdominal obesity (30-38.2% in men and 53.9-86.3% in women). The influence on the prevalence of metabolic syndrome was greater with the International Diabetes Federation (IDF) criteria (19.3-23.9% in men and 29.4-43.1% in women) than with the Adult Treatment Panel III (ATP III) criteria (26.1-28.6% in men and 37.3-44.1% in women). The areas under the receiver operating characteristic curve for metabolic risk clustering were highest at the umbilicus and midpoint. Given that the WC measurement protocol has substantial influence on the prevalence of abdominal obesity and metabolic syndrome, a predefined measurement site is required for all psychiatric studies.

Reduction of dorsolateral prefrontal cortex gray matter in late-life depression.

Postmortem studies have documented abnormalities in the dorsolateral prefrontal cortex (dlPFC) in depressed subjects. In this study we used magnetic resonance imaging to test for dlPFC volume differences between older depressed and non-depressed individuals. Eighty-eight subjects meeting DSM IV criteria for major depressive disorder and thirty-five control subjects completed clinical evaluations and cranial 3T magnetic resonance imaging. After tissue types were identified using an automated segmentation process, the dlPFC was measured in both hemispheres using manual delineation based on anatomical landmarks. Depressed subjects had significantly lower gray matter in the left and right dorsolateral prefrontal cortex (standardized to cerebral parenchyma) after controlling for age and sex. Our study confirmed the reduction of dorsolateral prefrontal cortex in elderly depressed subjects, especially in the gray matter. These regional abnormalities may be associated with psychopathological changes in late-life depression.

Risperidone for pre-existing severe tardive dyskinesia: a 48-week prospective follow-up study.

Atypical antipsychotics can alleviate the severity of tardive dyskinesia, but few studies have monitored their long-term effects. The present study investigated the effect of risperidone on pre-existing severe tardive dyskinesia among 40 patients with chronic schizophrenia over 48 weeks. The total Abnormal Involuntary Movement Scale (AIMS) score decreased in 35 patients (87.5%) and increased in three patients (7.5%). At the end of the 48-week trial, the mean total AIMS score decreased significantly, from 15.7+/-4.7 (baseline) to 10.6+/-4.4 (P<0.001), with a mean risperidone dosage of 3.6+/-1.5 mg/day. Twenty-three patients (57.5%) were responders with an average total AIMS score decrease of 8.0+/-2.7. Multiple logistic regression analysis controlling for age, gender, duration of illness, index hospitalization duration, risperidone dose, anticholinergic concomitant use and dystonia score change revealed that a change in the parkinsonism score was the most significant factor related to responders (odds ratio 3.476, 95% confidence interval 1.173-10.298). A significant improvement observed in tardive dyskinesia was noted at week 8, and this improvement persisted until week 48. The results show that the effect of risperidone on pre-existing tardive dyskinesia may be beneficial.

Cytochrome P-450 2D6*10 C188T polymorphism is associated with antipsychotic-induced persistent tardive dyskinesia in Chinese schizophrenic patients.

Typical antipsychotic treatment had been postulated to be a risk factor for the susceptibility to tardive dyskinesia (TD). The cytochrome P-450 debrisoquine/sparteine hydroxylase (CYP2D6) metabolizes a majority of antipsychotics and exhibits various phenotypes on enzymatic activities from poor metabolizers to ultrarapid metabolizers. The various phenotypes are encoded by polymorphic genetic variants on the CYP2D6 gene. Although several studies had explored the association between the CYP2D6*10 C188T polymorphism, which encodes the phenotype intermediate metabolizers, and TD in Orientals, the findings were inconclusive. In the present study, we examined the relationship between the CYP2D6*10 C188T polymorphism and the TD occurrence in 216 Chinese schizophrenic patients (113 patients with TD and 103 patients without TD) and explored the correlation between the TD severity assessed by the Abnormal Involuntary Movement Scale (AIMS) and each C188T genotype in the 113 TD patients. Using logistic regression analysis, we found a modest association (p = 0.045) between TD and C188T genotypes. This positive finding was only observed in male patients (p = 0.001), but not in females. Our findings also support the correlation between AIMS scores and C188T polymorphism within the TD group after adjusting for confounding effects with the multiple regression analysis (p = 0.033). We concluded that the CYP2D6*10 C188T polymorphism may be associated with the susceptibility to the occurrence of TD induced by typical antipsychotics, especially in male patients, and may also be correlated with AIMS scores in TD patients.

Association analysis of the dopamine D3 receptor gene ser9gly and brain-derived neurotrophic factor gene val66met polymorphisms with antipsychotic-induced persistent tardive dyskinesia and clinical expression in Chinese schizophrenic patients.

The association between the dopamine D3 receptor (DRD3) ser9gly genetic polymorphism and tardive dyskinesia (TD), a serious adverse motor disorder after long-term antipsychotic treatment, has been studied extensively in recent years. However, the existence of inconsistent reports makes the role of the DRD3 ser9gly polymorphism in TD development questionable. In rodent studies, the DRD3 expression could be controlled by the brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family. In this study, we examined the association between the DRD3 ser9gly and BDNF val66met genetic polymorphisms and TD occurrence in 216 schizophrenic patients (TD/non-TD = 102/114). In addition, we also studied the effects of the DRD3 ser9gly and BDNF val66met genotypes and their gene-gene interaction on the clinical expression of TD in these TD patients. We found that the TD patients who were heterozygous for the BDNF genotypes had significantly higher abnormal involuntary movement scale (AIMS) orofacial scores (corrected p = 0.021, Bonferroni correction), and a trend of higher AIMS total and limb-trunk scores than the combined homozygous analogs. The correlation between the DRD3 ser9gly genotypes and its interaction with the BDNF val66met polymorphism, and the three classes of AIMS scores were not statistically significant. Furthermore, neither the DRD3 nor the BDNF genotypes and alleles were demonstrated to be associated with TD occurrence. We concluded that the BDNF val66met genetic polymorphism may exert its effect on the clinically phenotypic variability after TD has occurred. Further replication studies with larger sample size and stringent definition for TD is necessary.

Risperidone for severe tardive dyskinesia: a 12-week randomized, double-blind, placebo-controlled study.

BACKGROUND: Risperidone has been reported to alleviate the severity of tardive dyskinesia, but without placebo control, the possibility of spontaneous tardive dyskinesia remission after discontinuing original conventional antipsychotics cannot be excluded. This 12-week randomized, double-blind, placebo-controlled study investigated the effect of risperidone on severe tardive dyskinesia. METHOD: Forty-nine DSM-IV schizophrenia patients with severe tardive dyskinesia were enrolled in the study. After a 4-week washout period, the subjects were randomly assigned to treatment with either risperidone or placebo. The risperidone dose was started at 2 mg/day and gradually increased to 6 mg/day over 6 weeks; the 6-mg/day dose was maintained for the remaining 6 weeks of the study. The subjects were evaluated every 2 weeks with the Abnormal Involuntary Movement Scale (AIMS) and the Extrapyramidal Symptom Rating Scale. The final mental status was assessed with the Brief Psychiatric Rating Scale. RESULTS: Twenty-two subjects in the risperidone group and 20 subjects in the placebo group completed the study; the mean baseline AIMS total score for all subjects was 15.9 +/- 4.6. At the end of the study, the mean AIMS total score decrease was 1.1 +/- 4.8 in the placebo group and 5.5 +/- 3.8 in the risperidone group (p <.05). Fifteen subjects (68%) in the risperidone group and 6 subjects (30%) in the placebo group were responders (p <.05). The risperidone responders had a mean AIMS total score decrease of 7.5 +/- 2.1. More significant tardive dyskinesia improvement among the risperidone group was noted from the eighth week and was mainly demonstrated in the buccolinguomasticatory a rea rather than in choreoathetoid movement of the extremities (p <.001). CONCLUSIONS: Risperidone, 6 mg/day, can improve tardive dyskinesia more significantly than discontinuing antipsychotics in patients with severe tardive dyskinesia, especially in the orofacial areas.

Association study of the estrogen receptor polymorphisms with tardive dyskinesia in schizophrenia.

Tardive dyskinesia (TD) is an involuntary movement disorder induced by long-term antipsychotic treatments. Estrogen is suggested to modulate dopamine receptors in the central nervous system and may decrease the incidence and/or relieve the symptoms of TD. In this study, 118 schizophrenia patients with antipsychotic-induced TD and 128 sex- and age-matched non-TD schizophrenia patients were recruited. All patients were assessed by the Abnormal Involuntary Movement Scale and genotyped for the polymorphisms of estrogen receptor-alpha gene (ESR 1). There was a marginal association of the genotypes determined by PVU II between TD and non-TD patients (p = 0.057), but not of the genotypes determined by XBA I (p = 0.896). However, further studies on other polymorphisms of ESR 1 or other estrogen receptors are necessary to clarify the role of estrogen in the pathogenesis of TD.