Mong Liang Lu

Posttraumatic stress disorder among professional and non-professional rescuers involved in an earthquake in Taiwan

This study investigated the prevalence of posttraumatic stress disorder (PTSD) among professional and non-professional rescue workers involved in the 1999 Chi-Chi Earthquake in Taiwan. One month following the disaster, 252 rescue workers (167 professional rescue workers, 85 non-professional volunteers) were surveyed with the Chinese version of the Davidson Trauma Scale (DTS-C) and the Chinese version of the SPAN (SPAN-C). Non-professional rescuers had significantly higher scores than professional rescuers on both the DTS-C and the SPAN-C. The prevalences of PTSD, as defined by a DTS-C score > or = 44, among professional and non-professional rescuers were 19.8% and 31.8%, respectively. Among the three subscales of the DTS-C, only scores on the numbness/avoidance subscale were significantly higher in the non-professional than in the professional rescue workers. The results of this study suggest that disaster rescue work is associated with a high level of stress even for highly trained professionals and may lead to mental health problems.

Genetic polymorphisms of cytochrome P450 enzymes influence metabolism of the antidepressant escitalopram and treatment response.

AIMS The antidepressant escitalopram (S-CIT) is metabolized by the cytochrome-P450 (CYP) enzymes CYP 2D6, 2C19 and 3A4. This study evaluated the impact of CYP2D6, 2C19 and 3A4 genetic polymorphisms on plasma concentrations of S-CIT and patient treatment response. MATERIALS & METHODS A total of 100 patients diagnosed with major depressive disorder were recruited to the study and their depression symptoms were assessed using the Hamilton Depression Rating Scale. The genetic polymorphisms *4, *5 and *10 on CYP2D6, *2, *3 and *17 on CYP2C19, and *18 on CYP3A4 were selected based on their function and respective allele frequencies in Asian populations. Polymorphisms were analyzed using the SNPstream genotyping system, PCR and direct sequencing methods. The steady-state serum concentrations of S-CIT and its metabolites S-desmethylcitalopram and S-didesmethylcitalopram were analyzed by HPLC. According to semiquantitative gene dose (SGD) and gene dose (GD) models for allele combinations of these polymorphisms, CYP2D6 was clustered into intermediate (0.5, 1 and 1.5 SGD) and extensive (2 SGD) metabolizers, while CYP2C19 was clustered into poor (0 GD) and extensive (1 and 2 GDs) metabolizers. RESULTS The group of patients with intermediate CYP2D6 metabolism (0.5 SGD) had a significantly higher frequency of remitters from major depressive disorder during the 8-week treatment (p = 0.0001). Furthermore, CYP2C19 poor metabolizers had significantly higher S-CIT serum levels than did extensive metabolizers at weeks 2, 4 and 8 (p < 0.05). The allele frequencies in CYP3A4*18 and CYP2C19*17 were too low to permit further subgroup analyses. CONCLUSION Our results suggest that the genetic polymorphisms in CYP2C19 may be influencing S-CIT serum concentrations, and that specific CYP2D6 polymorphisms may be predicting patient treatment outcomes based on gene dosage analyses.

The early effect of olanzapine and risperidone on insulin secretion in atypical-naïve schizophrenic patients.

Abstract: Recently, increasing attention has been drawn to the potential diabetogenic effect of atypical antipsychotics. The goal of this prospective study is to evaluate the early effect of olanzapine and risperidone treatment on pancreatic β-cell function in atypical-naive schizophrenic patients. Twenty-six subjects were assigned randomly to therapy with olanzapine or risperidone for 14 days. The metabolic parameters were quantitatively assessed by using the intravenous glucose tolerance test. The levels of fasting glucose, fasting insulin, lipid profiles, and leptin were also assessed. There were no significant within-group changes in weight or body mass index for both groups after 2 weeks of treatment. The levels of fasting glucose, fasting insulin, cholesterol, or leptin did not change in both groups. The triglyceride level significantly increased in olanzapine group. Glucose disappearance rate and insulin sensitivity did not change in both groups. Insulin secretion significantly decreased in olanzapine group. After 2 weeks of olanzapine treatment, schizophrenic patients decreased insulin secretory response to a hyperglycemic challenge. The results of this study support the hypothesis that olanzapine might directly impair pancreatic β-cell function.

Implication of serum concentration monitoring in patients with lithium intoxication

Abstract  The aim of the present study was to determine the relationships between serum lithium level, duration of lithium intoxication, severity of symptoms, and the outcome of the disease. Subjects with a serum lithium level of ≥1.2 mEq/L were included in the study. Seventy‐eight patients with lithium intoxication were identified between 1 July 1999 and 31 December 2002. The demographic characteristics, clinical manifestations, and concomitant medications were recorded. Most patients with acute lithium intoxication had mild symptoms, independent of the serum lithium levels. In patients with chronic lithium intoxication, the frequency of severe symptoms was higher than in those with acute intoxication. None of the 78 intoxicated patients in the present survey died or suffered from persistent neurological sequelae. Patients with concomitant medications, older age, and existing neurological illness may have an increased susceptibility to lithium toxicity. Regular monitoring of serum lithium level is essential for lithium‐treated patients. Clinicians should pay attention to patients with pre‐existing neurological illness, older age, or receiving medications that may interact with lithium.

Dopamine D2 receptor gene and alcoholism among four aboriginal groups and Han in Taiwan

Previous studies examining the putative association between DRD2 TaqI A1 and alcoholism have produced conflicting results. Major critiques of such studies include potential confounding arising from population admixture by inappropriate selection of controls, failure to screen out substance abusers from controls, and the failure to assess the severity of alcoholics. To address these issues, we compared the allelic frequency of two polymorphisms of DRD2, TaqI A and NcoI, among severe alcoholics and their ethnically matched nonalcoholic controls within four major aboriginal groups and Han (Chinese) in Taiwan. The sample of alcoholics and controls examined for the five groups included 36 and 31 (Atayal), 24 and 23 (Ami), 58 and 58 (Bunun), 35 and 35 (Paiwan), and 50 and 66 (Han). A borderline association between TaqI A1 and alcoholism among the Ami (P = 0.08) and an association between NcoI N1 and alcoholism among Han (P = 0.01) were found. Results of haplotype analysis further confirm that the frequency of haplotype A1N1 was higher in alcoholics than in controls for the Ami (P = 0.01) and Han (P = 0.03). If controls with tobacco abuse were excluded from the analysis, the results remained unchanged. Severity in medical complications of alcohol dependence with withdrawal symptoms was not associated with higher prevalence of DRD2 TaqI A1 or NcoI N1 alleles. The absence of an association between DRD2 and alcoholism among the three aboriginal groups suggests either a higher rate of phenocopies among aboriginal alcoholics or genetic heterogeneity in the susceptibility to alcoholism.

Effects of adjunctive metformin on metabolic traits in nondiabetic clozapine-treated patients with schizophrenia and the effect of metformin discontinuation on body weight: A 24-week, randomized, double-blind, placebo-controlled study

OBJECTIVE Many studies have shown that metformin can decrease body weight and improve metabolic abnormalities in patients with schizophrenia. Whether or not the beneficial effects can be sustained after discontinuation of metformin needs to be evaluated. We conducted a 24-week randomized, double-blind, placebo-controlled study to evaluate the effect of metformin on metabolic features in clozapine-treated patients with schizophrenia and followed their body weight after stopping the intervention for at least 24 weeks. METHOD The study was conducted between September 2008 and July 2011. We recruited patients with DSM-IV diagnosis of schizophrenia or schizoaffective disorder who had been taking clozapine for more than 3 months, were overweight or obese, or fulfilled at least 1 criteria of metabolic syndrome. Eligible patients were randomized to receive metformin 1,500 mg/d or placebo. We followed metabolic features at baseline and at weeks 2, 4, 8, 16, and 24 and rechecked body weight when the patients stopped the trial after at least 24 weeks. RESULTS A total of 55 subjects (28 in the metformin and 27 in the placebo group) were enrolled. There were no significant differences in all baseline characteristics between the 2 groups, except that patients in the metformin group had higher fasting plasma glucose levels (P = .03). After the 24-week intervention, body weight (P < .0001), body mass index (P < .0001), fasting plasma glucose (P < .0001), high-density lipoprotein cholesterol (P = .03), insulin level (P = .01), and homeostasis model assessment index (P = .02) had significant changes in the metformin group. At the end of the intervention, 8 patients (28.57%) lost more than 7% of their body weight in the metformin group. Mean body weight returned to baseline after patients stopped the intervention in the metformin group. CONCLUSIONS Metformin can significantly reduce body weight and reverse metabolic abnormalities in clozapine-treated patients with schizophrenia and preexisting metabolic abnormalities. However, the beneficial effects of metformin on body weight disappeared after discontinuing this medication.

Time course of the changes in antipsychotic-induced hyperprolactinemia following the switch to aripiprazole

Hyperprolactinemia is an important but neglected adverse effect of antipsychotic medication. All first generation antipsychotics and the second generation antipsychotics amisulpride and risperidone have been shown to cause marked elevation in serum prolactin levels, whereas most other second generation antipsychotics and aripiprazole appear to have little or no effect on serum prolactin levels. This study was aimed to assess the time course of changes in antipsychotic-induced hyperprolactinemia during the process of antipsychotic switching to aripiprazole. Twenty-three female schizophrenic subjects with risperidone- or sulpiride-induced symptomatic hyperprolactinemia were recruited into the study and 20 of them completed the trial. We added aripiprazole to the therapeutic dose first, then overlapped the preexisting antipsychotic treatment and aripiprazole, and finally tapered the preexisting antipsychotic treatment. Clinical status was assessed by using the Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression Severity Scale (CGI-S). Assessment scales and serum prolactin levels were measured at baseline, during the combination treatment period, and four weeks after having completed discontinuation of the preexisting antipsychotic treatment. Switching antipsychotic drugs to aripiprazole was effective in reducing serum prolactin levels and restoring menstruation in schizophrenic patients who received prolactin-raising antipsychotics. Mean serum prolactin levels at baseline, during combination period, and after the switch were 97.0+/-69.0 ng/ml, 27.2+/-10.6 ng/ml (p<0.001, vs. baseline), and 12.2+/-5.3 ng/ml (p<0.001, vs. baseline), respectively. None of the study subjects experienced any serious adverse effects during the switching process. No significant changes were noted in the PANSS and CGI-S scores during the switching process. The prolactin-normalizing effects of aripiprazole are likely caused by the unique characteristics of the dopamine partial agonist with its high affinity for dopamine D2 receptors.

The time-dependent change of insulin secretion in schizophrenic patients treated with olanzapine

The second generation antipsychotic drugs (SGAs) are effective in treating patients with schizophrenia and have been considered as the first line therapy. Recently, increasing attention has been drawn to the potential diabetogenic effect of these novel antipsychotics. The goal of this study was to evaluate the time-dependent effects of olanzapine treatment on pancreatic beta cell function in SGA-naïve schizophrenic patients. Forty-two schizophrenic subjects received olanzapine therapy for 8 weeks and thirty-three of them completed the trial. Of whom 33 completers (21 male, mean+/-SD age: 37.6+/-8.0 years) were inpatients and unexposed to SGA. The metabolic parameters were quantitatively assessed at weeks 0, 2, 4, and 8 by the intravenous glucose tolerance test. After 56-day olanzapine treatment, subjects had significant increases in body weight and as well as in the levels of triglyceride, total cholesterol, and low-density lipoprotein. Insulin secretion significantly decreased at week 2, returned to baseline at week 4, and significantly increased at week 8. Of the total samples, 18.2% and 33.3% of them met the criteria for significant weight gain and metabolic syndrome after 8-week olanzapine treatment, respectively. This study indicates that olanzapine-treated schizophrenic patients displayed biphasic changes in insulin secretion to a hyperglycemic challenge. The results of this study support that olanzapine might directly influence pancreatic beta cell function.

Cabergoline-induced psychotic exacerbation in schizophrenic patients

INTRODUCTION Hyperprolactinemia is a well-recognized side effect of antipsychotic treatment. Cabergoline, a dopamine agonist, has been introduced on the market to treat hyperprolactinemia, even secondary to antipsychotic use. CASE REPORT In this article, we described two schizophrenic patients who received cabergoline to treat their antipsychotic-induced hyperprolactinemia and developed a subsequent psychotic exacerbation. The first patient received amisulpride as antipsychotic medication, and the second one took risperidone and fluoxetine for her psychotic and depressive symptoms, respectively. Both patients improved significantly their psychotic symptoms in 1 week without changing their former antipsychotic regimens. DISCUSSION To the best of our knowledge, we found no previous report of cabergoline-induced psychotic exacerbation in schizophrenic patients who received antipsychotics. We brought up questions whether schizophrenic patients on amisulpride or with the addition of fluoxetine may have higher risk to experience psychotic worsening. We also highlighted the possible role of dose-dependent nature in cabergoline-induced psychotic exacerbation, suggesting that the single starting dose of 0.5 mg or higher might be unsafe in schizophrenic patients. CONCLUSION These cases suggest that cabergoline, like other dopaminergic agents, should be used with caution in psychotic patients and the dose should be as low as possible.

The Chinese version of the Davidson Trauma Scale : A practice test for validation

Abstract The Chinese version of the Davidson Trauma Scale (DTS‐C) was developed to respond to the need of Chinese‐speaking individuals. The DTS is a validated self‐rating scale used in the diagnosis of posttraumatic stress disorder (PTSD). The DTS‐C is translated from DTS through a two‐stage translation. Subjects were drawn from a sample of 210 survivors of the 21 September 1999, Chi‐Chi Earthquake. The scale showed good internal consistency (Cronbachs α = 0.97) and test–retest reliability (r = 0.88). Concurrent validity was obtained against the clinical diagnostic interview, with a diagnostic accuracy of 0.85 at DTS‐C score of 44. It showed that the sensitivity was 0.9, specificity 0.81, positive likelihood ratio 4.74, and negative likelihood ratio 0.12. The recommended stratum‐specific likelihood ratios were 0.10 (95% CI: 0.05–0.20) for the score range 0–39, 4 (2.22–7.23) for the score range of 40–59, and 6.14 (3.42–11.02) for the scores above 60. In PTSD diagnosed subjects, the factor structures closely resembled the DSM‐IV grouping of PTSD symptoms. The psychometric strength of DTS‐C is reliable for its future use, particularly for screening for subjects with possible diagnosis of PTSD.