Tzu-Ting Chen

Association analysis of polymorphisms in the N-methyl-d-aspartate (NMDA) receptor subunit 2B (GRIN2B) gene and tardive dyskinesia in schizophrenia

Tardive dyskinesia (TD) is a neurological disorder characterized by irregular, non-rhythmic, choreoathetotic and involuntary movements in single or multiple body regions. Chronic administration of typical antipsychotic agents, which predominantly act on dopamine receptors, implicates the dopamine system in susceptibility to TD. An alternative to this dopaminergic supersensivity hypothesis in understanding the pathogenesis of TD is the glutamatergic neurotoxicity hypothesis, which implicates the N-methyl-D-aspartate (NMDA) receptor in TD pathogenesis. In the present study, the association between three polymorphisms (T-200G, C366G and C2664T) of the GRIN2B gene, which encodes the 2B subunit of the NMDA receptor, and the occurrence and severity of TD were investigated in 273 Chinese schizophrenic patients receiving long-term antipsychotic treatment (TD: 142, non-TD: 133). There was no significant association between patients genotype and allele frequencies and TD occurrence. Among the TD patients, the differences in the total scores on the Abnormal Involuntary Movement Scale (AIMS) among the three genotypes of each polymorphism were not significant. Because the three studied markers are in weak linkage disequilibrium with each other, haplotype-based association was not carried out. We conclude that genetic variations in the human GRIN2B gene probably do not play a major role in susceptibility to, or severity of TD.

Cardiac tamponade in an infant : a rare complication of central venous catheterisation

A 2994g infant suffered cardiac tamponade from an infusion of total parenteral nutrition through an indwelling central venous catheter. The infant survived as a result of early diagnosis and aggressive therapeutic intervention. Cardiac tamponade secondary to central venous catheterisation is rare, but potentially lethal. Possible mechanisms are direct puncture by the catheter tip, or osmotic injury from the use of hypertonic solutions. To avoid this complication, the catheter tip should be prevented from entering the right atrium and its position should be checked periodically by chest X ray. Cardiac tamponade should be considered in any patient with a central venous catheter whose clinical condition deteriorates suddenly. Diagnostic or therapeutic pericardiocentesis should be employed as the first measure and time should not be wasted on other diagnostic procedures.

Improved body weight and metabolic outcomes in overweight or obese psychiatric patients switched to amisulpride from other atypical antipsychotics.

Switching to a different second-generation antipsychotic (SGA) with a lower risk of weight gain is recommended for overweight or obese psychiatric patients undergoing SGA treatment. However, there have been no complete reports regarding the long-term metabolic effects of switching to amisulpride. In this open-label 1-year study, we investigated the effects on body weight and other metabolic profiles when psychiatric patients treated with another SGA were switched to amisulpride treatment. Forty-six schizophrenia or schizoaffective inpatients with a body mass index greater than 27 kg/m2 were enrolled in the switch group. These patients were cross-titrated to amisulpride treatment and followed up for 1 year prospectively. Another 46 inpatients matched with the baseline body mass index of those in the switch group were enrolled as the control group retrospectively. The results showed that the switch group had greater weight loss than the control group (7.80 ± 6.67 vs 2.60 ± 6.23 kg, respectively; repeated-measure analysis of variance, P < 0.0005). During the treatment course, the amisulpride-treated patients showed significantly decreased fasting triglyceride, total cholesterol, glucose, and insulin resistance levels; decreased diastolic blood pressure and pulse rate; and a significant increase in high-density lipoprotein cholesterol levels after switching to amisulpride (all with a P < 0.05). The prevalence of metabolic syndrome in amisulpride-treated patients also decreased significantly from 65.2% to 30.4% (McNemar test, P < 0.0005). These findings suggest that switching to amisulpride could be an effective treatment of overweight or obese psychiatric patients treated previously with other SGAs.

Clozapine Induces Autophagic Cell Death in Non-Small Cell Lung Cancer Cells

Background/Aims: Previous studies have shown that patients with schizophrenia have a lower incidence of cancer than the general population, and several antipsychotics have been demonstrated to have cytotoxic effects on cancer cells. However, the mechanisms underlying these results remain unclear. The present study aimed to investigate the effect of clozapine, which is often used to treat patients with refractory schizophrenia, on the growth of non-small cell lung carcinoma cell lines and to examine whether autophagy contributes to its effects. Methods: A549 and H1299 cells were treated with clozapine, and cell cytotoxicity, cell cycle and autophagy were then assessed. The autophagy inhibitor bafilomycin A1 and siRNA-targeted Atg7 were used to determine the role of autophagy in the effect of clozapine. Results: Clozapine inhibited A549 and H1299 proliferation and increased p21 and p27 expression levels, leading to cell cycle arrest. Clozapine also induced a high level of autophagy, but not apoptosis, in both cell lines, and the growth inhibitory effect of clozapine was blunted by treatment with the autophagy inhibitor bafilomycin A1 or with an siRNA targeting atg7. Conclusions: Clozapine inhibits cell proliferation by inducing autophagic cell death in two non-small cell lung carcinoma cell lines. These findings may provide insights into the relationship between clozapine use and the lower incidence of lung cancer among patients with schizophrenia.

Depression and anxiety among patients with somatoform disorders, panic disorder, and other depressive/anxiety disorders in Taiwan

The aim of this study is to compare the severity of depression and anxiety in individuals with somatoform disorders, panic disorder, other depressive/anxiety disorders, and healthy controls in a Han Chinese population. According to the DSM-IV-TR-based diagnostic interviews, we recruited 152 subjects with somatoform disorders (SG), 56 with panic disorder (PG), 85 with other depressive/anxiety disorders (OG), and 179 without any psychiatric disorder (NG). The four groups reported on the Beck Depression Inventory-II (BDI-II) and Beck Anxiety Inventory (BAI) for depressive and anxiety symptoms, respectively. Correlation analysis and multivariate regression analysis were used to determine the effects of demographic factors and psychiatric diagnoses on depressive and anxiety symptoms separately. BDI-II scores were not significantly different in SG, PG, and OG but were higher than NG. SG and PG had the highest BAI scores, whereas NG had the lowest. Multiple linear regression analyses revealed that the associated factors for BDI-II were gender, residential location, somatoform disorders, panic disorder, major depressive disorder (MDD), and generalized anxiety disorder, whereas BAI was significantly associated with somatoform disorders, panic disorder, and MDD. Our results strongly suggest the inclusion of clinical assessment of depressive and anxious symptoms in patients with somatoform disorders.

Switching from clozapine to zotepine in patients with schizophrenia: a 12-week prospective, randomized, rater blind, and parallel study.

Abstract Clozapine is the most effective antipsychotic for patients with treatment-refractory schizophrenia, but many adverse effects are noted. Clinicians usually hesitate to switch from clozapine to other antipsychotics because of the risk of a re-emergence or worsening of the psychosis, although empirical studies are very limited. Zotepine, an atypical antipsychotic with a pharmacologic profile similar to clozapine, was found to be an effective treatment for patients with treatment-resistant schizophrenia in Japan. This 12-week study is the first prospective, randomized, and rater-blind study to investigate the efficacy and tolerability of switching from clozapine to zotepine. Fifty-nine patients with schizophrenia, who had taken clozapine for at least 6 months with a Clinical Global Impression–Severity score of at least 3, were randomly allocated to the zotepine and the clozapine groups. At the end of the study, 52 patients (88%) had completed the trial. The 7 withdrawal cases were all in the zotepine group. The final mean (SD) dose of zotepine and clozapine was 397.1 (75.7) versus 377.1 (62.5) mg/d, respectively. Patients in the zotepine group showed a significant increase in the Brief Psychiatric Rating Scale [mean (SD), 4.7 (8.7) vs −1.3 (6.3); P = 0.005], more general adverse effects as revealed by the Udvalg for Kliniske Undersogelser Rating Scale [mean (SD), 1.74 (3.9) vs −0.2 (2.8); P = 0.039], more extrapyramidal adverse effects as demonstrated by the Simpson and Angus Scale [mean (SD), 1.29 (3.5) vs 0.17 (2.1); P = 0.022], an increased use of propranolol (37.1% vs 0%, P < 0.0001) and anticholinergics (25.7% vs 0%, P = 0.008), and an increased level of prolactin (29.6 vs −3.8 ng/ mL, P < 0.0005), compared with the clozapine group. The results suggested that switching from clozapine to zotepine treatment should be done with caution.

Application of the Chinese Version of the Whiteley Index-7 for Detecting DSM-5 Somatic Symptom and Related Disorders

BACKGROUNDnThe Whiteley Index-7 (WI-7) is frequently used for evaluating patients with suspected hypochondriasis. However, information about its use on somatic symptom and related disorders in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) is still lacking. This study investigated the psychometric properties of the Mandarin Chinese version of the WI-7 and its application to evaluation of somatic symptom and related disorders.nnnMETHODSnParticipants completed the WI-7 and received diagnostic interview based on both Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) and DSM-5 criteria. Exploratory factor analysis was performed, and the test-retest reliability and the internal consistency of the WI-7 were assessed. Receiver Operating Characteristic curves were established, and the area under the curve was calculated to determine the cutoff point to distinguish DSM-IV somatoform disorders and DSM-5 somatic symptom and related disorders, respectively.nnnRESULTSnA total of 471 subjects were recruited for this study. The exploratory factor analysis of the WI-7 identified a single factor. The internal consistency and test-retest reliability of the WI-7 were 0.829 and 0.836, respectively. The area under Receiver Operating Characteristic curve using WI-7 to distinguish DSM-5 somatic symptom and related disorders is 0.660, higher than that when applying to distinguish DSM-IV somatoform disorders. The sensitivity and specificity at an optimal cutoff point of 0/1 are 0.645 and 0.675, respectively.nnnCONCLUSIONnThe Mandarin Chinese version of the WI-7 is a potentially useful tool to detect individuals with DSM-5 somatic symptom and related disorders.

Harm avoidance and persistence are associated with somatoform disorder psychopathology: A study in Taiwan.

BACKGROUNDnWhether personality features affect the development of somatoform disorders and their psychopathologies is an important issue. Aim of this study was to resolve this issue by comparing indicators of psychopathology and personality features in subjects with somatoform disorders and healthy controls.nnnMETHODSnThis study recruited 148 subjects with somatoform disorders and 146 healthy controls. The severity of psychopathology was measured with the Patient Health Questionnaire-15 (PHQ-15), Health Anxiety Questionnaire (HAQ), Beck Depression Inventory-II (BDI-II), and Beck Anxiety Inventory (BAI). The Tridimensional Personality Questionnaire (TPQ) was used to assess personality features. Demographic data, psychopathology indicators, and TPQ scores were compared between groups. Correlation and multivariate linear regression analysis were used to identify the personality dimensions or demographic variables associated with psychopathology.nnnRESULTSnThe somatoform group had lower novelty seeking (NS) and reward dependence (RD) and higher harm avoidance (HA) and severity of psychopathologies. Multiple regression analysis revealed that fatigability, persistence, gender, and education level were predictive of PHQ-15; HA, educational level, persistence, and dependence were predictive of HAQ; HA, persistence, education level, and NS were predictive of BDII-II; and fatigability, education level, persistence, and anticipatory worry were predictive of BAI. The development of somatoform disorders was associated with fatigability, age, residence location, education level, and attachment.nnnLIMITATIONSnThe limitations include heterogeneity of the diagnosis, the high proportion of undifferentiated somatoform disorder, and the cross-sectional study design.nnnCONCLUSIONnHA/fatigability, persistence, and education level are associated with each type of psychopathology. Fatigability is a powerful predictor of somatoform disorder development.

The effect of cerebrospinal fluid dilution of isobaric 0.5% bupivacaine used for spinal anaesthesia

A prospective study was conducted to see the effect on spinal anaesthesia of the dilution of isobaric 0.5% bupivacaine with cerebrospinal fluid. Sixty patients were randomly allocated to three groups. In group 1, patients received 3 ml isobaric 0.5% bupivacaine intrathecally without aspirating cerebrospinal fluid. In groups 2 and 3, cerebrospinal fluid 1 ml and 2 ml was aspirated respectively and mixed with 3 ml isobaric 0.5% bupivacaine. A total volume of 4 ml in group 2 and 5 ml in group 3 was administered. Thus, the volume of cerebrospinal fluid remained unchanged. Pinprick analgesia and motor block was evaluated from induction until recovery. No differences in onset time, duration and‘two segments regression’ were noticed. The only statistical difference was the time to reach complete motor block, which was shorter in group I as compared to groups 2 and 3 (6.9 SD 1.4 min versus 11.3 SD 3.0 and 13.5 SD 3.9 min respectively). The mean value of maximum decrease in systolic blood pressure was small, being less than 15% of the pre‐operative value for each group. In conclusion, the effect of diluting isobaric 0.5% bupivacaine with cerebrospinal fluid, 1 ml and 2 ml, is minimal and it is an unnecessary procedure with limited clinical effect.

The relation between the patient health questionnaire-15 and DSM somatic diagnoses

BackgroundOur purpose was to examine the reliability and validity of the Chinese version of the Patient Health Questionnaire-15 (PHQ-15) in Taiwan, and to explore its relation to somatoform disorders (DSM-IV)xa0and to somatic symptom and related disorders (DSM-5).MethodsWe recruited 471 individuals, 151 with somatoform disorders and 200 with somatic symptom and related disorders. Subjects completed the Chinese version of the PHQ-15, Beck Depression Inventory-II (BDI-II), Beck Anxiety Inventory (BAI), and received a DSM-IV- and DSM-5-based diagnostic interview. We performed exploratory factor analysis and assessed test-retest reliability, internal consistency, and correlation with BDI-II/BAI to confirm reliability and validity, and carried out ROC curve analysis to determine suitability for evaluation or screening purposes. PHQ-15 scores were compared between patients with various DSM-IV psychiatric diagnoses (such as DSM-IV somatoform disorders, panic disorder, other anxiety/depressive disorders) or no DSM-IV diagnosis and patients with DSM-5 somatic symptom and related disorders or no DSM-5 diagnosis.ResultsThe Chinese version identified cardiopulmonary, pain-fatigue, and gastrointestinal as major factors and had good reliability (0.803–0.930), internal consistency (0.637–0.861), and correlation coefficients with BDI-II/BAI (0.407–0.619, 0.536–0.721, respectively). The PHQ-15 scores were similar in patients with somatoform disorders and patients with panic disorder; higher in patients with somatoform disorders and panic disorder than in patients with other anxiety/depressive disorders; and significantly higher in patients with somatic symptom and related disorders than in patients without this diagnosis. The AUC of the PHQ-15 was 0.678 (cutoff 6/7) for screening somatoform disorders (DSM-IV) and 0.725 (cutoff 4/5) for screening somatic symptom and related disorders (DSM-5).ConclusionsThe Chinese version of the PHQ-15 is suitable for evaluating somatic symptom and related disorders. The preponderance of somatic symptom disorder in our sample, lack of evaluation of functional disorders, and recruitment solely from psychiatric clinics are possible limitations.