Severe hypertriglyceridemia secondary to venlafaxine use in an older adult on dialysis -case report.

BACKGROUND: Although the prescribing information for Venlafaxine extended release includes a discussion about possible increases in total cholesterol and triglycerides (TG) seen in healthier adult patients during premarketing clinical trials, no post-marketing studies or case reports, that discuss the effects of venlafaxine on TG in elderly patients with chronic kidney disease. CASE PRESENTATION: We report a 71 year-old male patient with end-stage renal disease on hemodialysis, with a history of coronary artery disease, mild hyperlipidemia, and hypertension. This patient twice demonstrated the severe rises in triglycerides while taking the antidepressant, i.e., venlafaxine, and discontinuing the long-term use of fenofirate. The adverse drug reaction sub-committee at the hospital rated the second event as a "probable reaction" using the Naranjo nomogram, accordingly. CONCLUSIONS: This case demonstrates the risk of changes in lipid profiles while taking venlafaxine and receiving on and off fenofibrate therapy in the older adult patient with chronic kidney disease and under hemodialysis. Regular monitoring for lipid changes after starting venlafaxine is strongly advised for patients with existing risk factors.

Sarcosine therapy for obsessive compulsive disorder: a prospective, open-label study.

BACKGROUND: Several lines of evidence implicate glutamatergic neurotransmission in the pathophysiology of obsessive compulsive disorder (OCD). Sarcosine is an endogenous antagonist of glycine transporter-1. By blocking glycine uptake, sarcosine may increase the availability of synaptic glycine and enhance N-methyl-d-aspartate (NMDA) subtype glutamatergic neurotransmission. In this 10-week open-label trial, we examined the potential benefit of sarcosine treatment in OCD patients. METHOD: Twenty-six outpatients with OCD and baseline Yale-Brown Obsessive Compulsive Scale (YBOCS) scores higher than 16 were enrolled. Drug-naive subjects (group 1, n = 8) and those who had discontinued serotonin reuptake inhibitors for at least 8 weeks at study entry (group 2, n = 6) received sarcosine monotherapy. The other subjects (group 3, n = 12) received sarcosine as adjunctive treatment. A flexible dosage schedule of sarcosine 500 to 2000 mg/d was applied. The primary outcome measures were Y-BOCS and Hamilton Anxiety Inventory, rated at weeks 0, 2, 4, 6, 8, and 10. Results were analyzed by repeated-measures analysis of variance. RESULTS: Data of 25 subjects were eligible for analysis. The mean ± SD Y-BOCS scores decreased from 27.6 ± 5.8 to 22.7 ± 8.7, indicating a mean decrease of 19.8% ± 21.7% (P = 0.0035). Eight (32%) subjects were regarded as responders with greater than 35% reduction of Y-BOCS scores. Five of the responders achieved the good response early by week 4. Although not statistically significant, drug-naive (group 1) subjects had more profound and sustained improvement and more responders than the subjects who had received treatment before (groups 2 and 3). Sarcosine was tolerated well; only one subject withdrew owing to transient headache. CONCLUSION: Sarcosine treatment can achieve a fast therapeutic effect in some OCD patients, particularly those who are treatment naive. The study supports the glycine transporter-1 as a novel target for developing new OCD treatment. Large-series placebo-controlled, double-blind studies are recommended.

Women urinate in the standing position do not increase post-void residual urine volumes.

AIMS: The effects of standing while voiding have seldom been investigated in women. We evaluate urodynamic parameters of voiding while standing in healthy women using uroflowmetry and post-void residual urine volume assessment. Results are compared with crouching and sitting. METHODS: Between July and October, 2008, a total of 30 healthy, nulliparous female volunteers were enrolled. Ages were 22-37 (mean: 28±4). Urodynamic studies were performed for all in sitting, crouching and standing positions; 3, 3 and 5 times in each position, respectively. Volunteers used homemade auxiliary appliances for collecting urine from the urethra and draining it forward when standing. Volume, maximum flow rate, mean flow rate and post-void residual urine volume were compared. RESULTS: Maximum and average flow rates in the sitting and standing positions were significantly different, but not between sitting and crouching or between crouching and standing. There were no differences in voided volume and post-void residual urine volume. There's no apparent learning curve for women in the standing position. CONCLUSIONS: Though flow rates are decreased while standing, post-void residual volume is not significantly different. Women have another choice for voiding in public restrooms.

Different cutoff points for different trimesters? The use of Edinburgh Postnatal Depression Scale and Beck Depression Inventory to screen for depression in pregnant Taiwanese women.

OBJECTIVE: Validating self-reported questionnaires to detect depression during pregnancy, compared to depression during postpartum, has gained much less attention. Furthermore, it is unknown whether it is appropriate to use the same cutoff point to detect depression on different trimesters of pregnancy. The aims of this study, conducted in pregnant Taiwanese women, were: (a) to validate the Taiwanese version of the Edinburgh Postnatal Depression Scale (EPDS-T) and the second edition of the Beck Depression Inventory (BDI-II); (b) to compare the EPDS-T and the BDI-II on their validity in detecting depression; and (c) to determine if these scales have different cutoff points in detecting major depressive disorder for different trimesters. METHOD: One hundred eighty-five pregnant Taiwanese women who completed the EPDS-T and the BDI-II were interviewed by psychiatrists with the structural interview Mini-International Neuropsychiatric Interview (MINI) to establish a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition diagnosis of major depressive disorder. We analyzed and compared the sensitivity, specificity and validity of the EPDS-T and the BDI-II against the MINI diagnosis on the second and third trimesters. RESULTS: We identified 12/13 as the optimal cutoff of the EPDS-T, at which the sensitivity of the scale was 83% and the specificity was 89%. The optimal cutoff of the BDI-II was 11/12, at which the sensitivity of the scale was 74% and the specificity was 83%. The area under the curve of the receiver operating characteristic analysis was 0.92 for the EPDS-T and 0.84 for the BDI. There exist different optimal cutoff points of the EPDS-T for detecting major depression during different trimesters: 13/14 for the second trimester and 12/13 for the third trimester. No different optimal cutoff point for the BDI-II was found for different trimesters. CONCLUSION: The EPDS-T has satisfactory sensitivity and specificity and better validity than the BDI-II for detecting major depressive disorder during pregnancy in pregnant Taiwanese women. We suggest that more studies with larger sample sizes be performed to confirm if there exist different cutoff points in detecting depression for different trimesters of gestation.

The Effects of an Exercise Program on Anxiety Levels and Metabolic Functions in Patients With Anxiety Disorders.

The purpose of this study was to evaluate the effects of a home-based (HB) exercise program on anxiety levels and metabolic functions in patients with anxiety disorders in Taiwan. Purposive sampling was used to recruit 86 participants for this randomized, experimental study. Participants were asked to complete a pretest before the 3-month exercise program, a posttest at 1 week, and a follow-up test at 3 months after the exercise program. Study measures included four Self-Report Scales and biophysical assessments to collect and assess personal data, lifestyle behaviors, anxiety levels, and metabolic control functions. Of the 86 study participants, 83 completed the posttest and the 3-month follow-up test, including 41 in the experimental group and 42 in the control group. Participants in the experimental group showed significant improvements in body mass index, high-density lipoprotein cholesterol levels, and the level of moderate exercise after the program relative to the control group, as analyzed by generalized estimating equations mixed-model repeated measures. State and trait anxiety levels were also significantly improved from pretest to follow-up test in the experimental group. Finally, the prevalence of metabolic syndrome declined for participants in the experimental group. The HB exercise program produced positive effects on the metabolic indicators and anxiety levels of Taiwanese adults with anxiety disorders. Health providers should consider using similar HB exercise programs to help improve the mental and physical health of patients with anxiety disorders in their communities.

Glycine transporter I inhibitor, N-methylglycine (sarcosine), added to clozapine for the treatment of schizophrenia.

BACKGROUND: Agonists at the N-methyl-D-aspartate (NMDA)-glycine site (D-serine, glycine, D-alanine and D-cycloserine) and glycine transporter-1 (GlyT-1) inhibitor (N-methylglycine, or called sarcosine) both improve the symptoms of stable chronic schizophrenia patients receiving concurrent antipsychotics. Previous studies, however, found no advantage of D-serine, glycine, or D-cycloserine added to clozapine. The present study aims to determine the effects of sarcosine adjuvant therapy for schizophrenic patients receiving clozapine treatment. METHODS: Twenty schizophrenic inpatients enrolled in a 6-week double-blind, placebo-controlled trial of sarcosine (2 g/day) which was added to their stable doses of clozapine. Measures of clinical efficacy and side-effects were determined every other week. RESULTS: Sarcosine produced no greater improvement when co-administered with clozapine than placebo plus clozapine at weeks 2, 4, and 6. Sarcosine was well tolerated and no significant side-effect was noted. CONCLUSIONS: Unlike patients treated with other antipsychotics, patients who received clozapine treatment exhibit no improvement by adding sarcosine or agonists at the NMDA-glycine site. Clozapine possesses particular efficacy, possibly related to potentiation of NMDA-mediated neurotransmission. This may contribute to the clozapine's unique clinical efficacy and refractoriness to the addition of NMDA-enhancing agents.

A crossover study on lipid and weight changes associated with olanzapine and risperidone.

RATIONALE: The results from case-control and retrospective studies revealed that olanzapine might be associated with more increased risks of metabolic dysfunction than risperidone. The crossover design can minimize the influence of individual variation in metabolic profiles and demographic variables, such as age, sex, concomitant medication use and personal life styles. OBJECTIVES: We design a crossover study to evaluate the metabolic effect of olanzapine and risperidone. METHODS: Fifteen schizophrenic patients were shifted from olanzapine and risperidone or from risperidone and olanzapine due to poor treatment response. The body weights, lipid profiles and fasting glucose levels were assessed before medication switch and 3 months after crossover. RESULTS: In the seven patients taking risperidone at the time of inclusion (risperidone-first group), after shifting to olanzapine, there was a significant increase in triglyceride level (p=0.048) and body weight (p=0.008). In the other eight patients (olanzapine-first group), after shift to risperidone, there was a decrease in triglyceride level (p=0.009), body weight (p=0.049) and body mass index (BMI; p=0.04). When comparing the metabolic profiles in all patients after olanzapine and after risperidone (irrespective of the order of treatment), the mean triglyceride level (p=0.001), body weight (p=0.001) and BMI (p=0.015) were significantly higher in patients receiving olanzapine than in those receiving risperidone. Furthermore, there was a small increase in total cholesterol level (p=0.091) and a small decrease in high-density lipoprotein (HDL) level (p=0.061) in olanzapine group, but the differences did not reach a significant level. There was no significant difference between olanzapine and risperidone in fasting glucose and low-density lipoprotein (LDL). CONCLUSIONS: This study confirms that elevated levels of triglyceride and body weight could be associated with the use of olanzapine as compared with risperidone. The changes in body weights and lipid profiles should be closely monitored in patients during treatment with atypical antipsychotic drugs.

Hypoalbuminemia in drug-free patients with major depressive disorder compared with a dietary matched control group: a clinical meaning beyond malnutrition.

Serum albumin (sALB) is routinely determined in blood tests and is an excellent predictor of risk for many medical illnesses. Hypoalbuminemia has been sporadically reported in patients with psychiatric disorders, such as major depressive disorder and schizophrenia. We compared sALB levels between 19 drug-free patients of major depressive disorder with a control group of matching diets. We conducted this study by controlling the nutrition factor by assessing patient's diets, as well as other possible confounding factors such as sex, age, body mass index (BMI), liver function, and exercise, while focusing on hypoalbuminemia in patients with major depressive disorder. There is no difference in age, gender distribution, and dietary frequency on protein and albumin intake between the patient and control group. The sALB levels of the group with major depressive disorder were significantly reduced (p=0.049). The severity of depression is negatively correlated to the sALB level (r=-0.46, p=0.04). Hypoalbuminemia has clinical meanings on severity of depression and is independent of malnutrition. However, our results can only be seen as very preliminary and should be confirmed by larger studies.

Barratt Impulsivity and Neural Regulation of Physiological Arousal.

BACKGROUND: Theories of personality have posited an increased arousal response to external stimulation in impulsive individuals. However, there is a dearth of studies addressing the neural basis of this association. METHODS: We recorded skin conductance in 26 individuals who were assessed with Barratt Impulsivity Scale (BIS-11) and performed a stop signal task during functional magnetic resonance imaging. Imaging data were processed and modeled with Statistical Parametric Mapping. We used linear regressions to examine correlations between impulsivity and skin conductance response (SCR) to salient events, identify the neural substrates of arousal regulation, and examine the relationship between the regulatory mechanism and impulsivity. RESULTS: Across subjects, higher impulsivity is associated with greater SCR to stop trials. Activity of the ventromedial prefrontal cortex (vmPFC) negatively correlated to and Granger caused skin conductance time course. Furthermore, higher impulsivity is associated with a lesser strength of Granger causality of vmPFC activity on skin conductance, consistent with diminished control of physiological arousal to external stimulation. When men (n = 14) and women (n = 12) were examined separately, however, there was evidence suggesting association between impulsivity and vmPFC regulation of arousal only in women. CONCLUSIONS: Together, these findings confirmed the link between Barratt impulsivity and heightened arousal to salient stimuli in both genders and suggested the neural bases of altered regulation of arousal in impulsive women. More research is needed to explore the neural processes of arousal regulation in impulsive individuals and in clinical conditions that implicate poor impulse control.

Assessing the construct validity of the Chinese-Version Schizotypal Personality Questionnaire-Brief on male and female undergraduate students.

BACKGROUND: Screening for the schizotypal personality trait is one strategy to identify people who may be susceptible to early psychosis or be at high risk for prodromal psychosis. The Schizotypal Personality Questionnaire-Brief (SPQ-B) has been widely used to assess the schizotypal personality and has been translated into Chinese. However, the psychometric properties of the Chinese-version scale have yet to be evaluated. PURPOSE: This study evaluates the construct validity of the Chinese-version SPQ-B on a sample of male and female undergraduate students in Taiwan. METHODS: A cross-sectional design with convenient sampling was used for this study. The data were collected using the Chinese-version SPQ-B between October 2008 and June 2009. Participants included 513 male and 675 female undergraduate students in Taiwan. The factor construct validity of the scale was examined by confirmatory factor analysis using structural equation modeling with SPSS AMOS version 17 software. RESULTS: The results show that the three-factor model fits the data better than the one-factor model for both male and female participants. The male participants scored significantly higher than their female counterparts in terms of total scale, interpersonal subscales, and disorganized subscales. CONCLUSIONS/IMPLICATIONS FOR PRACTICE: The Chinese version of the SPQ-B adequately achieves three-factor construct validity for undergraduate students. The scale may be used to screen for the schizotypal personality trait in both male and female college students to identify those at an elevated risk for mental illness.

Metabolic Abnormality and Sleep Disturbance are Associated with Clinical Severity of Patients with Schizophrenia.

Schizophrenic patients suffer from more metabolic or sleep problems. Little is known about risk factors. We recruited 17 patients with chronic schizophrenia from the rehabilitation center in a medical center in Taiwan and measured their demographic data, cognitive performance, and physical fitness, metabolic profiles and sleep parameters. They were divided into two groups according to clinical severity, then compared in terms of metabolic and sleep parameters. Those with more severe symptomatology had more metabolic abnormality and shorter slow wave sleep (SWS). Our findings suggest clinical symptoms as linked with heavier body weight, wider neck circumference, elevated blood pressure, and shorter SWS. Further studies are warranted to confirm the preliminary finding and to elucidate the underlying mechanism.

Sensitivity and specificity of the Chinese version of the Schizotypal Personality Questionnaire-Brief for identifying undergraduate students susceptible to psychosis.

BACKGROUND: Early interventions can improve treatment outcomes for individuals with major psychiatric disorders and with nonspecific symptoms but increasingly impaired cognitive perception, emotions, and behaviour. One way used to identify people susceptible to psychosis is through the schizotypal personality trait. Persons with schizotypal characteristics have been identified with the widely used Schizotypal Personality Questionnaire-Brief. However, no suitable instruments are available to screen individuals in the Taiwanese population for evidence of early psychotic symptoms. OBJECTIVES: The purpose of this study was to test the sensitivity and specificity of the Chinese version of the Schizotypal Personality Questionnaire-Brief for identifying undergraduate students' susceptibility to psychosis. DESIGN: Two-stage, cross-sectional survey design. SETTING AND PARTICIPANTS: The self-administered scale was tested in a convenience sample of 618 undergraduate students at a medical university in Taiwan. Among these students, 54 completed the scale 2 weeks apart for test-retest reliability, and 80 were tested to identify their susceptibility to psychosis. DATA COLLECTION AND ANALYSIS: In Stage I, participants with scores in the top 6.5% were classified as the high-score group (n=40). The control group (n=40) was randomly selected from the remaining participants with scores <15 and matched by gender. These 80 students were asked to participate in psychiatric interviews in Stage II. The instrument was tested for reliability using intraclass correlation coefficients and the Kuder-Richardson formula 20. The instrument was analysed for optimal sensitivity and specificity using odds-ratio analysis and receiver operating characteristic curves. RESULTS: The 22-item Chinese version of the Schizotypal Personality Questionnaire-Brief had a 2-week test-retest reliability of 0.82 and internal consistency of 0.76. The optimal cut-off score was 17, with odds ratios of 24.4 and an area under the receiver operating characteristic curves of 0.83. The instrument had a sensitivity of 80.0% and specificity of 85.9% in identifying undergraduate students' susceptibility to psychosis. CONCLUSIONS: The Chinese version Schizotypal Personality Questionnaire-Brief is a reliable instrument, but should not be used as a screening tool until its psychometric properties have been evaluated in more detail. Other screening tools need to be used in future studies with the CSPQ-B to improve the accuracy of identifying susceptibility to psychosis among young adults.

RGS4 polymorphisms predict clinical manifestations and responses to risperidone treatment in patients with schizophrenia.

OBJECTIVE: Polymorphisms of the gene encoding the regulator of G-protein signaling subtype 4 (RGS4) are associated with schizophrenia. This study aims to investigate the association of 4 RGS4 polymorphisms (single nucleotide polymorphisms [SNPs] 1, 4, 7, and 18), implicated in previous studies, with baseline symptoms and treatment response to risperidone in patients with schizophrenia. METHODS: One hundred twenty patients with acutely exacerbated schizophrenia who had never been treated by atypical antipsychotics were recruited. They received optimal treatment of risperidone for up to 42 days in the inpatient research unit. Patients' social functions were monitored by Nurses' Observation Scale for Inpatients Evaluation and clinical manifestations, by Positive and Negative Syndrome Scale. RESULTS: At baseline status, the A/A genotype at SNP7 of RGS4 was associated with poorer social function when compared with the G/G genotype. After risperidone treatment, the A/A genotype at SNP1 was associated with greater improvement at social function, and the A/A genotype at SNP18 was associated with greater improvement at social function, Positive and Negative Syndrome Scale total score, and positive- and negative-symptom subscale. CONCLUSIONS: These findings suggest that RGS4 variances influence clinical manifestations of schizophrenia as well as the treatment response to risperidone, suggesting that RGS4 plays a role in the fundamental process of disease pathophysiology.

Risperidone-related weight gain: genetic and nongenetic predictors.

OBJECTIVE: A serious side effect of atypical antipsychotics is increased body weight, which leads to further morbidity and nonadherence to medication. It has been suggested that both genetic and nongenetic variables may influence antipsychotics-related weight gain. This study aimed to simultaneously explore the effects of multiple candidate genes and environment factors on body weight of schizophrenia patients who received risperidone, a commonly used atypical antipsychotic agent. METHODS: One hundred twenty-three ethnically Han Chinese inpatients with acutely exacerbated schizophrenia were given risperidone monotherapy for up to 42 days. Body weight and clinical manifestations were assessed biweekly. Drug efficacy was measured by the Positive and Negative Syndrome Scale (PANSS), and safety was evaluated by the Extrapyramidal Symptom Rating Scale (ESRS) and the UKU Side Effect Rating Scale. We collected body weight as the response value. Potential prognostic factors were baseline body weight, age, sex, diagnosis subtypes, risperidone dosage, PANSS total scores, treatment duration (weeks 0-6), and 15 genetic variants [across 10 candidate genes: 5-HT1A, 5-HT2A, 5-HT2C, 5-HT6, D1, D2, D3, and alpha1-adrenergic receptors, brain-derived neurotrophic factor (BDNF), and cytochrome P450 2D6 (CYP2D6)]. Because there were repeated assessments, multiple linear regression with the generalized estimating equation (GEE) method was used to adjust the within-subject dependence. RESULTS: Of 15 genetic polymorphisms examined, 5-HT2A 102-T/C, 5-HT2C -759-C/T, 5-HT6 267-C/T, BDNF 66-Val/Met, and CYP2D6 188-C/T significantly influenced body weight, and so did baseline body weight, age, gender, schizophrenia subtype, and treatment duration and efficacy. CONCLUSIONS: These results suggest that numerous genetic and nongenetic factors affect antipsychotics-related weight gain.