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A growing body of evidence now proposes that machine learning and deep learning techniques can serve as a vital foundation for the pharmacogenomics of antidepressant treatments in patients with major depressive disorder (MDD). In this review, we focus on the latest developments for pharmacogenomics research using machine learning and deep learning approaches together with neuroimaging and multi-omics data. First, we review relevant pharmacogenomics studies that leverage numerous machine learning and deep learning techniques to determine treatment prediction and potential biomarkers for antidepressant treatments in MDD. In addition, we depict some neuroimaging pharmacogenomics studies that utilize various machine learning approaches to predict antidepressant treatment outcomes in MDD based on the integration of research on pharmacogenomics and neuroimaging. Moreover, we summarize the limitations in regard to the past pharmacogenomics studies of antidepressant treatments in MDD. Finally, we outline a discussion of challenges and directions for future research. In light of latest advancements in neuroimaging and multi-omics, various genomic variants and biomarkers associated with antidepressant treatments in MDD are being identified in pharmacogenomics research by employing machine learning and deep learning algorithms. [ABSTRACT FROM AUTHOR]

Early detection and prevention of Alzheimer's disease (AD) is important. The current treatment for early AD is acetylcholine esterase inhibitors (AChEIs); however, the efficacy is poor. Besides, AChEI did not show efficacy in mild cognitive impairment (MCI). Beta-amyloid (Aβ) deposits have been regarded to be highly related to the pathogenesis of AD. However, many clinical trials aiming at the clearance of Aβ deposits failed to improve the cognitive decline of AD, even at its early phase. There should be other important mechanisms unproven in the course of AD and MCI. Feasible biomarkers for the diagnosis and treatment response of AD are lacking to date. The N-methyl-D-aspartate receptor (NMDAR) activation plays an important role in learning and memory. On the other hand, oxidative stress has been regarded to contribute to aging with the assumption that free radicals damage cell constituents and connective tissues. Our recent study found that an NMDAR enhancer, sodium benzoate (the pivotal inhibitor of D-amino acid oxidase [DAAO]), improved the cognitive and global function of patients with early-phase AD. Further, we found that peripheral DAAO levels were higher in patients with MCI and AD than healthy controls. We also found that sodium benzoate was able to change the activity of antioxidant. These pieces of evidence suggest that the NMDAR function is associated with anti-oxidation, and have potential to be biomarkers for the diagnosis and treatment response of AD. [ABSTRACT FROM AUTHOR]

Objective: Melatonin has been considered to have an essential role in the pathophysiology of Alzheimer's disease (AD) for its regulatory function on circadian rhythm and interaction with glutamate for the modulation of learning and memory. Previous studies revealed that melatonin levels decreased in patients with AD. However, melatonin supplement didn't show promising efficacy for AD. This study compared trough melatonin levels among elderly people with different severities of cognitive deficits. Methods: We enrolled 270 elder individuals (consisting four groups: healthy elderly, amnestic mild cognitive impairment [MCI], mild AD, and moderate-severe AD) in the learning cohort. Trough melatonin levels in plasma were measured using ELISA. Cognitive function was evaluated by Clinical Dementia Rating Scale (CDR) and Mini-Mental State Examination (MMSE). An independent testing cohort, also consisting of four groups, was enrolled for ascertainment. Results: In the learning cohort, trough melatonin levels decreased in the MCI group but elevated in the mild and moderate to severe AD groups. Trough melatonin levels were associated with CDR and MMSE in MCI or AD patients significantly. In the testing cohort, the results were similar to those in the learning cohort. Conclusion: This study demonstrated that trough melatonin levels in the peripheral blood were decreased in MCI but increased with the severity of AD. The finding supports the trials indicating that melatonin showed efficacy only in MCI but not in AD. Whether trough melatonin level has potential to be a treatment response biomarker for AD, especially its early phase needs further studies. [ABSTRACT FROM AUTHOR]

INTRODUCTION Obstructive sleep apnea (OSA) is a serious sleep disorder characterized by repetitive episodes of paused or shallow breathing during sleep. Patients with OSA often have excessive daytime sleepiness. The role of cigarette smoking in OSA remains controversial. The aim of this study was to examine the relationship between cigarette smoking and OSA. METHODS In this retrospective chart review, we reviewed 18-month sleep laboratory charts in central Taiwan. We collected data regarding sleep, current cigarette smoking status, sex, age, body mass index (BMI), neck circumference, Epworth Sleepiness Scale score, and polysomnographic sleep parameters. In total, 733 subjects were recruited; among these, 151 were smokers and 582 were nonsmokers. RESULTS Smokers had significantly higher apnea--hypopnea index (p<0.001) for non-rapid eye movement sleep stage, higher apnea--hypopnea index (p<0.001) for total sleep time, and higher snore frequency (p<0.001) in t-test analysis. They also demonstrated higher Epworth Sleepiness Scale scores, shorter sleep times, lower percentage of slow-wave (deep) sleep, and longer snore times. However, no significant association was found between cigarette smoking and OSA after adjusting for sex, age, and BMI (OR=1.02, 95% CI: 0.66--1.57). CONCLUSIONS We did not find any significant association between cigarette smoking and OSA after adjusting for age, sex, and BMI. Further well-designed prospective controlled cohort studies might clarify the relationship between cigarette smoking and OSA. [ABSTRACT FROM AUTHOR]

Brain stimulation techniques can modulate cognitive functions in many neuropsychiatric diseases. Pilot studies have shown promising effects of brain stimulations on Alzheimer's disease (AD). Brain stimulations can be categorized into non-invasive brain stimulation (NIBS) and invasive brain stimulation (IBS). IBS includes deep brain stimulation (DBS), and invasive vagus nerve stimulation (VNS), whereas NIBS includes transcranialmagnetic stimulation (TMS), transcranial direct current stimulation (tDCS), transcranial alternating current stimulation (tACS), electroconvulsive treatment (ECT), magnetic seizure therapy (MST), cranial electrostimulation (CES), and non-invasive VNS. We reviewed the cutting-edge research on these brain stimulation techniques and discussed their therapeutic effects on AD. Both IBS and NIBS may have potential to be developed as novel treatments for AD; however, mixed findings may result from different study designs, patients selection, population, or samples sizes. Therefore, the efficacy of NIBS and IBS in AD remains uncertain, and needs to be further investigated. Moreover,more standardized study designs with larger sample sizes and longitudinal follow-up are warranted for establishing a structural guide for future studies and clinical application. [ABSTRACT FROM AUTHOR]

With ever-increasing elder populations, age-related cognitive decline, which is characterized as a gradual decline in cognitive capacity in the aging process, has turned out to be a mammoth public health concern. Since genetic information has become increasingly important to explore the biological mechanisms of cognitive decline, the search for genetic biomarkers of cognitive aging has received much attention. There is growing evidence that single-nucleotide polymorphisms (SNPs) within the ADAMTS9, BDNF, CASS4, COMT, CR1, DNMT3A, DTNBP1, REST, SRR, TOMM40, circadian clock, and Alzheimer's diseases-associated genes may contribute to susceptibility to cognitive aging. In this review, we first illustrated evidence of the genetic contribution to disease susceptibility to age-related cognitive decline in recent studies ranging from approaches of candidate genes to genome-wide association studies. We then surveyed a variety of association studies regarding age-related cognitive decline with consideration of gene--gene and gene--environment interactions. Finally, we highlighted their limitations and future directions. In light of advances in precision medicine and multi-omics technologies, future research in genomic medicine promises to lead to innovative ideas that are relevant to disease prevention and novel drugs for cognitive aging. [ABSTRACT FROM AUTHOR]

Importance: Antipsychotics are used increasingly in youth for nonpsychotic and off-label indications, but cardiometabolic adverse effects and (especially) type 2 diabetes mellitus (T2DM) risk have raised additional concern.Objective: To assess T2DM risk associated with antipsychotic treatment in youth.Data Sources: Systematic literature search of PubMed and PsycINFO without language restrictions from database inception until May 4, 2015. Data analyses were performed in July 2015, and additional analyses were added in November 2015.Study Selection: Longitudinal studies reporting on T2DM incidence in youth 2 to 24 years old exposed to antipsychotics for at least 3 months.Data Extraction and Synthesis: Two independent investigators extracted study-level data for a random-effects meta-analysis and meta-regression of T2DM risk.Main Outcomes and Measures: The coprimary outcomes were study-defined T2DM, expressed as cumulative T2DM risk or as T2DM incidence rate per patient-years. Secondary outcomes included the comparison of the coprimary outcomes in antipsychotic-treated youth with psychiatric controls not receiving antipsychotics or with healthy controls.Results: Thirteen studies were included in the meta-analysis, including 185,105 youth exposed to antipsychotics and 310,438 patient-years. The mean (SD) age of patients was 14.1 (2.1) years, and 59.5% were male. The mean (SD) follow-up was 1.7 (2.3) years. Among them, 7 studies included psychiatric controls (1,342,121 patients and 2,071,135 patient-years), and 8 studies included healthy controls (298,803 patients and 463,084 patient-years). Antipsychotic-exposed youth had a cumulative T2DM risk of 5.72 (95% CI, 3.45-9.48; P < .001) per 1000 patients. The incidence rate was 3.09 (95% CI, 2.35-3.82; P < .001) cases per 1000 patient-years. Compared with healthy controls, cumulative T2DM risk (odds ratio [OR], 2.58; 95% CI, 1.56-4.24; P < .0001) and incidence rate ratio (IRR) (IRR, 3.02; 95% CI, 1.71-5.35; P < .0001) were significantly greater in antipsychotic-exposed youth. Similarly, compared with psychiatric controls, antipsychotic-exposed youth had significantly higher cumulative T2DM risk (OR, 2.09; 95% CI, 1.50-52.90; P < .0001) and IRR (IRR, 1.79; 95% CI, 1.31-2.44; P < .0001). In multivariable meta-regression analyses of 10 studies, greater cumulative T2DM risk was associated with longer follow-up (P < .001), olanzapine prescription (P < .001), and male sex (P = .002) (r(2) = 1.00, P < .001). Greater T2DM incidence was associated with second-generation antipsychotic prescription (P ≤ .050) and less autism spectrum disorder diagnosis (P = .048) (r(2) = 0.21, P = .044).Conclusions and Relevance: Although T2DM seems rare in antipsychotic-exposed youth, cumulative risk and exposure-adjusted incidences and IRRs were significantly higher than in healthy controls and psychiatric controls. Olanzapine treatment and antipsychotic exposure time were the main modifiable risk factors for T2DM development in antipsychotic-exposed youth. Antipsychotics should be used judiciously and for the shortest necessary duration, and their efficacy and safety should be monitored proactively. [ABSTRACT FROM AUTHOR]

Major depressive disorder (MDD) and Parkinson's disease (PD) share symptoms such as tremor. Bupropion, a norepinephrine-dopamine reuptake inhibitor, shows weak dopamine transporter (DAT) occupancy. We report here on a patient with MDD whose hand tremors might have been misdiagnosed as PD by single-photon emission computed tomography (SPECT) under bupropion use. A 66-year-old male patient with MDD had been receiving bupropion 150 mg per day for 6 months. His mood symptoms improved partially with bupropion treatment, however, hand tremors persisted. The neurological examination revealed bilateral hand tremors without other typical signs for PD. The SPECT using Tc-99m TRODAT-1 revealed decreased DAT binding capacity in bilateral striata. Under the impression of atypical PD, the patient was advised to take anti-Parkinson's drug. Bupropion was discontinued for 14 days to confirm the test. The follow-up SPECT after 14 days found improvement for the uptake ratio of striata. From then onward, the anti-Parkinson's drug was not used due to the lack of typical sign(s) for PD. The patient's mental and physical status remained stable without worsening of hand tremors during follow-up. Tc-99m TRODAT-1 SPECT is helpful for the evaluation of DAT and the diagnosis of PD. However, the interpretation of the SPECT image might be biased by the use of certain drugs such as bupropion for its binding to DAT. Bupropion may decrease the Tc-99m TRODAT-1 binding to DAT. The effect of drugs on DAT should be carefully assessed while interpreting the Tc-99m TRODAT-1 image. Our findings suggest that all drugs that may alter DAT occupancy should be listed as the reference for Tc-99m TRODAT-1 image reading. [ABSTRACT FROM AUTHOR]

Background Late-life depression is common among elderly patients. Ignorance of the health problem, either because of under-diagnosis or under-treatment, causes additional medical cost and comorbidity. For a better health and quality of life (QoL), evaluation, prevention and treatment of late-life depression in elderly patients is essential. Methods This study examined (1) the differences of clinical characteristics, degree of improvement on QoL and functionality on discharge between non-depressed and depressed elderly inpatients and (2) factors associated with QoL on discharge. Four hundred and seventy-one elderly inpatients admitted to a geriatric evaluation and management unit (GEMU) from 2009 to 2010 were enrolled in this study. Comprehensive geriatric assessment including the activities of daily living (ADL), geriatric depression scale, and mini-mental state examination were conducted. QoL was assessed using the European Quality of Life-5 Dimensions and the European Quality of Life-5 Dimensions Visual Analog Scale on discharge. Information on hospital stay and Charlson comorbidity index were obtained by chart review. Chi-square tests, independent t-tests, Mann--Whitney U tests and multiple linear regressions were used in statistical analysis. Results Worse QoL and ADL on discharge were found among the depressed. Depressive symptoms, female gender, duration of hospital stay, and rehabilitation were significant factors affecting QoL on discharge in linear regression models. Conclusions The importance of the diagnosis and treatment of depression among elderly inpatients should not be overlooked during hospital stay and after discharge. Greater efforts should be made to improve intervention with depressed elderly inpatients. [ABSTRACT FROM AUTHOR]

Background Facial emotion perception (FEP) can affect social function. We previously reported that parts of five tested single-nucleotide polymorphisms (SNPs) in the MET and AKT1 genes may individually affect FEP performance. However, the effects of SNP-SNP interactions on FEP performance remain unclear. Methods This study compared patients with high and low FEP performances (n = 89 and 93, respectively). A particle swarm optimization (PSO) algorithm was used to identify the best SNP barcodes (i.e., the SNP combinations and genotypes that revealed the largest differences between the high and low FEP groups). Results The analyses of individual SNPs showed no significant differences between the high and low FEP groups. However, comparisons of multiple SNP-SNP interactions involving different combinations of two to five SNPs showed that the best PSO-generated SNP barcodes were significantly associated with high FEP score. The analyses of the joint effects of the best SNP barcodes for two to five interacting SNPs also showed that the best SNP barcodes had significantly higher odds ratios (2.119 to 3.138; P < 0.05) compared to other SNP barcodes. In conclusion, the proposed PSO algorithm effectively identifies the best SNP barcodes that have the strongest associations with FEP performance. Conclusions This study also proposes a computational methodology for analyzing complex SNP-SNP interactions in social cognition domains such as recognition of facial emotion. [ABSTRACT FROM AUTHOR]

IMPORTANCE In addition to dopaminergic hyperactivity, hypofunction of the A/-methyl-D-aspartate receptor (NMDAR) has an important role in the pathophysiology of schizophrenia. Enhancing NMDAR-mediated neurotransmission is considered a novel treatment approach. To date, several trials on adjuvant NMDA-enhancing agents have revealed beneficial, but limited, efficacy for positive and negative symptoms and cognition. Another method to enhance NMDA function is to raise the levels of D-amino acids by blocking their metabolism. Sodium benzoate is a D-amino acid oxidase inhibitor. OBJECTIVE To examine the clinical and cognitive efficacy and safety of add-on treatment of sodium benzoate for schizophrenia. DESIGN, SETTING, AND PARTICIPANTS A randomized, double-blind, placebo-controlled trial in 2 major medical centers in Taiwan composed of 52 patients with chronic schizophrenia who had been stabilized with antipsychotic medications for 3 months or longer. INTERVENTIONS Six weeks of add-on treatment of 1 g/d of sodium benzoate or placebo. MAIN OUTCOMES AND MEASURES The primary outcome measure was the Positive and Negative Syndrome Scale (PANSS) total score. Clinical efficacy and adverse effects were assessed biweekly. Cognitive functions were measured before and after the add-on treatment RESULTS Benzoate produced a 21% improvement in PANSS total score and large effect sizes (range, 1.16-1.69) in the PANSS total and subscales, Scales for the Assessment of Negative Symptoms-20 items, Global Assessment of Function, Quality of Life Scale and Clinical Global Impression and improvement in the neurocognition subtests as recommended by the National Institute of Mental Health's Measurement and Treatment Research to Improve Cognition in Schizophrenia initiative, including the domains of processing speed and visual learning. Benzoate was well tolerated without significant adverse effects. CONCLUSIONS AND RELEVANCE Benzoate adjunctive therapy significantly improved a variety of symptom domains and neurocognition in patients with chronic schizophrenia. The preliminary results show promise for D-amino acid oxidase inhibition as a novel approach for new drug development for schizophrenia. [ABSTRACT FROM AUTHOR]

Background: Facial emotion perception is a major social skill, but its molecular signal pathway remains unclear. The MET/AKT cascade affects neurodevelopment in general populations and face recognition in patients with autism. This study explores the possible role of MET/AKT cascade in facial emotion perception. Methods: One hundred and eighty two unrelated healthy volunteers (82 men and 100 women) were recruited. Four single nucleotide polymorphisms (SNP) of MET (rs2237717, rs41735, rs42336, and rs1858830) and AKT rs1130233 were genotyped and tested for their effects on facial emotion perception. Facial emotion perception was assessed by the face task of Mayer-Salovey-Caruso Emotional Intelligence Test (MSCEIT). Thorough neurocognitive functions were also assessed. Results: Regarding MET rs2237717, individuals with the CT genotype performed better in facial emotion perception than those with TT (p = 0.016 by ANOVA, 0.018 by general linear regression model [GLM] to control for age, gender, and education duration), and showed no difference with those with CC. Carriers with the most common MET CGA haplotype (frequency = 50.5%) performed better than non-carriers of CGA in facial emotion perception (p = 0.018, df = 1, F = 5.69, p = 0.009 by GLM). In MET rs2237717/AKT rs1130233 interaction, the C carrier/G carrier group showed better facial emotion perception than those with the TT/AA genotype (p = 0.035 by ANOVA, 0.015 by GLM), even when neurocognitive functions were controlled (p = 0.046 by GLM). Conclusions: To our knowledge, this is the first study to suggest that genetic factors can affect performance of facial emotion perception. The findings indicate that MET variances and MET/AKT interaction may affect facial emotion perception, implicating that the MET/AKT cascade plays a significant role in facial emotion perception. Further replication studies are needed. [ABSTRACT FROM AUTHOR]

In pharmacogenomics studies, gene-gene interactions play an important role in characterizing a trait that involves complex pharmacokinetic and pharmacodynamic mechanisms, particularly when each involved feature only demonstrates a minor effect. In addition to the candidate gene approach, genome-wide association studies (GWAS) are widely utilized to identify common variants that are associated with treatment response. In the wake of recent advances in scientific research, a paradigm shift from GWAS to wholegenome sequencing is expected, because of the reduced cost and the increased throughput of next-generation sequencing technologies. This review first outlines several promising methods for addressing gene-gene interactions in pharmacogenomics studies. We then summarize some candidate gene studies for various treatments with consideration of gene-gene interactions. Furthermore, we give a brief overview for the pharmacogenomics studies with the GWAS approach and describe the limitations of these GWAS in terms of gene-gene interactions. Future research in translational medicine promises to lead to mechanistic findings related to drug responsiveness in light of complex gene-gene interactions and will probably make major contributions to individualized medicine and therapeutic decision-making. [ABSTRACT FROM AUTHOR]

Recent evidence indicates that enhancing N-methyl-D-aspartate (NMDA) neurotransmission with the treatment of NMDA/glycine site agonists, such as D-serine, or a glycine transporter-1 (GlyT-1) antagonist, N-methylglycine (sarcosine), can improve symptoms of schizophrenia. To compare these two novel approaches, 60 patients with chronic schizophrenia were enrolled into a 6-wk double-blind, placebocontrolled trial of add-on treatments at the reported effective dosages (2 g/d). Clinical assessments were conducted every other week. Treatment grouprtreatment duration interaction analysis by multiple linear regression showed that sarcosine was superior to placebo at all four outcome measures of Positive and Negative Syndrome Scale (PANSS) total (p=0.005), Scale for the Assessment of Negative Symptoms (SANS) (p=0.021), Quality of Life (QOL) (p=0.025), and Global Assessment of Functioning (GAF) (p=0.042). However, D-serine did not differ significantly from placebo in any measure. Sarcosine treatment was better than D-serine in effect sizes for all outcome measures. Sarcosine also surpassed placebo in most of the measures of five PANSS factors and five SANS subscales. All treatments were well tolerated. These findings suggest that the GlyT-1 inhibitor is more efficacious than the NMDA/glycine site agonist in treatment for schizophrenia, including life quality and global function, at the dosages tested. [ABSTRACT FROM AUTHOR]

Neuroleptic malignant syndrome (NMS) is one of the most severe'iatrogenic emergencies in clinical service. The symptoms including sudden consciousness change, critical temperature elevation and electrolytes imbalance followed by mutli-organ system failure were common in NMS. In addition to aggressive interventions with intravenous fluid resuscitation and antipyretics, several antidotes have been suggested to prevent further progression of the muscle damage. Dantrolene has been reported to be one of the most effective treatments for NMS. However, the adverse effects of dantrolene treatment for NMS have not yet been evaluated thoroughly. Here we report a young male patient with bipolar I disorder who developed NMS after rapid tranquilization with haloperidol. Dantrolene was given intravenously for the treatment of NMS. However, fever accompanied with local tenderness, hardness with clear border and swelling with heat over the patient's left forearm occurred on the sixth day of dantrolene treatment. Venous thromboembolism (VTE) over intravenous indwelling site at the patient's forearm was noted and confirmed by Doppler ultrasound. The patient's VTE recovered after heparin and warfarin thrombolytic therapy. To our knowledge, this is the first case report demonstrating the possible relationship between dantrolene use and VTE in a patient with antipsychotic treatment. Although the causal relationship and the underlying pathogenesis require further studies, dantrolene should be used with caution for patients with NMS. [ABSTRACT FROM AUTHOR]

Ketamine, a noncompetitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, has multiple clinical uses. On the other hand, ketamine abuse or recreational use has been gaining increasing attention. Induction of mania and psychotic symptoms has been reported in a patient receiving IV ketamine therapy for reflex sympathetic dystrophy. We here report a 26 year-old man who abused ketamine by inhalation for 12 months and developed manic-like symptoms after ketamine use. This case suggests a possible relationship between manic symptoms and ketamine abuse. To the best of our knowledge, this may be the first report regarding mania after recreational use of ketamine. [ABSTRACT FROM AUTHOR]

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Electroacupuncture (EA) is widely used to treat disorders of the nervous system, such as stroke. The aim of the present study was to investigate the effect of EA on cerebral blood flow (CBF) in cerebral ischemic rats. We developed an animal model of cerebral ischemia (CI) by occluding the blood flow of both common carotid arteries in Sprague-Dawley (SD) rats; 2 or 15 Hz EA was applied to both Zusanli acupoints. The levels of nitric oxide (NO) in the peripheral blood and amounts of calcitonin gene-related peptide (CGRP) in the cerebral cortex and thalamus were measured. In addition, L-N (G)-nitro arginine methyl ester (L-NAME) was used to measure the changes in CBF induced by EA in rats with and without CI. The results indicated that both 2 and 15 Hz EA increase the mean CBF in rats with and without CI. However, neither 2 nor 15 Hz EA induced changes in levels of NO in peripheral blood or changes in CGRP levels in cerebral cortex and thalamus. In addition, L-NAME did not change the increase in CBF. We concluded that both 2 and 15 Hz EA at both Zusanli acupoints induced the increase of CBF in rats with and without CI. Whether the effect of EA is related to NO or CGRP will be investigated in a future study. [ABSTRACT FROM AUTHOR]

Context Agents that enhance N-methyl-D-aspartate (NMDA) function through the glycine modulatory site (D-serine, glycine, or D-cycloserine) or through glycine transporter 1 (sarcosine) improve the symptoms of patients with stable chronic schizophrenia. Objective To determine whether NMDA-glycine site agonists or glycine transporter-1 inhibitors have better efficacy and whether NMDA receptor-enhancing agents have beneficial effects for acute exacerbation of schizophrenia. Design Randomized, double-blind, placebo-controlled trial. Setting Inpatient units of 2 major medical centers in Taiwan. Patients Sixty-five schizophrenic inpatients with acute exacerbation. Interventions Six weeks of treatment with sarcosine (2 g/d), D-serine (2 g/d), or placebo and concomitant optimal risperidone therapy. Main Outcome Measures Positive and Negative Syndrome Scale (PANSS) and Scale for the Assessment of Negative Symptoms (SANS) (20 and 17 items) total scores. Results The sarcosine group revealed more reductions in PANSS total scores than the placebo (P = .04) and D-serine (P<.001) groups. Sarcosine adjunctive treatment was also superior to placebo in reducing SANS-20 (P = .007) and SANS-17 (P = .003) scores and to D-serine in decreasing SANS-20 (P = .006) and SANS-17 (P = .002) scores. The PANSS-general, PANSS-cognitive, and PANSS-depressive symptoms scores and SANS-alogia and SANS-blunted affect scores improved significantly more in sarcosine-cotreated patients than in risperidone monotherapy patients (P≤.02 for all). Sarcosine adjunctive therapy also surpassed D-serine in terms of PANSS-general, PANSS-positive, PANSS-negative, and PANSS-depressive symptoms scores (P≤.04 for all). D-Serine and risperidone cotreatment did not differ significantly from risperidone monotherapy in all efficacy domains. Conclusions This first short-term treatment study on NMDA receptor-enhancing agents suggests that sarcosine, superior to D-serine, can benefit not only patients with long-term stable disease but also acutely ill persons with schizophrenia. This finding indicates that a glycine transporter 1 inhibitor may be more efficacious than NMDA-glycine site agonists for adjuvant treatment of schizophrenia, at least during the acute phase. Further studies are needed. [ABSTRACT FROM AUTHOR]

Background: Polymorphisms within intron 7 of the tryptophan hydroxylase (TPH1) gene were found to be associated with alcohol dependence in different ethnic groups, including the aboriginal Bunun group in Taiwan. This study aimed to identify genetic variants at the TPH1 locus and to examine their associations with alcoholism. We hypothesized that the polymorphism of TPH1 gene is functional and influences the human circadian rhythm to contribute to the pathophysiology of alcohol dependence. Methods: DNA from the Taiwanese Han and Bunun was subjected to sequence for screening genetic variation in the coding and promoter regions of the TPH1 locus. Polymorphisms among individuals with alcohol dependence and control subjects in two ethnic groups in Taiwan were investigated. Results: Three variants in the TPH1 promoter region were identified, and the markers are in complete linkage disequilibrium in both populations. Positive associations at both allelic and genotypic levels were obtained between case and control groups in the Bunun. Expression studies demonstrated that the variants indeed affected reporter gene activity in human choriocarcinoma and colon adenocarcinoma cell lines. Conclusions: Polymorphisms in the promoter region may influence the function of the TPH1 gene and further influence the proclivity of alcohol dependence in one ethnic group in Taiwan. The associations between TPH1 genotypes and alcoholism may deserve further investigation. [ABSTRACT FROM AUTHOR]

Rationale. Risperidone doses for acute schizophrenia were rather high in most recent studies. Objectives. We tested a hypothesis that fine-tuning risperidone dosage to relieve side effects still yields efficacy. Clinical factors influencing the dosing were also determined. Methods. One hundred and forty-six schizophrenia inpatients with acute exacerbation entered a prospective, 6-week, repeated measures study. Risperidone doses were titrated to 6 mg/day (if tolerable) within 7 days, but were lowered thereafter if adverse reactions appeared. Efficacy and safety were measured biweekly. Results. Forty-eight patients tolerated the 6-mg/day target dose well, while the other 98 received lower final doses (mean±SD=3.4±0.9 mg/day) to curtail adverse effects. At endpoint, 64.3% of the low-dose patients and 43.8% of the high-dose subjects responded to treatment [≥20% reduction in the Positive and Negative Syndrome Scale (PANSS) total score] (P=0.018). In detail, the low-dose individuals were significantly superior in percentage changes in the PANSS total and general-subscale scores at endpoint. The low-dose group also tended to improve more (albeit statistically insignificantly) in the PANSS positive and negative subscales and other efficacy measures. Compared to the patients with undifferentiated subtype, those with disorganized subtype received higher dosage by 0.90 mg/day, after controlling for other variables (P=0.008). Paranoid subtype was similar to undifferentiated subtype in drug doses. Patients with longer illness duration also showed a trend to use higher dosage (P=0.078). Conclusions. These findings suggest that dosage adjustment to diminish side effects does not compromise risperidone response and that disorganized patients and perhaps patients with longer illness duration are prone to receive larger doses. [ABSTRACT FROM AUTHOR]

Aim This study examined the reliability and validity for Taiwanese populations of three Chinese-version tasks of the Mayer--Salovey--Caruso Emotional Intelligence Test (MSCEIT): a face task (FT), emotional-management task (EMT) and emotional-relations task (ERT). Background For patients with schizophrenia and affective disorders, one aspect of successful outcomes of treatment and nursing care in primary healthcare is patients' ability to manage emotions (Russell & Potter 2002). Emotional management is the ability to modulate one's own and others' feelings to deal with stress and to promote self-understanding and growth (Mayer et al. 2003, Green et al. 2005). This ability can be assessed in western populations using the MSCEIT, as recommended by a National Institute of Mental Health conference breakout group, Measurement and Treatment Research to Improve Cognition in Schizophrenia (NIMHMATRICS) (Green et al. 2005). The MSCEIT is a valid and reliable self-administered tool to assess emotional intelligence that is a cognitive- and emotional-processing ability (Mayer et al. 2003). However, no scale assessing these abilities in Taiwanese populations was found in a literature review. The MSCEIT includes eight tasks in four branches: perceiving emotions, facilitating emotions, understanding emotions and managing emotions (Mayer et al. 2003). The perceiving-emotions branch includes face and picture tasks that measure ability to recognise feelings. The facilitatingemotions branch includes two tasks that measure ability to generate emotions to foster ideas. The understanding-emotions branch includes two tasks that measure ability to understand simple and complex emotions. The managingemotion branch contains EMT and ERT that measure ability to manage emotions in solving problems. This study followed the NIMH-MATRICS suggestion to assess emotional-management ability using three tasks (FT, EMT and ERT). In the FT, participants identify degree of facial expression. In the EMT, participants identify effectiveness of strategies to manage their emotions to solve problems. In the ERT, participants identify effectiveness of strategies needed to incorporate emotions into decision-making involving other people (Mayer et al. 2003). Methods A non-experimental cross-sectional survey was used with a convenience sample of three groups of adults (age ≥18 years). Group 1 (53 undergraduate and graduate students) was used for reliability testing. Group 2 (40 security guards and maintenance personnel) and group 3 (38 clinical patients with schizophrenia and affective disorders) were used for validity testing. Participants in group 2 and 3 had no significant differences in age and educational level. After the study site's institutional ethics committee approved the study, data were collected. The study purposes and procedures were explained, and subjects' confidentiality and anonymity were assured. All individuals signed written informed consent before participation. Data were collected by personal data sheet, three Chineseversion MSCEIT tasks (Mayer et al. 2003) and the Wong and Law Emotional Intelligence Scale (WLEIS) (Shi & Wang 2007). The personal data sheet recorded sex, age, educational level and marital status. The three Chinese-version MSCEIT tasks tested participants' emotional intelligence. The WLEIS tested the criterion validity of MSCEIT subscales. The WLEIS is a 16-item self-report measure with a seven-point Likerttype scale for assessing emotional intelligence based on a trait-oriented model. The 49 items of the three Chinese-version MSCEIT tasks were satisfactorily translated and back-translated from English to Mandarin Chinese in this study. The 20-item FT includes four item parcels, each with five responses on a fivepoint scale. The 20-item EMT includes five parcels with four responses each. The nine-item ERT includes three parcels with three responses each. The stability of MSCEIT subscales was established by intra-class correlation coefficients (ICCs) for group 1. Item-scale correlations were analysed by Pearson's coefficients. MSCEIT internal consistency was established by Cronbach's alpha for three groups. The criterion validity of the MSCEIT tasks was analysed by the ICC correlations between their scores and the WLEIS scores for group 3. Differences between the three groups were assessed by ANOVA ANOVA. Results The total sample was on average 29.9 years old (SD 9.54), with 13.91 years (SD 2.78) of education. The majority was women (n = 78, 60%). Subjects' mean scores by group and Cronbach's alpha for each task are reported in Table 1. For group 1, the six-week, test--retest correlation for 49 items was 0.76 (ICC), with confidence interval 0.337-0.802. High ERT scores were associated with high EMT (r = 0.53, p<0.01) and FT (r = 0.37, p < 0.05), but EMT and FT scores were not significantly associated. In validity testing, high WLEIS scores were mildly correlated with high FT (ICC = 0.28), EMT (ICC = 0.31) and ERT (ICC = 0.23) for 38 clinical patients with schizophrenia and affective disorders, but only EMT reached significance. In cross-sample validity testing, the three groups differed significantly in scores for the three tasks (Table 1). Conclusions This study provides evidence for the stability, internal consistency, criterion validity and cross-sample validity of three Chinese-version MSCEIT tasks, which are stable subscales for assessing emotional intelligence. Cronbach's alpha and item--scale correlations indicate that FT and ERT form coherent subscales. Our EMT scores had a lower internal consistency than that previously reported (Mayer et al. 2003), suggesting that EMT may not be appropriate to use separately for Taiwanese people. However, we found the three MSCEIT tasks had low correlations with the WLEIS for clinical psychiatric patients. This unexpected finding may be attributable to the two scales assessing different types of emotional intelligence (Goldin et al. 2008). The MSCEIT measures test-related emotional intelligence and the WLEIS measures self-perceptions about emotional intelligence. Finally, the cross-sample test showed that the three tasks had enough sensitivity to measure performance differences between different groups. To conclude, the construct validity of the three Chinese-version MSCEIT tasks needs to be examined by factor analysis on larger clinical samples with psychotic disorders. The tasks are reliable tools that may be suitable for measuring ability to manage emotions in Taiwanese individuals with psychosis. Relevance to clinical practice Emotional intelligence plays a meaningful role in clinical nursing practice (Akerjordet & Severinsson 2007). Managing emotions such as aggression, anger, fear, anxiety and depression is a mental health issue in primary healthcare for both health providers and psychotic patients (Russell & Potter 2002). The three Chinese-version MSCEIT tasks include 49 items that can easily be applied to assess ability to manage emotions. These tasks can help in assessing the emotional intelligence of Taiwanese individuals with mental illness. The three tasks may also be used to evaluate treatment effects or nursing care outcomes aimed at improving patients' ability to manage emotions in solving daily problems. [ABSTRACT FROM AUTHOR]

Objective: This study investigated the effect of the 102-T/C polymorphism in the 5-HT[sub 2A] receptor gene on risperidone efficacy. Method: One hundred Han Chinese patients with acutely exacerbated schizophrenia were given risperidone for up to 42 days. The patients were genotyped for 5-HT[sub 2-] polymorphisms. Psychopathology was measured biweekly with the Positive and Negative Syndrome Scale while the patients were taking risperidone. Generalized estimating equation methods were used to analyze the effects of treatment duration, T/C genotypes, and other prognostic factors on Positive and Negatve Syndrome Scale performance. Results: Patients with the C/C genotype had lower total scores, negative subscale scores, and general psychopathology scores but not positive subscale scores on the Positive and Negative Syndrome Scale than patients with the 102-T/C genotype Patients with the T/C and T/T genotypes had comparable total and subscale scores. The number of previous hospitalizations and the dose of risperidone also affected Positive and Negative Syndrome Scale total scores. [ABSTRACT FROM AUTHOR]