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Objective Emotional labor is known to be a risk factor for emotional distress. This study aimed to evaluate specific stressors according to the type of occupation and identify protective and adverse factors.Methods We recruited 349 workers engaged in emotional labor in a suburban city. They were assessed using scales regarding emotional status, job stress, resilience, and job satisfaction. Correlation and regression analyses were performed to evaluate their emotional state according to their stress level. A mediation model using structural equation modeling was utilized to identify the mediating effects of resilience and workplace satisfaction.Results The correlation analysis indicated that the level of workplace stress was statistically correlated with depressed mood and anxiety and showed a significant inverse correlation with individuals’ resilience and job satisfaction. According to the regression analysis, in private institution workers, “emotional disharmony and hurt” had a statistically significant negative effect on their emotional state, and in public institution workers, “emotional demands and regulation” were prominent. Resilience partially mediated the relationship between emotional stress and anxiety/depressive symptoms.Conclusion Our findings indicate that the causes of stress differed according to the working environment. Preventive strategies such as resilience training and relieving stress on individual factors are needed to promote mental health.

Additional file 1: Table S1. Participants’ sociodemographic characteristics. Table S2. Logistic regression analysis of factors associated with the experience of depressive symptoms.

Gang Wang,1,2 Changsu Han,3 Chia-Yih Liu,4 Sandra Chan,5 Tadafumi Kato,6,7 Wilson Tan,8 Lili Zhang,9 Yu Feng,9 Chee H Ng10 1The National Clinical Research Center for Mental Disorder & Beijing Key Laboratory of Mental Disorders, Beijing Anding Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China; 3Department of Psychiatry, Korea University College of Medicine, Seoul, South Korea; 4Department of Psychiatry, Chang Gung Medical Center, and Chang Gung University School of Medicine, Taoyuan City, Taiwan; 5Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 6RIKEN Center for Brain Science, Wako, Saitama, Japan; 7Department of Psychiatry and Behavioral Science, Juntendo University Graduate School of Medicine, Tokyo, Japan; 8Regional Medical Affairs, Janssen Pharmaceutical Companies of Johnson and Johnson, Singapore, Singapore; 9Medical Affairs, Xian Janssen Pharmaceutical Ltd, Beijing, People’s Republic of China; 10Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, AustraliaCorrespondence: Chee H NgThe Melbourne Clinic, 130 Church Street, Richmond, Victoria 3121, AustraliaTel +61 3 9420 9350Fax +61 3 9421 0704Email cng@unimelb.edu.auWilson Tan Regional Medical AffairsJanssen Pharmaceutical Companies of Johnson and Johnson, 2 Science Park Drive, #07-13, Ascent, Singapore Science Park 1, 118222, SingaporeTel +65-69187930Email wtan27@its.jnj.comPurpose: Consensus is lacking on the management of treatment-resistant depression (TRD), resulting in significant variations on how TRD patients are being managed in real-world practice. A survey explored how clinicians managed TRD across Asia, followed by an expert panel that interpreted the survey results and provided recommendations on how TRD could be managed in real-world clinical settings.Methods: Between March and July 2018, 246 clinicians from Hong Kong, Japan, Mainland China, South Korea, and Taiwan completed a survey related to their treatment approaches for TRD.Results: The survey showed physicians using more polytherapy (71%) compared to maintaining patients on monotherapy (29%). The most commonly (23%) administered polytherapy involved antidepressant augmentation with antipsychotics that 19% of physicians also indicated as their most important approach for managing TRD. The highest number of physicians (34%) ranked switching to another class of antidepressants as their most important approach, while 16% and 9% chose antidepressant combinations and electroconvulsive therapy (ECT), respectively.Conclusion: Taking into account the survey results, the expert panel made general recommendations on the management of TRD. TRD partial-responders to antidepressants should be considered for augmentation with second-generation antipsychotics. For non-responders, switching to another class of antidepressants ought to be considered. TRD patients achieving remission with acute treatment should consider continuing their antidepressants for at least another 6 months to prevent relapse. ECT is a treatment consideration for patients with severe depression or persistent symptoms despite multiple adequate trials of antidepressants. Physicians should also consider the response, tolerability and adherence to the current and previous antidepressants, the severity of symptoms, comorbidities, concomitant medications, preferences, and cost when choosing a TRD treatment approach for each individual patient.Keywords: Asia, treatment-resistant depression, diagnosis, management

Changsu Han,1 Gang Wang,2 Sandra Chan,3 Tadafumi Kato,4,5 Chee H Ng,6 Wilson Tan,7 Lili Zhang,8 Yu Feng,8 Chia-Yih Liu9 1Department of Psychiatry, Korea University College of Medicine, Seoul, South Korea; 2The National Clinical Research Center for Mental Disorder & Beijing Key Laboratory of Mental Disorders Beijing Anding Hospital & The Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China; 3Department of Psychiatry, The Chinese University of Hong Kong, Hong Kong, People’s Republic of China; 4RIKEN Center for Brain Science, Wako, Saitama, Japan; 5Department of Psychiatry and Behavioral Science, Juntendo University Graduate School of Medicine, Tokyo, Japan; 6Department of Psychiatry, The University of Melbourne, Melbourne, Victoria, Australia; 7Regional Medical Affairs, Janssen Pharmaceutical Companies of Johnson and Johnson, Singapore, Singapore; 8Medical Affairs, Xian Janssen Pharmaceutical Ltd, Beijing, People’s Republic of China; 9Department of Psychiatry, Chang Gung Medical Center and Chang Gung University School of Medicine, Taoyuan City, TaiwanCorrespondence: Chia-Yih LiuDepartment of Psychiatry, Chang Gung Medical Center and Chang Gung University School of Medicine, No. 5, Fuching Street, Guishan District, Taoyuan City, TaiwanTel +886-3-3281200 Ext 2439Email liucy752@cgmh.org.twWilson TanRegional Medical Affairs, Janssen Pharmaceutical Companies of Johnson and Johnson, 2 Science Park Drive, #07– 13, Ascent, Singapore Science Park 1, Singapore 118222, SingaporeTel +65-69187930Email wtan27@its.jnj.comPurpose: An Asia-Pacific expert consensus defined treatment-resistant depression (TRD) as failure of ≥ 2 antidepressants given at adequate doses for 6– 8 weeks during a major depressive episode. A survey examined how TRD was being diagnosed in real-world practices across Asia. An expert panel then interpreted the results and provided practical recommendations.Methods: Between March and July 2018, 246 clinicians from Hong Kong, Japan, Mainland China, South Korea, and Taiwan were surveyed on how they identified TRD patients according to their own definitions.Results: Most physicians described antidepressant failure as “no response” (79%) or “inadequate response” (82%); fewer chose “failure to achieve remission” (45%). About 40% did not routinely use clinical tools to assess response. Around 52% defined adequate dose target as achieving the label’s upper dose limit. About 58% would treat for 4– 8 weeks before determining antidepressant failure. Most (76%) required the ≥ 2 qualifying antidepressant failures to be from different classes. Approximately 60% considered antidepressant failure(s) from previous depressive episode(s) when diagnosing TRD.Conclusion: Considering the survey results, antidepressant failure can be defined as a failure to achieve remission, or more practically as < 50% improvement in depressive symptoms or inability to return to work/study, and confirmed with a clinical tool. TRD diagnosis also requires ≥ 2 qualifying antidepressant failures within the same depressive episode; from the same or different classes; and achieving at least the minimum effective antidepressant dose for 6– 8 weeks.Keywords: Asia, treatment-resistant depression, diagnosis, management

Older adults commonly experience somatic symptoms, and those who do are more likely to have depressive disorders as well. Our goal in this study is to examine the influence of the number and severity of somatic symptoms on the severity of depressive symptoms, including suicidality, in elderly adults.This study was conducted as part of the Ansan Geriatric (AGE) Study, a community-based cohort study in Ansan City, South Korea. A total of 3,210 elderly adults aged 60 years or over (1,388 males and 1,770 females) participated in this study. The Korean version of the Beck Depression Inventory (BDI) was used to measure depressive symptoms and suicidality. Somatic symptoms were assessed by the Patient Health Questionnaire-15 (PHQ-15).Both mild and severe somatic symptoms significantly increased the risk for severe depression and high suicidality. Severe somatic symptoms doubled the risk for severe depression and suicidal intent.Somatic symptoms not fully explained as medical illnesses are closely associated with late-life depression, even after adjustments for comorbid physical illnesses and other confounding factors. The presence of somatic symptoms concurrent with, but not fully explained by comorbid physical illness or disability, seems to be an independent marker for predicting the severity of late-life depression and suicidality.

An embedded compression (EC) is a technique that can compress on-the-fly the frame data when stored in video memory; it has been used to effectively reduce the system memory requirements. In this paper, we propose a lossy EC algorithm that uses hybrid coding scheme of feedforward DPCM and modified four-level BTC, which aims at the target specification of the 4 × 2 block-wise random access at 50 % compression ratio. The algorithmic characteristics of the proposed algorithm are twofold: the first is the error-aware quantization scheme to definitely reduce the total error in a block and the last is the hybrid DPCM/BTC coding scheme to effectively handle various texture patterns that can occur in a block. The architectural advantage stems from the feedforward DPCM that breaks off the inherent dependency between the prediction and quantization present in the conventional DPCM, which helps reduce the implementation burden as well as speed up the overall processing. Comparative evaluation shows that the proposed algorithm outperforms the existing ones by 0.77–6.39 dB.

Proposed is an adaptive scalar quantization scheme. The main advantage is to improve coding performance by suppressing the sum of absolute quantization errors (SAQE) under half the maximal SAQE, assuming that the errors have uniform distribution. This fact was proven and demonstrated, integrated into H.264.

This paper proposes a high performance hardware architecture design for the H.264/AVC CAVLC encoder. The proposed architecture can make a realtime process for 1920×1080 @ 30p. With the synthesis constraint of a 114MHz clock, the hardware cost of the proposed design is 7389 gates based on SS65LP 65nm technology.

Schizophrenia (SCZ) is a common and severe mental disorder. Genetic factors likely play a role in its pathophysiology as well as in treatment response. In the present study, we investigated the effects of several single nucleotide polymorphisms (SNPs) within 9 genes involved with antipsychotic (AP) mechanisms of action. Two independent samples were recruited. The Korean sample included 176 subjects diagnosed with SCZ and 326 healthy controls, while the Italian sample included 83 subjects and 194 controls. AP response as measured by the positive and negative syndrome scale (PANSS) was the primary outcome, while the secondary outcome was the SCZ risk. Exploratory analyses were performed on (1) symptom clusters response (as measured by PANSS subscales); (2) age of onset; (3) family history; and (4) suicide history. Associations evidenced in the primary analyses did not survive to the FDR correction. Concerning SCZ risk, we partially confirmed the associations among COMT and MAPK1 genetic variants and SCZ. Finally, our exploratory analysis suggested that CHRNA7 and HTR2A genes may modulate both positive and negative symptoms responses, while PLA2G4A and SIGMAR1 may modulate respectively positive and negative symptoms responses. Moreover, GSK3B, HTR2A, PLA2G4A, and S100B variants may determine an anticipation of SCZ age of onset. Our results did not support a primary role for the genes investigated in AP response as a whole. However, our exploratory findings suggested that these genes may be involved in symptom clusters response.

Background: Bipolar disorder (BPD) is a common and severe mental disorder. The involvement of genetic factors in the pathophysiology of BPD is well known. In the present study, we tested the association of several single-nucleotide polymorphisms (SNPs) within 3 strong candidate genes (CACNA1C, CHRNA7, and MAPK1) with BPD. These genes are involved in monoamine-related pathways, as well as in dendrite development, neuronal survival, synaptic plasticity, and memory/learning. Methods: One hundred and thirty-two subjects diagnosed with BPD and 326 healthy controls of Korean ancestry were genotyped for 40 SNPs within CACNA1C, CHRNA17, and MAPK1. Distribution of alleles and block of haplotypes within each gene were compared in cases and controls. Interactions between variants in different loci were also tested. Results: Significant differences in the distribution of alleles between the cases and controls were detected for rs1016388 within CACNA1C, rs1514250, rs2337980, rs6494223, rs3826029 and rs4779565 within CHRNA7, and rs8136867 within MAPK1. Haplotype analyses also confirmed an involvement of variations within these genes in BPD. Finally, exploratory epistatic analyses demonstrated potential interactive effects, especially regarding variations in CACNA1C and CHRNA7. Limitations: Limited sample size and risk of false-positive findings. Discussion: Our data suggest a possible role of these 3 genes in BPD. Alterations of 1 or more common brain pathways (e.g., neurodevelopment and neuroplasticity, calcium signaling) may explain the obtained results.

Objective Pharmacogenomic-based antidepressant treatment (PGATx) may result in more precise pharmacotherapy of major depressive disorder (MDD) with better drug therapy guidance. Methods An 8-week, randomized, single-blind clinical trial was conducted to evaluate the effectiveness and tolerability of PGATx in 100 patients with MDD. All recruited patients were randomly allocated either to PGATx (n=52) or treatment as usual (TAU, n=48) groups. The primary endpoint was a change of total score of the Hamilton Depression Rating Scale-17 (HAMD-17) from baseline to end of treatment. Response rate (at least 50% reduction in HAMD-17 score from baseline), remission rate (HAMD-17 score ≤7 at the end of treatment) as well as the change of total score of Frequency, Intensity, and Burden of Side Effects Ratings (FIBSER) from baseline to end of treatment were also investigated. Results The mean change of HAMD-17 score was significantly different between two groups favoring PGATx by -4.1 point of difference (p=0.010) at the end of treatment. The mean change in the FIBSER score from baseline was significantly different between two treatment groups favoring PGATx by -2.5 point of difference (p=0.028). The response rate (71.7 % vs. 43.6%, p=0.014) were also significantly higher in PGATx than in TAU at the end of treatment, while the remission rate was numerically higher in PGATx than in TAU groups without statistical difference (45.5% vs. 25.6%, p=0.071). The reason for early drop-out associated with adverse events was also numerically higher in TAU (n=9, 50.0%) than in PGATx (n=4, 30.8%). Conclusion The present study clearly demonstrate that PGATx may be a better treatment option in the treatment of MDD in terms of effectiveness and tolerability; however, study shortcomings may limit a generalization. Adequately-powered, well-designed, subsequent studies should be mandatory to prove its practicability and clinical utility for routine practice.

Introduction Mood disorders are common and disabling disorders. Despite the availability of over 100 psychotropic compounds, only one-third of patients benefit from first-line treatments. Over the past 20 years, many studies have focused on the biological factors modulating disease risk and response to treatments, but with still inconclusive data. In order to improve our current knowledge, in this study, we investigated the role of a set of genes involved in different pathways (neurotransmission, neuroplasticity, circadian rhythms, transcription factors, signal transduction and cellular metabolism) in the treatment outcome of major depressive disorder (MDD) and bipolar disorder (BD) after naturalistic pharmacological treatment. Methods Totals of 242 MDD, 132 BD patients and 326 healthy controls of Asian ethnicity (Koreans) were genotyped for polymorphisms within 19 genes. Response and remission after 6–8 weeks of treatment with antidepressants and mood stabilizers were evaluated. In secondary analyses, genetic associations with disease risk and some disease-associated features (age of onset, suicide attempt and psychotic BD) were also tested. Results None of the variants within the investigated genes was significantly associated with treatment outcomes. Some marginal association (uncorrected p

We investigated the effect of a set of SNPs within 5 genes identified by GWASs as possible risk genes for schizophrenia (SCZ) in two independent samples, comprising 176 SCZ patients and 326 controls of Korean origin and 83 SCZ patients and 194 controls of Italian origin. The PANSS was used to assess psychopathology severity and antipsychotic response (AR). Several clinical features were assessed at recruitment. In the Korean sample, the SP4 gene haplotype rs2282888-rs2237304-rs10272006-rs12673091 (p = 0.02) was associated with SCZ. In the Italian sample, PPP3CC rs11780915 (genotypic: p = 0.006; allelic: p = 0.001) and rs2249098 (genotypic: p = 0.0004; allelic: p = 0.00006) were associated with SCZ, as well as the PPP3CC rs11780915-rs10108011-rs2249098 and the ZNF804A rs7603001-rs1344706 haplotypes (p = 0.03 and p = 0.02). Several RORA variants were associated with AR in both the samples, although only the haplotype rs1020729-rs1871858 in the Korean sample survived to the statistical correction (p = 0.01). Exploratory analyses suggested that: (1) PPP3CC, ST8SIA2, and SP4 genes may modulate psychotic symptoms, and (2) RORA and ZNF804A genes may influence AR. Our results partially support a role for these genes in SCZ and AR. Analyses in well phenotyped samples may help to refine the role of the genes identified by GWASs.

Background: Vortioxetine was approved by the U.S. Food and Drug Administration (FDA) in September 2013 for treating major depressive disorder (MDD). Thus far, a number of randomized, double-blind, placebo-controlled clinical trials (RCTs) of vortioxetine have been conducted in patients with MDD. We performed a meta-analysis to increase the statistical power of these studies and enhance our current under standing of the role of vortioxetine in the treatment of MDD. Methods: We performed an extensive search of databases and the clinical trial registry. The mean change in total scores on the 24-item Hamilton Rating Scale for Depression (HAM-D) and the Montgomery– Asberg Depression Rating Scale (MADRS) from the baseline were the primary outcome measures. The secondary efficacy measures were the response and remission rates, as defined by a 50% or greater reduction in HAM-D/MADRS total scores and as a score of 10 or less in the MADRS and 7 or less in the HAM-D total scores at the end of treatment. Results: We included 7 published and 5 unpublished shortterm (6–12 wk) RCTs in our meta-analysis. Vortioxetine was significantly more effective than placebo, with an effect size (standardized mean difference [SMD]) of –0.217 (95% confidence interval [CI] –0.313 to –0.122) and with odds ratios (ORs) for response and remission of 1.652 (95% CI 1.321 to 2.067) and 1.399 (95% CI 1.104 to 1.773), respectively. Those treated with vortioxetine did not differ significantly from those treated with selective norepinephrine reuptake inhibitors/agomelatine with regard to the SMD of the primary outcome measure (0.081, –0.062 to 0.223) or for response (OR 0.815, 95% CI 0.585 to 1.135) and remission (OR 0.843, 95% CI 0.575 to 1.238) rates. Discontinuation owing to lack of efficacy (OR 0.541, 95% CI 0.308 to 0.950) was significantly less common among those treated with vortioxetine than among those who received placebo, whereas discontinuation owing to adverse events (AEs; OR 1.530, 95% CI 1.144 to 2.047) was significantly more common among those treated with vortioxetine than among those receiving placebo. There was no significant difference in discontinuation rates between vortioxetine and comparators owing to inefficacy (OR 0.983, 95% CI 0.585 to 1.650), whereas discontinuation owing to AEs was significantly less common in the vortioxetine than in the comparator group (OR 0.728, 95% CI 0.554 to 0.957). Limitations: Studies examining the role of vortioxetine in the treatment of MDD are limited. Conclusion: Although our results suggest that vortioxetine may be an effective treatment option for MDD, they should be interpreted and translated into clinical practice with caution, as the meta-analysis was based on a limited number of heterogeneous RCTs.

We investigated the relative efficacy and tolerability of aripiprazole once monthly (AOM) versus paliperidone palmitate (PP) for treating schizophrenia. Extensive databases searches on short-term, placebo-controlled, randomized studies of AOM and PP were performed. Indirect treatment comparisons were performed between the two long-acting injectable antipsychotics (LAIAs). The primary efficacy endpoint was the mean change in the Positive and Negative Syndrome Scale total score from baseline between each LAIA and placebo. The effect sizes were mean differences and odds ratio (ORs) with 95% confidence intervals (CIs) for the primary efficacy endpoint and safety/tolerability between two LAIAs, respectively. Mean difference in the primary efficacy endpoint was significantly different, favouring AOM over PP (OR: -6.4; 95% CI: -11.402 to -1.358); sensitivity analyses and noninferiority test (AOM vs. PP) confirmed the primary results. The overall early dropout rate was not significantly different between AOM and PP (OR: 1.223; 95% CI: 0.737-2.03). However, there was a significant difference in the early dropout rate in terms of lack of efficacy favouring AOM over PP (OR: 0.394; 95% CI: 0.185-0.841). Within the context of the inherent limitations of the current analysis, our results may suggest that there may be relative advantages for AOM over PP in the short-term treatment of schizophrenia.

Introduction: Schizophrenia (SCZ) is one of the most disabling psychiatric disorders. Genetic factors play an important role in both SCZ liability and its treatment outcome. In the present paper, we investigated the effects of several single nucleotide polymorphisms (SNPs) within ten strong candidate genes involved with antipsychotics (APs) mechanisms of action. Methods: Two independent samples were investigated in the present study. Totals of 176 SCZ subjects and 326 controls of Korean ancestry, and 83 SCZ subjects and 194 controls of Italian ancestry were recruited and genotyped. SCZ risk and other parameters were also investigated. Results: Concerning APs response, only a nominal association with HOMER1 rs3822568 in the Korean sample was found. In the haplotype analysis, rs9801117 C–rs12668837 C–rs4621754 A haplotype within ESYT2 and NCAPG2 genes was associated with APs response in the same sample. As for secondary outcomes, rs7439 within PKDCC and rs12668837 within NCAPG2 were associated with SCZ risk in the Italian sample. In the haplotype analysis, rs2788478 G–rs2657375 T–rs1039621 A within the region between WDR60 and ESYT genes and rs2013 C (ESYT2)–rs6459896 A (NCAPG2) haplotypes were associated with SCZ in the same sample. No association was found in the Korean sample. Finally, our exploratory data suggest a possible modulation of HOMER1, ARC, BDNF, TXNRD2, WDR60, and ESYT2 genes in the APs response to specific symptom clusters. Conclusion: Our results did not support a primary role for the genes investigated in the APs response. On the other hand, our secondary results suggest a possible involvement of NACPG2 and PKDCC in SCZ liability. Finally, our exploratory findings may deserve further investigations in specific studies.

Introduction: Ample evidence suggested a role of sigma-1 receptor in affective disorders since the interaction of numerous antidepressants with sigma receptors was discovered. A recent study on Japanese subjects found a genetic variant within the encoding gene SIGMAR1 (rs1800866A>C) associated with major depressive disorder (MDD). We aimed to evaluate the same polymorphism in both MDD and bipolar disorder (BD) as well as its relationship to response to treatment with antidepressants and mood stabilizers. Methods: A total of 238 MDD patients treated for an acute episode of depression, 132 BD patients in treatment with mood stabilizers for a manic or mixed episode, and 324 controls were genotyped for rs1800866. At discharge, response to treatments was evaluated in MDD and BD patients by the Hamilton Rating Scale for Depression (HRSD) and the Young Mania Rating Score (YMRS), respectively. Results: In our Korean sample, allele frequencies were different from those reported in other Asian and non-Asian populations. The CC genotype was associated with BD and, as a trend, with MDD. No significant effect was observed on response to antidepressants in MDD or mood stabilizers in BD, although the CC genotype was more frequent among BD patients experiencing a mixed episode. Conclusion: The present findings are the first to propose the putative role of genetic variants within SIGMAR1 and sigma-1 receptor in BD. Sigma-1 receptor can modulate a number of central neurotransmitter systems as well as some other signaling pathways (e.g., neurotrophin and growth factor signaling) which are seemingly involved in BD and other mood disorders.

Background: We investigated phosphodiesterase 7B (PDE7B), neuromedin B receptor (NMBR) and epilepsy progressive myoclonus type 2A (EPM2A) genes in schizophrenia (SCZ). To the best of our knowledge, these genes have been poorly investigated in studies of SCZ. Methods: Five hundred and seventy-three SCZ inpatients of Korean ethnicity and 560 healthy controls were genotyped for 2 PDE7B, 3 NMBR and 3 EPM2A polymorphisms. Differences in the allelic and genetic frequencies among healthy subjects and patients were calculated using the χ2 statistics. Repeated-measure ANOVA was used to test possible influences of single-nucleotide polymorphisms on treatment efficacy. In case of positive findings, clinical and demographic variables were added as covariates, in order to investigate possible stratification bias. Results: The rs2717 and rs6926279 within the NMBR gene and rs702304 and rs2235481 within the EPM2A gene were associated with SCZ liability. rs1415744 was also associated with Positive and Negative Symptom Scale negative clinical improvement. The results remained the same after inclusion of the covariates and were partially confirmed in the allelic and haplotype analyses. Conclusion: Our preliminary findings suggest a possible role of NMBR and EPM2A genes in SCZ susceptibility and, for the second one, also in antipsychotic pharmacogenetics. Nonetheless, further research is needed to confirm our findings.

Vortioxetine has a beneficial pharmacological profile for reducing anxiety and depression. Recently, a number of randomized, double-blind, placebo-controlled clinical trials (RCTs) of vortioxetine have been conducted in patients with generalized anxiety disorder (GAD); however, the results from GAD RCTs are inconsistent. With an extensive search of databases and clinical trial registries, four published short-term RCTs were identified and included in the present meta-analysis. The mean change in total scores on the Hamilton Anxiety Rating Scale (HAMA) from baseline was the primary endpoint. The secondary endpoints included the response and remission rates, as defined by a ≥50% reduction in HAMA total scores and a ≤7 change in the HAMA total score at the end of treatment. In addition, the mean change in the HAMA total score from baseline in the subgroup with a HAMA total score ≥25 at baseline was included. Vortioxetine was significantly more effective than was placebo, with a standardized mean difference (SMD) of −0.118 (95% CIs, −0.203 to −0.033, P = 0.007). In particular, those with severe GAD (HAMA total score ≥25 at baseline) had a significantly greater benefit from vortioxetine than those without (SMD = −0.338, 95% CIs = −0.552 to −0.124, p = 0.002). The odds ratios (ORs) for vortioxetine for response and remission were 1.221 (95% CIs, 1.027 to 1.452, P = 0.024) and 1.052 (95% CIs, 0.853 to 1.296, P = 0.637), respectively. Discontinuation due to adverse events (AEs) (OR = 1.560, 1.006 to 2.419, p = 0.047) was marginally higher in vortioxetine than placebo treatment, whereas discontinuation due to any reason (OR = 0.971, 0.794 to 1.187, p = 0.771) and inefficacy (OR = 0.687, 0.380 to 1.243, p = 0.215) were not significantly different among treatment groups. Although our results suggest that vortioxetine may have a potential as an another treatment option for GAD (especially for severe GAD), they should be interpreted and translated into clinical practice with caution, as the meta-analysis was based on a limited number of RCTs.

Aim: The present study aimed to explore whether 24 single nucleotide polymorphisms (SNPs) within the CACNA1C gene were associated with schizophrenia (SCZ) and antipsychotic response. Methods: A sample of 176 SCZ inpatients and 326 healthy controls of Korean ethnicity was collected for this purpose. Psychopathological status was evaluated at baseline and at discharge using the Positive and Negative Syndrome Scale (PANSS). Results: In the case-control study, rs1006737 (P=0.05) and rs2239104 (P= 0.03) were associated with SCZ. Further, the rs10848635-rs1016388-rs1006737 haplotype was also associated with SCZ (P=0.03, simulate P=0.02). In the pharmacogenetic analyses, we did not find any association among the investigated SNPs and improvement in the PANSS total score. However, rs723672 and rs1034936 were associated with improvement in the PANSS positive subscale (respectively, P =0.02 and 0.05), rs2283271 in the negative subscale (P=0.01), rs10848635 and rs1016388 in the general subscale (respectively, P =0.03 and 0.04), and the rs3819536-rs2238062 haplotype (global statistics, P=0.1; simulate P=0.04). Conclusions: Our findings further support a role for the CACNA1C gene, particularly for the rs1006737, in SCZ. Further, five SNPs were associated with improvement in PANSS subscales, suggesting a role for this gene in antipsychotic response as well. However, taking into account the limitations of the present study, further research is needed to confirm our findings.

The present study aimed to explore whether four single nucleotide polymorphisms (SNPs) within the AHI1 gene could be associated with schizophrenia (SCZ) and whether they could predict the clinical outcomes in SCZ patients treated with antipsychotics. Four hundred twenty-six (426) in-patients with SCZ and 345 controls were genotyped for four AHI1 SNPs (rs11154801, rs7750586, rs9647635 and rs9321501). Baseline and clinical measures for SCZ patients were assessed through the Positive and Negative Syndrome Scale (PANSS). Allelic and genotypic frequencies in SCZ subjects were compared with those of controls using the chi(2) statistics. The repeated-measure ANOVA was used for the assessment of treatment outcomes measured by PANSS changes. The case-control analysis did not show any difference in the genotypic distribution of the SNPs, while in the allelic analysis, a weak association was found between the rs9647635 A allele and SCZ. Furthermore, in the haplotype analysis, three haplotypes resulted in being associated with SCZ. On the other hand, two SNPs (rs7750586 and rs9647635) were associated with clinical improvement of negative symptoms in the allelic analysis, although in the genotypic analysis, only trends of association were found for the same SNPs. Our findings suggest a possible influence of AHI1 variants on SCZ susceptibility and antipsychotic response, particularly concerning negative symptomatology. Subsequent well-designed studies would be mandatory to confirm our results due to the methodological shortcomings of the present study.

Background Genome-wide association studies (GWAS) represent the current frontier in pharmacogenomics. Thousands of subjects of Caucasian ancestry have been included in previous GWAS investigating antidepressant response. GWAS focused on this phenotype are lacking in Asian populations. Methods A sample of 109 major depressive disorder (MDD) patients of Korean origin in antidepressant treatment was collected. Phenotypes were response and remission according to the Hamilton Rating Scale for Depression (HRSD). Genome-wide genotyping was performed using the Illumina Human Omni2.5-8 platform. The same phenotypes were used in the STAR*D level 1 (n = 1677) for independent replication. In order to corroborate findings and increase the comparability between the two datasets, three levels of analysis (SNPs, genes and pathways) were carried out. Bonferroni correction, permutations, and replication across samples were used to reduce the risk of false positives. Results Among the genes replicated across the two samples (permutated p