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1.
Schizophr Res ; 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31471246

RESUMO

BACKGROUND: Blonanserin is a second-generation antipsychotic used for the treatment of schizophrenia. This study determined the efficacy, safety and pharmacokinetics of a blonanserin transdermal patch in patients with acutely exacerbated schizophrenia. METHODS: This double-blind, multicenter, phase 3 study consisted of a 1-week observation period during which patients were treated with two patches of placebo, followed by a 6-week double-blind period where patients were randomized (1:1:1) to receive once-daily blonanserin 40 mg, blonanserin 80 mg, or placebo patches. The primary endpoint was the change from baseline in the total Positive and Negative Symptom Scale (PANSS) score. Safety assessments included treatment-emergent adverse events (TEAEs). RESULTS: Between December 2014 and October 2018, patients were recruited and randomly assigned to blonanserin 40 mg (n = 196), blonanserin 80 mg (n = 194), or placebo (n = 190); of these, 77.2% completed the study. Compared with placebo, blonanserin significantly improved PANSS total scores at 6 weeks (least square mean [LSM] difference vs placebo: -5.6 with blonanserin 40 mg; 95% confidence interval [CI] -9.6, -1.6; adjusted p = 0.007, and - 10.4 with blonanserin 80 mg; 95% CI -14.4, -6.4; adjusted p < 0.001). Blonanserin was well tolerated; the most common TEAEs reported were application-site erythema and pruritus, akathisia, tremor, and insomnia. CONCLUSIONS: Blonanserin transdermal patch improved the symptoms of acute schizophrenia with acceptable tolerability.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31461559

RESUMO

AIM: Recent studies revealed that the interplay between polygenic risk scores (PRSs) and large copy number variants (CNVs: >500kb) is essential for the etiology of schizophrenia (SCZ). To replicate previous findings, including for smaller CNVs (>10kb), the PRSs between SCZ with and without CNVs were compared. METHODS: The PRSs were calculated for 724 SCZ and 1,178 controls, genotyped using array-based comparative genomic hybridization and single nucleotide polymorphisms chips, and comparisons were made between cases and controls, or between subjects with and without "clinically significant" CNVs. RESULTS: Firstly, we replicated the higher PRS in SCZ compared to that in controls (without taking into account of the CNVs). For "clinically significant" CNVs, defined by American College of Medical Genetics ("pathogenic" and "uncertain clinical significance, likely pathogenic" CNVs), 66 SCZ carried "clinically significant" CNVs, whereas 658 SCZ had no such CNVs. In the comparison of PRSs between cases with/without the CNVs, despite no significant difference in PRS, significant enrichment of the well-established risk CNVs (22q11.2 deletion and 47,XXY/47,XXX) were observed in the lowest decile of PRSs in SCZ with the CNVs. CONCLUSION: Although the present study failed to replicate the significant difference in PRS between SCZ with and without "clinically significant" CNVs, SCZ with well-established risk CNVs tended to have a lower PRSs. Therefore, we speculate the CNVs in SCZ with lower PRSs may contain "genuine" risk; PRS is a possible tool for prioritizing "clinically significant" CNVs because power of the CNV association analysis is limited due to their rarity. This article is protected by copyright. All rights reserved.

3.
Transl Psychiatry ; 9(1): 205, 2019 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-31455759

RESUMO

Over 3000 candidate gene association studies have been performed to elucidate the genetic underpinnings of schizophrenia. However, a comprehensive evaluation of these studies' findings has not been undertaken since the decommissioning of the schizophrenia gene (SzGene) database in 2011. As such, we systematically identified and carried out random-effects meta-analyses for all polymorphisms with four or more independent studies in schizophrenia along with a series of expanded meta-analyses incorporating published and unpublished genome-wide association (GWA) study data. Based on 550 meta-analyses, 11 SNPs in eight linkage disequilibrium (LD) independent loci showed Bonferroni-significant associations with schizophrenia. Expanded meta-analyses identified an additional 10 SNPs, for a total of 21 Bonferroni-significant SNPs in 14 LD-independent loci. Three of these loci (MTHFR, DAOA, ARVCF) had never been implicated by a schizophrenia GWA study. In sum, the present study has provided a comprehensive summary of the current schizophrenia genetics knowledgebase and has made available all the collected data as a resource for the research community.

4.
Neuropsychopharmacol Rep ; 39(3): 252-255, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31283862

RESUMO

AIM: There have been no previous reports on the efficacy and safety of suvorexant for insomnia in people with psychiatric disorders. METHODS: This one-week, prospective, single-arm, clinical trial of fixed dose of suvorexant (20 mg if ages 18-64 or 15 mg if age ≥ 65 years) for insomnia included 57 patients with psychiatric disorders who had experienced any of the following insomnia symptoms for four or more nights during the week prior to the start of the study: total sleep time (TST) <6 hours, time to sleep onset (TSO) ≥30 minutes, or two or more episodes of wake after sleep onset. RESULTS: The mean age of the patients was 49.4 ± 17.3 years; 54.4% were women, 49.1% had a major depressive disorder, and 77.2% completed the trial. Compared with the baseline scores (the mean scores for the two days before the start of the study), taking suvorexant was associated with significant improvements in TST, TSO, wake time after sleep onset, and the patients' sleep satisfaction level at week 1. Adverse events included at least one adverse event (43.9%), sleepiness (28.8%), fatigue (11.5%), nightmares (5.8%), headache (3.8%), dizziness (3.8%), and vomiting (1.9%). CONCLUSION: Suvorexant was beneficial for the treatment of insomnia in people with psychiatric disorders. However, this study was of short duration and included only a relatively small number of patients. A larger, long-term study is needed to investigate the efficacy and safety of suvorexant for insomnia in people with psychiatric disorders.

5.
Neuropsychopharmacol Rep ; 39(3): 256-259, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31283865

RESUMO

OBJECTIVE: It is unknown whether there are differences in efficacy and safety between quetiapine extended-release, 300 mg/d (QUEXR300), and olanzapine, 5-20 mg/d (OLA), for Japanese patients with bipolar depression. METHODS: We conducted a Bayesian analysis of data from phase 3 studies in Japan of QUEXR300 and OLA. Outcomes were remission rate (primary), response rate, improvement on the Montgomery-Åsberg Depression Rating Scale and 17-item Hamilton Depression Rating Scale scores, discontinuation rate, and incidence of individual adverse events. We calculated the standardized mean difference (SMD) and the risk ratio (RR) and 95% credible interval (95% CrI) for continuous and dichotomous data, respectively. RESULTS: There were no significant differences between QUEXR300 and OLA for any of the efficacy outcomes. QUEXR300 was associated with a higher incidence of somnolence than OLA (RR = 5.517; 95% CrI = 1.563, 19.787), while OLA was associated with greater increase body weight (SMD = -0.488; 95% CrI = -0.881, -0.089) and blood prolactin levels (SMD = -0.642; 95% CrI = -1.073, -0.213) than QUEXR300, and a greater decrease in high-density lipoprotein cholesterol levels (SMD = -0.408; 95% CrI = -0.785, -0.030) than QUEXR300. CONCLUSION: Although the two drugs' efficacy did not differ, OLA increased the risk of metabolic syndrome and QUEXR300 the risk of somnolence. A large scale, long-term, head-to-head comparison study of QUEXR300 vs OLA for Japanese patients with bipolar depression is needed to confirm the results of the current study.

6.
Artigo em Inglês | MEDLINE | ID: mdl-31350882

RESUMO

BACKGROUND: This systematic review and meta-analysis included double-blind, randomized, placebo-controlled trials of brexpiprazole adjunctive treatment (0.5-3 mg/d) for major depressive disorder (MDD) where antidepressant treatment had failed. METHODS: The outcomes were the response rate (primary), remission rate (secondary), Montgomery Åsberg Depression Rating Scale score (MADRS; secondary), Sheehan Disability Scale scores (SDS; secondary), Clinical Global Impression-Improvement/Severity scores (CGI-I/S), discontinuation rate, and individual adverse events. A subgroup meta-analysis of the data at week 6 compared outcomes by dose >2 mg/d or ≤2 mg/d (2 mg/d is the recommended dose). RESULTS: We identified nine studies (n=3391). Compared with placebo, brexpiprazole (any dose) was superior for response rate (risk ratio [RR]=0.93, 95% confidence interval [95%CI]= 0.89-0.97, number needed to treat [NNT]=17), remission rate (RR=0.95, 95%CI=0.93-0.98, NNT=25), MADRS score (standardized mean difference [SMD]=-0.20, 95%CI=-0.29, -0.11), SDS score (SMD=-0.12, 95%CI=-0.21, -0.04), and CGI-I/S scores, but was associated with a higher discontinuation rate, akathisia, insomnia, restlessness, somnolence, and weight increase. Doses >2 mg/d had a significantly higher RR for response rate than ≤2 mg/d (0.96 vs. 0.89); moreover, compared with placebo, doses >2 mg/d were associated with higher incidences of akathisia (RR=4.58) and somnolence (RR=7.56) as well as were marginally associated with a higher incidence of weight increase (RR=3.14, p=0.06). Compared with placebo, doses ≤2 mg/d were associated with higher incidences of akathisia (RR=2.28) and weight increase (RR=4.50). CONCLUSIONS: Brexpiprazole adjunctive treatment is effective for MDD when antidepressant treatment fails. At 6 weeks, doses ≤2 mg/d presented a better risk/benefit balance than >2 mg/d.

7.
J Affect Disord ; 257: 314-320, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31302520

RESUMO

BACKGROUND: Sleep disturbance in bipolar disorder (BD) is common and is associated with a risk for mood episode recurrence. Thus, it is important to identify factors that are related to sleep disturbance in BD. This cross-sectional study investigated the association between exposure to light at night (LAN) and sleep parameters in patients with BD. METHODS: The sleep parameters of 175 outpatients with BD were recorded using actigraphy at their homes for seven consecutive nights and were evaluated using the Insomnia Severity Index (ISI). The average LAN intensity in the bedroom during bedtime and rising time was measured using a portable photometer, and the participants were divided into two groups: "Light" (≥5 lx) and "Dark" (<5 lx). The association between LAN and sleep parameters was tested with multivariable analysis by adjusting for potential confounder such as age, gender, current smoker, mood state, day length, daytime light exposure, and sedative medications. RESULTS: After adjusting for potential confounder, the actigraphy sleep parameters showed significantly lower sleep efficiency (mean, 80.1%vs. 83.4%; p = 0.01), longer log-transformed sleep onset latency (2.9 vs. 2.6 min; p = 0.01), and greater wake after sleep onset (51.4 vs. 41.6 min; p = 0.02) in the Light group than in the Dark group. Whereas, there were no significant differences in the ISI scores between the groups. LIMITATIONS: This was a cross-sectional study; therefore, the results do not necessarily imply that LAN causes sleep disturbance. CONCLUSIONS: Reducing LAN exposure may contribute to improved sleep quality in patients with BD.

8.
J Psychiatr Res ; 116: 151-156, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31247358

RESUMO

OBJECTIVES: Controlled artificial daylight exposure, such as light therapy, is effective in bipolar depression, but the association between uncontrolled daytime light and depressive symptoms in bipolar disorder (BD) is unclear. This study investigated the association between daytime light exposure under real-life situations and depressive symptom in patients with BD. METHODS: This cross-sectional study enrolled 181 outpatients with BD. The average daytime light intensity and the total duration of light intensity of ≥1000 lux were recorded over 7 consecutive days using an actigraph that measured ambient light. Depressive symptoms were assessed using Montgomery-Åsberg Depression Rating Scale, and scores of ≥8 points were treated as depressed state. RESULTS: Ninety-seven (53.6%) subjects were depressed state. At higher average daytime light intensity tertiles, the proportion of depressed state was significantly lower (P for trend, 0.003). In multivariable analysis adjusted for age, employment status, age at onset of BD, Young Mania Rating Scale score, bedtime, and physical activity, the highest tertile group in average daytime light intensity suggested a significantly lower odds ratio (OR) for depressed state than the lowest tertile group (OR, 0.33; 95% confidence interval [CI], 0.14-0.75; P = 0.009). Similarly, the longest tertile group in light intensity ≥1000 lux duration was significantly associated with lower OR for depressed state than lowest tertile group (OR, 0.42; 95% CI, 0.18-0.93; P = 0.033). CONCLUSIONS: The findings suggest that greater daytime light exposure in daily life is associated with decreased depressive symptoms in BD.

9.
Nat Hum Behav ; 3(5): 471-477, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31089300

RESUMO

Cigarette smoking is a risk factor for a wide range of human diseases1. To investigate the genetic components associated with smoking behaviours in the Japanese population, we conducted a genome-wide association study of four smoking-related traits using up to 165,436 individuals. In total, we identified seven new loci, including three loci associated with the number of cigarettes per day (EPHX2-CLU, RET and CUX2-ALDH2), three loci associated with smoking initiation (DLC1, CXCL12-TMEM72-AS1 and GALR1-SALL3) and LINC01793-MIR4432HG, associated with the age of smoking initiation. Of these, three loci (LINC01793-MIR4432HG, CXCL12-TMEM72-AS1 and GALR1-SALL3) were found by conducting an additional sex-stratified genome-wide association study. This additional analysis showed heterogeneity of effects between sexes. The cross-sex linkage disequilibrium score regression2,3 analysis also indicated that the genetic component of smoking initiation was significantly different between the sexes. Cross-trait linkage disequilibrium score regression analysis and trait-relevant tissue analysis showed that the number of cigarettes per day has a specific genetic background distinct from those of the other three smoking behaviours. We also report 11 diseases that share genetic basis with smoking behaviours. Although the current study should be carefully considered owing to the lack of replication samples, our findings characterized the genetic architecture of smoking behaviours. Further studies in East Asian populations are warranted to confirm our findings.

10.
J Psychiatr Res ; 115: 121-128, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31128502

RESUMO

This study evaluated the efficacy and safety/tolerability of quetiapine extended-release 300 mg/day (QUEXR300), quetiapine immediate-release 600 mg/day (QUEIR600), and quetiapine immediate-release 300 mg/day (QUEIR300) formulations for treating bipolar depression. A random-effect network meta-analysis of 8-week, double-blind, randomized placebo-controlled trials was used to determine the most optimal agent for intervention. Remission rate was set as the primary outcome. Secondary outcomes were response rate, improvement in the Montgomery-Åsberg Depression Rating Scale score, discontinuation rate, and the incidence of individual adverse events. Seven eligible studies including 3267 participants were included in the meta-analysis. The QUEIR600, QUEIR300, and QUEXR300 groups were superior to the placebo group in every efficacy outcome; however, there were no significant differences in the efficacy outcomes among the treatment groups. All treatment groups exhibited higher incidences of extrapyramidal symptoms, dry mouth, somnolence, constipation, and increase in body weight than the placebo group. The QUEIR600 and QUEIR300 groups had higher incidences of dizziness than the placebo group. The QUEIR600 group had a higher discontinuation rate due to adverse events than the placebo group, and the QUEIR300 group had higher blood HbA1c levels than the placebo group. The QUEIR600 and QUEXR300 groups had higher incidences of ≥7% weight gain than the placebo group. The QUEXR300 group had a higher incidence of fatigue than the QURIR300 and placebo groups. In conclusion, there were no significant differences in the efficacies of QUEIR600, QUEIR300, and QUEXR300 in treating bipolar depression; moreover, tolerance to QUEIR600 might be worse than the other treatments.

11.
Neuropsychopharmacol Rep ; 39(3): 241-246, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31026388

RESUMO

AIM: Whether patients with adult bipolar disorder (BD) who have been clinically stabilized with lithium or lamotrigine should continue this medication is not established fully. This systematic review and meta-analysis evaluated the efficacy and safety of lithium and lamotrigine for maintenance treatment in clinically stable patients with adult BD. METHODS: This meta-analysis included only double-blind, randomized, placebo-controlled trials with an enrichment design that selected patients who responded acutely to lithium or lamotrigine. Reports prior to November 15, 2018, were retrieved from the PubMed/Cochrane Library/Embase. The primary outcome was the relapse rate due to any mood episode at the study endpoint. Other outcomes were relapse rates due to a manic/hypomanic/mixed episode or depression at the study endpoint, discontinuation rate, death, and death by suicide. Risk ratios (RRs) (95% confidence intervals) were calculated. When the random-effects model showed significant differences between groups, the number-needed-to-treat (NNT) was estimated. RESULTS: The search retrieved two studies regarding lithium (N = 218) and four evaluating lamotrigine (N = 706). Both drugs were superior to placebo for reducing the relapse rate due to any mood episode [lithium: RR = 0.52 (0.41-0.66), P < 0.00001, I2  = 0%, NNT = 2.3 (1.6-4.2); lamotrigine: RR = 0.81 (0.70-0.93), P = 0.004, I2  = 0%, NNT = 8.3 (5.0-25.0)] and all-cause discontinuation. There were no significant differences in other outcomes between lithium or lamotrigine and the placebo groups. CONCLUSION: Both drugs showed benefit for preventing relapse in clinically stable patients with adult BD. However, the number of studies and patients in this analysis was small.

12.
Nat Genet ; 51(3): 379-386, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30718926

RESUMO

To understand the genetics of type 2 diabetes in people of Japanese ancestry, we conducted A meta-analysis of four genome-wide association studies (GWAS; 36,614 cases and 155,150 controls of Japanese ancestry). We identified 88 type 2 diabetes-associated loci (P < 5.0 × 10-8) with 115 independent signals (P < 5.0 × 10-6), of which 28 loci with 30 signals were novel. Twenty-eight missense variants were in linkage disequilibrium (r2 > 0.6) with the lead variants. Among the 28 missense variants, three previously unreported variants had distinct minor allele frequency (MAF) spectra between people of Japanese and European ancestry (MAFJPN > 0.05 versus MAFEUR < 0.01), including missense variants in genes related to pancreatic acinar cells (GP2) and insulin secretion (GLP1R). Transethnic comparisons of the molecular pathways identified from the GWAS results highlight both ethnically shared and heterogeneous effects of a series of pathways on type 2 diabetes (for example, monogenic diabetes and beta cells).


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Diabetes Mellitus Tipo 2/genética , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Adulto , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Frequência do Gene/genética , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Desequilíbrio de Ligação/genética , Masculino , Polimorfismo de Nucleotídeo Único/genética
13.
Transl Psychiatry ; 9(1): 52, 2019 01 31.
Artigo em Inglês | MEDLINE | ID: mdl-30705256

RESUMO

Major depressive disorder (MDD) is a common and disabling psychiatric disorder. A recent mega analysis of genome-wide association studies (GWASs) identified 44 loci associated with MDD, though most of the genetic etiologies of the MDD/psychological distress remain unclear. To further understand the genetic basis of MDD/psychological distress, we conducted a GWAS in East Asia with more than 10,000 participants of Japanese ancestry who had enrolled in a direct-to-consumer genetic test. After quality control on the genotype data, 10,330 subjects with a total of 8,567,708 imputed SNPs were eligible for the analysis. The participants completed a self-administered questionnaire on their past medical history and health conditions that included the 6-item Kessler screening scale (K6 scale) for psychological distress (cut-off point of 5) and past medical history of MDD, resulting in 3981 subjects assigned to "psychologically distressed group" [cases], and the remaining 6349 subjects were assigned to the "non-psychologically distressed group" [controls]. In this GWAS, we found an association with genome-wide significance at rs6073833 (P = 7.60 × 10-9) in 20q13.12. This is, to the best of our knowledge, the first large-scale GWAS for psychological distress using data from direct-to-consumer (DTC) genetic tests in a population of non-European-ancestry, and the present study thus detected a novel locus significantly associated with psychological distress in the Japanese population.


Assuntos
Transtorno Depressivo Maior/genética , Estresse Psicológico/genética , Adulto , Grupo com Ancestrais do Continente Asiático/genética , Feminino , Loci Gênicos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único
15.
Neuropsychiatr Dis Treat ; 14: 2915-2922, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30464475

RESUMO

Purpose: Although previous meta-analyses of randomized trials in the world literature have provided strong evidence that supports the efficacy and safety of memantine for the treatment of patients with Alzheimer's disease (AD), it is unclear whether the drug is beneficial in the treatment of Japanese patients with moderate to severe AD because of differences in the formulation and regimen of memantine and the cholinesterase inhibitor (ChEI) used in combination with memantine between the drugs made in Japan and those made in other countries. To address this issue, we conducted a meta-analysis on the efficacy and safety of memantine using data from only double-blind, randomized, placebo-controlled trials (DBRPCTs) in Japan on Japanese patients with moderate to severe AD. Patients and methods: Our primary analysis was conducted using data from both memantine monotherapy (memantine vs placebo) and memantine combination therapy (memantine+ChEI vs ChEI+placebo) studies. The primary outcomes measured were cognitive function and behavioral disturbances. The secondary outcomes measured were the subscale scores of Behavioral Pathology in Alzheimer's Disease (Behave-AD), discontinuation rate, and individual adverse events. Results: Four DBRPCTs (n=1,328) were detected. Memantine was superior to the control in cognitive functions (standardized mean difference [SMD]=-0.31, 95% CI=-0.53, -0.10) and behavioral disturbances (SMD=-0.16, 95% CI=-0.28, -0.05). Only memantine monotherapy was superior in both outcomes. It was also superior to the control in delusions, aggression, and diurnal rhythm disturbances based on the Behave-AD subscale scores. Although memantine was associated with a lower incidence of AD progression than that of the control, the incidence of somnolence was higher with memantine. There were no significant differences in other safety outcomes, including all-cause discontinuation, between the groups. Conclusion: Our results suggest that memantine is useful for the treatment of patients in Japan with moderate to severe AD even though our meta-analysis comprised only four DBRPCTs.

16.
J Alzheimers Dis ; 2018 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-30452419

RESUMO

 A systematic review and meta-analysis of the efficacy/safety of intravenous immunoglobulin (IVIG) administration in mild-to-moderate Alzheimer's disease (AD) patients was performed. Six randomized double-blind, placebo-controlled trials (n = 801) were included in this study. No significant difference in cognitive function was observed between the groups. Moreover, IVIG was inferior to placebo in behavioral disturbances (mean difference = 2.19). Further, IVIG administration was associated with a higher incidence of rash than placebo. Our results do not support IVIG administration for mild-to-moderate AD, suggesting that IVIG is not effective to treat mild-to-moderate AD and that it deteriorates behavioral and psychological symptoms of dementia in mild-to-moderate AD.

17.
Hum Psychopharmacol ; : e2681, 2018 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-30480343

RESUMO

OBJECTIVE: Long-acting injectable (LAI) aripiprazole is recommended to be combined with oral aripiprazole for 2 weeks after its introduction. However, we often experience patients who require more than 2 weeks of combined use. Therefore, differences in combination periods need to be examined. METHODS: This was a case-control study. We surveyed prescription profiles for oral aripiprazole administration in conjunction with LAI aripiprazole introduction and assessed the clinical course during a 12-week follow-up period. RESULTS: Among 121 patients, 58 (47.9%) were administered both oral and LAI aripiprazole for more than 2 weeks. Although there was no significant difference in treatment failure (defined as psychiatric hospitalization or discontinuation of LAI aripiprazole from any cause) between the two groups, the group that was administered oral aripiprazole for more than 2 weeks received less additional benzodiazepines compared with that of the 2 weeks group (adjusted odds ratio, 0.055; 95% confidence interval [0.0060, 0.50]; p < 0.01). CONCLUSIONS: Our data support a flexible co-administration period for oral and LAI aripiprazole in consideration of the pharmacokinetics, but further studies are needed.

18.
Artigo em Inglês | MEDLINE | ID: mdl-30406404

RESUMO

Vascular endothelial growth factor (VEGF) is involved in the development of major depressive disorder (MDD). Recently, a genome-wide association study has revealed that four VEGF-related single nucleotide polymorphisms (SNPs) (i.e., rs4416670, rs6921438, rs6993770 and rs10738760) were independently associated with circulating VEGF levels. The current study investigated the relationship between brain volume and these four SNPs in first-episode drug-naïve MDD patients. A total of 38 first-episode drug-naïve MDD patients and 39 healthy subjects (HS) were recruited and underwent high-resolution T1-weighted imaging. Blood samples were collected from all the participants for serum VEGF assays and VEGF-related SNPs genotyping. Genotype-diagnosis interactions related to whole-brain cortical thickness and hippocampal subfield volumes were evaluated for the four SNPs. The results revealed a genotype-diagnosis interaction only for rs6921438 (i.e., the MDD patients and HS with the G/G genotype versus the MDD patients and HS with A-carrier genotype) in the subiculum of the left hippocampus (p < 0.05), and not the other SNPs. There was a volume reduction in the left subiculum of G/G genotype patients compared with the other groups. The "hypochondriasis" scores of the HAMD-17 scale were significantly higher in the G/G genotype patients than the A-carrier genotype patients. The association was observed between VEGF-related SNP rs6921438 and subiculum atrophy in first-episode drug-naïve MDD patients.

19.
Neuropsychiatr Dis Treat ; 14: 2519-2530, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30319261

RESUMO

Purpose: The purpose of this study was to compare the efficacy and safety of brexpiprazole 4 mg/day (B4) and 2 mg/day (B2) for treating acute schizophrenia. Patients and methods: We performed three categorical meta-analyses (B4 vs placebo, B2 vs placebo, and B4 vs B2) of double-blind, randomized placebo-controlled trials (DBRCTs) that reported improvements in the Positive and Negative Syndrome Scale (PANSS) scores, response rate, Clinical Global Impression-Improvement and Severity (CGI-I and CGI-S) scores, discontinuation rate, and incidence of individual adverse events. Results: We identified three DBRCTs with 1,444 patients. Both B4 and B2 were superior to placebo for PANSS total score (B4: standardized mean difference [SMD] =-0.30, 95% CI =-0.43, -0.17; B2: SMD =-0.30, 95% CI =-0.46, -0.13), PANSS negative score, response rate, CGI-S score, and CGI-I score. B2, but not B4, was superior to placebo for the PANSS positive score. However, there was considerable heterogeneity in the meta-analysis for B4's PANSS positive score, which disappeared after excluding a 2018 Japanese study from the meta-analysis that included more patients on a high-dose antipsychotic prior to their participation. A meta-analysis that excluded the data from the abovementioned patients showed B4 to be superior to the placebo in terms of the PANSS positive score (SMD =-0.22, 95% CI =-0.40, -0.03). B2, but not B4, was associated with a lower incidence of all-cause discontinuation compared with placebo. Both B4 and B2 were superior to placebo for discontinuation due to adverse events and schizophrenia, but both were associated with a higher incidence of weight gain compared with placebo. B4 was also associated with a higher risk of extrapyramidal symptoms than B2. Conclusion: Both B4 and B2 benefitted patients with schizophrenia, particularly those who were not previously on high-dose antipsychotics. Both the regimens were well-tolerated, but carried a risk of weight gain and extrapyramidal symptoms, although the latter risk was higher for B4 than B2.

20.
Schizophr Bull ; 2018 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-30285260

RESUMO

Genome-wide association studies (GWASs) have identified >100 susceptibility loci for schizophrenia (SCZ) and demonstrated that SCZ is a polygenic disorder determined by numerous genetic variants but with small effect size. We conducted a GWAS in the Japanese (JPN) population (a) to detect novel SCZ-susceptibility genes and (b) to examine the shared genetic risk of SCZ across (East Asian [EAS] and European [EUR]) populations and/or that of trans-diseases (SCZ, bipolar disorder [BD], and major depressive disorder [MDD]) within EAS and between EAS and EUR (trans-diseases/populations). Among the discovery GWAS subjects (JPN-SCZ GWAS: 1940 SCZ cases and 7408 controls) and replication dataset (4071 SCZ cases and 54479 controls), both comprising JPN populations, 3 novel susceptibility loci for SCZ were identified: SPHKAP (Pbest = 4.1 × 10-10), SLC38A3 (Pbest = 5.7 × 10-10), and CABP1-ACADS (Pbest = 9.8 × 10-9). Subsequent meta-analysis between our samples and those of the Psychiatric GWAS Consortium (PGC; EUR samples) and another study detected 12 additional susceptibility loci. Polygenic risk score (PRS) prediction revealed a shared genetic risk of SCZ across populations (Pbest = 4.0 × 10-11) and between SCZ and BD in the JPN population (P ~ 10-40); however, a lower variance-explained was noted between JPN-SCZ GWAS and PGC-BD or MDD within/across populations. Genetic correlation analysis supported the PRS results; the genetic correlation between JPN-SCZ and PGC-SCZ was ρ = 0.58, whereas a similar/lower correlation was observed between the trans-diseases (JPN-SCZ vs JPN-BD/EAS-MDD, rg = 0.56/0.29) or trans-diseases/populations (JPN-SCZ vs PGC-BD/MDD, ρ = 0.38/0.12). In conclusion, (a) Fifteen novel loci are possible susceptibility genes for SCZ and (b) SCZ "risk" effect is shared with other psychiatric disorders even across populations.

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