新津 富央

Dopamine supersensitivity psychosis (DSP) is a key factor contributing to the development of antipsychotic treatment-resistant schizophrenia. We examined the efficacy and safety of blonanserin (BNS) and olanzapine (OLZ) as adjuncts to prior antipsychotic treatment in patients with schizophrenia and DSP in a 24-week, multicenter (17 sites), randomized, rater-blinded study with two parallel groups (BNS and OLZ add-on treatments) in patients with schizophrenia and DSP: the ROADS Study. The primary outcome was the change in the Positive and Negative Syndrome Scale (PANSS) total score from baseline to week 24. Secondary outcomes were changes in the PANSS subscale scores, Clinical Global Impressions, and Extrapyramidal Symptom Rating Scale (ESRS), and changes in antipsychotic doses. The 61 assessed patients were allocated into a BNS group (n = 26) and an OLZ group (n = 29). The PANSS total scores were reduced in both groups (mean ± SD: -14.8 ± 24.0, p = 0.0042; -10.5 ± 12.9, p = 0.0003; respectively) with no significant between-group difference (mean, -4.3, 95 %CI 15.1-6.4, p = 0.42). The BNS group showed significant reductions from week 4; the OLZ group showed significant reductions from week 8. The ESRS scores were reduced in the BNS group and the others were reduced in both groups. The antipsychotic monotherapy rates at the endpoint were 26.3 % (n = 6) for BNS and 23.8 % (n = 5) for OLZ. The concomitant antipsychotic doses were reduced in both groups with good tolerability. Our results suggest that augmentations with BNS and OLZ are antipsychotic treatment options for DSP patients, and BNS may be favorable for DSP based on the relatively quick responses to BNS observed herein.

Background: The novel corona virus infection (COVID-19) quickly became a pandemic state. Identifying characteristics of "possible super spreaders", suggested as a dominant cause of rapid spreading transmission, will help us to design proper prevention strategies. Methods: We conducted a nation-wide online survey to investigate the relationship of perception and anxiety levels about COVID-19 to the possible risk behaviors for spread of the virus in Japan. We recruited a total of 4,000 citizens, who responded to the questionnaire including several questions regarding the level of fear and anxiety about COVID-19, infection preventive behaviors and access to media with trust level about the virus as well as some demographic and socioeconomic data during March 27th and 28th, 2020. Findings: Thirteen-point-three percent of the participants rated "1" on a nine-point Likert with respect to the knowledge about COVID-19. Ten-point-one percent and 11.7% presented no anxiety of being infected and transmission to others. Ten-point-eight percent showed no worry about symptomatic aggravation. Eight-point-one percent had no serious concern about expanding infection. The distribution of these items was highly correlated with each other. Participants with the low level of knowledge about COVID-19 were likely to less frequently access any information sources and neither trust them. They were less anxious about their health status, and less likely to put precautionary behaviors such as washing hands and avoiding crowded spaces, suggested by statistical analyses. Interpretation: The present study suggests that it is greatly important to enlighten those have no concerns about this crisis of COVID-19 and modify their risk behavior via various ways, in order to prevent and control this viral pandemic. Funding: This study was funded by the management grand provided to Chiba University Graduate School of Medicine and the Japan Society for the Promotion of Science KAKENHI grants.

Manic switch is a relevant issue when treating bipolar depression. Some risk factors have been suggested, but unequivocal findings are lacking. We therefore investigated predictors of switch from depression to mania in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) sample. Manic switch was defined as a depressive episode followed by a (hypo)manic or mixed episode within the following 12 weeks. We assessed possible predictors of switch using generalized linear mixed models (GLMM). 8403 episodes without switch and 512 episodes with switch (1720 subjects) were included in the analysis. Several baseline variables were associated with a higher risk of switch. They were younger age, previous history of: rapid cycling, severe manic symptoms, suicide attempts, amphetamine use and some pharmacological and psychotherapeutic treatments. During the current depressive episode, the identified risk factors were: any possible mood elevation, multiple mania-associated symptoms with at least moderate severity, and comorbid panic attacks. In conclusion, our study suggests that both characteristics of the disease history and clinical features of the current depressive episode may be risk factors for manic switch. (C) 2015 Elsevier Ltd. All rights reserved.

Background: The psychological impact of dual-disasters (earthquakes and a nuclear accident), on affected communities is unknown. This study investigated the impact of a dual-disaster (earthquakes and radioactive contamination) on the prevalence of psychological distress in a landlocked city within the Tohoku area, Japan. Methods. A cross-sectional mail-in survey with a random sample of inhabitants from Ichinoseki city was conducted eleven months after the disasters, and data from 902 respondents were analyzed by logistic regression models, with multiple imputation methodology. The K6 was used to determine psychological distress. Results: The estimated prevalence of psychological distress was 48.0 percent. House damage due to earthquakes and anxiety about radioactive contamination were significantly associated with psychological distress (p &lt 0.05), while an interactive effect between house damage and anxiety about radioactive contamination was not significant. Being female, middle-to-low educational status and unemployed were additional risk factors for psychological distress. Conclusions: This dual-disaster was associated with a moderate prevalence of psychological distress in the area. The impact of the earthquake and radioactive contamination appeared additive. © 2014Niitsu et al. licensee BioMed Central Ltd.

A number of candidate gene studies focused on major depression (MD) and antidepressant (AD) efficacy have been carried out, but results mainly remain inconclusive. We performed a comprehensive meta-analysis of published candidate gene studies focused on AD efficacy in MD to evaluate the cumulative evidence. A random-effect model was applied to study the polymorphisms with genotypic counts available from at least three independent studies. On the base of previous evidence, the analysis was stratified by ethnicity (Caucasian, Asian, and other/mixed), and AD class (SSRIs and mixed/other ADs).Genotypic data were available for 16 polymorphisms in 11 genes. After the exclusion of 5-HTTLPR in SLC6A4 included in another recent meta-analysis, 15 polymorphisms in 11 genes were included in the present meta-analysis (BDNF rs6265, SLC6A4 STin2, HTR1A rs6295, HTR2A rs6311, rs6313 and rs7997012, HTR6 rs1805054, TPH1 rs1800532, SLC6A2 rs5569, COMT rs4680, GNB3 rs5443, FKBP5 rs1360780 and rs3800373, and ABCB1 rs1045642 and rs2032582).Our results suggested that BDNF rs6265 (Val66Met) heterozygous genotype was associated with better SSRIs response compared to the homozygous genotypes, particularly in Asians (OR=1.53, 95%CI 1.12-2.07, p=0.007). SLC6A4 STin2, HTR2A rs6311 and rs7997012, GNB3 rs5443, FKBP5 rs1360780 and rs3800373, and ABCB1 rs2032582 showed associations with AD efficacy, but these results were highly dependent on one or two single studies.In conclusion, our findings suggested the BDNF Val66Met as the best single candidate involved in AD response, with a selective effect on SSRI treatment. Our overall results supported no major effect of any single gene variant on AD efficacy. © 2013 Elsevier Inc.

Cognitive impairments in schizophrenia are associated with suboptimal psychosocial performance. Several lines of evidence have suggested that endoplasmic reticulum protein sigma-1 receptors were involved in cognitive impairments in patients with schizophrenia and that the sigma-1 receptor agonist fluvoxamine was effective in treating cognitive impairments in animal models of schizophrenia and in some patients with schizophrenia. A randomized, double-blind, placebo-controlled, parallel trial of fluvoxamine adjunctive therapy in patients with schizophrenia was performed. A total of 48 patients with chronic schizophrenia were enrolled. Subjects were randomly assigned to an 8-week administration of add-on fluvoxamine (n - 24, titrated up to 150 mg/d) or placebo (n = 24) in a total 12-week double-blind trial. The primary outcome measure was the Cambridge Neuropsychological Test Automated Battery (CANTAB), assessing visual memory, working memory, attention, and executive function. The secondary outcome measures were the Positive and Negative Syndrome Scale, the Scale for the Assessment of Negative Symptoms, the Quality of Life Scale, and the Montgomery-angstrom sberg Depression Rating Scale. Fluvoxamine was well tolerated. No significant time x group interaction effects were observed in the scores of the CANTAB, Positive and Negative Syndrome Scale, Scale for the Assessment of Negative Symptoms, Quality of Life Scale, or the Montgomery-angstrom sberg Depression Rating Scale. However, in secondary analyses, the change from baseline to end point on the Spatial Working Memory strategy score (executive function) of CANTAB improved in the fluvoxamine group. This study suggests no major benefit of fluvoxamine adjunctive therapy to improve cognitive impairments in patients with schizophrenia. Nevertheless, a further study using a large sample size will be needed to confirm the secondary analyses findings.

Background: Meta-analyses have identified serum levels of brain-derived neurotrophic factor (BDNF) as a potential biomarker for major depressive disorder (MDD). However, at the time, commercially available human ELISA kits are unable to distinguish between proBDNF (precursor of BDNF) and mature BDNF because of limited BDNF antibody specificity. In this study, we examined whether serum levels of proBDNF, mature BDNF, and matrix metalloproteinase-9 (MMP-9), which converts proBDNF to mature BDNF, are altered in patients with MDD. Methodology/Principal Findings: Sixty-nine patients with MDD and 78 age-and gender-matched healthy subjects were enrolled. Patients were evaluated using 17 items on the Structured Interview Guide for the Hamilton Depression Rating Scale. Cognitive impairment was evaluated using the CogState battery. Serum levels of proBDNF, mature BDNF, and MMP-9 were measured using ELISA kits. Serum levels of mature BDNF in patients with MDD were significantly lower than those of normal controls. In contrast, there was no difference in the serum levels of proBDNF and MMP-9 between patients and normal controls. While neither proBDNF nor mature BDNF serum levels was associated with clinical variables, there were significant correlations between MMP-9 serum levels and the severity of depression, quality of life scores, and social function scores in patients. Conclusions/Significance: These findings suggest that mature BDNF may serve as a biomarker for MDD, and that MMP-9 may play a role in the pathophysiology of MDD. Further studies using larger sample sizes will be needed to investigate these results.