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Background: We report the final results of treatment with aripiprazole, blonanserin, and paliperidone from the Japan Useful Medication Program for Schizophrenia (JUMPs), a 104-week naturalistic study., Methods: JUMPs was an open-label, three-arm, randomized, parallel-group, 104-week study. Patients aged ≥ 20 years with schizophrenia requiring antipsychotic treatment or a switch from previous therapy were enrolled. The primary endpoint was treatment discontinuation rate over 104 weeks. Secondary endpoints included remission rate, Personal and Social Performance (PSP), safety, Positive and Negative Syndrome Scale (PANSS), and quality of life (QOL; EuroQol-5 dimension)., Results: In total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). Treatment discontinuation rates (aripiprazole, 80.5%; blonanserin, 81.2%; paliperidone, 71.4%) were not significantly different (p = 0.2385) among the treatment groups at 104 weeks; comparable outcomes were observed for endpoints, including remission (42.9%, 46.7%, and 45.8%), PANSS, and safety. In the overall cohort, while the improvement in the PSP total score at Week 104 was not significantly different from baseline, a significant improvement (p < 0.05) in QOL and total PANSS scores (including all subscales) was observed at Week 104 compared with baseline. Multivariable analysis identified a shorter disease duration and a higher chlorpromazine-equivalent antipsychotic dosage level (≥ 1000 mg) before switching to monotherapy as predictors of treatment discontinuation., Conclusions: The 104-week treatment outcomes were comparable between groups; the overall trend of improvement in remission rate, safety, and QOL suggests the importance of continued treatment., Clinical Trial Registration: UMIN-Clinical Trials Registry UMIN000007942 (public release date: 14/05/2012)., (© 2024. The Author(s).)

An increase in systemic blood pressure causes bleeding and ischemia owing to peripheral vascular breakdown, leading to various forms of organ damage. The brain, eyes, kidneys, and cardiovascular system are known target organs for hypertension. To our knowledge, no reports in Japan describe, in detail, the types of antihypertensive drugs used to treat hypertension in cats or its underlying causes. Therefore, we aimed to investigate the use of antihypertensive drugs in domestic cats with hypertension in Japan, the causes of hypertension, and the vital prognosis of these patients. In the present survey, we found that amlodipine was used alone (60/80 cats) or concomitantly (20/80 cats) in all cat patients with hypertension in Japan. We also determined that blood pressure measurements were not yet routinely performed on cats at veterinary clinics in Japan. Furthermore, we have new information suggesting that amlodipine administration in cats with hypertension, which lowers systolic arterial pressure levels to within the normal range (<140 mmHg), may have a negative impact on their survival. Routine blood pressure measurements for cats during their regular health checkups can help identify hypertension, and proper interpretation of blood pressure readings can facilitate suitable treatment measures.

Despite establishing conventional risk factors and preventive medicine for cardiovascular diseases (CVD), there remains a notable lack of research for identifying social determinants of health (SDOH). The aim of this study was to identify the SDOH domains contributing to health inequities perceived by Japanese CVD citizens. An online survey was conducted among 2,083 Japanese CVD patients from November 7 to 13, 2023, to assess their perceptions of 19 social determinants of health (SDOH) domains and their impact on health inequities. Using the 5-point Likert scale, a high level of agreement was defined as over 50% selecting "Agree" or "Strongly Agree." The "Health inequity perception score (HIPS)" was calculated by assigning 1 point for 'Agree' and 2 points for 'Strongly Agree.' Additionally, patient factors that defined a group with HIPS above the median were also evaluated. High agreement was noted in 7 out of 19 domains: "Employment" (61%), "Food Insecurity" and "Environmental Condition" (each at 60%), "Poverty" (58%), "Early Childhood Development and Education" (57%), "Housing Instability and Quality" (56%), and "Access to Health Service" (52%). Young age, high annual income, high educational level, and living alone were significantly associated with high HIPS. This study highlights that several SDOH factors commonly acknowledged in Western contexts are also recognized as contributors to health inequities among Japanese CVD patients.

This study aimed to comprehensively evaluate whether income affects long-term health outcomes for older patients who underwent percutaneous coronary intervention (PCI) provided by a universal health coverage system. Data were from the Latter Stage Elderly Healthcare Insurance database in Fukuoka Prefecture, Japan. A total of 5625 individuals aged ≥65 years who underwent PCI in 2014-2016 were included. Cox proportional hazards models were used to assess the association between income status and the incidence of health outcomes. With a median follow-up of 1095 days, 554 acute myocardial infarction (AMI) cases, 1075 stroke cases, 1690 repeat revascularization cases, and 1094 deaths were observed. Risk of all-cause mortality decreased significantly with increasing income level in both unadjusted and adjusted Cox regression models. Patients in the low-income level had a significantly higher rate of AMI (log-rank P  = 0.003), stroke (log-rank P  = 0.039), and all-cause mortality (log-rank P  = 0.001) compared with patients in the high-income level. Observed rates for repeat revascularization also were high in the first year after PCI. In the Japanese universal health setting, low-income patients had a comparatively higher mortality risk after PCI. Poor long-term outcomes might be attributed to patients' baseline characteristics rather than treatment processes.

Aim: Globally, evidence from short-term studies is insufficient for the guidelines to uniformly recommend a particular antipsychotic(s) for the maintenance treatment of schizophrenia. Therefore, long-term comprehensive evaluation of antipsychotics is required from a social rehabilitation perspective, especially for drugs that have not yet been studied. The Japan Useful Medication Program for Schizophrenia (JUMPs) is a large-scale, long-term naturalistic study to present pivotal 52-week data on the continuity of second-generation antipsychotics (SGA: aripiprazole, blonanserin, and paliperidone)., Methods: JUMPs was an open-label, three-arm, randomized, parallel-group, 52-week study. Enrolled patients had schizophrenia, were ≥20 years old, and required antipsychotic treatment or switched from previous therapy. The primary endpoint was treatment discontinuation rate over 52 weeks. Secondary outcomes included remission rate, social functioning, and quality-of-life scores [Personal and Social Performance Scale (PSP) and EuroQol-5 dimensions], and safety., Results: In total, 251 patients received aripiprazole (n = 82), blonanserin (n = 85), or paliperidone (n = 84). The discontinuation rate (P = 0.9771) and remission rates (P > 0.05) over 52 weeks did not differ significantly between the three treatment groups. The discontinuation rates were 68.3%, 68.2%, and 65.5% in the aripiprazole, blonanserin, and paliperidone groups, respectively. Significant improvements (all P < 0.05) from baseline in PSP scores were observed at start of monotherapy, week 26, and week 52 in the overall cohort and blonanserin group and at week 26 in the aripiprazole group. The adverse event profile favored blonanserin., Conclusion: All three SGAs evaluated in this study showed similar treatment discontinuation rates in patients with chronic schizophrenia in Japan., (© 2021 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Objective : The purpose of this study was to examine the relationship between peritraumatic reactions, posttraumatic stress disorder (PTSD) symptoms, and pain in people injured in train disasters. Methods : The participants were injured in a train crash in Japan that left more than 100 dead. There were 218 participants in the analysis, with a mean age of 37.50 ± 14.67 years. Peritraumatic reactions were assessed using the Peritraumatic Distress Inventory. PTSD symptoms were evaluated using the Impact of Event Scale-Revised Japanese-language version. Pain was measured using the Visual Analog Scale. Results : Peritraumatic reactions did not directly affect PTSD symptoms but were found to be associated via latent variables. Regarding pain and PTSD symptoms, intrusive memories were more associated with pain than other symptoms were. There was an associative path from intrusion to pain, but no such path from pain to intrusion. Conclusions : Our results suggest that a therapeutic approach to intrusion may be effective in ameliorating the pain caused by injury. Future research should examine integrated treatment approaches for both PTSD and pain, rather than just for aspects of PTSD. J. Med. Invest. 68 : 85-89, February, 2021.

Aim: Sex differences in serum folate concentrations are well known, but no studies have investigated the association between serum folate levels and schizophrenia based on sex. With this study in a Japanese population, we examined the difference in serum folate levels between patients with schizophrenia and non-psychiatric controls stratified by sex. The relations among serum folate levels, plasma total homocysteine (tHcy), and serum vitamin B6 (pyridoxal) levels were also examined using data from our previous studies., Methods: The serum folate concentrations of 482 patients diagnosed with schizophrenia and 1350 non-psychiatric control subjects were measured. We conducted an analysis of covariance to examine the differences in serum folate levels between the two groups based on sex. Spearman's rank correlation was used to evaluate the relations among folate, tHcy, and vitamin B6 levels., Results: In the control group, serum folate concentrations were higher in women than in men. Lower levels of serum folate were observed in both male and female patients with schizophrenia. An inverse correlation between serum folate and plasma tHcy and a weak positive correlation between serum folate and vitamin B6 were observed in the combined cohort., Conclusion: Our findings suggest that: (i) a low serum folate level may be associated with schizophrenia regardless of sex; and (ii) folate administration may be beneficial for the treatment of schizophrenia. In schizophrenic patients with low serum folate levels, folate administration might result in improvements in high tHcy and an increase in low vitamin B6 levels., (© 2020 The Authors Psychiatry and Clinical Neurosciences © 2020 Japanese Society of Psychiatry and Neurology.)

Purpose: A computed tomography (CT)-based hip navigation system is a useful tool for achieving precise implant alignment angle. However, it has the disadvantage of prolonged procedure duration. A prolonged procedure duration may increase the incidence of postoperative surgical site infection (SSI) or periprosthetic joint infection (PJI) following primary THA. Studies identifying whether CT-based hip navigation system increases the incidence of SSI and PJI compared to the free-hand technique for total hip arthroplasty (THA) are rare. The study aimed to assess whether the CT-based hip navigation system can cause SSI and PJI compared to the free-hand technique., Methods: We investigated 366 patients with osteoarthritis who completed the minimum 2-year follow-up and underwent primary THAs (n = 435), including 70 hips in 62 patients of the non-navigation group and 365 hips in 304 patients of the navigation group. We compared the incidence rate of SSI and PJI between the non-navigation group and navigation group., Results: Only three patients in the navigation group (0.8%) developed SSI or PJI, while no patient developed SSI or PJI in the non-navigation group. There was no significant difference in the incidence rate of SSI or PJI between the two groups (P = 1.0), although the mean operation time in the navigation group was about 20 min longer., Conclusions: CT-based hip navigation system may not be associated with SSI or PJI after primary THA, although it prolongs the operation time.

Aim: Matrix metalloproteinase-9 (MMP-9) has been shown to modulate synaptic plasticity and may contribute to the pathophysiology of schizophrenia. This study investigated the peripheral levels of MMP-9 and its association with cognitive functions in patients with schizophrenia to see the possible involvement of MMP-9 in pathophysiology of schizophrenia, especially in cognitive decline., Methods: We measured the plasma levels of MMP-9 in 257 healthy controls and 249 patients with schizophrenia, including antipsychotic drug-free patients. We also explored the possible association between plasma MMP-9 levels and cognitive performance in healthy controls and patients with schizophrenia using the Wechsler Adult Intelligence Scale, Third Edition (WAIS- III), the Wechsler Memory Scale-Revised (WMS-R), and the Rey Auditory Verbal Learning Test (AVLT)., Results: We found that the plasma levels of MMP-9 were significantly higher in patients with schizophrenia, including antipsychotic drug-free patients, than in healthy controls. We found a significant negative association between plasma MMP-9 levels and cognitive performance in controls and patients with schizophrenia., Conclusion: Together, these convergent data suggest a possible biological mechanism for schizophrenia, whereby increased MMP-9 levels are associated with cognitive impairment., (© 2020 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Society of NeuropsychoPharmacology.)

Background: Lithium is the first-line drug for the treatment of bipolar disorders (BDs); however, not all patients responded. Glycogen synthase kinase (GSK) 3β and brain-derived neurotrophic factor (BDNF) play a role in the therapeutic action of lithium. Since structural variations were reported in these genes, it is possible that these genomic variations may be involved in the therapeutic responses to lithium., Method: Fifty patients with BDs and 50 healthy subjects (mean age 55.0 ± 15.0 years; M/F 19/31) participated. We examined structural variation of the GSK3β and BDNF genes by real-time PCR. We examined the influence of structural variation of these genes on the therapeutic responses to lithium and the occurrence of antidepressant-emergent affective switch (AEAS). The efficacy of lithium was assessed using the Alda scale, and AEAS was evaluated using Young Mania Rating Scale., Results: Although we examined structural variations within intron II and VII of the GSK3 ® gene and from the end of exon IV to intron IV and within exon IX of the BDNF gene, no structural variation was found in BDs. Whereas 5 of 50 patients exhibited three copies of the genomic region within exon IV of the BDNF gene, all healthy subjects had two copies. No difference in the therapeutic efficacy of lithium was found between patients with three and two copies. No difference in the occurrence of AEAS was found between the two groups., Conclusion: The amplification of the BDNF gene influenced neither the therapeutic responses to lithium nor the occurrence of AEAS., (© 2019 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Society of Neuropsycho Pharmacology.)

Past reports showed good mid-term results of RHA for Japanese patients. However, few reports have compared the mid- to long-term results for RHA in Japanese patients with and without osteoarthritis. Therefore, this study investigated the mid- to long-term results of RHA in Japanese patients with osteoarthritis compared to those without. We conducted a retrospective review of a consecutive series of 92 hips in 80 patients (59 men and 21 women). The minimum follow-up period was 5 years. The JOA hip scoring system was used to clinically evaluate hip function. In the radiological assessment, stem-shaft angle, inclination of the acetabular component, postoperative complications, and adverse reactions around RHA were evaluated. The 10-year survival rate using the Kaplan-Meier method was investigated to compare patients with and without osteoarthritis. A significant difference was observed between the preoperative and postoperative JOA hip scores of either group. Also, the radiological assessment revealed no significant changes in either group. All three revision THAs were performed on patients in the only non-osteoarthritis group. In the osteoarthritis group, the 10-year survival rate was 94% (95% CI 81.8-100) in males and 100% (95% CI 100) for females; in the non-osteoarthritis group, the rate was 80% (95% CI 55.1-100) in males and 66.7% (95% CI 13.3-100) for females. In conclusion, this study showed good mid- to long-term clinical results for young Japanese osteoarthritis patients, with less satisfactory mid- to long-term results in patients without osteoarthritis.

We evaluated clinical outcomes of disseminated intravascular coagulation (DIC) in patients with hematological malignancies treated with synthetic protease inhibitors (SPIs) and compared the effects of gabexate mesilate (FOY) and nafamostat mesilate (FUT). We retrospectively examined 127 patients [acute myeloid leukemia (n = 48), acute lymphoblastic leukemia (n = 25), and non-Hodgkin lymphoma (n = 54)] with DIC, who were diagnosed according to Japanese Ministry of Health, Labour and Welfare criteria and treated with SPIs [FOY (n = 55) and FUT (n = 72)] at our hospital from 2006 to 2015. The DIC resolution rates on days 7 and 14 were 42.6% and 62.4%, respectively. No significant differences were observed in DIC resolution rates between the FUT and FOY groups [40.3% vs. 45.5% (day 7), P = 0.586; 56.3% vs. 69.8% (day 14), P = 0.179, respectively]. Multivariate analysis revealed that response to chemotherapy was the only independent predictor of DIC resolution on days 7 and 14 (ORR 2.81, 95% CI 1.32-5.98, P = 0.007; ORR 2.51, 95% CI 1.12-5.65, P = 0.026). Resolution of DIC was correlated with improvement of background hematological malignancies, and no significant differences were observed between the two SPIs.

Introduction: The influence of stem sagittal alignment on clinical outcomes is unclear in total hip arthroplasty (THA). The purpose of this study is to assess the relationship between stem sagittal alignment and clinical and radiographic outcomes using 3D-CT., Materials and Methods: We performed 370 consecutive primary THAs between 2009 and 2013. After exclusion, 102 hips in 89 patients using single tapered-wedge stem were included. Mean follow-up was 4.7 years. Stem sagittal alignment was measured using CT, and patients were divided into flexion and neutral alignment groups. Clinical and radiographic outcomes were compared between two groups. Furthermore, we evaluated the anterior femoral offset and initial contact state., Results: There were no significant differences in clinical or radiographic outcomes between two groups. CT data analysis and multiple regression analysis showed flexion alignment increased anterior femoral offset (AFO) and Gruen zone 4 contact area., Conclusions: There was no significant difference in clinical or radiographic outcomes between flexion and neutral alignment of the tapered-wedge stem at an average of 4.7 years of follow-up. The increase of AFO and distal contact area in flexion alignment could affect the improvement of impingement-free range of flexion and intraoperative fracture.

Background: Groin pain and functional limitations may occur after total hip arthroplasty (THA) due to iliopsoas impingement (IPI). We aimed to determine the risk factors and thresholds of cup protrusion for symptomatic IPI., Methods: This retrospective case-control study evaluated 569 primary THAs performed by a single surgeon in a single center. In all THAs, the cup was inserted with the assistance of the computed tomography-based navigation system. Twenty-two THAs (3.9%) were identified to have symptoms of IPI and included in the IPI group. Control group 1 comprised 547 THAs. Control group 2 (66 THAs) was formed by recruiting 3 data-matched controls per patient in control group 1. Risk factors for IPI were assessed in the IPI group and control group 1. Further analysis was performed in the IPI group and control group 2 to evaluate cup protrusion parameters measured on computed tomography images and radiographs., Results: Multivariate logistic regression analysis confirmed that the anterolateral approach was associated with a higher risk of IPI (odds ratio [OR], 4.20); however, its goodness of fit was low. Axial protrusion length ≥12 mm (OR, 23.29; sensitivity = 72.7; specificity = 91.0) and sagittal protrusion length ≥4 mm (OR, 61.60; sensitivity = 86.4; specificity = 78.8) were determined as independent predictors of symptomatic IPI. In the linear regression analyses, higher native acetabular version and lower cup anteversion and inclination were related to cup protrusion., Conclusions: This study determined the thresholds of cup protrusion length for IPI and identified associated factors increasing cup protrusion, which are useful for surgeons in determining cup position and alignment., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Several previous studies have investigated an association between leukocyte telomere length (LTL) and schizophrenia (SCZ). However, results have been largely inconsistent, partially due to the relatively small sample sizes in each study and heterogeneity caused by various uncontrolled confounders (e.g., duration of illness or hospitalization, lifetime antipsychotic dose, and LTL assay methods). Here, we investigate the association of LTL with SCZ with the quantitative polymerase chain reaction method in independent cohorts consisting of 1241 patients with SCZ and 1042 controls (the largest independent sample in this field). Furthermore, we examined whether duration of hospitalization and lifetime antipsychotic dose had an effect on LTL in SCZ. In all samples, we observed significantly longer LTL in patients with SCZ relative to controls. In subgroup analyses, we observed that longer telomeres in SCZ were only visible in elderly patients and not in patients under 50 years old. Moreover, significantly longer LTL in elderly patients with SCZ was only specific to those with long-term hospitalization, but not outpatients or those with short-term hospitalization. This may be because the former received more appropriate lifestyle management. Meanwhile, lifetime antipsychotic dose had no effect on LTL. Our findings suggest that consideration of the effect of age and duration of hospitalization on LTL may improve our understanding of controversial results obtained in previous studies of telomeres in SCZ., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Genome-wide association studies (GWASs) have identified several susceptibility loci for bipolar disorder (BD) and shown that the genetic architecture of BD can be explained by polygenicity, with numerous variants contributing to BD. In the present GWAS (Phase I/II), which included 2964 BD and 61 887 control subjects from the Japanese population, we detected a novel susceptibility locus at 11q12.2 (rs28456, P=6.4 × 10 -9 ), a region known to contain regulatory genes for plasma lipid levels (FADS1/2/3). A subsequent meta-analysis of Phase I/II and the Psychiatric GWAS Consortium for BD (PGC-BD) identified another novel BD gene, NFIX (P best =5.8 × 10 -10 ), and supported three regions previously implicated in BD susceptibility: MAD1L1 (P best =1.9 × 10 -9 ), TRANK1 (P best =2.1 × 10 -9 ) and ODZ4 (P best =3.3 × 10 -9 ). Polygenicity of BD within Japanese and trans-European-Japanese populations was assessed with risk profile score analysis. We detected higher scores in BD cases both within (Phase I/II) and across populations (Phase I/II and PGC-BD). These were defined by (1) Phase II as discovery and Phase I as target, or vice versa (for 'within Japanese comparisons', P best ~10 -29 , R 2 ~2%), and (2) European PGC-BD as discovery and Japanese BD (Phase I/II) as target (for 'trans-European-Japanese comparison,' P best ~10 -13 , R 2 ~0.27%). This 'trans population' effect was supported by estimation of the genetic correlation using the effect size based on each population (liability estimates~0.7). These results indicate that (1) two novel and three previously implicated loci are significantly associated with BD and that (2) BD 'risk' effect are shared between Japanese and European populations.

Objectives: According to the dopamine hypothesis, several studies on the gene for the dopamine receptor D2 (DRD2) have been conducted. However, no trait biomarkers on DRD2 are available. We examined whether the methylation rates in the upstream region of DRD2 in leukocytes are different in schizophrenia (SCZ) subjects compared to control subjects., Methods: We selected seven CpG sites in the upstream region of DRD2 that may theoretically bind major transcription factors. The methylation rates in these regions of 50 medicated and 18 drug-naïve SCZ subjects were compared with those of age-matched control subjects., Results: The methylation rates were significantly lower in medicated (CpG2, P < 0.0001; CpG4, P = 0.013; CpG7, P < 0.0001; and average: 12.9 ± 1.8 vs. 14.1 ± 2.2, P = 0.005) and drug-naïve SCZ subjects (CpG1, P = 0.006; CpG2, P = 0.001; CpG3, P = 0.001; CpG5, P = 0.02; CpG6, P = 0.015; CpG7, P = 0.027; and average: 9.86 ± 0.9 vs. 11.2 ± 1.3, P = 0.002)., Conclusions: We confirmed low methylation rates in the upstream region of DRD2 in both medicated and drug-naïve SCZ subjects. Low methylation rates of DRD2 in leukocytes may be a trait biomarker for SCZ.

Background: Initial fixation is a key factor in the success of cementless THA using a tapered wedge stem. The purpose of this study was to use three-dimensional templating software to examine the correlation between quantitative contact state and important clinical radiological outcomes, specifically stem subsidence, stress shielding, and cortical hypertrophy., Methods: We conducted a retrospective consecutive review of 75 hips in 70 patients over a minimum 3-year follow-up period. X-rays and CT scans were investigated to assess preoperative planning, quantify the contact state of implant and femur, and assess stem alignment, stem subsidence, stress shielding, and cortical hypertrophy. We evaluated the correlation between radiological outcomes and three-dimensional quantitative contact state according to Gruen Zone in each Dorr classification., Results: Density mapping indicated that stem subsidence increased postoperatively if the stem had less cortical contact in the middle to distal portion of the implant in terms of initial fixation. Cases having too much cortical contact in the distal portion of the implant tended to have increased stress shielding. We found no correlation between cortical hypertrophy and the contact state of implant and femur., Conclusions: Density mapping with three-dimensional templating software can be useful in predicting stem subsidence and stress shielding following cementless THA with a tapered wedge stem. Further analysis is required to accurately depict the correlation between cortical hypertrophy and the contact state.

Introduction: Acute coagulopathy of trauma has been much discussed recently. However, the changes in coagulation markers after trauma in the elderly are unknown. Furthermore, the baseline fibrinogen level is high in elderly patients, and the question remains as to whether fibrinogen levels also decrease early and the degree of decrease in elderly trauma patients. The purpose of this study was to compare coagulation markers including the fibrinogen level on admission in younger and elderly severe trauma patients., Methods: A cohort of severe trauma patients (Injury Severity Score (ISS) ≥16), admitted from January 2011 to June 2014, with coagulation markers including the fibrinogen level on admission available, was reviewed retrospectively. The patients were divided into a younger (16-64 years old) and an older (≥65 years old) group based upon their age at presentation. Activated partial thromboplastin time (aPTT), international normalized ratio (INR), fibrinogen, and D-dimer were compared between the younger and older groups., Results: There were 251 patients who met the inclusion criteria for this analysis. The younger group included 117 patients and the older group included 134 patients. The median aPTT (26.3 vs 27.5s, P=0.001) and median D-dimer levels (18.8 vs 40.2 μg/dL, P=0.006) were significantly higher in the older group. However, the fibrinogen level (205 vs 248 mg/dL, P<0.001) was significantly higher in the older group. The regression lines of fibrinogen and age in non-massive transfusion and massive transfusion cases are given by Y=1.03 X+185 (r=0.24, r(2)=0.06, P<0.001) and Y=0.86 X+134 (r=0.25, r(2)=0.06, P=0.09) respectively, and the fibrinogen levels tended to increase with older age in severe trauma patients., Conclusions: The fibrinogen level did not show a low value as it can in younger patients in elderly patients. Therefore, the fibrinogen level is difficult to use as an early indicator of acute blood loss with haemorrhage in elderly severe trauma patients, as it can be used in younger patients. Thus, it is necessary to keep in mind that the fibrinogen level increases by approximately 1mg/dL when the age increases by 1 year and to carefully observe the fibrinogen level even if the admission level is not low., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Objective: Catechol-O-methyltransferase (COMT) is an enzyme that participates in the metabolic inactivation of dopamine and norepinephrine, and the Met allele of the COMT Val158Met polymorphism is associated with lower enzymatic activity. The purpose of the present study was to investigate whether this functional variant is associated with obsessive-compulsive disorder (OCD) and the clinical responses in OCD., Methods: We first performed a case-control association study between the COMT Val158Met polymorphism and OCD (171 cases and 944 controls). Then, we examined the association between this polymorphism and the clinical responses in 91 of the OCD patients., Results: Our study did not find a significant association between the Met allele and OCD risk or between the Met allele and clinical responses (p > 0.05)., Conclusion: The present case-control/pharmacogenetic study did not provide clear evidence that the COMT Val158Met polymorphism is a predictor of OCD or of OCD patients' clinical responses., (Copyright © 2015 John Wiley & Sons, Ltd.)

Abnormal hexanucleotide repeat expansion of C9ORF72 is known to cause neurodegenerative disorders such as frontotemporal dementia. Additionally, patients with psychotic symptoms are more likely to have abnormal hexanucleotide repeat expansion than are patients without them. We investigated the hexanucleotide repeat sizes of C9ORF72 in 466 Japanese schizophrenia patients. We found no abnormal hexanucleotide repeat expansion. In conclusion, C9ORF72 may not be responsible for schizophrenia susceptibility in the Japanese population.

Objective: Severe depression may be a risk factor for diagnostic conversion into bipolar disorder (BD), and psychotic depression (PD) has been consistently associated with BD. The aims of the present study were to investigate the stability of the diagnosis of severe depression and the differences between PD and non-psychotic severe depression (non-PD), as well as to assess the effectiveness of electroconvulsive therapy (ECT)., Methods: Patients who were hospitalised for severe depression (diagnosed according to ICD-10) both with and without psychotic symptoms (n=89; mean age=55.6 years, SD=13.9) from 2001 to 2010 were retrospectively assessed., Results: By the 75th month of follow-up assessments, 11(12.4%) patients had developed BD. Among these 11 converters, nine had developed BD within 1 year after admission. Only sub-threshold hypomanic symptoms were significantly related to developing BD. The number of depressive episodes and history of physical diseases were significantly increased in non-PD compared with PD patients, whereas ECT was significantly increased in PD compared with non-PD patients. There was a significant association between length of stay at the hospital and the number of days between admission and ECT., Conclusion: Sub-threshold hypomanic symptoms may represent a prodrome of BD or an indicator of an already manifest phenotype, especially in older patients, which suggests cautious use of antidepressants. In severe depression, non-PD may often occur secondary to physical diseases and patients may experience increased recurrences compared with PD patients, which may be a more 'primary' disorder and often requires ECT treatments. ECT is effective for severe depression regardless of the presence of any psychotic feature; the earlier ECT is introduced, the better the expected treatment outcome.

Pre-existing antibodies against adeno-associated virus (AAV), caused by natural AAV infections, interfere with recombinant AAV vector-mediated gene transfer. We studied the prevalence of neutralizing antibodies against AAV serotypes 1, 2, 5, 8, and 9 in healthy subjects (n = 85) and hemophilia patients (n = 59) in a Japanese population. For healthy subjects, the prevalence of neutralizing antibodies against AAV serotypes 1, 2, 5, 8, and 9 was 36.5%, 35.3%, 37.6%, 32.9%, and 36.5%, respectively, while that in hemophilia patients was 39.7%, 28.8%, 35.6%, 32.9%, and 27.4%, respectively. There was no difference in the prevalence of neutralizing antibody against each AAV serotype between the healthy subjects and the hemophilia patients. The prevalence of neutralizing antibodies against all AAV serotypes increased with age in both healthy subjects and hemophilia patients. High titers of neutralizing antibodies against AAV2 (≥1:224) and AAV8 (≥1:224) were more evident in older individuals (≥42 years old). Approximately 50% of all screened individuals were seronegative for neutralizing antibodies against each AAV tested, while approximately 25% of individuals were seropositive for each AAV serotype tested. The prevalence of seronegativity for all AAV serotypes was 67.0% (healthy subjects, 68.6%; hemophilia patients, 65.0%) and 18.6% (healthy subjects, 20.5%; hemophilia patients, 15.7%) in young (<42 years old) and older subjects (≥42 years old), respectively. The findings from this study suggested that young subjects are more likely to be eligible for gene therapy based on AAV vectors delivered via an intravascular route because of the low prevalence of antibodies to AAV capsids., (© 2013 Wiley Periodicals, Inc.)

The physical benefits of subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) patients are well documented, but the mental benefits are uncertain, particularly in Japanese patients. This study evaluated the clinical and neuropsychological characteristics before and after STN-DBS surgery in Japanese PD patients. PD patients (n=13, age 67.0 ± 7.8 years) were evaluated pre-surgery (baseline) and at 1 and 6 months post-surgery by two trained psychiatrists. The motor symptoms were assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) motor score. The neuropsychological and psychiatric tests performed were the Mini-Mental State Examination, the Wisconsin Card Sorting Test (WCST), the Verbal Fluency Test (VFT), the Hamilton Depression Rating Scale and the Hamilton Anxiety Rating Scale (HAM-A). The UPDRS motor score (p<0.001) and HAM-A score (p=0.004) showed significant improvement at 1 month post-surgery, but a significant decline was observed in the WCST total error (p=0.005) and the semantic VFT score (p<0.001). The phonetic VFT also showed a substantial decline (p=0.015) at 1 month post-surgery. At 6 months post-surgery, the improvement in the UPDRS motor score was maintained, and the scores on the neuropsychological and psychiatric tests had returned to baseline. Although bilateral STN-DBS did not appear to have long-term effects on neuropsychological and psychiatric outcomes, the microlesion effects associated with STN-DBS appear to increase the risk of transient cognitive and psychiatric complications. These complications should be monitored by careful observation of neurological and psychiatric symptoms., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Previous studies suggest that elevated blood homocysteine levels and the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism are risk factors for schizophrenia. However, the effects of gender and MTHFR C677T genotypes on blood homocysteine levels in schizophrenia have not been consistent. We first investigated whether plasma total homocysteine levels were higher in patients with schizophrenia than in controls with stratification by gender and by the MTHFR C677T genotypes in a large cohort (N = 1379). Second, we conducted a meta-analysis of association studies between blood homocysteine levels and schizophrenia separately by gender (N = 4714). Third, we performed a case-control association study between the MTHFR C677T polymorphism and schizophrenia (N = 4998) and conducted a meta-analysis of genetic association studies based on Japanese subjects (N = 10 378). Finally, we assessed the effect of plasma total homocysteine levels on schizophrenia by a mendelian randomization approach. The ANCOVA after adjustment for age demonstrated a significant effect of diagnosis on the plasma total homocysteine levels in all strata, and the subsequent meta-analysis for gender demonstrated elevated blood homocysteine levels in both male and female patients with schizophrenia although antipsychotic medication might influence the outcome. The meta-analysis of the Japanese genetic association studies demonstrated a significant association between the MTHFR C677T polymorphism and schizophrenia. The mendelian randomization analysis in the Japanese populations yielded an OR of 1.15 for schizophrenia per 1-SD increase in plasma total homocysteine. Our study suggests that increased plasma total homocysteine levels may be associated with an increased risk of schizophrenia., (© The Author 2014. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)

Typical antipsychotic drugs were introduced in 1950's. Atypical antipsychotics developed in 1990's and 2000's have been reported to show superiority over typical antipsychotics. However, when comparison was made with a low dose of a typical drug, the superiority disappeared in some studies. Both types of antipsychotics have in common a pharmacological property to decrease dopamine D2 receptor neurotransmission. Polypharmacy once prevailed in Japan and a high dose therapy once dominated in western countries should not be used anymore. The proper dose of typical antipsychotics is much lower than the dose used previously. Typical as well as atypical antipsychotics should be used as monotherapy with a proper dosage. It is of clinical significance for treatment staffs to become to pay more attention to quality of life and rehabilitation of patients.

Schizophrenia (SCZ) is a complex psychiatric disease with a lifetime morbidity rate of 0.5-1.0 %. To date, aberrant DNA methylation in SCZ has been reported in several studies. However, no comprehensive studies using medication-free subjects with SCZ have been conducted. In addition, most of these studies have been limited to the analysis of the CpG sites in CpG islands (CGIs) in the gene promoter regions, so little is known about the DNA methylation signatures across the whole genome in SCZ. Genome-wide DNA methylation profiling (485,764 CpG sites) of peripheral leukocytes was conducted in the first set of samples (24 medication-free patients with SCZ and 23 non-psychiatric controls) using Infinium HumanMethylation450 Beadchips. Second, a monozygotic twin study was performed using three pairs of monozygotic twins that were discordant for SCZ. Finally, the data from these two independent cohorts were compared. A total of 234 differentially methylated CpG sites that were common between these two cohorts were identified. Of the 234 CpG sites, 153 sites (65.4 %) were located in the CGIs and in the regions flanking CGIs (CGI: 40.6 %; CGI shore: 13.3 %; CGI shelf: 11.5 %). Of the 95 differently methylated CpG sites in the CGIs, most of them were located in the promoter regions (promoter: 75.8 %; gene body: 14.7 %; 3'-UTR: 2.1 %). Aberrant DNA methylation in SCZ was identified at numerous loci across the whole genome in peripheral leukocytes using two independent sets of samples. These findings support the notion that altered DNA methylation could be involved in the pathophysiology of SCZ.

The appropriate therapeutic serum valproate level in maintenance therapy for bipolar disorder is not well known. We studied the serum valproate levels in seventeen bipolar I and twenty-four bipolar II disorder outpatients who had been treated with stable doses of valproate successfully for at least 12 months as prophylactic therapy. The trough serum valproate levels were 52.2 +/- 20.4 microg/ml in bipolar I, and 41.0 +/- 18.3 microg/ml in bipolar II disorder patients, respectively. A greater trend towards a higher trough level (p = 0.07) was indicated in the bipolar I disorder group. We speculate that these valproate levels may be an approximation to the appropriate valproate levels in maintenance therapy and that there may be a correlation between the level of valproate required for stabilization and the subtype of the bipolar disorder. However, when interpreting these findings, certain limitations to this study? Need to be taken into account as follows. The sample size was small. We could not look at a group on valproate that had relapsed and a group that had dropped out of maintenance therapy. Further studies are needed.

Unlabelled: To comprehensively characterize the contribution of virological factors as well as interleukin-28B (IL28B) single-nucleotide polymorphisms (SNPs) in determining treatment responses in pegylated-interferon plus ribavirin (Peg-IFN/RBV) therapy for chronic hepatitis C virus (HCV)-1b infection, we undertook a retrospective cohort analysis for the pretreatment dominant complete HCV open reading frame (ORF) amino-acid (aa) sequence study in 103 consecutive HCV-1b Japanese patients. The dominant HCV sequences classified by the response were subjected to systematic sliding-window comparison analysis to characterize response-specific viral sequences, along with IL28B SNP analyses (rs8099917). In each comparison of the patients between with and without rapid viral response (RVR), nonearly viral response (nEVR), sustained virological response (SVR), or relapse, the following regions were extracted as most significantly associated with the different responses respectively: nonstructural protein 5A (NS5A) aa.2224-2248 (P = 1.2E-07); core aa.70 (P = 4E-04); NS5A aa.2340-2382 (P = 7.0E-08); and NS5A aa.2360-2377 (P = 1.1E-05). Those NS5A regions nearly coincided with the interferon (IFN) sensitivity-determining region (NS5A aa.2209-2248) and the IFN/RBV resistance-determining region (NS5A aa.2339-2379). In a multivariate analysis, the IL28B SNP (odds ratio [OR] = 16.8; P = 0.009) and NS5A aa.2340-2382 (OR = 13.8; P = 0.0003) were extracted as the two most-significant independent variables contributing to the final outcome., Conclusion: In Peg-IFN/RBV therapy, polymorphisms in IL28B, NS5A aa.2224-2248, core aa.70, and, most important, NS5A aa.2340-2382 have a tremendous influence on treatment response in association with viral kinetics, resulting in significantly different outcomes in chronic HCV-1b infection., (Copyright © 2012 American Association for the Study of Liver Diseases.)

Background: Antimicrobial stewardship has not always prevailed in a wide variety of medical institutions in Japan., Methods: The infection control team was involved in the review of individual use of antibiotics in all inpatients (6348 and 6507 patients/year during the first and second annual interventions, respectively) receiving intravenous antibiotics, according to the published guidelines, consultation with physicians before prescription of antimicrobial agents and organisation of education programme on infection control for all medical staff. The outcomes of extensive implementation of antimicrobial stewardship were evaluated from the standpoint of antimicrobial use density, treatment duration, duration of hospital stay, occurrence of antimicrobial-resistant bacteria and medical expenses., Results: Prolonged use of antibiotics over 2 weeks was significantly reduced after active implementation of antimicrobial stewardship (2.9% vs. 5.2%, p < 0.001). Significant reduction in the antimicrobial consumption was observed in the second-generation cephalosporins (p = 0.03), carbapenems (p = 0.003), aminoglycosides (p < 0.001), leading to a reduction in the cost of antibiotics by 11.7%. The appearance of methicillin-resistant Staphylococcus aureus and the proportion of Serratia marcescens to Gram-negative bacteria decreased significantly from 47.6% to 39.5% (p = 0.026) and from 3.7% to 2.0% (p = 0.026), respectively. Moreover, the mean hospital stay was shortened by 2.9 days after active implementation of antimicrobial stewardship., Conclusion: Extensive implementation of antimicrobial stewardship led to a decrease in the inappropriate use of antibiotics, saving in medical expenses, reduction in the development of antimicrobial resistance and shortening of hospital stay., (© 2012 Blackwell Publishing Ltd.)

Aims: The purpose of the present study was to investigate the correlation between cognitive function and clinical variables in people with schizophrenia., Methods: The subjects were 61 stabilized outpatients with schizophrenia (DSM-IV). Their mean age was 40.1 (SD = 12.2) years. All subjects gave written informed consent to participate in the research. Cognitive function was evaluated using the Brief Assessment of Cognition in Schizophrenia. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale, the Calgary Depression Scale for Schizophrenia, and the Drug-Induced Extrapyramidal Symptoms Scale., Results: The Positive and Negative Syndrome Scale Negative syndrome score was significantly correlated with verbal memory score (r = -0.37, P < 0.01), working memory score (r = 0.38, P < 0.01), attention and speed of information processing score (r = -0.51, P < 0.01), verbal fluency score (r = -0.39, P < 0.01), and composite score (r = -0.54, P < 0.01). In addition, the Drug-Induced Extrapyramidal Symptoms Scale score was significantly correlated with attention and speed of information processing (r = -0.45, P < 0.01), and composite score (r = -0.41, P < 0. 01). Dose of antipsychotics and anti-Parkinson drugs was not significantly correlated with the Brief Assessment of Cognition in Schizophrenia scores., Conclusions: These results indicate that cognitive dysfunction of people with schizophrenia might be associated with negative and drug-induced extrapyramidal symptoms, suggesting that their minimization would be important for improving cognitive dysfunction., (© 2012 The Authors. Psychiatry and Clinical Neurosciences © 2012 Japanese Society of Psychiatry and Neurology.)

Genome-wide association and follow-up studies have reported an association between schizophrenia and rs12807809 of the NRGN gene on chromosome 11q24.2. We investigated the association of five linkage disequilibrium-tagging SNPs and haplotypes that cover the NRGN gene with schizophrenia in a Japanese sample of 2,019 schizophrenia patients and 2,574 controls to determine whether rs12807809 is the most strongly associated variant for schizophrenia in the vicinity of the NRGN gene. We found that the rs12807809-rs12278912 haplotype of the NRGN gene was associated with schizophrenia (global P = 0.0042). The frequencies of the TG and TA haplotypes of rs12807809-rs12278912 in patients were higher (OR = 1.14, P = 0.0019) and lower (OR = 0.85, P = 0.0053), respectively, than in the controls. We did not detect any evidence of association of schizophrenia with any SNPs; however, two nominal associations of rs12278912 (OR = 1.10, P = 0.057) and rs2075713 (OR = 1.10, P = 0.057) were observed. Furthermore, we detected an association between the rs12807809-rs12278912 haplotype and NRGN expression in immortalized lymphoblasts derived from 45 HapMap JPT subjects (z = 2.69, P = 0.007) and confirmed the association in immortalized lymphoblasts derived from 42 patients with schizophrenia and 44 healthy controls (z = 3.09, P = 0.002). The expression of the high-risk TG haplotype was significantly lower than the protective TA haplotype. The expression was lower in patients with schizophrenia than in controls; however, this difference was not statistically significant. This study provides further evidence of the association of the NRGN gene with schizophrenia, and our results suggest that there is a link between the TG haplotype of rs12807809-rs12278912, decreased expression of NRGN and risk of developing schizophrenia., (Copyright © 2012 Wiley Periodicals, Inc.)

The assessment of cognitive function is important for patients with schizophrenia because cognitive impairment is a core feature of the disease, and is a major determinant of functional outcome. To implement a practical assessment tool, we previously developed the Japanese-language version of the Brief Assessment of Cognition in Schizophrenia that objectively measures cognitive domains relevant to outcome. Meanwhile, the U.S. Food and Drug Administration took the position that a drug to improve coghition should show changes on an additional measure (a co-primary), in addition to an accepted consensus cognitive performance measure that is considered functionally meaningful. Thus, four potential co-primary measures, two measures of functional capacity and two interview-based measures of cognition, were evaluated for psychometric properties and validity. The Schizophrenia Cognition Rating Scale (SCoRS) is one of the interview-based measures of cognition. It consists of 20 questions to measure attention, memory, reasoning and problem solving, working memory, language production, and motor skills, which are related to day-to-day functioning. University of California at San Diego Performance-Based Skills Assessment (UPSA) is one of the measures of functional capacity. For its clinical application, we developed the Japanese-language version of the SCoRS (SCoRS-J) and UPSA (UPSA-J) through back-translation into English.

Alterations in centrosomal function have been suggested in the pathology of schizophrenia. The molecule pericentriolar material 1 (PCM1) is involved in maintaining centrosome integrity and in the regulation of the microtubule cytoskeleton. PCM1 forms a complex at the centrosome with the disrupted-in-schizophrenia 1 (DISC1) protein, which is a major susceptibility factor for schizophrenia. The association between genetic variants in the PCM1 gene and schizophrenia has been reported by several case-control studies, linkage studies and a meta-analysis. The aims of this study are to replicate the association between four single-nucleotide polymorphisms (SNPs) in the PCM1 gene and schizophrenia in a Japanese population (1496 cases and 1845 controls) and to perform a meta-analysis of the combined sample groups (3289 cases and 3567 controls). We failed to find a significant association between SNPs or haplotypes of the PCM1 gene and schizophrenia in the Japanese population (P>0.28). The meta-analysis did not reveal an association between the four examined SNPs and schizophrenia. Our data did not support genetic variants in the PCM1 gene as a susceptibility locus for schizophrenia., (Copyright © 2011 Elsevier B.V. All rights reserved.)

The epithelial membrane protein 1 (EMP1) plays a role in neuronal differentiation and neurite outgrowth, which are involved in the pathogenesis of major depressive disorder (MDD). We sought to determine whether the EMP1 gene is implicated in MDD. We determined the mRNA expression levels of the EMP1 gene in peripheral-blood leukocytes of patients and control subjects (n=27 each). Next, we performed case-control association analyses (MDD, n=182; controls, n=350) in the Japanese population. The level of expression of the EMP1 mRNA was significantly lower in medication-free patients compared with control subjects (P<0.001). The association analysis revealed an absence of association between the polymorphisms studied and MDD, whereas a gender-specific association was observed between male controls and male patients for marker rs7315725 (permutation P=0.039). Our results suggest that the EMP1 gene may be implicated in the pathophysiology of MDD in the Japanese population., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: The CogState Schizophrenia Battery (CSB), a computerized cognitive battery, covers all the same cognitive domains as the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery but is briefer to conduct. The aim of the present study was to evaluate the criterion and construct validity of the Japanese language version of the CSB (CSB-J) in Japanese patients with schizophrenia., Methodology/principal Findings: Forty Japanese patients with schizophrenia and 40 Japanese healthy controls with matching age, gender, and premorbid intelligence quotient were enrolled. The CSB-J and the Brief Assessment of Cognition in Schizophrenia, Japanese-language version (BACS-J) were performed once. The structure of the CSB-J was also evaluated by a factor analysis. Similar to the BACS-J, the CSB-J was sensitive to cognitive impairment in Japanese patients with schizophrenia. Furthermore, there was a significant positive correlation between the CSB-J composite score and the BACS-J composite score. A factor analysis showed a three-factor model consisting of memory, speed, and social cognition factors., Conclusions/significance: This study suggests that the CSB-J is a useful and rapid automatically administered computerized battery for assessing broad cognitive domains in Japanese patients with schizophrenia.

The phosphodiesterase 4B (PDE4B) interacts with disrupted-in-schizophrenia 1 (DISC1), which is a known genetic risk factor for schizophrenia, bipolar disorder and major depressive disorder (MDD). PDE4B is also important in the regulation of cAMP signaling, a second messenger implicated in learning, memory, and mood. In this study, we determined mRNA expression levels of the PDE4B gene in the peripheral blood leukocytes of patients with MDD and control subjects (n = 33, each). Next we performed two-stage case-controlled association analyses (first set; case = 174, controls = 348; second set; case = 481, controls = 812) in the Japanese population to determine if the PDE4B gene is implicated in MDD. In the leukocytes, a significantly higher expression of the PDE4B mRNA was observed in the drug-naïve MDD patients compared with control subjects (P < 0.0001) and the expression of the MDD patients significantly decreased after antidepressant treatment (P = 0.030). In the association analysis, we observed significant allelic associations of four SNPs (the most significant, rs472952; P = 0.002) and a significant haplotypic association (permutation P = 0.019) between the PDE4B gene and MDD in the first-set samples. However, we could not confirm these significant associations in the following independent second-set of samples. Our results suggest that the PDE4B gene itself does not link to MDD but the elevated mRNA levels of PDE4B might be implicated in the pathophysiology of MDD.

Background: Pericentrin (PCNT) interacts with disruption-in-schizophrenia 1 (DISC1), a known genetic risk factor for schizophrenia, bipolar disorder and major depressive disorder (MDD). We sought to determine whether the PCNT gene is implicated in MDD., Methods: We performed case-control association analyses in the Japanese population. We analyzed 9 single nucleotide polymorphisms (SNPs) in 173 patients with MDD and 348 healthy controls., Results: We found a significant allelic association between 3 SNPs (rs3788265, rs2073376 and rs2073380) of the PCNT gene and MDD (p = 0.006, 0.005 and 0.021, respectively). After correction for multiple testing, 2 SNPs (rs3788265 and rs2073376) retained significant allelic associations with MDD. In addition, we found a significant association between the 2 marker haplotypes (r3788265 and rs2073376) and MDD (permutation p = 0.011)., Limitations: Our sample was small and comprised only Japanese participants. In addition, owing to the late onset of MDD, it is possible that the disorder will develop in at least some participants in our control group. Finally, we did not show how SNPs of the PCNT gene alter its function., Conclusion: Our results suggest that genetic variations in the PCNT gene may play a significant role in the etiology of MDD in the Japanese population.

In recent years, the problem of interpersonal relationships has been reported to be associated with various adolescent psychiatric problems. Egocentrism is one factor related to the problem of interpersonal relationships. The Adolescent Egocentrism-Sociocentrism (AES) scale is used to assess egocentrism in Western countries, but no such scale has been developed in Japan. The purpose of our current study was to develop the Japanese version of the AES scale and investigate the relationship between the egocentrism assessed by the AES scale and the self-consciousness assessed by the Japanese version of the self-consciousness scale. The original version of the AES scale was first translated into Japanese using the forward-backward method and examined for factorial reliability and validity. The results demonstrated that the Japanese version of the AES scale shows adequate factorial reliability and validity, but different from the original version the "egocentrism personal fable" subscale which measures the feeling that oneself is special and unique was not extracted in the Japanese version. We found a moderate correlation between the non-social focuses of the AES scale and the public self-consciousness subscale of the self-consciousness scale. This correlation suggests that a strong attention of others' view on oneself results in the avoidance of others. The Japanese version of the AES scale can examine egocentrism adequately together with sociocentrism and non-social focuses. As this scale is self-reporting and easy to complete, it may have practical utility in a clinical setting.

Genetic variants of the transcription factor 7-like 2 (TCF7L2) gene affect the risk of type 2 diabetes in populations with multiple ethnic groups. However, a comprehensive survey of this gene has not been done for a Japanese population. Thus, we conducted this gene-based association study, in which the common genetic variants were analyzed. Using 24 Japanese type 2 diabetic subjects, we first screened a 9.5 kb region, which included the entire coding sequence, to assess potential functional variants of TCF7L2. Sequencing revealed a common coding variant (Pro477Thr) in exon 14 of TCF7L2 that was not enrolled in the public SNP database. Nineteen SNPs and the microsatellite DG10S478 were genotyped across the gene in 2,877 unrelated Japanese subjects. This independent screen identified the previously reported rs7903146 with a strongest association (allele P = 0.0001, odds ratio = 1.59 [95% confidence interval 1.25-2.01]), but there was no significant association between Pro477Thr and type 2 diabetes (allele P = 0.64). Expression of the Pro477Thr variant did not alter TCF7L2 expression in 30 lymphoblast cells. Although a genotypic effect of Pro477Thr on expression of TCF7L2 was not apparent, Pro477Thr was identified as a common variant of TCF7L2 in 2,877 Japanese subjects. Further functional studies are required to determine the possible effect of this coding variant on type 2 diabetes.

This preliminary study was performed to test the reliability and validity of the Brief Assessment of Cognition in Schizophrenia (BACS) as an assessment tool in a Japanese-language version (BACS-J). The subjects for the present study were 30 outpatients with chronic schizophrenia. Each subject gave written informed consent to participate in the research. Cronbach's alpha for the BACS-J was 0.77. The BACS-J composite score was significantly correlated with all primary measures of BACS-J (verbal memory, working memory, motor speed, verbal fluency, attention, and executive function). All BACS-J primary measures and the composite score were significantly correlated between two assessments. The mean score of the Digit Sequencing Task and composite score on the second assessment were significantly larger than those on the first assessment. All BACS-J primary measures except the Symbol Coding Task were significantly correlated with relevant standard neurocognitive tests. Also, the BACS-J composite score was significantly correlated with all standard neurocognitive tests except the Continuous Performance Test. A principal components analysis with varimax rotation resulted in a three-factor solution (executive function and memory; motor speed and general cognitive functions; and working memory). This preliminary study indicates that the BACS-J is a reliable and practical scale to evaluate cognitive function.

Accumulating evidence suggests that both homocysteine metabolism and monoaminergic neurotransmitter systems are important in schizophrenia pathology. We hypothesized that the gene PNPO (pyridoxine 5'-phosphatase oxidase gene) might be a candidate for susceptibility to schizophrenia because PNPO encodes pyridoxamine 5'-phosphate oxidase (EC 1.4.3.5), a rate-limiting enzyme in pyridoxal 5'-phosphate (PLP, vitamin B(6)) synthesis. PLP is a metabolically-active form of vitamin B(6) and thus, is required as a co-factor for enzymes involved in both homocysteine metabolism and synthesis of neurotransmitters such as catecholamine. We examined 8 single nucleotide polymorphisms (SNPs) in PNPO and its 5'-flanking regions in 359 schizophrenia patients and 582 control subjects. Four marker regions of PNPO showed significant levels of allelic associations with schizophrenia (the highest was rs2325751, P=0.004). In addition, the haplotype case-control study revealed a significant association (permutation P<0.00001) between PNPO and schizophrenia. These findings suggest that variations in PNPO may contribute to overall genetic risk for schizophrenia in the Japanese population.

PDLIM5 modulates neuronal calcium signaling, co-localizes with synaptic vesicles of neurotransmitters and positive association between its gene and schizophrenia was reported but its relation is still ambiguous. The differential expression of the PDLIM5 gene both in the brain and in the lymphoblasts has been found in schizophrenia compared to control subjects. In this study, we measured the expression level of the PDLIM5 gene transcripts in the peripheral leukocytes from 19 medication-free and 21 chronically medicated schizophrenic patients as well as age- and sex-matched control subjects using a quantitative real-time PCR method. The mRNA levels of the PDLIM5 gene in the leukocytes of medication-free schizophrenic patients were significantly higher than those of control subjects. On the other hand, our group has previously shown that its mRNA expression in the leukocytes of medication-free major depressive patients was significantly lower compared with controls. There was no difference in the PDLIM5 mRNA levels between chronic schizophrenic patients with antipsychotic medication and their controls. Further, we failed to find any genetic association between the PDLIM5 gene and schizophrenia with six single nucleotide polymorphics (SNPs) of the PDLIM5 gene in Japanese subjects (279 subjects each) and there was no significant relation between PDLIM5 gene and schizophrenia with the haplotype analysis (P=0.48), either. We suggest that the higher expression levels of the PDLIM5 mRNA in the peripheral leukocytes may be a candidate marker for medication-free schizophrenic patients.

This study investigated the relationship between subjective and objective quality of life and assessed predictors in people with schizophrenia. The study population consisted of 99 stabilized outpatients with schizophrenia (DSM-IV) who had been regularly receiving outpatient treatment at the Department of Psychiatry, The Tokushima University Hospital. Subjective and objective quality of life were estimated using the Schizophrenia Quality of Life Scale and the Quality of Life Scale, respectively. Psychiatric symptoms were also measured with the Brief Psychiatric Rating Scale and the Calgary Depression Scale for Schizophrenia. Scores on the Schizophrenia Quality of Life Scale Motivation and Energy scales significantly correlated with the Quality of Life Scale total scores -.40 (p <.001), and with the scores on Interpersonal Relations subscale -.42 (p <.001), Instrumental Role subscale -.28 (p = .005), Intrapsychic Foundations subscale -.39 (p<.001), and Common Objects and Activities subscale -.25 (p =.014). The Schizophrenia Quality of Life Scale Psychosocial scale significantly correlated with only the Quality of Life Scale total score -.20 (p =.05), and there was no significant correlation between the scores on the Schizophrenia Quality of Life Scale Symptoms and Side-effects scales and the Quality of Life Scale. Stepwise regression analyses showed that the Calgary Depression Scale for Schizophrenia score was the most important predictor of each scale of the Schizophrenia Quality of Life Scale, and the Brief Psychiatric Rating Scale Negative Symptoms score was the most important predictor of the Quality of Life Scale total score and each subscale. These results suggest that subjective and objective quality of life have different predictors and should be considered as separate and complementary outcome variables.

Objective: To determine how Japanese patients with lung cancer weigh potential survival, chemotherapy response rate, and symptom relief against the potential toxicity of different treatments in cancer chemotherapy., Methods and Patients: We used a questionnaire describing a hypothetical situation about stage IV non-small-cell lung cancer. Seventy-three patients with lung cancer who had received chemotherapy and 120 patients with other respiratory disease as the control group were asked to rate the minimal benefit that would make two hypothetical treatments acceptable. For "chance of cure," "response but not cure," and "symptom relief," the subjects could give answers from 1% to 100% and for prolonging life could give answers from 1 to 60 months., Results: Patients with lung cancer were significantly more likely than were patients with other respiratory diseases to accept either intensive or less-intensive treatments for a potentially small benefit for "chance of cure," "response but not cure," and "symptom relief". The degree of survival advantage that patients require before accepting cancer treatment with its associated toxicity varied widely. If their lives were prolonged 3 months, 19% and 21% of patients with lung cancer would choose to receive intensive and less-intensive treatment, respectively. When the chance of symptom relief was 70%, 73% of patients with lung cancer were willing to choose intensive chemotherapy. Factor associated with patients' choice of chemotherapy in both groups was age., Conclusion: Oncologists must consider the substantial range of attitudes to chemotherapy among patients when making treatment decisions and they must give patients the opportunity to be included in this process.

ABO types obtained from evidentiary samples have been used effectively to obtain the initial information leading to the apprehension of culprits in Japanese criminal investigations. A simple ABO genotyping method using multiplex sequence-specific PCR and capillary electrophoresis was developed as a supplement to serological ABO typing. Limitations in predicting a phenotype based on genotype were evaluated using 1134 randomly selected Japanese peripheral blood samples. A concordance rate of 99.82% (1132/1134 samples) was found between genotypes and phenotypes defined as Groups A, B, AB, and O. Sequencing analysis revealed that one discrepant sample contained an O allele having a previously unreported point mutation at the primer binding site in exon 6, and another discrepant sample contained an O allele lacking the guanine deletion at nt 261 (the O301 allele). Therefore, the existence of such alleles must be given some consideration when predicting phenotype based on genotype.