Neural Basis for the Ability of Atypical Antipsychotic Drugs to Improve Cognition in Schizophrenia

Cognitive impairments are considered to largely affect functional outcome in patients with schizophrenia, other psychotic illnesses, or mood disorders. Specifically, there is much attention to the role of psychotropic compounds acting on serotonin (5-HT) receptors in ameliorating cognitive deficits of schizophrenia. It is noteworthy that atypical antipsychotic drugs (AAPDs), e.g., clozapine, melperone, risperidone, olanzapine, quetiapine, aripiprazole, perospirone, blonanserin, and lurasidone, have variable affinities for these receptors. Among the 5-HT receptor subtypes, the 5-HT(1A) receptor is attracting particular interests as a potential target for enhancing cognition, based on preclinical and clinical evidence. The neural network underlying the ability of 5-HT(1A) agonists to treat cognitive impairments of schizophrenia likely includes dopamine, glutamate, and gamma-aminobutyric acid neurons. A novel strategy for cognitive enhancement in psychosis may be benefited by focusing on energy metabolism in the brain. In this context, lactate plays a major role, and has been shown to protect neurons against oxidative and other stressors. In particular, our data indicate chronic treatment with tandospirone, a partial 5-HT(1A) agonist, recover stress-induced lactate production in the prefrontal cortex of a rat model of schizophrenia. Recent advances of electrophysiological measures, e.g., event-related potentials, and their imaging have provided insights into facilitative effects on cognition of some AAPDs acting directly or indirectly on 5-HT(1A) receptors. These findings are expected to promote the development of novel therapeutics for the improvement of functional outcome in people with schizophrenia

Study of childcare anxieties and way coping in O city

本研究の目的は,母親たちが育児に関して直面している不安を把握し,その不安に対する保健師の対処の実態を明らかにすることである｡そこでO市にあるN保健センターの家庭訪問と月1回の育児相談会において,保健師が受けた育児に関する相談を分析した｡対象はN保健センター管内の4つの地区で,1歳2ヶ月未満の児を持つ母親からの216件の相談内容である｡その結果,母親たちの育児不安で最も多かったのは児の身体や栄養についてであった｡さらに不安は出産順位によっても差があり,また児の月齢により変化し,その内容は児の成長発達と深く関係していた｡そして,育児に関する情報は増えているものの,個別性に欠けていることや,母親たちの知識に偏りがあることも明らかになった｡これらの結果をもとに,現在の母親が抱える不安の傾向を考察し,N保健センターで実施している育児支援活動を踏まえ,母親の不安の対処について検討した｡The purpose of this study is to identify childcare anxieties of mothers and how public health nurses cope with them. The data was collected from the contents of 216 consultations of mothers with children under 14th months of age carried by public health nurses of N public health center, O city. It was revealed that most of the consultations were about child's physical and nutritious concerns. The childcare anxieties associated with growth and birth order and the child's age in months. Moreover, we found that even though there is a large volume of information available about childcare, it is too general. Based on the research findings, we made clear tendency of childcare anxiety of mothers and how the public health nurses coped with them

Pituitary Volume and Socio-Cognitive Functions in Individuals at Risk of Psychosis and Patients With Schizophrenia

Objectives: Increased pituitary volume, which probably reflects hypothalamic-pituitary-adrenal (HPA) hyperactivity, has been reported in patients with schizophrenia and individuals at risk of psychosis. On the basis of potential role of abnormal HPA axis function on cognitive impairments in psychosis, we aimed to examine possible relations between the pituitary volume and socio-cognitive impairments in these subjects.Methods: This magnetic resonance imaging study examined the pituitary gland volume in 38 subjects with at-risk mental state (ARMS) [of whom 4 (10.5%) exhibited the transition to schizophrenia], 63 patients with schizophrenia, and 61 healthy controls. Social and cognitive functions of the ARMS and schizophrenia groups were assessed using the Brief Assessment of Cognition in Schizophrenia (BACS), the Schizophrenia Cognition Rating Scale (SCoRS), and the Social and Occupational Functioning Assessment Scale (SOFAS).Results: Both the ARMS and schizophrenia groups had a significantly larger pituitary volume compared to controls. In the schizophrenia group, the pituitary volume was negatively associated with the BACS working memory score. No association was found between the pituitary volume and clinical variables (medication, symptom severity) in either clinical group.Conclusion: Our findings support the notion of common HPA hyperactivity in the ARMS and schizophrenia groups, but abnormal HPA axis function may contribute differently to cognitive deficits according to the illness stages of schizophrenia

Long-Term Effects of Labor Market Conditions on Family Formation for Japanese Youth

This study aims to examine how each cohort's family formation is affected by labor market conditions experienced in youth in Japan. Although deterioration in youth employment opportunities has often been blamed for Japan's declining marriage and fertility rates, the effects of slack labor market conditions on marriage and fertility are theoretically unclear. We estimate the effects of regional labor market conditions on marriage and fertility, controlling for nation-wide year effects and prefecture fixed effects, and find the following. First, the male unemployment rate is negatively correlated with marriage of women in the local labor market, although the correlation is weak and concentrated on the less educated group. Second, high school-educated women who experienced a recession while entering the labor market are less likely to have children and tend to marry later. In contrast, a recession at entry to the labor market rather increases fertility among college-educated women. The overall impact of labor market conditions experienced in youth on family formation is relatively weak, compared to the substantial losses in earnings and employment stability documented by the existing studies

Serum galectin-9 levels are elevated in the patients with type 2 diabetes and chronic kidney disease

Background: Galectin-9 (Gal-9) induces apoptosis in activated T helper 1 (T(H)1) cells as a ligand for T cell immunoglobulin mucin-3 (Tim-3). Gal-9 also inhibits the G1 phase cell cycle arrest and hypertrophy in db/db mice, the hallmark of early diabetic nephropathy, by reversing the high glucose-induced up-regulation of cyclin dependent kinase inhibitors such as p27(Kip1) and p21(Cip1). Methods: We investigated the serum levels of Gal-9 in the patients with type 2 diabetes and various stages of chronic kidney disease (CKD) (n = 182). Results: Serum Gal-9 levels in the patients with type 2 diabetes were 131.9 +/- 105.4 pg/ml and Log(10)Gal-9 levels significantly and positively correlated with age (r = 0.227, p = 0.002), creatinine (r = 0.175, p = 0.018), urea nitrogen (r = 0.162, p = 0.028) and osmotic pressure (r = 0.187, p = 0.014) and negatively correlated with estimated glomerular filtration rate (eGFR) (r = -0.188, p = 0.011). Log(10)Gal-9 levels increased along with the progression of GFR categories of G1 to G4, and they were statistically significant by Jonckheere-Terpstra test (p = 0.012). Log(10)Gal-9 levels remained similar levels in albuminuria stages of A1 to A3. Conclusion: The elevation of serum Gal-9 in the patients with type 2 diabetes is closely linked to GFR and they may be related to the alteration of the immune response and inflammation of the patients with type 2 diabetes and CKD

Criterion and Construct Validity of the CogState Schizophrenia Battery in Japanese Patients with Schizophrenia

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

Required muscle mass for preventing lifestyle-related diseases in Japanese women

Research articl

The Fission Yeast Stress-Responsive MAPK Pathway Promotes Meiosis via the Phosphorylation of Pol II CTD in Response to Environmental and Feedback Cues

The RRM-type RNA-binding protein Mei2 is a master regulator of meiosis in fission yeast, in which it stabilizes meiosis-specific mRNAs by blocking their destruction. Artificial activation of Mei2 can provoke the entire meiotic process, and it is suspected that Mei2 may do more than the stabilization of meiosis-specific mRNAs. In our current study using a new screening system, we show that Mei2 genetically interacts with subunits of CTDK-I, which phosphorylates serine-2 residues on the C-terminal domain of RNA polymerase II (Pol II CTD). Phosphorylation of CTD Ser-2 is essential to enable the robust transcription of ste11, which encodes an HMG-type transcription factor that regulates the expression of mei2 and other genes necessary for sexual development. CTD Ser-2 phosphorylation increases under nitrogen starvation, and the stress-responsive MAP kinase pathway, mediated by Wis1 MAPKK and Sty1 MAPK, is critical for this stress response. Sty1 phosphorylates Lsk1, the catalytic subunit of CTDK-I. Furthermore, a feedback loop stemming from activated Mei2 to Win1 and Wis4 MAPKKKs operates in this pathway and eventually enhances CTD Ser-2 phosphorylation and ste11 transcription. Hence, in addition to starting meiosis, Mei2 functions to reinforce the commitment to it, once cells have entered this process. This study also demonstrates clearly that the stress-responsive MAP kinase pathway can modulates gene expression through phosphorylation of Pol II CTD

Post-intervention Status in Patients With Refractory Myasthenia Gravis Treated With Eculizumab During REGAIN and Its Open-Label Extension

OBJECTIVE: To evaluate whether eculizumab helps patients with anti-acetylcholine receptor-positive (AChR+) refractory generalized myasthenia gravis (gMG) achieve the Myasthenia Gravis Foundation of America (MGFA) post-intervention status of minimal manifestations (MM), we assessed patients' status throughout REGAIN (Safety and Efficacy of Eculizumab in AChR+ Refractory Generalized Myasthenia Gravis) and its open-label extension. METHODS: Patients who completed the REGAIN randomized controlled trial and continued into the open-label extension were included in this tertiary endpoint analysis. Patients were assessed for the MGFA post-intervention status of improved, unchanged, worse, MM, and pharmacologic remission at defined time points during REGAIN and through week 130 of the open-label study. RESULTS: A total of 117 patients completed REGAIN and continued into the open-label study (eculizumab/eculizumab: 56; placebo/eculizumab: 61). At week 26 of REGAIN, more eculizumab-treated patients than placebo-treated patients achieved a status of improved (60.7% vs 41.7%) or MM (25.0% vs 13.3%; common OR: 2.3; 95% CI: 1.1-4.5). After 130 weeks of eculizumab treatment, 88.0% of patients achieved improved status and 57.3% of patients achieved MM status. The safety profile of eculizumab was consistent with its known profile and no new safety signals were detected. CONCLUSION: Eculizumab led to rapid and sustained achievement of MM in patients with AChR+ refractory gMG. These findings support the use of eculizumab in this previously difficult-to-treat patient population. CLINICALTRIALSGOV IDENTIFIER: REGAIN, NCT01997229; REGAIN open-label extension, NCT02301624. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that, after 26 weeks of eculizumab treatment, 25.0% of adults with AChR+ refractory gMG achieved MM, compared with 13.3% who received placebo

Minimal Symptom Expression' in Patients With Acetylcholine Receptor Antibody-Positive Refractory Generalized Myasthenia Gravis Treated With Eculizumab

The efficacy and tolerability of eculizumab were assessed in REGAIN, a 26-week, phase 3, randomized, double-blind, placebo-controlled study in anti-acetylcholine receptor antibody-positive (AChR+) refractory generalized myasthenia gravis (gMG), and its open-label extension