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BACKGROUND: Healthcare providers frequently help traumatized people and are regularly exposed to indirect trauma from their work, resulting in negative psychological responses, such as secondary traumatic stress. Empathy has been associated with patient's quality of care and secondary traumatic stress among healthcare providers. However, the relationship between dispositional empathy and secondary traumatic stress has not been fully elucidated. This study used person- and variable-centered approaches to explore the nature of this relationship. METHODS: A total of 1,006 Japanese public health nurses working in the Tohoku region and Saitama prefecture completed questionnaires that included scales assessing dispositional empathy, secondary traumatic stress, and burnout. First, we examined predictors of secondary traumatic stress using multiple linear regression analysis. Then, we conducted a latent profile analysis to classify participants into unique groups based on four subscales of dispositional empathy (i.e., empathic concern, perspective taking, personal distress, fantasy) and secondary traumatic stress. Finally, we compared the mean values of the study variables across these groups. RESULTS: The multiple regression indicated that in those working in Saitama prefecture, lifetime traumatic experiences, work-related distress, and personal distress were positively related to secondary traumatic stress, but perceived support was negatively related to secondary traumatic stress. Latent profile analysis extracted four unique subgroups. Group 1 displayed the highest secondary traumatic stress levels. Group 2 was characterized by the highest level of empathic concern, personal distress, and fantasy and the lowest perspective taking. Group 3 had a moderate secondary traumatic stress level. Group 4 had the lowest secondary traumatic stress and personal distress scores. In these four groups, the burnout scale (exhaustion, cynicism, and professional efficacy) showed a pattern similar to the secondary traumatic stress scale. CONCLUSIONS: Our person-centered approach showed that this sample of public health nurses could be classified into four unique groups based on their empathy and secondary traumatic stress scores. Although this group of public health nurses was not large, one group displayed high personal distress levels and high secondary traumatic stress levels. Further research is needed to determine effective interventions for this group.
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Esgotamento Profissional , Fadiga de Compaixão , Empatia , Enfermeiros de Saúde Pública , Enfermagem em Saúde Pública , Humanos , Esgotamento Profissional/psicologia , Fadiga de Compaixão/psicologia , População do Leste Asiático , Satisfação no Emprego , Enfermeiros de Saúde Pública/classificação , Enfermeiros de Saúde Pública/psicologia , Inquéritos e Questionários , Enfermagem em Saúde Pública/métodosRESUMO
BACKGROUND: First responders to disasters are at risk of developing post-traumatic stress disorder (PTSD). The trajectories of post-traumatic stress symptom severity differ among individuals, even if they are exposed to similar events. These trajectories have not yet been reported in non-Western first responders. AIMS: We aimed to explore post-traumatic stress symptom severity trajectories and their risk factors in first responders to the 2011 Great East Japan Earthquake (GEJE) - a historically large earthquake that resulted in a tsunami and a nuclear disaster. METHOD: A total of 55 632 Japan Ground Self-Defense Force (JGSDF) personnel dispatched to the GEJE were enrolled in this 7-year longitudinal cohort study. PTSD symptom severity was measured using the Impact of Event Scale-Revised. Trajectories were identified using latent growth mixture models (LGMM). Nine potential risk factors for the symptom severity trajectories were analysed using multinomial logistic regression. RESULTS: Five symptom severity trajectories were identified: 'resilient' (54.8%), 'recovery' (24.6%), 'incomplete recovery' (10.7%), 'late-onset' (5.7%), and 'chronic' (4.3%). The main risk factors for the four non-resilient trajectories were older age, personal disaster experiences and working conditions. These working conditions included duties involving body recovery or radiation exposure risk, longer deployment length, later or no post-deployment leave and longer post-deployment overtime. CONCLUSIONS: The majority of first responders to GEJE were resilient and developed few or no PTSD symptoms. A substantial minority experienced late-onset and chronic symptom severity trajectories. The identified risk factors can inform policies for prevention, early detection and intervention in individuals at risk of developing symptomatic trajectories.
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BACKGROUND: Red algae have been reported to improve lipid and glucose metabolism in rats. We investigated the effects of Palmaria palmata (P. palmata), a red alga from northern Japan, on lipid metabolism and glycemic control in participants with hypercholesterolemia. METHODS: We conducted an 8-week, randomized, double-blind, placebo-controlled, and parallel-group comparison trial. The study enrolled Japanese participants with a serum low-density protein cholesterol (LDL-C) ≥120 mg/dL. The participants were randomly assigned to take either capsules containing P. palmata (2 g/day) or placebo capsules. The primary endpoint was the change in LDL-C from baseline to week 8 and the secondary endpoints were the changes in other lipid parameters and glycemic control. RESULTS: Of the 104 participants completed the study protocol. There were no significant differences in change in LDL-C, body mass index, waist circumference, or glycemic control between the two groups. However, serum triglyceride showed significantly greater improvement in women in the P. palmata group (-9.0 [-25.0, +5.0]) vs. those in the placebo group (-1.0 [-11.0, +19.0]; p = .03). CONCLUSIONS: The present study did not show that P. palmata had significant effect on serum LDL-C nor glycemic control, but hypertriglyceridemia could be ameliorated by administration of P. palmata in women.
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Glicemia/efeitos dos fármacos , Hipercolesterolemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Rodófitas/química , Animais , Método Duplo-Cego , Humanos , Pessoa de Meia-Idade , RatosRESUMO
Life-threatening experiences can result in the development of post-traumatic stress disorder. We have developed an animal model for post-traumatic stress disorder (PTSD) using a shuttle box in rats. In this paradigm, the rats were exposed to inescapable foot-shock stress (IS) in a shuttle box, and then an avoidance/escape task was performed in the same box 2 weeks after IS. A previous study using this paradigm revealed that environmental enrichment (EE) ameliorated avoidance/numbing-like behaviors, but not hyperarousal-like behaviors, and EE also elevated hippocampal brain-derived neurotrophic factor (BDNF) expression. However, the differential effects of EE components, i.e., running wheel (RW) or toy rotation, on PTSD-like behaviors has remained unclear. In this experiment, we demonstrated that RW, toy rotation, and EE (containing RW and toy rotation) ameliorated avoidance/numbing-like behaviors, induced learning of avoidance responses, and improved depressive-like behaviors in traumatized rats. The RW increased the hippocampal mRNA expression of neurotrophic factors, especially BDNF and glial-cell derived neurotrophic factor. Toy rotation influenced FK506 binding protein 5 mRNA expression, which is believed to be a regulator of the hypothalamic-pituitary-adrenal (HPA)-axis system, in the hippocampus and amygdala. This is the first report to elucidate the differential mechanistic effects of RW and toy rotation. The former appears to exert its effects via neurotrophic factors, while the latter exerts its effects via the HPA axis. Further studies will lead to a better understanding of the influence of environmental factors on PTSD.
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Fatores de Crescimento Neural/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transtornos de Estresse Pós-Traumáticos/genética , Transtornos de Estresse Pós-Traumáticos/metabolismo , Proteínas de Ligação a Tacrolimo/genética , Tonsila do Cerebelo/metabolismo , Animais , Aprendizagem da Esquiva , Comportamento Animal , Fator Neurotrófico Derivado do Encéfalo/genética , Modelos Animais de Doenças , Reação de Fuga , Fator Neurotrófico Derivado de Linhagem de Célula Glial/genética , Hipocampo/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Masculino , Atividade Motora , Fator de Crescimento Neural/genética , Sistema Hipófise-Suprarrenal/metabolismo , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Wistar , Transtornos de Estresse Pós-Traumáticos/psicologiaRESUMO
Aim: The objective of this study was to evaluate the potential of hydrogen in preventing and treating psychiatric symptoms, particularly depressed mood and loss of interest, and to explore its underlying mechanisms. A mouse model exhibiting inflammation-derived depressive symptoms was used for the investigation. Methods: Institute of Cancer Research mice were subjected to a 7-day intervention of either 30% hydrogen or 40 g per day of air via jelly intake. On the final day, lipopolysaccharide (LPS) was intraperitoneally administered at 5 mg/kg to induce inflammation-related depressive symptoms. Behavioral and biochemical assessments were conducted 24 h post-LPS administration. Results: Following LPS administration, a decrease in spontaneous behavior was observed; however, this effect was mitigated in the group treated with hydrogen. The social interaction test revealed a significant reduction in interactions with unfamiliar mice in the LPS-treated group, whereas the hydrogen-treated group exhibited no such decrease. No significant changes were noted in the forced-swim test for either group. Additionally, the administration of LPS in the hydrogen group did not result in a decrease in zonula occludens-1, a biochemical marker associated with barrier function at the cerebrovascular barrier and expressed in tight junctions. Conclusion: Hydrogen administration demonstrated a preventive effect against the LPS-induced loss of interest, suggesting a potential role in symptom prevention. However, it did not exhibit a suppressive effect on depressive symptoms in this particular model. These findings highlight the nuanced impact of hydrogen in the context of inflammation-induced psychiatric symptoms, indicating potential avenues for further exploration and research.
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Burnout and secondary traumatic stress (STS), also referred to as compassion fatigue, are undeniable negative consequences experienced by healthcare professionals when working with patients. As frontline healthcare professionals are essential to communities, it is crucial to understand their mental health and how they cope with negative psychological responses. This study investigated the relationships between burnout, STS, compassion satisfaction, dispositional empathy, and stress management among Japanese healthcare professionals and students taking care of patients in clinical practice. The participants were 506 Japanese healthcare professionals and students (doctors, nurses, medical students, and nursing students) affiliated with Japanese Ministry of Defense Hospitals. The data were collected from March 2020 to May 2021. We assessed burnout, STS, and compassion satisfaction using the Professional Quality of Life Scale, dispositional empathy using the Interpersonal Reactivity Index, and coping with stress using the Coping Orientation to Problems Experienced Inventory (Brief-COPE). Exploratory factor analysis of the Brief-COPE yielded three factors: active coping; support-seeking; and indirect coping. Personal distress, a self-oriented emotional empathy index, was related to higher burnout and STS scores and lower compassion satisfaction. Empathic concern, an other-oriented emotional empathy index, was associated with lower burnout and higher compassion satisfaction. Active coping strategies were associated with lower burnout and higher compassion satisfaction, whereas indirect coping strategies were associated with higher burnout and STS scores. In a comparison of empathy in professional categories, nurses presented higher personal distress than nursing students, and medical doctors showed lower fantasy tendencies than medical students. These results imply the complex relationships between empathy, coping strategies, and psychological responses among healthcare professionals. Further longitudinal study is needed to explore these complex relationships and to develop more precise and effective psycho-educational interventions to prevent burnout and STS.
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Importance: Peacekeepers in United Nations missions experience potentially traumatic events, resulting in increased risk for posttraumatic stress disorder (PTSD). Understanding the course and risk factors of PTSD symptom severity is crucial to ensure personnel safety. Objective: To investigate the incidence of PTSD, symptom severity trajectories, and potential risk factors associated with adverse trajectories among Japanese peacekeepers deployed in South Sudan. Design, Setting, and Participants: Data for this 6-year prospective cohort study were collected from December 2011 to December 2018 from Japan Ground Self-Defense Force personnel deployed at the United Nations Mission in South Sudan, corresponding to before and up to 78 months after deployment. Of 3799 potential participants, 80 were excluded because of multiple deployments and 757 because of missing data, incomplete responses, or not providing informed consent. Therefore, 2962 participants were included in the analysis. Data analysis was performed from February 2022 to February 2024. Exposure: The participants were deployed to United Nations Mission in South Sudan for 6 months. Main Outcomes and Measures: The 22-item Impact of Event Scale-Revised was used to assess PTSD symptoms, with 25 or more points indicating probable PTSD (p-PTSD). Sociodemographic data were collected, and the 30-item General Health Questionnaire was administered before deployment to identify risk factors for PTSD symptom severity. Results: In the 2962 participants studied (2901 [97.9%] male; mean [SD] age, 33.9 [7.2] years), the incidence of p-PTSD was 3.95%. Latent growth mixture models identified 4 symptom severity trajectories: resilient (2143 [72.3%]), recovery (479 [16.2%]), protracted (182 [6.1%]), and delayed (158 [5.3%]). Multinomial logistic regression showed that sleep disturbance was a common risk factor for the 2 most severe trajectories (protracted: odds ratio [OR], 1.29; 95% CI, 1.08-1.54; delayed: OR, 1.26; 95% CI, 1.03-1.53), whereas older age (OR, 1.25; 95% CI, 1.06-1.48), anxiety and dysphoria (OR, 1.45; 95% CI, 1.20-1.75), and general illness (OR, 1.30; 95% CI, 1.06-1.59) were associated with the protracted trajectory. Conclusions and Relevance: This cohort study found that approximately 4% of the participants developed p-PTSD and identified 4 distinct PTSD symptom trajectories. The findings suggest that addressing sleep disturbance and general health issues could effectively prevent PTSD symptoms among peacekeepers.
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Transtornos de Estresse Pós-Traumáticos , Humanos , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Masculino , Adulto , Feminino , Sudão do Sul/epidemiologia , Estudos Prospectivos , Japão/epidemiologia , Fatores de Risco , Militares/psicologia , Militares/estatística & dados numéricos , Destacamento Militar/psicologia , Destacamento Militar/estatística & dados numéricos , Incidência , Índice de Gravidade de Doença , População do Leste AsiáticoRESUMO
The stigma that military personnel feel toward mental illness and mental healthcare hinders their access to mental health services. Stigma is influenced by culture-specifically, that held by military personnel is closely related to military culture. To our knowledge, this is the first large-scale investigation aimed at identifying the factors, including demographic factors and elements of military culture, related to stigma among members of the Japan Ground Self-Defense Force. An anonymous questionnaire was administered to 4754 members. The questionnaire included items regarding demographic factors, history of psychiatric visits, military rank, overseas deployment experience, disaster relief experience, supervisor leadership, unit cohesion, general psychological distress, stigma toward perceived mental illness, and attitudes toward help-seeking. Multiple regression analysis was used to identify the various factors related to stigma. Responses were obtained from 4305 (90.5%) participants, among which 3723 (78.3%) were valid. Multiple regression analyses revealed that a variety of factors including age, psychiatric consultation, leadership, and cohesiveness were markedly associated with stigma and attitudes toward help-seeking. This study revealed that various factors including demographic factors and military culture factors such as supervisor leadership and unit cohesion are related to stigma and attitudes toward mental health services among Japan Ground Self-Defense Force personnel. Further studies are needed to examine the results in depth.
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Transtornos Mentais , Serviços de Saúde Mental , Militares , Humanos , Japão , Transtornos Mentais/terapia , Transtornos Mentais/psicologia , Estigma Social , Aceitação pelo Paciente de Cuidados de Saúde/psicologiaRESUMO
OBJECTIVE: SPI1, also referred to as PU.1, is an Ets family transcription factor that interacts with IRF2, IRF4, and IRF8. In view of the significance of the type I interferon pathway in systemic lupus erythematosus (SLE), this study was undertaken to investigate a possible association between SPI1 polymorphisms and SLE. METHODS: A case-control association study was performed using 6 tag single-nucleotide polymorphisms (SNPs), as well as a SNP located upstream of SPI1 previously found to be associated with acute myelogenous leukemia, in 400 Japanese patients with SLE and 450 healthy controls. Resequencing of all exons and known regulatory regions was performed to identify functional polymorphisms. Association of genotype and SPI1 expression was examined using the GENEVAR database and reporter assays. RESULTS: A significant association was detected in 2 SNPs in intron 2 (rs10769258 and rs4752829) (P = 0.005 and P = 0.008, respectively, under the dominant model). The association was stronger in patients with nephropathy. Resequencing identified a potentially functional polymorphism in the 3'-untranslated region (3'-UTR), rs1057233, which was in strong linkage disequilibrium with the SNPs in intron 2. The number of risk alleles at rs1057233 was strongly correlated with SPI1 messenger RNA (mRNA) level in the database analysis (P = 0.0002), and was confirmed by a reporter assay. Interestingly, rs1057233 alters a target sequence for microRNA hsa-miR-569 (miR-569). Transfection experiments demonstrated that miR-569 inhibits expression of a reporter construct with the 3'-UTR sequence containing the nonrisk allele but not the risk allele. CONCLUSION: Our findings indicate that a SNP in the 3'-UTR of SPI1 is associated with elevated SPI1 mRNA level and with susceptibility to SLE.
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Povo Asiático/genética , Lúpus Eritematoso Sistêmico/etnologia , Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas Proto-Oncogênicas/genética , Transativadores/genética , Regiões 3' não Traduzidas/genética , Adulto , Povo Asiático/estatística & dados numéricos , Feminino , Genes Reporter/genética , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Fatores de Risco , Transfecção , Adulto JovemRESUMO
Functional APRIL (TNFSF13) is a secreted trimer generated by furin protease cleavage. We previously reported the association of APRIL haplotypes formed by two nonsynonymous polymorphisms, Gly67Arg and Asn96Ser, with systemic lupus erythematosus. Here, we tested the hypothesis that polymorphisms and/or alternative splicing may influence the generation of soluble APRIL (sAPRIL). HEK 293T cells were transfected with plasmids containing one of the six combinations of splicing isoforms (α or ß) and haplotypes (susceptible, neutral, or protective). APRIL concentrations were quantitated in the cell lysates and supernatants using an enzyme-linked immunosorbent assay (ELISA). The association between splicing efficiency and polymorphisms was analyzed using quantitative reverse transcription polymerase chain reaction (RT-PCR). The efficiency of cleavage by furin protease was analyzed using western blotting. Although both splicing isoforms were cleaved by furin protease, sAPRIL was not detected in the supernatant of the cells transfected with the ß isoform, regardless of the haplotype. This suggested that, similarly to B-cell activating factor (BAFF), one of the major APRIL splicing isoforms may not be secreted as a functional molecule. Furthermore, the secretion of sAPRIL was decreased in the transfectants expressing the protective haplotype. An association between the polymorphisms and splicing efficiency or furin cleavage efficiency was not detected. In conclusion, these observations suggested that both alternative splicing and polymorphisms may affect the generation of functional sAPRIL.
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Lúpus Eritematoso Sistêmico/genética , Polimorfismo de Nucleotídeo Único , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/genética , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Sequência de Aminoácidos , Células HEK293 , Humanos , Dados de Sequência Molecular , Isoformas de Proteínas/genética , Transfecção , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral/químicaRESUMO
Glutamate is one of the key molecules involved in signal transduction in the brain, and dysfunction of glutamate signaling could be linked to schizophrenia. The SLC1A1 gene located at 9p24 encodes the glutamate transporter EAAT3/EAAC1. To investigate the association between the SLC1A1 gene and schizophrenia in the Japanese population, we genotyped 19 tagging single nucleotide polymorphisms (tagSNPs) in the SLC1A1 gene in 576 unrelated individuals with schizophrenia and 576 control subjects followed by replication in an independent case-control study of 1,344 individuals with schizophrenia and 1,344 control subjects. In addition, we determined the boundaries of the copy number variation (CNV) region in the first intron (Database of Genomic Variants, chr9:4516796-4520549) and directly genotyped the CNV because of significant deviation from the Hardy-Weinberg equilibrium. The CNV was not associated with schizophrenia. Four SNPs showed a possible association with schizophrenia in the screening subjects and the associations were replicated in the same direction (nominal allelic P < 0.05), and, among them, an association with rs7022369 was replicated even after Bonferroni correction (allelic nominal P = 5 × 10(-5) , allelic corrected P = 2.5 × 10(-4) , allelic odds ratio, 1.30; 95% CI: 1.14-1.47 in the combined subjects). Expression analysis quantified by the real-time quantitative polymerase chain reaction in the postmortem prefrontal cortex of 43 Japanese individuals with schizophrenia and 11 Japanese control subjects revealed increased SLC1A1 expression levels in individuals homozygous for the rs7022369 risk allele (P = 0.003). Our findings suggest the involvement of SLC1A1 in the pathogenesis of schizophrenia.
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Transportador 3 de Aminoácido Excitatório/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Esquizofrenia/genética , Alelos , Encéfalo/patologia , Variações do Número de Cópias de DNA/genética , Transportador 3 de Aminoácido Excitatório/metabolismo , Feminino , Testes Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Mudanças Depois da Morte , Reprodutibilidade dos TestesRESUMO
Chromatin remodeling may play a role in the neurobiology of schizophrenia and the process, therefore, may be considered as a therapeutic target. The SMARCA2 gene encodes BRM in the SWI/SNF chromatin-remodeling complex, and associations of single nucleotide polymorphisms (SNPs) to schizophrenia were found in two linkage disequilibrium blocks in the SMARCA2 gene after screening of 11 883 SNPs (rs2296212; overall allelic P = 5.8 x 10(-5)) and subsequent screening of 22 genes involved in chromatin remodeling (rs3793490; overall allelic P = 2.0 x 10(-6)) in a Japanese population. A risk allele of a missense polymorphism (rs2296212) induced a lower nuclear localization efficiency of BRM, and risk alleles of intronic polymorphisms (rs3763627 and rs3793490) were associated with low SMARCA2 expression levels in the postmortem prefrontal cortex. A significant correlation in the fold changes of gene expression from schizophrenic prefrontal cortex (from the Stanley Medical Research Institute online genomics database) was seen with suppression of SMARCA2 in transfected human cells by specific siRNA, and of orthologous genes in the prefrontal cortex of Smarca2 knockout mice. Smarca2 knockout mice showed impaired social interaction and prepulse inhibition. Psychotogenic drugs lowered Smarca2 expression while antipsychotic drugs increased it in the mouse brain. These findings support the existence of a role for BRM in the pathophysiology of schizophrenia.
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Montagem e Desmontagem da Cromatina , Proteínas de Ligação a DNA/metabolismo , Esquizofrenia/metabolismo , Fatores de Transcrição/metabolismo , Adulto , Idoso , Sequência de Aminoácidos , Animais , Povo Asiático , Estudos de Casos e Controles , Linhagem Celular , Núcleo Celular/química , Núcleo Celular/metabolismo , Estudos de Coortes , Proteínas de Ligação a DNA/genética , Feminino , Expressão Gênica , Humanos , Relações Interpessoais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Córtex Pré-Frontal/química , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Transporte Proteico , Psicotrópicos/administração & dosagem , Esquizofrenia/tratamento farmacológico , Esquizofrenia/genética , Esquizofrenia/fisiopatologia , Alinhamento de Sequência , Fatores de Transcrição/química , Fatores de Transcrição/genéticaRESUMO
Glutamate, the principal excitatory neurotransmitter of the brain, participates in a multitude of physiologic and pathologic processes, including learning and memory. Glutathione, a tripeptide composed of the amino acids glutamate, cysteine, and glycine, serves important cofactor roles in antioxidant defense and drug detoxification, but glutathione deficits occur in multiple neuropsychiatric disorders. Glutathione synthesis and metabolism are governed by a cycle of enzymes, the γ-glutamyl cycle, which can achieve intracellular glutathione concentrations of 1-10mM. Because of the considerable quantity of brain glutathione and its rapid turnover, we hypothesized that glutathione may serve as a reservoir of neural glutamate. We quantified glutamate in HT22 hippocampal neurons, PC12 cells and primary cortical neurons after treatment with molecular inhibitors targeting three different enzymes of the glutathione metabolic cycle. Inhibiting 5-oxoprolinase and γ-glutamyl transferase, enzymes that liberate glutamate from glutathione, leads to decreases in glutamate. In contrast, inhibition of γ-glutamyl cysteine ligase, which uses glutamate to synthesize glutathione, results in substantial glutamate accumulation. Increased glutamate levels following inhibition of glutathione synthesis temporally precede later effects upon oxidative stress.
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Ácido Glutâmico/biossíntese , Glutationa/metabolismo , Neurônios/metabolismo , Animais , Butionina Sulfoximina/farmacologia , Linhagem Celular Tumoral , Inibidores Enzimáticos/farmacologia , Hipocampo/citologia , Imidazolinas/farmacologia , Isoxazóis/farmacologia , Camundongos , Piroglutamato Hidrolase/antagonistas & inibidores , Piroglutamato Hidrolase/metabolismo , Ratos , gama-Glutamiltransferase/antagonistas & inibidores , gama-Glutamiltransferase/metabolismoRESUMO
Although large-scale studies established many susceptibility genes to systemic lupus erythematosus (SLE), effect of each gene is not sufficiently large to be used alone to identify individuals with strong genetic predisposition. In this study, we analyzed the cumulative number of risk alleles at eight established susceptibility loci, HLA-DRB1, IRF5, STAT4, BLK, TNFAIP3, TNIP1, FCGR2B and TNFSF13, in 282 Japanese female SLE and 222 healthy female controls. The average number of risk alleles was significantly increased in SLE (8.07±1.60) than healthy controls (7.02±1.64) (P=1.63 × 10(-12)). Significant gene-gene interaction was not detected. When the subjects carrying seven risk alleles were used as a reference, the odds ratio (OR) for individuals carrying 10 and 11-13 risk alleles were 4.17 (95% confidence interval (CI) 1.89-9.19, P=0.0002) and 8.77 (95% CI 1.92-40.0, P=0.0016), respectively. In contrast, subjects with ≤4 risk alleles were significantly decreased in SLE (OR 0.15, CI 0.03-0.67, P=0.007). The proportion of the patients with neurologic disorder was significantly increased in those carrying ≥10 risk alleles than those with <10 (OR 2.30, CI 1.09-4.83, P=0.025). This study suggested that the cumulative number of risk alleles may efficiently distinguish groups with high and low genetic predisposition to SLE and its severe manifestation.
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Lúpus Eritematoso Sistêmico/genética , Alelos , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Cadeias HLA-DRB1/genética , Humanos , Fatores Reguladores de Interferon/genética , Razão de Chances , Fatores de Risco , Fator de Transcrição STAT4/genéticaRESUMO
Subthreshold depression (StD) is a depressive state that does not fulfil the criteria for major depressive disorder (MDD); however, StD has a risk for progression to MDD, and early intervention is therefore needed. Recently, a method for extracting neural extracellular vesicles (NEVs) excreted from neural cells of the brain from blood has been established, and microRNAs (miRNAs) encapsulated in NEVs are attracting interest because of their potential correlation to the pathogenesis of psychiatric disorders. However, miRNAs closely related to StD are still unknown. Therefore, to try to identify miRNAs closely related to the degree of StD, we examined the correlations between expression levels of some candidate miRNAs in NEVs and Patient Health Questionnaire-9 (PHQ-9) scores in subjects. Total RNAs in NEVs were extracted from serum of young adult males who had PHQ-9 scores of less than 10 (n = 9). Expression levels of eight miRNAs that were previously reported to be depression-associated miRNAs (let-7a-5p, miR-17-5p, miR-26b-5p, miR-34a-5p, miR-132-3p, miR-182-5p, miR-212-3p, and miR-1202) were measured using real-time PCR. Two of the eight miRNAs (miR-17-5p and miR-26b-5p) were stably detected. The relative expression levels of miR-17-5p showed a significant positive correlation with PHQ-9 scores (r = 0.85, p < 0.01), while those of miR-26b-5p showed no significance. Although a larger-scale analysis is needed due to the small number of subjects, these findings suggest that miR-17-5p in NEVs is a potential biomarker for StD.
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Depressão/diagnóstico , Vesículas Extracelulares/metabolismo , MicroRNAs/sangue , Adulto , Biomarcadores/sangue , Depressão/complicações , Transtorno Depressivo Maior/etiologia , Transtorno Depressivo Maior/prevenção & controle , Progressão da Doença , Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Risco , Inquéritos e QuestionáriosRESUMO
Because of the involvement of the brain in the pathophysiology of psychiatric disorders, obtaining information on the biochemical features that directly contribute to symptoms is challenging. The present study aimed to assess fatty acid-binding protein 7 (FABP7) expressed specifically in the brain and detectable in the peripheral blood and to investigate the correlation between blood FABP7 concentration and symptoms. We recruited 30, 29, and 35 patients with schizophrenia, bipolar disorder, and depression and evaluated using the Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale (YMRS), and Hamilton Depression Rating Scale (HAMD-21), respectively. Plasma FABP7 concentrations correlated with PANSS scores (R2 = 0.3305, p < 0.001) but not with other scales. In the analysis of the relationship between five dimensions of schizophrenia symptoms derived from the PANSS 5-factor model and measured plasma FABP7 concentrations, severities of depression/anxiety, cognition, and positive symptom were significantly correlated with plasma FABP7 concentrations. Further molecular investigation of the functional and kinetic analyses of FABP7 is necessary to understand the relationship of this protein with schizophrenia pathology. Nevertheless, the present study suggests that FABP7 can be a biological indicator reflecting the pathogenesis of schizophrenia and has potential applications as a biomarker for diagnosis and symptom assessment.
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Esquizofrenia , Ansiedade , Cognição , Depressão/psicologia , Proteína 7 de Ligação a Ácidos Graxos , Humanos , Escalas de Graduação Psiquiátrica , Proteínas Supressoras de TumorRESUMO
AIM: This study assessed the validity and reliability of the Secondary Traumatic Stress Scale-Japanese Version. METHODS: The original Secondary Traumatic Stress Scale was translated into Japanese, and Japanese items were back-translated to English to confirm the accuracy of the translation. A total of 870 public health nurses from the Tohoku region in Japan completed the Secondary Traumatic Stress Scale-Japanese Version. An exploratory factor analysis was conducted to identify the number of components. Moreover, 351 public health nurses from the Saitama prefecture in Japan also completed the scale. A confirmatory factor analysis was performed with the factor structure identified in the exploratory factor analysis. RESULTS: The exploratory factor analysis identified two components: one associated with client-related distress and the other with trauma-related distress. The confirmatory factor analysis confirmed the two-factor structure. The two-factor structure model was better than the three-factor model presented in the original validation study for the English version of the scale. The two-factor model had good internal consistency for the overall product and the subscales. Pearson correlations showed that this model had good convergent validity against the Maslach Burnout Inventory, a psychological measure similar to the Secondary Traumatic Stress Scale. Finally, the two-factor model had good discriminant validity against the Maslach Burnout Inventory. CONCLUSION: This study identified two components of the Secondary Traumatic Stress Scale-Japanese Version that differ from the three components found in the original English version. The differences in the factor structure might indicate that the factor structure was culturally influenced.
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Fadiga de Compaixão , Análise Fatorial , Humanos , Japão/epidemiologia , Reprodutibilidade dos Testes , TraduçõesRESUMO
Many gene variants are involved in the susceptibility to schizophrenia and some of them are expected to be associated with other human characters. Recently reported meta-analysis of genetic associations revealed nucleotide variants in synaptic vesicular transport/Golgi apparatus genes with schizophrenia. In this study, we selected the dymeclin gene (DYM) as a candidate gene for schizophrenia. The DYM gene encodes dymeclin that has been identified to be associated with the Golgi apparatus and with transitional vesicles of the reticulum-Golgi interface. A three-step case-control study of total of 2105 Japanese cases of schizophrenia and 2087 Japanese control subjects was carried out for tag single-nucleotide polymorphisms (SNPs) in the DYM gene and an association between an SNP, rs833497, and schizophrenia was identified (allelic P=2 × 10(-5), in the total sample). DYM is the causal gene for Dyggve-Melchior-Clausen syndrome and this study shows the second neuropsychiatric disorder in which the DYM gene is involved. The present data support the involvement of Golgi function and vesicular transport in the presynapse in schizophrenia.
Assuntos
Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Proteínas/genética , Esquizofrenia/genética , Adulto , Encéfalo/metabolismo , Estudos de Casos e Controles , Feminino , Estudo de Associação Genômica Ampla , Complexo de Golgi/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Japão , Masculino , Pessoa de Meia-Idade , Modelos GenéticosRESUMO
Previously, we found that a Japanese diet was associated with psychological status, and a combination of rice and miso was related to mental and physical health. We hypothesized that the intake of a rice-based diet affected mental and physical health and aimed to investigate the consequences of a dietary intervention with rice. We conducted a randomized, open-label, parallel-group clinical trial that included 60 participants, who were randomly assigned to receive either rice-based meals or meals with other cereals for three daily meals over 2 months. The participants were surveyed for psychological status and biochemical changes. Sleep quality index scores showed significant improvement after the rice-based intervention. Additionally, blood oxidative stress levels were reduced in the rice-diet group compared with the no-rice-diet group. Although the molecular mechanisms should be investigated in detail, our findings suggest that controlling oxidative stress through the intake of a rice-centered diet may be key to improving sleep quality.
Assuntos
Dieta , Oryza , Estresse Oxidativo , Sono/fisiologia , Pressão Sanguínea , Índice de Massa Corporal , Temperatura Corporal , Peso Corporal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos e Questionários , Triglicerídeos/sangue , Circunferência da CinturaRESUMO
The dopamine and glutamate hypotheses reflect only some of the pathophysiological changes associated with schizophrenia. We have proposed a new "comprehensive progressive pathophysiology model" based on the "dopamine to glutamate hypothesis." Repeated administration of methamphetamine (METH) at a dose of 2.5â¯mg/kg in rats has been used to assess dynamic changes in the pathophysiology of schizophrenia. Previous use of this model suggested N-methyl-d-aspartate receptor (NMDA-R) dysfunction, but the mechanism could only be inferred from limited, indirect observations. In the present study, we used this model to investigate changes in the expression of NMDA-R subunits. Repeated administration of METH significantly decreased the gene expression levels of glutamate ionotropic receptor NMDA type subunit (Grin) subtypes Grin1 and Grin2c in the prefrontal cortex (PFC), Grin1 and Grin2a in the hippocampus (HPC), and Grin1, Grin2b, and Grin2d in the striatum (ST).We observed a significant difference in Grin1 expression between the PFC and ST. Furthermore, repeated administration of METH significantly decreased the protein expression of GluN1 in both cytosolic and synaptosomal fractions isolated from the PFC, and significantly decreased the protein expression of GluN1 in the cytosolic fraction, but not the synaptosomal fraction from the ST. These regional differences may be due to variations in the synthesis of GluN1 or intracellular trafficking events in each area of the brain. Considering that knockdown of Grin1 in mice affects vulnerability to develop schizophrenia, these results suggest that this model reflects some of the pathophysiological changes of schizophrenia, combining both the dopamine and glutamate hypotheses.