Japanese public health nurses classified based on empathy and secondary traumatic stress: variable-centered and person-centered approaches.

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.

Identifying factors related to stigma toward psychiatric illness and mental health services and attitudes of help-seeking among Japan Ground Self-Defense Force members.

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.

Risk and resilience in trajectories of post-traumatic stress symptoms among first responders after the 2011 Great East Japan Earthquake: 7-year prospective cohort study.

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.

Plasma fatty acid-binding protein 7 concentration correlates with depression/anxiety, cognition, and positive symptom in patients with schizophrenia.

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.

Validity and reliability of the Secondary Traumatic Stress Scale-Japanese version.

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.

Neural extracellular vesicle-derived miR-17 in blood as a potential biomarker of subthreshold depression.

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.

Impact of a Rice-Centered Diet on the Quality of Sleep in Association with Reduced Oxidative Stress: A Randomized, Open, Parallel-Group Clinical Trial.

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.

Assessment of Factors Associated With Long-term Posttraumatic Stress Symptoms Among 56 388 First Responders After the 2011 Great East Japan Earthquake.

Importance: First responders are at risk for developing symptoms of posttraumatic stress disorder (PTSD). Little is known about the risk factors for developing PTSD during a years-long period after complex mass disasters. Objective: To explore the long-term course of PTSD symptoms and to identify risk factors and their relative association with PTSD among first responders dispatched to the 2011 Japanese earthquake, tsunami, and nuclear disaster. Design, Setting, and Participants: This 6-year, large, prospective cohort study was part of a continuous longitudinal study of Japan Ground Self-Defense Force first responders. The data were collected at 1, 6, 12, 24, 36, 48, 60, and 72 months after mission completion from 2011 to 2017. Of approximately 70 000 eligible participants, 56 388 were enrolled in this study. Data were analyzed from 2017 to 2020. Exposures: Stress exposures owing to personal or professional disaster experience (eg, duties with body recovery or radiation exposure risk) and working conditions (eg, deployment length, postdeployment overtime work). Main Outcomes and Measures: The Impact of Event Scale-Revised score assessed PTSD symptoms; scores of at least 25 were defined as probable PTSD. Cox proportional hazards regression models assessed the risk factors for incidence of probable PTSD. Results: Among the 56 388 participants, 97.1% were men, and the median age at enrollment was 34 (range, 18-63) years. A probable PTSD rate was 2.7% at 1 month and showed a downward trend in the first year and a subsequent plateau. The cumulative incidence of probable PTSD was 6.75%. The severity of PTSD symptoms demonstrated a high degree of rank-order stability over time. Rather than professional disaster experience, sociodemographic factors and working conditions were independently associated with the incidence of probable PTSD: personal experience of the disaster (hazard ratio [HR], 1.96; 95% CI, 1.72-2.24), deployment length of at least 3 months (HR vs <1 month, 1.75; 95% CI, 1.52-2.02), increased age (HR for ≥46 vs ≤25 years, 2.28; 95% CI, 1.79-2.92), and postdeployment overtime work of at least 3 months (HR vs little to none, 1.61; 95% CI, 1.39-1.87). Conclusions and Relevance: Given these findings, in the future, first responders' PTSD symptoms might be mitigated by shortening deployment length, avoiding postdeployment overtime work, and paying special attention to the needs of personnel with personal experience of the disaster or older age. Efforts to alleviate responders' initial symptoms will be required.

Psychological and physical condition of Japan maritime self-defense force personnel who performed disaster-relief missions after the 2011 great east Japan earthquake.

The Great East Japan Earthquake, which occurred on March 11, 2011, was the most powerful earthquake ever recorded in Japan. In the present study, we examine personnel from the Japan Maritime Self-Defense Force who performed disaster relief in the earthquake's aftermath, focusing on the associated psychological and physical impacts. Overall, 8733 personnel were examined. In both July-August 2011 (M1) and July 2012 (M2), these personnel answered the Impact of Events Scale-Revised, the Kessler Psychological Distress Scale, and the Disaster Relief Questionnaire. We also analyzed the sample's physical examination records for the periods before and after the earthquake, using as controls a sample of peers who were not dispatched to the disaster area (N = 32,270). The psychological examinations showed that, in M1, holding the rank of private/sergeant (odds ratio [OR] = 2.13), performing body-recovery duties (OR = 1.94), and having disaster-affected family members (OR = 2.13) were significant risk factors for high post-traumatic stress response (PTSR). In M2, performing body-recovery duties (OR = 1.45) and having disaster-affected family members (OR = 2.60) were significant risk factors for high PTSR. Also, being woman (OR = 2.18) and having disaster-affected family members (OR = 1.68) were significant risk factors for high general psychological distress. For the physical examinations, the mean alanine transaminase in the dispatched group (31.73 ± 25.21) was significantly higher than that in the non-dispatched group (29.56 ± 21.03). These findings suggest that personnel involved in disaster relief experience psychological impacts in the subacute stage, but that these impacts attenuate one year after the event.

Effect of interaction between a specific subtype of child abuse and the FKBP5 rs1360780 SNP on DNA methylation among patients with bipolar disorder.

BACKGROUND: Child abuse is a risk factor for mood disorders, and linked to decreased DNA methylation (DNAm) of FKBP5 intron 7 through interactions with the single nucleotide polymorphism (SNP) rs1360780. However, no study has investigated which specific subtypes of child abuse are related to decreased DNAm of FKBP5 intron 7 in mood disorders. We therefore aimed to examine the relationship among various subtypes of child abuse, rs1360780, and the DNAm level of FKBP5 intron 7. METHODS: A total of 190 subjects (87 patients with major depressive disorder [MDD], 61 patients with bipolar disorder [BD], and 42 healthy controls) participated. The Child Abuse and Trauma Scale (CATS) was used to evaluate child abuse. Whole blood was processed for genotyping, and pyrosequencing was conducted to assess the DNAm level of FKBP5 intron 7. A multiple regression analysis was used to analyze the DNAm level as a dependent variable, and the CATS subtypes and rs1360780 were used as independent variables. RESULTS: Emotional abuse/neglect, one of the specific subtypes of child abuse, was related to lower DNAm of FKBP5 intron 7 interacting with rs1360780 in the BD patients. There were no significant results in the MDD patients or the controls. LIMITATIONS: Since the study was limited to Japanese individuals, particularly those with MDD and BD, the findings are not generalizable. Furthermore, as child abuse was measured retrospectively, there may be recall bias. CONCLUSIONS: This finding indicates that a specific subtype of child abuse may play an important role in the development of BD.

Changes in subunit composition of NMDA receptors in animal models of schizophrenia by repeated administration of methamphetamine.

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 2.5 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.

Investigation of the impact of preconditioning with lipopolysaccharide on inflammation-induced gene expression in the brain and depression-like behavior in male mice.

Although several recent studies have suggested that neuroinflammation plays a role in depression, both medication and neuroinflammatory preventive strategies have been poorly investigated. Recent studies have indicated that preconditioning with lipopolysaccharide (LPS) reduces the damage that occurs following ischemic stroke and brain trauma. However, to date, the effects of LPS preconditioning on psychiatric symptoms have not been reported. Thus, we assessed gene expression and behavioral changes affected by preconditioning with low-dose (LD) LPS in male mice with systemic inflammation induced by administration of high-dose (HD) LPS. mRNA expression analyses of cytokine-, glial-, and oxidative stress-associated genes revealed that majority of these genes responded to HD LPS. Differential gene expression in the presence and absence of LD LPS preconditioning, identified a subset of genes that may contribute to the mechanism of LPS preconditioning in the brain. Notably, LPS preconditioning attenuated an increase in expression of the astrocyte marker Gfap caused by systemic inflammation, suggesting that astrocytes have a key role in endotoxin tolerance in the brain induced by LPS preconditioning. As increased astrocyte in the brain of patients with depression is suggested to contribute to the pathophysiology of major depression, LPS preconditioning might be applicable to the prevention and treatment of depression. Unfortunately, in this study, LPS preconditioning did not show a reversal effect on behavior decline due to high-dose LPS-induced systemic inflammation. Alternative aspects of behavioral changes should be assessed to identify behavioral components that are affected by LPS preconditioning. Nonetheless, the findings in the present study indicate the possibility of the mechanism of endotoxin tolerance induction in the brain via astrocyte regulation by LPS preconditioning. Since there has been reported pharmacological significance of astrocytes in psychiatric disorders, regulation of endotoxin tolerance might be a key method to control psychiatric symptoms.

Effects of Palmaria palmata on lipid metabolism and glycemic control in participants with hypercholesterolemia in a randomized double-blind placebo-controlled trial.

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.

The effects of eicosapentaenoic acid dietary supplementation on behavioral parameters and expression of hippocampal brain-derived neurotrophic factor in an animal model of post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a trauma- and stressor-related disorder, characterized by bi-directional symptomatic manifestations of increase in both hyperarousal/hypervigilance and numbing/avoidance. In our previous reports, we have proposed an animal model of PTSD using avoidance/escape task sessions in the shuttle box after delivering an inescapable foot-shock traumatization in the same box (Wakizono et al., 2007), and demonstrated the efficacy of 2-week administration of antidepressant on the hyperarousal/hypervigilant behavioral parameters (Sawamura et al., 2004) in the model. In this study, we observed a partial but significant efficacy of oral supplementation of eicosapentaenoic acid (EPA) for five weeks on the numbing/avoidance behavior in the experimental model. Additionally, western blot analyses using brain-derived neurotrophic factor (BDNF) monoclonal antibody revealed a decreased expression of BDNF protein, in the hippocampal region of the rats, due to foot-shock traumatization and a significantly increased expression of BDNF protein after oral EPA supplementation. The results indicate a possibility that alteration of the numbing/avoidance behavior parallels the expression of hippocampal BDNF in the rat brain. The present study suggests a possibility that EPA supplementation in the treatment of PTSD ameliorates persistent numbing/avoidance symptoms. (185 words).

Caffeic acid reduces oxidative stress and microglial activation in the mouse hippocampus.

A number of studies have indicated the benefits of coffee consumption on physical and mental health; however, scientific evidence on these effects, in particular of the benefits to brain function, has not been determined. In the present study, we aimed to determine the benefits of caffeic acid in the nervous system. For this purpose, we administered doses of 0 or 300 mg/kg for 30 days to mice that were not otherwise affected. We analyzed survival of newly born cells, oxidative stress, inflammatory marker expression, and microglial activation in the hippocampus. We found that caffeic acid had no effect on the expression levels of neurotrophic factors and inflammatory or anti-inflammatory cytokines. However, caffeic acid-treated mice exhibited significantly lower levels of 4-hydroxynonenal, an oxidative stress marker, in the hippocampus, as well as significantly fewer activated microglia. Abnormally high oxidative stress, as well as activated microglia accumulation are both considered to relate to the pathophysiology of neurological and psychiatric disorders. The present study demonstrates the physiological effects of caffeic acid and may explain the suggested benefits of coffee consumption on brain health.

Relationship between the subtypes of child abuse and affective temperaments: Comparison of depression and bipolar disorder patients and healthy controls using the reclassified Child Abuse and Trauma Scale.

BACKGROUND: We previously reported that child abuse indirectly predicts the diagnosis of major depressive disorder (MDD) or bipolar disorder (BP) based on higher scores of affective temperaments; however, the subtypes of child abuse have not been examined sufficiently. Therefore, in the present study, we used the reclassified version of the Child Abuse and Trauma Scale (CATS) to determine how the subtypes of child abuse affect affective temperaments. METHODS: A total of 502 participants (212 healthy controls, 163 patients with MDD and 127 patients with BP) were administered the Japanese version of the CATS; the Japanese version of the Temperament Evaluation of Memphis, Pisa, Paris, and San Diego Autoquestionnaire; and the Japanese version of the Patient Health Questionnaire-9. Data were analyzed by exploratory and confirmatory factor analyses, as well as by univariate and multivariate analyses. RESULTS: A five-factor structure was appropriate for the CATS. The MDD group scored significantly higher on all subtypes of the reclassified CATS than did the control group. Among the subscales of the reclassified CATS, physical abuse and loneliness/psychological stress were significant predictors of affective temperaments, although all subscales were significantly associated with affective temperaments compared to the original CATS. LIMITATIONS: Since child abuse was assessed retrospectively, there might be recall bias. Furthermore, as the study was limited to Japanese individuals, particularly those with mood disorders, the findings might not be generalizable. CONCLUSIONS: This study revealed that the subtypes of child abuse (especially physical abuse and loneliness/psychological stress) might be associated with MDD and BP.

The reduced bactericidal activity of neutrophils as an incisive indicator of water-immersion restraint stress and impaired exercise performance in mice.

The incisive evaluation of psychological stress may be required to determine the exercise performance of stressed hosts. We investigated objective markers of psychological stress that reflect exercise performance, focusing on the neutrophil function. We used murine water-immersion restraint (WIR) stress for our assessments. After receiving WIR for 1 or 2 h, mice were exercised on an airtight treadmill that monitors their respiratory exchange ratio. The neutrophil function was analyzed after WIR stress. Although the control mice (without WIR) showed good combustion of both carbohydrates and lipids as energy sources during treadmill exercise, mice that underwent 2-h WIR did not combust carbohydrates or lipids effectively, drastically reducing their performance. In contrast, the 1-h WIR mice showed carbohydrate combustion (albeit a slow response) but did not use lipids for energy, thereby running longer than the 2-h WIR mice but shorter than the control mice. The bactericidal activity of neutrophils, but not their superoxide production or microsphere-phagocytic activity, was significantly reduced by 1-h WIR and further reduced by 2-h WIR, indicating a significant association between WIR stress and exercise performance. The neutrophil bactericidal activity may be a good indicator of psychological stress and a useful tool for precisely assessing exercise performance.

Effect of bifidobacterium breve A-1 on anxiety and depressive symptoms in schizophrenia: A proof-of-concept study.

BACKGROUND: Studies of probiotics have suggested they have a positive effect on anxiety and depressive symptoms in humans. This study investigated the effect of consuming the probiotic Bifidobacterium breve A-1 on anxiety and depressive symptoms in patients with schizophrenia and explored its effect on immune products such as cytokines and chemokines. METHODS: In this open-label single-arm study, all participants received B. breve strain A-1 (1011 cfu/day) for 4 weeks followed by 4 weeks of observation. The primary outcome was the Hospital Anxiety and Depression Scale (HADS) score. Secondary outcomes were anxiety and depressive symptoms on the Positive and Negative Syndrome Scale (PANSS), blood test findings, and fecal microbiome composition. RESULTS: Twenty-nine outpatients completed the study. HADS total score and PANSS anxiety/depression score were significantly improved at 4 weeks. Based on the criterion of a greater than 25% reduction in HADS total score at 4 weeks from baseline, there were 12 responders and 17 non-responders. Responders were found to have fewer negative symptoms, reduced intake of dairy products, and higher relative abundance of Parabacteroides in the gut microbiome than non-responders. Moreover, IL-22 and TRANCE expression was significantly increased at 4 weeks from baseline in responders but not in non-responders. LIMITATIONS: This open-label, single-arm study cannot exclude a placebo effect. CONCLUSIONS: The results suggest the potential effect of B. breve A-1 in improving anxiety and depressive symptoms in patients with schizophrenia. Further studies should investigate this effect in patients with other psychiatric conditions and assess dietary habits and the gut microbiome.

Sulforaphane Augments Glutathione and Influences Brain Metabolites in Human Subjects: A Clinical Pilot Study.

Schizophrenia and other neuropsychiatric disorders await mechanism-associated interventions. Excess oxidative stress is increasingly appreciated to participate in the pathophysiology of brain disorders, and decreases in the major antioxidant, glutathione (GSH), have been reported in multiple studies. Technical cautions regarding the estimation of oxidative stress-related changes in the brain via imaging techniques have led investigators to explore peripheral GSH as a possible pathological signature of oxidative stress-associated brain changes. In a preclinical model of GSH deficiency, we found a correlation between whole brain and peripheral GSH levels. We found that the naturally occurring isothiocyanate sulforaphane increased blood GSH levels in healthy human subjects following 7 days of daily oral administration. In parallel, we explored the potential influence of sulforaphane on brain GSH levels in the anterior cingulate cortex, hippocampus, and thalamus via 7-T magnetic resonance spectroscopy. A significant positive correlation between blood and thalamic GSH post- and pre-sulforaphane treatment ratios was observed, in addition to a consistent increase in brain GSH levels in response to treatment. This clinical pilot study suggests the value of exploring relationships between peripheral GSH and clinical/neuropsychological measures, as well as the influences sulforaphane has on functional measures that are altered in neuropsychiatric disorders.

Differential effects of voluntary wheel running and toy rotation on the mRNA expression of neurotrophic factors and FKBP5 in a post-traumatic stress disorder rat model with the shuttle-box task.

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.