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Abstract Aim The etiology of bipolar disorder (BD) remains unknown; however, lipid abnormalities in BD have received increasing attention in recent years. In this study, we examined the expression levels of enzyme proteins associated with the metabolic pathway of phosphoinositides (PIs) and their downstream effectors, protein kinase B (Akt1) and glycogen synthase kinase 3β (GSK3β), which have been assumed to be the targets of mood stabilizers such as lithium, in the postmortem brains of patients with BD. Methods The protein expression levels of phosphatidylinositol 4‐phosphate 5‐kinase type‐1 gamma (PIP5K1C), phosphatidylinositol 4‐kinase alpha (PIK4CA), phosphatase and tensin homolog deleted from chromosome 10 (PTEN), Akt1, and GSK3β were measured using enzyme‐linked immunosorbent assays and multiplex fluorescent bead‐based immunoassays in the prefrontal cortex (PFC). Specifically, PTEN, Akt1, GSK3β, and PIP5K1C were measured in seven BD patients and 48 controls. Additionally, PIK4CA was analyzed in 10 cases and 34 controls. Results PTEN expression levels were markedly decreased in the PFCs of patients with BD, whereas those of Akt and GSK3β were prominently elevated. Moreover, patients medicated with lithium exhibited higher Akt1 expression levels and lower PTEN expression levels in comparison with the untreated group. Conclusion Our results suggest that the expression levels of Akt1/GSK3β and its upstream regulator PTEN are considerably altered.

Abstract Aim This study aimed to clarify the abnormalities in dopamine transporter (DAT) availability in drug‐naive adult patients with attention‐deficit/hyperactivity disorder (ADHD) and the relationship between ADHD symptoms and abnormalities in DAT availability. Methods Single‐photon emission tomography (SPECT) was performed using iodine‐123‐β‐carbomethoxy‐3β‐(4‐iodophenyltropane) (I‐123 β CIT) as a tracer to measure in vivo DAT availability in 20 drug‐naive patients with ADHD [mean age ± standard deviation (SD)]: 25 ± 3.44 years; male:female = 11:9] and 20 age‐ and sex‐matched healthy controls (HCs) (mean age ± SD: 23.9 ± 2.27 years). Comparisons of DAT availability between HCs and adult patients with ADHD and the association between symptom severity and DAT availability within the ADHD group were analyzed using Statistical Parametric Mapping 12. Results Drug‐naive adults with ADHD showed significantly reduced DAT availability in the bilateral nucleus accumbens compared with HCs. Correlation analyses revealed a negative correlation between the severity of inattentive symptoms in adult patients with ADHD and DAT availability in the bilateral heads of the caudate nucleus, indicating the association between severe inattentive symptoms and lower DAT availability in the caudate nucleus. Conclusion In drug‐naive adult patients with ADHD, DAT availability was reduced in the nucleus accumbens, an important part of the reward system. This finding indicates the importance of the DAT in the reward system in the pathogenesis of ADHD. Inattentiveness was associated with DAT availability in the caudate nucleus, suggesting involvement of the cortico‐striato‐thalamo‐cortical circuit.

BackgroundDopamine transporter single-photon emission computed tomography (DAT-SPECT) is a crucial tool for evaluating patients with Parkinson’s disease (PD). However, its implication is limited by inter-site variability in large multisite clinical trials. To overcome the limitation, a conventional prospective correction method employs linear regression with phantom scanning, which is effective yet available only in a prospective manner. An alternative, although relatively underexplored, involves retrospective modeling using a statistical method known as “combatting batch effects when combining batches of gene expression microarray data” (ComBat).MethodsWe analyzed DAT-SPECT-specific binding ratios (SBRs) derived from 72 healthy older adults and 81 patients with PD registered in four clinical sites. We applied both the prospective correction and the retrospective ComBat correction to the original SBRs. Next, we compared the performance of the original and two corrected SBRs to differentiate the PD patients from the healthy controls. Diagnostic accuracy was assessed using the area under the receiver operating characteristic curve (AUC-ROC).ResultsThe original SBRs were 6.13 ± 1.54 (mean ± standard deviation) and 2.03 ± 1.41 in the control and PD groups, respectively. After the prospective correction, the mean SBRs were 6.52 ± 1.06 and 2.40 ± 0.99 in the control and PD groups, respectively. After the retrospective ComBat correction, the SBRs were 5.25 ± 0.89 and 2.01 ± 0.73 in the control and PD groups, respectively, resulting in substantial changes in mean values with fewer variances. The original SBRs demonstrated fair performance in differentiating PD from controls (Hedges’s g = 2.76; AUC-ROC = 0.936). Both correction methods improved discrimination performance. The ComBat-corrected SBR demonstrated comparable performance (g = 3.99 and AUC-ROC = 0.987) to the prospectively corrected SBR (g = 4.32 and AUC-ROC = 0.992) for discrimination.ConclusionAlthough we confirmed that SBRs fairly discriminated PD from healthy older adults without any correction, the correction methods improved their discrimination performance in a multisite setting. Our results support the utility of harmonization methods with ComBat for consolidating SBR-based diagnosis or stratification of PD in multisite studies. Nonetheless, given the substantial changes in the mean values of ComBat-corrected SBRs, caution is advised when interpreting them.

Abstract Aims Schizophrenia is a chronic relapsing psychiatric disorder that is characterized by many symptoms and has a high heritability. There were studies showing that the phospholipid abnormalities in subjects with schizophrenia (Front Biosci, S3, 2011, 153; Schizophr Bull, 48, 2022, 1125; Sci Rep, 7, 2017, 6; Anal Bioanal Chem, 400, 2011, 1933). Disturbances in prefrontal cortex phospholipid and fatty acid composition have been reported in subjects with schizophrenia (Sci Rep, 7, 2017, 6; Anal Bioanal Chem, 400, 2011, 1933; Schizophr Res, 215, 2020, 493; J Psychiatr Res, 47, 2013, 636; Int J Mol Sci, 22, 2021). For exploring the signaling pathways contributing to the lipid changes in previous study (Sci Rep, 7, 2017, 6), we performed two types of transcriptome analyses in subjects with schizophrenia: an unbiased transcriptome analysis solely based on RNA‐seq data and a correlation analysis between levels of gene expression and lipids. Methods RNA‐Seq analysis was performed in the postmortem prefrontal cortex from 10 subjects with schizophrenia and 5 controls. Correlation analysis between the transcriptome and lipidome from 9 subjects, which are the same samples in the previous lipidomics study (Sci Rep, 7, 2017, 6). Results Extraction of differentially expressed genes (DEGs) and further sequence and functional group analysis revealed changes in gene expression levels in phosphoinositide 3‐kinase (PI3K)‐Akt signaling and the complement system. In addition, a correlation analysis clarified alterations in ether lipid metabolism pathway, which is not found as DEGs in transcriptome analysis alone. Conclusions This study provided results of the integrated analysis of the schizophrenia‐associated transcriptome and lipidome within the PFC and revealed that lipid‐correlated alterations in the transcriptome are enriched in specific pathways including ether lipid metabolism pathway.

Abstract Schizophrenia is a multifactorial disorder, the genetic architecture of which remains unclear. Although many studies have examined the etiology of schizophrenia, the gene sets that contribute to its symptoms have not been fully investigated. In this study, we aimed to identify each gene set associated with corresponding symptoms of schizophrenia using the postmortem brains of 26 patients with schizophrenia and 51 controls. We classified genes expressed in the prefrontal cortex (analyzed by RNA-seq) into several modules by weighted gene co-expression network analysis (WGCNA) and examined the correlation between module expression and clinical characteristics. In addition, we calculated the polygenic risk score (PRS) for schizophrenia from Japanese genome-wide association studies, and investigated the association between the identified gene modules and PRS to evaluate whether genetic background affected gene expression. Finally, we conducted pathway analysis and upstream analysis using Ingenuity Pathway Analysis to clarify the functions and upstream regulators of symptom-related gene modules. As a result, three gene modules generated by WGCNA were significantly correlated with clinical characteristics, and one of these showed a significant association with PRS. Genes belonging to the transcriptional module associated with PRS significantly overlapped with signaling pathways of multiple sclerosis, neuroinflammation, and opioid use, suggesting that these pathways may also be profoundly implicated in schizophrenia. Upstream analysis indicated that genes in the detected module were profoundly regulated by lipopolysaccharides and CREB. This study identified schizophrenia symptom-related gene sets and their upstream regulators, revealing aspects of the pathophysiology of schizophrenia and identifying potential therapeutic targets.

Objective: This study aimed to assess the efficacy and safety of quadripulse transcranial magnetic stimulation-50 (QPS-50) in patients with intractable epilepsy. Methods: Four patients were included in the study. QPS-50, which induces long-term depression in healthy subjects, was administered for 30 min on a weekly basis for 12 weeks. Patients’ clinical symptoms and physiological parameters were evaluated before, during, and after the repeated QPS-50 period. We performed two control experiments: the effect in MEP (Motor evoked potential) size after a single QPS-50 session with a round coil in nine healthy volunteers, and a follow-up study of physiological parameters by repeated QPS-50 sessions in four other healthy participants. Results: Motor threshold (MT) decreased during the repeated QPS-50 sessions in all patients. Epileptic symptoms worsened in two patients, whereas no clinical worsening was observed in the other two patients. In contrast, MT remained unaffected for 12 weeks in all healthy volunteers. Conclusions: QPS-50 may not be effective as a treatment for intractable epilepsy. Significance: In intractable epilepsy patients, administering repeated QPS-50 may paradoxically render the motor cortex more excitable, probably because of abnormal inhibitory control within the epileptic cortex. The possibility of clinical aggravation should be seriously considered when treating intractable epilepsy patients with non-invasive stimulation methods.

BackgroundSchizophrenia (SZ) is a disorder diagnosed by specific symptoms and duration and is highly heterogeneous, clinically and pathologically. Although there are an increasing number of studies on the association between genetic and environmental factors in the development of SZ, the actual distribution of the population with different levels of influence of these factors has not yet been fully elucidated. In this study, we focused on stress as an environmental factor and stratified SZ based on the expression levels of stress-responsive molecules in the postmortem prefrontal cortex.MethodsWe selected the following stress-responsive molecules: interleukin (IL) -1β, IL-6, IL-10, tumor necrosis factor-α, interferon-γ, glucocorticoid receptor, brain-derived neurotrophic factor, synaptophysin, S100 calcium-binding protein B, superoxide dismutase, postsynaptic density protein 95, synuclein, apolipoprotein A1 (ApoA1), ApoA2, and solute carrier family 6 member 4. We performed RNA sequencing in the prefrontal gray matter of 25 SZ cases and 21 healthy controls and conducted a hierarchical cluster analysis of SZ based on the gene expression levels of stress-responsive molecules, which yielded two clusters. After assessing the validity of the clusters, they were designated as the high stress-response SZ group and the low stress-response SZ group, respectively. Ingenuity Pathway Analysis of differentially expressed genes (DEGs) between clusters was performed, and Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining was conducted on four cases each in the high and low stress-response SZ groups to validate DNA damage.ResultsWe found higher prevalence of family history of SZ in the low stress-response SZ group (0/3 vs. 5/4, p = 0.04). Pathway analysis of DEGs between clusters showed the highest enrichment for DNA double-strand break repair. TUNEL staining showed a trend toward a lower percentage of TUNEL-positive cells in the high stress-response SZ group.ConclusionOur results suggest that there are subgroups of SZ with different degrees of stress impact. Furthermore, the pathophysiology of these subgroups may be associated with DNA damage repair. These results provide new insights into the interactions and heterogeneity between genetic and environmental factors.

BackgroundEvaluating and controlling confounders are necessary when investigating molecular pathogenesis using human postmortem brain tissue. Particularly, tissue pH and RNA integrity number (RIN) are valuable indicators for controlling confounders. However, the influences of these indicators on the expression of each gene in postmortem brain have not been fully investigated. Therefore, we aimed to assess these effects on gene expressions of human brain samples.MethodsWe isolated total RNA from occipital lobes of 13 patients with schizophrenia and measured the RIN and tissue pH. Gene expression was analyzed and gene sets affected by tissue pH and RIN were identified. Moreover, we examined the functions of these genes by enrichment analysis and upstream regulator analysis.ResultsWe identified 2,043 genes (24.7%) whose expressions were highly correlated with pH; 3,004 genes (36.3%) whose expressions were highly correlated with RIN; and 1,293 genes (15.6%) whose expressions were highly correlated with both pH and RIN. Genes commonly affected by tissue pH and RIN were highly associated with energy production and the immune system. In addition, genes uniquely affected by tissue pH were highly associated with the cell cycle, whereas those uniquely affected by RIN were highly associated with RNA processing.ConclusionThe current study elucidated the influence of pH and RIN on gene expression profiling and identified gene sets whose expressions were affected by tissue pH or RIN. These findings would be helpful in the control of confounders for future postmortem brain studies.

Abstract The present study aimed to clarify the characteristics of young evacuees who had missed the Comprehensive Health Check of the Fukushima Health Management Survey (FHMS) after the Great East Japan Earthquake in 2011. The FHMS has been conducted as a prospective cohort study to evaluate the health status of evacuees annually after the great earthquake in 2011. This study focused on the annual participation rate in the Comprehensive Health Check of evacuees aged between 20 and 37 years in 2011 who evacuated due to the Fukushima Daiichi Nuclear Power Plant accident. The characteristics of subjects who did not participate after the second survey year were identified with a multivariate logistic regression model. The participation rate was estimated at 26.6% (9720 among 36,502 residents) and 15.6% (5691 residents) in 2011 and 2012, respectively. The logistic regression model revealed the following characteristics at baseline as independent predictors of non-participation after the second year of the survey: age ≤ 24 years (adjusted odds ratio 2.11, 95% CI 1.84–2.42), 25–29 years of age (1.28, 1.13–1.45), men (1.52, 1.38–1.69), evacuation outside the municipality but within Fukushima prefecture (1.54, 1.40–1.70), evacuation outside the Fukushima prefecture (1.40, 1.21–1.63), anemia (1.23, 1.06–1.43), smoking habit (1.34, 1.21–1.48), and drinking habit (1.20, 1.09–1.32). A medical history of heart disease showed opposite odds ratios, which indicate the association with continuous participation (0.43, 0.26–0.72, respectively). We observed deteriorated participation in the prospective study of the Comprehensive Health Check of the FHMS among evacuees of a younger age group, men, those evacuated outside their municipalities, and those with history of anemia, smoking and drinking habits. Hence, the cohort study may have missed certain population groups with worse health behaviors. Thus, it is necessary to consider various measures to increase the participation rate in the disaster cohort study to understand the long-term health effects of disasters on younger residents in evacuation zones.

Abstract This study aimed to evaluate the sequential changes in the proportion of anemia among young women over eight years after the Great East Japan Earthquake in 2011 using a prospective study of the Fukushima Health Management Survey. This study focused on the women aged between 20 and 44 who lived in the evacuation area of the nuclear power plant accident. The yearly age-adjusted proportion of anemia was accessed with data between July 2011 and March 2019. A total of 9,198 women participated in the health checkup in 2011, albeit the participation was decreased to 1,241 in 2018. The age-adjusted proportion of anemia was 16.7% in 2012 and then declined after 2013 (p with Cochran-Armitage trend test = 0.03). The multivariate regression analysis identified

Abstract Although the prevalence of cognitive impairment and depression is higher in patients with atrial fibrillation (AF) than in the general population, the mechanism has not been fully examined and impact of catheter ablation (CA) of AF also remains unclear. Recently, the development of near-infrared spectroscopy (NIRS) has enabled noninvasive measurements of regional cerebral blood volume and brain activity, in terms of cerebral oxyhemoglobin in the cerebral cortex. We assessed brain activities by NIRS, depressive symptoms by the Center for Epidemiologic Studies Depression Scale (CES-D) and cognitive function by Mini-Mental State Examination (MMSE). We then compared the results between AF patients (paroxysmal AF n = 18 and persistent AF n = 14) and control subjects (n = 29). Next, we also followed up persistent AF patients who kept sinus rhythm at 3 months after CA (n = 8) and measured their brain activities using NIRS, CES-D and MMSE after CA to investigate the associations of changes in brain activities with changes in both CES-D and MMSE. Our results showed that (1) frontal and temporal brain activities were lower in patients with persistent AF than both in control subjects and paroxysmal AF patients (P

IntroductionAttention-deficit/hyperactivity disorder (ADHD) is a neuropsychiatric disorder whose primary symptoms are hyperactivity, impulsivity, and inattention. Historically, ADHD was recognized as a disease of childhood and adolescence. However, many patients are known to have persistent symptoms into adulthood. Many researchers consider the neuropathology of ADHD to be based on abnormalities in multiple parallel and intersecting pathways rather than a single anatomical area, but such alterations remain to be clarified.MethodsUsing diffusion tensor imaging, we investigated differences in the global network metrics estimated by graph theory and the degree of connectivity between adjacent voxels within a white matter (WM) fascicle defined by the density of the diffusing spins (connectometry) between 19 drug-naive Japanese patients with adult ADHD and 19 matched healthy controls (HCs). In adult patients with ADHD, we examined the relationships between the symptomatology of ADHD and global network metrics and WM abnormalities.ResultsCompared with HCs, adult patients with ADHD showed a reduced rich-club coefficient and decreased connectivity in widely distributed WMs such as the corpus callosum, the forceps, and the cingulum bundle. Correlational analyses demonstrated that the general severity of ADHD symptoms was associated with several global network metrics, such as lower global efficiency, clustering coefficient, small worldness, and longer characteristic path length. The connectometry revealed that the severity of hyperactive/impulsive symptoms was associated with overconnectivity in the corticostriatal, corticospinal, and corticopontine tracts, the inferior fronto-occipital fasciculus, and the extreme capsule but dysconnectivity in the cerebellum. The severity of inattentive symptoms was associated with dysconnectivity in the intracerebellar circuit and some other fibers.ConclusionThe results of the present study indicated that patients with treatment-naive adult ADHD showed disrupted structural connectivity, which contributes to less efficient information transfer in the ADHD brain and pathophysiology of ADHD.Trial registrationUMIN Clinical Trials Registry (UMIN-CTR) UMIN000025183, Registered: 5 January 2017.

IntroductionOn March 11, 2011, the Great East Japan Earthquake occurred in Japan, with a nuclear accident subsequently occurring at the Fukushima Daiichi Nuclear Power Plant. The disaster forced many evacuees to change particular aspects of their lifestyles. However, the effect of evacuation on the new-onset of hyperuricemia have not been sufficiently elucidated. This study assessed the association between evacuation and new-onset hyperuricemia after the earthquake based on the Fukushima Health Management Survey from a lifestyle and socio-psychological perspective.Materials and methodsThis is a 7-year prospective longitudinal study included 18,140 residents (6,961 men and 11,179 women) with non-hyperuricemia who underwent both the Comprehensive Health Check and the Mental Health and Lifestyle Survey in fiscal year 2011. Associations between new-onset hyperuricemia and lifestyle- and disaster-related factors, including evacuation, were estimated using a Cox proportional hazards regression model analysis. Hyperuricemia was defined as uric acid levels > 7.0 mg/dL for men and > 6.0 mg/dL for women.ResultsDuring a median follow-up of 4.3 years, 2,996 participants (1,608 men, 23.1%, 1,388 women, 12.4%) newly developed hyperuricemia. Significant associations were observed between evacuation and onset of hyperuricemia in women (adjusted hazard ratio 1.18, 95% confidence interval, 1.05-1.32, p = 0.007), but not in men (adjusted hazard ratio 1.11, 95% confidence interval, 0.99-1.24, p = 0.067).DiscussionEvacuation after a natural disaster is an independent risk factor for the new-onset of hyperuricemia in women. The possibility of hyperuricemia developing in response to natural disasters should be considered.

Abstract Aim Clozapine is currently the only effective drug for treatment‐resistant schizophrenia; nonetheless, its pharmacological mechanism remains unclear, and its administration is limited because of severe adverse effects. By comparing the binding proteins of clozapine and its derivative olanzapine, which is safer but less effective than clozapine, we attempted to clarify the mechanism of action specific to clozapine. Methods First, using the polyproline rod conjugates attached with clozapine or olanzapine, clozapine‐binding proteins in extracts from the cerebra of 7‐week‐old ICR mice were isolated and separated by sodium dodecyl sulfate‐polyacrylamide gel electrophoresis (SDS‐PAGE) and analyzed by liquid chromatography‐tandem mass spectrometry (LC‐MS/MS) to identify proteins. Second, the effect of clozapine on tubulin polymerization was determined turbidimetrically. Finally, the cellular effects of clozapine were observed in HeLa cells by immunofluorescence microscopy. Results Alpha and β tubulins were the most abundant clozapine‐binding proteins. We also found that clozapine directly binds with α and β tubulin heterodimers to inhibit their polymerization to form microtubules and disturbs the microtubule network, causing mitotic arrest in HeLa cells. Conclusion These results suggest that α and β tubulin heterodimers are targeted by the clozapine and the microtubules are involved in the etiology of schizophrenia.

Background: The relationship between radiation levels and mental health status after a nuclear disaster is unknown. We examined the association between individual external radiation doses and psychological distress or post-traumatic stress after the Fukushima Daiichi nuclear power plant accident in March 2011 in Japan. Methods: The Mental Health and Lifestyle Survey was conducted from January 2012. Based on the estimated external radiation doses for the first 4 months, a total of 64,184 subjects were classified into

A Mental Health and Lifestyle Survey (MHLS) has been conducted yearly as part of the Fukushima Health Management Survey since 2012, in order to monitor different health issues related to long-term evacuation of affected people after the 2011 Fukushima disaster. This survey is a mail-based one of nearly 210,000 affected people living in the evacuation zone at the time of the disaster. Another purpose of the MHLS is to provide efficient interventions by telephone based on the results of the survey. Significant findings contributing to understanding of non-radiological health effects caused by long-term evacuation were obtained from the MHLS, directly connecting to telephone-based interventions for over 3,000 respondents per year. In this article, the mental health outcomes of the MHLS, including depressive symptoms and posttraumatic responses, are reviewed, and the usefulness of telephone-based interventions is discussed. The evidence showed that, despite improvement of core mental health outcomes, the prevalence of respondents at high risk of some psychiatric problems remained high compared to that among the general population in Japan. In particular, several mental health consequences of respondents staying outside of Fukushima Prefecture were higher than those staying inside Fukushima. Along with further efforts to increase the response rate, we need to continue and modify the MHLS to meet the requirements of the affected people and communities.

BackgroundThe burden of psychological distress and post-traumatic stress disorder (PTSD) has been suggested as a factor in developing type 2 diabetes mellitus. However, longitudinal features in psychological distress- and PTSD-related new-onset diabetes mellitus have not been thoroughly evaluated.MethodsThe association between probable depression and probable PTSD and the risk of developing new-onset diabetes mellitus was evaluated in a 7-year prospective cohort of evacuees of the Great East Japan Earthquake in 2011. Probable depression was defined as a Kessler 6 scale (K6) ≥ 13 and probable PTSD as a PTSD Checklist—Stressor-Specific Version (PCL-S) ≥ 44.ResultsThe log-rank test for the Kaplan–Meier curve for new-onset diabetes mellitus was significant between K6 ≥ 13 vs. < 13 and PCL-S ≥ 44 vs. < 44 in men but not in women. In men, both K6 ≥ 13 and PCL-S ≥ 44 remained significant in the Cox proportional hazards model after multivariate adjustment for established risk factors and disaster-related factors, including evacuation, change in work situation, sleep dissatisfaction, and education.ConclusionThe post-disaster psychological burden of probable depression and probable PTSD was related to new-onset diabetes in men but not in women. In post-disaster circumstances, prevention strategies for new-onset diabetes might consider sex differences in terms of psychological burden.

The risk for people evacuated from Fukushima following the Great East Japan Earthquake of developing cancer from radiation exposure may be lower than that associated with smoking and alcohol drinking. However, the perception of those risks may change risk-related behavior. Therefore, we investigated whether the perceived risk of radiation exposure was associated with the initiation and/or cessation of smoking and of drinking alcohol following the disaster.Participants were 82,197 people aged ≥20 years who completed the Fukushima Health Management Study survey. A multivariable logistic regression model, with adjusted odds ratios (AORs) and 95 % confidence intervals (CIs), was used to calculate the risk of (1) starting smoking (or drinking) among people who did not smoke (or drink) before the earthquake, and (2) quitting smoking (or drinking) among people who smoked (or drank) before the earthquake; the main factor was perceived risk of developing cancer from radiation.The AORs for starting smoking among participants who perceived radiation exposure risks as unlikely, likely, and very likely, compared with very unlikely, were 0.96(0.78–1.18), 1.17(0.95–1.45), and 1.69(1.39–2.06), respectively (Trend p

Abstract The debate regarding the need for hospital evacuation and the evacuation distance remains rather chaotic. Furthermore, the relationship between hospital evacuation and the prognoses of psychiatric inpatients has not yet been investigated. We aimed to reveal the association between the long-term prognosis of psychiatric inpatients evacuated immediately following the Fukushima Daiichi Nuclear Power Plant accident and their backgrounds. In this retrospective cohort study, 777 psychiatric inpatients who were immediately evacuated from their hospitals following the accident were included for analysis. Survival time was the primary outcome. We conducted univariable and multivariable analyses to examine the associations between mortality and linear distance of evacuation and different backgrounds, including psychiatric/physical traits. Univariable analysis showed that the estimated survival time among patients was significantly associated with their evacuation distance. A multivariable analysis showed that a longer evacuation distance had a significantly lower hazard ratio (HR) and resulted in lower mortality. In contrast, older patients with physical complications of respiratory disease (International Statistical Classification of Diseases and Related Health Problems 10th revision, J00–99) and genitourinary disease (N00–99) showed a significantly higher HR and had a higher mortality than patients without these complications. To prevent death among elderly psychiatric inpatients with physical comorbidities during disasters, the evacuation destination should be determined taking into consideration the evacuees’ tolerance for long-distance transportation and the availability of post-evacuation care in the destination hospitals.

Abstract Post-traumatic stress disorder (PTSD) and obesity share common risk factors; however, the effect of obesity on recovery from PTSD has not been assessed. We examined the association between body mass index (BMI) and recovery from PTSD after the Great East Japan Earthquake. We analyzed 4356 men and women with probable PTSD aged ≥ 16 years who were living in evacuation zones owing to the radiation accident in Fukushima, Japan. Recovery from probable PTSD was defined as Post-traumatic Stress Disorder Checklist-specific scores

Abstract Background It has been reported that psychological stress affects bone metabolism and increases the risk of fracture. However, the relationship between bone fractures and post-traumatic stress disorder (PTSD) is unclear. This study aimed to evaluate the effects of disaster-induced PTSD symptoms on fracture risk in older adults. Methods This study evaluated responses from 17,474 individuals aged ≥ 65 years without a history of fractures during the Great East Japan Earthquake who answered the Mental Health and Lifestyle Survey component of the Fukushima Health Management Survey conducted in 2011. The obtained data could determine the presence or absence of fractures until 2016. Age, sex, physical factors, social factors, psychological factors, and lifestyle factors were subsequently analyzed. Survival analysis was then performed to determine the relationship between the fractures and each factor. Thereafter, univariate and multivariate Cox proportional hazard models were constructed to identify fracture risk factors. Results In total, 2,097 (12.0%) fractures were observed throughout the follow-up period. Accordingly, univariate and multivariate Cox proportional hazard models showed that PTSD symptoms (total PTSD checklists scoring ≥ 44) [hazard ratio (HR): 1.26; 95% confidence interval (CI): 1.10–1.44; P = 0.001], history of cancer (HR: 1.49; 95% CI: 1.24–1.79; P

Abstract Background People living in temporary housing for long periods after a disaster are at risk of poor mental health. This study investigated the post-disaster incidence and remission of common mental disorders among adults living in temporary housing for the 3 years following the 2011 Great East Japan Earthquake. Methods Three years after the disaster, face-to-face interviews were conducted with 1089 adult residents living in temporary housing in the disaster area, i.e., the shelter group, and a random sample of 852 community residents from non-disaster areas of East Japan. The World Health Organization Composite International Diagnostic Interview was used to diagnose DSM-IV mood, anxiety, and alcohol use disorders. Information on demographic variables and disaster experiences was also collected. Results Response rates were 49 and 46% for the shelter group and the community residents, respectively. The incidence of mood/anxiety disorder in the shelter group was elevated only in the first year post-disaster compared to that of the general population. The rate of remission for mood and anxiety disorders was significantly lower in the shelter group than in the community residents. The proportion seeking medical treatment was higher in the shelter group. Conclusions The onset of common mental disorders increased in the first year, but then levelled off in the following years among residents in temporary housing after the disaster. Remission from incident post-disaster mental disorders was slower in the shelter group than in the general population. Post-disaster mental health service could consider the greater incidence in the first year and prolonged remission of mental disorders among survivors with a long-term stay in temporary housing after a disaster.

Abstract Background While the prevalence of post-disaster musculoskeletal pain has been documented, its associated disaster-related factors have not been investigated. This study was to investigate the association of lifestyle factors associated with musculoskeletal pain after the Great East Japan Earthquake. Methods We conducted a cross-sectional study of 34,919 participants, aged 40–89 years, without any major disabilities at about 1 year after the disaster. The participants were asked about their musculoskeletal pain (low back and limb pain) and lifestyle factors: use of evacuation shelters or temporary housing at any point of time, job loss after the disaster, decreased income after the disaster, current smoking status, current drinking status, lack of sleep, regular exercise, and participation in recreational or community activities. Furthermore, psychological factors, such as traumatic reactions, psychological distress, and uncomfortable symptoms, affecting musculoskeletal pain were assessed. We used multinomial logistic regression analysis to calculate odds ratios of each lifestyle factor for prevalent and prevalent plus exacerbated musculoskeletal pain. Results Musculoskeletal pain prevalence was 32.8%: 27.6% for prevalent and 5.2% for prevalent plus exacerbated musculoskeletal pain. Multivariable adjusted odds ratios and 95% confidence intervals of lifestyle factors associated with prevalent and prevalent plus exacerbated musculoskeletal pain were as follows: shelter use (prevalent: 1.02, 0.96–1.08; exacerbated: 1.44, 1.29–1.60), job loss (prevalent: 1.03, 0.96–1.10; exacerbated: 1.30, 1.16–1.47), decreased income (prevalent: 1.13, 1.05–1.21; exacerbated: 1.29, 1.14–1.45), current heavy drinking (prevalent: 1.33, 1.21–1.47; exacerbated: 1.38, 1.14–1.68), insomnia (prevalent: 1.22, 1.15–1.29; exacerbated: 1.50, 1.36–1.65), exercising almost daily (prevalent: 0.83, 0.77–0.91; exacerbated: 0.80, 0.68–0.95), and participating in community activities often (prevalent: 0.83, 0.75–0.92; exacerbated: 0.76, 0.61–0.95). Conclusions Prevalent and exacerbated musculoskeletal pain were inversely associated with exercising almost daily and participating in recreational or community activities sometimes or often, and positively associated with decreased income, current heavy drinking, and insomnia. Besides, the use of evacuation shelters or temporary housing/job loss was positively associated only with exacerbated musculoskeletal pain. These results suggest that post-disaster lifestyle factors are potentially associated with musculoskeletal pain. To achieve better post-disaster pain management, further studies are needed to confirm the consistency of these results in other disasters and to highlight the underlying causative mechanisms.

Abstract Aims The brain function that detects deviations in the acoustic environment can be evaluated with mismatch negativity (MMN). MMN to sound duration deviance has recently drawn attention as a biomarker for schizophrenia. Nonhuman animals, including rats, also exhibit MMN‐like potentials. Therefore, MMN research in nonhuman animals can help to clarify the neural mechanisms underlying MMN production. However, results from preclinical MMN studies on duration deviance have been conflicting. We investigated the effect of sound frequency on MMN‐like potentials to duration deviance in rats. Methods Event‐related potentials were recorded from an electrode placed on the primary auditory cortex of free‐moving rats using an oddball paradigm consisting of 50‐ms duration tones (standards) and 150‐ms duration tones (deviants) at a 500‐ms stimulus onset asynchrony. The sound frequency was set to three conditions: 3, 12, and 50 kHz. Results MMN‐like potentials that depended on the short‐term stimulus history of background regularity were only observed in the 12‐kHz tone frequency condition. Conclusions MMN‐like potentials to duration deviance are subject to tone frequency of the oddball paradigm in rats, suggesting that rats have distinct sound duration recognition ability.

Background: Dietary patterns may be linked to the incidence of type 2 diabetes mellitus (T2DM) after disasters. We investigated the association between dietary patterns and new-onset T2DM in evacuees of the Great East Japan Earthquake and the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident. Methods: Among the 22,740 non-diabetic participants aged 20–89 years who completed the dietary assessment in the Fukushima Health Management Survey between July 2011 and November 2012, the incidence of T2DM was evaluated until 2018. Principal component analysis with varimax rotation was applied to derive dietary patterns based on a validated, short-form food frequency questionnaire. The identified dietary patterns were categorized as typical Japanese, juice, and meat. Results: The cumulative incidence of T2DM was 18.0 and 9.8 per 1000 person-years in men and women, respectively, during the follow-up period. The multiple-adjusted hazard ratio (95% confidence interval) of the highest vs. lowest quartile of the typical Japanese pattern scores for T2DM was 0.80 (0.68, 0.94; P for trend = 0.015) in total, 0.85 (0.68, 1.06; P for trend = 0.181) in men, and 0.76 (0.60, 0.95; P for trend = 0.04) in women. Conclusions: A typical Japanese dietary pattern may be associated with a reduced new-onset T2DM risk in evacuees, especially women, after the Great East Japan Earthquake and the FDNPP accident.

Summary: In schizophrenia (SCZ), neurons in the brain tend to undergo gross morphological changes, but the related molecular mechanism remains largely elusive. Using Kif3b+/− mice as a model with SCZ-like behaviors, we found that a high-betaine diet can significantly alleviate schizophrenic traits related to neuronal morphogenesis and behaviors. According to a deficiency in the transport of collapsin response mediator protein 2 (CRMP2) by the KIF3 motor, we identified a significant reduction in lamellipodial dynamics in developing Kif3b+/− neurons as a cause of neurite hyperbranching. Betaine administration significantly decreases CRMP2 carbonylation, which enhances the F-actin bundling needed for proper lamellipodial dynamics and microtubule exclusion and may thus functionally compensate for KIF3 deficiency. Because the KIF3 expression levels tend to be downregulated in the human prefrontal cortex of the postmortem brains of SCZ patients, this mechanism may partly participate in human SCZ pathogenesis, which we hypothesize could be alleviated by betaine administration.

Background: Betaine is known to act against various biological stresses and its levels were reported to be decreased in schizophrenia patients. We aimed to test the role of betaine in schizophrenia pathophysiology, and to evaluate its potential as a novel psychotherapeutic. Methods: Using Chdh (a gene for betaine synthesis)-deficient mice and betaine-supplemented inbred mice, we assessed the role of betaine in psychiatric pathophysiology, and its potential as a novel psychotherapeutic, by leveraging metabolomics, behavioral-, transcriptomics and DNA methylation analyses. Findings: The Chdh-deficient mice revealed remnants of psychiatric behaviors along with schizophrenia-related molecular perturbations in the brain. Betaine supplementation elicited genetic background-dependent improvement in cognitive performance, and suppressed methamphetamine (MAP)-induced behavioral sensitization. Furthermore, betaine rectified the altered antioxidative and proinflammatory responses induced by MAP and in vitro phencyclidine (PCP) treatments. Betaine also showed a prophylactic effect on behavioral abnormality induced by PCP. Notably, betaine levels were decreased in the postmortem brains from schizophrenia, and a coexisting elevated carbonyl stress, a form of oxidative stress, demarcated a subset of schizophrenia with “betaine deficit-oxidative stress pathology”. We revealed the decrease of betaine levels in glyoxylase 1 (GLO1)-deficient hiPSCs, which shows elevated carbonyl stress, and the efficacy of betaine in alleviating it, thus supporting a causal link between betaine and oxidative stress conditions. Furthermore, a CHDH variant, rs35518479, was identified as a cis-expression quantitative trait locus (QTL) for CHDH expression in postmortem brains from schizophrenia, allowing genotype-based stratification of schizophrenia patients for betaine efficacy. Interpretation: The present study revealed the role of betaine in psychiatric pathophysiology and underscores the potential benefit of betaine in a subset of schizophrenia. Fund: This study was supported by the Strategic Research Program for Brain Sciences from AMED (Japan Agency for Medical Research and Development) under Grant Numbers JP18dm0107083 and JP19dm0107083 (TY), JP18dm0107129 (MM), JP18dm0107086 (YK), JP18dm0107107 (HY), JP18dm0107104 (AK) and JP19dm0107119 (KH), by the Grant-in-Aid for Scientific Research on Innovative Areas from the MEXT under Grant Numbers JP18H05435 (TY), JP18H05433 (AH.-T), JP18H05428 (AH.-T and TY), and JP16H06277 (HY), and by JSPS KAKENHI under Grant Number JP17H01574 (TY). In addition, this study was supported by the Collaborative Research Project of Brain Research Institute, Niigata University under Grant Numbers 2018–2809 (YK) and RIKEN Epigenetics Presidential Fund (100214–201801063606-340120) (TY). Keywords: Schizophrenia, Chdh, DNA methylation, Postmortem brain, Carbonyl stress, iPS cell

Recent studies have lent support to the possibility that inflammation is associated with the pathology of schizophrenia. In the study of measurement of inflammatory mediators, which are markers of inflammation, elevated inflammatory cytokine levels in the brain and blood have been reported in patients with schizophrenia. Several postmortem brain studies have also reported changes in the expression of inflammatory cytokines. However, it is not clear how these elevated inflammatory cytokines interact with other inflammatory mediators, and their association with the pathology of schizophrenia. We comprehensively investigated the expression of 30 inflammatory mediators in the superior temporal gyrus (STG) of 24 patients with schizophrenia and 26 controls using a multiplex method. Overall, inflammatory mediator expression in the STG was mostly unchanged. However, the expression of interleukin (IL)1-α and interferon-gamma-inducible protein (IP)-10 was decreased [IL-1α, median (IQR), 0.51 (0.37–0.70) vs. 0.87 (0.47–1.23), p = 0.01; IP-10, 13.99 (8.00–36.64) vs. 30.29 (10.23–134.73), p = 0.05], whereas that of IFN-α was increased [2.34 (1.84–4.48) vs. 1.94 (1.39–2.36), p = 0.04] in schizophrenia, although these alterations did not remain significant after multiple testing. Clustering based on inflammatory mediator expression pattern and analysis of upstream transcription factors using pathway analysis revealed that the suppression of IL-1α and IP-10 protein expression may be induced by regulation of a common upstream pathway. Neuroinflammation is important in understanding the biology of schizophrenia. While neuroimaging has been previously used, direct observation to determine the expression of inflammatory mediators is necessary. In this study, we identified protein changes, previously unreported, using comprehensive protein analysis in STG. These results provide insight into post-inflammatory alternation in chronic schizophrenia.

We aimed to explore the effects of prolonged radiation risk perceptions on mental health after the Fukushima nuclear power plant accident occurred in 2011. We investigated the longitudinal associations of radiation risk perceptions five years after the accident with psychological distress and posttraumatic stress symptoms two years later among non-evacuee community residents of Fukushima prefecture. A two-wave questionnaire survey was administered for 4,900 randomly sampled residents in 49 municipalities of Fukushima prefecture excluding the evacuation area designated by the Japanese government. Radiation risk perceptions were assessed with a seven-item scale. Psychological distress and posttraumatic stress symptoms were measured by the K6 and the six-item abbreviated version of the Posttraumatic Stress Disorder Checklist-Specific version, respectively. We investigated the associations of radiation risk perceptions in the first survey conducted in 2016 with psychological distress and posttraumatic stress symptoms in the follow-up survey conducted in 2017–18, controlling for the baseline level of distress or symptoms using multivariate logistic regression analyses. Valid responses were obtained from 1,148 residents (23.4%). Higher risk perceptions of radiation exposure in the first survey predicted later posttraumatic stress symptoms but not psychological distress after controlling for baseline symptoms or distress. High risk perceptions of radiation exposure after nuclear power plant accidents can lead to posttraumatic stress symptoms.

Background The prevalence of depression and/or anxiety disorders is reported to be higher in patients with heart failure (HF) than in the general population, and patients with HF also have coexisting cognitive problems. Recently, the development of near‐infrared spectroscopy (NIRS) has enabled noninvasive measurements of regional cerebral blood volume and brain activity, in terms of cerebral oxyhemoglobin in the cerebral cortex, with a high time resolution. The aim of the current study was to determine the associations between frontal brain activity and depressive symptoms, anxiety status, and cognitive function in patients with HF. Methods and Results We measured and compared frontal brain activity determined by NIRS during a verbal fluency task in patients with HF (n=35) and control subjects (n=28). The Center for Epidemiologic Studies Depression Scale for assessment of depressive symptoms, State‐Trait Anxiety Inventory for assessment of anxiety status, Mini‐Mental State Examination for assessment of cognitive function, and NIRS were simultaneously conducted. NIRS showed that frontal brain activity was significantly lower in the HF group than in the control subjects (28.5 versus 88.0 mM·mm; P

Abstract Mice with the C3H background show greater behavioral propensity for schizophrenia, including lower prepulse inhibition (PPI), than C57BL/6 (B6) mice. To characterize as‐yet‐unknown pathophysiologies of schizophrenia, we undertook proteomics analysis of the brain in these strains, and detected elevated levels of Mpst, a hydrogen sulfide (H2S)/polysulfide‐producing enzyme, and greater sulfide deposition in C3H than B6 mice. Mpst‐deficient mice exhibited improved PPI with reduced storage sulfide levels, while Mpst‐transgenic (Tg) mice showed deteriorated PPI, suggesting that “sulfide stress” may be linked to PPI impairment. Analysis of human samples demonstrated that the H2S/polysulfides production system is upregulated in schizophrenia. Mechanistically, the Mpst‐Tg brain revealed dampened energy metabolism, while maternal immune activation model mice showed upregulation of genes for H2S/polysulfides production along with typical antioxidative genes, partly via epigenetic modifications. These results suggest that inflammatory/oxidative insults in early brain development result in upregulated H2S/polysulfides production as an antioxidative response, which in turn cause deficits in bioenergetic processes. Collectively, this study presents a novel aspect of the neurodevelopmental theory for schizophrenia, unraveling a role of excess H2S/polysulfides production.

Abstract Depression is implicated as a risk factor for the recurrence of inflammatory bowel disease (IBD). Near-infrared spectroscopy (NIRS) and brain-derived neurotrophic factor (BDNF) are useful tools for evaluation of brain activity and a depressive state, respectively. The aim of this study was to clarify the association between brain activity or depressive symptoms and IBD using NIRS and BDNF. This study included 36 ulcerative colitis (UC) patients, 32 Crohn’s disease (CD) patients, and 17 healthy controls (HC). Center for Epidemiologic Studies Depression Scale (CES-D) scores were determined, NIRS was performed, and serum BDNF levels were measured in all subjects. NIRS showed that the mean oxygenated hemoglobin concentration was significantly lower in the frontal lobe in the UC group than in the HC group (HC 167 ± 106 vs. UC 83.1 ± 85.3, p

The present study aimed to clarify the associations among radiation exposure or psychological exposure to the Fukushima nuclear power plant accident (i.e., fear/anxiety immediately after the accident), current radiation anxiety, and psychological distress among non-evacuee community residents in Fukushima five years after the Great East Japan Earthquake, which occurred in March 2011. A questionnaire survey was administered to a random sample of non-evacuee community residents from 49 municipalities of Fukushima prefecture from February to April 2016, and data from 1684 respondents (34.4%) were analyzed. Environmental radiation levels at the time of the accident were ascertained from survey meter data, while environmental radiation levels at the time of the survey were ascertained from monitoring post data. In the questionnaire, immediate fear/anxiety after the accident, current radiation anxiety, and psychological distress were measured using a single-item question, a 7-item scale, and K6, respectively. Multilevel linear or logistic regression models were applied to analyze the determinants of radiation anxiety and psychological distress. The findings showed that environmental radiation levels at the time of the survey were more strongly associated with radiation anxiety than radiation levels immediately after the accident. Disaster-related experiences, such as direct damage, disaster-related family stress, and fear/anxiety after the accident, and demographic characteristics (e.g., younger age, being married, low socioeconomic status) were significantly associated with radiation anxiety. Environmental radiation levels at the time of the accident or survey were not significantly associated with psychological distress. Radiation anxiety largely mediated the association between fear/anxiety after the accident and psychological distress. In addition to environmental radiation levels, respondents’ radiation anxiety was affected by multiple factors, such as disaster-related experiences and demographic characteristics. Radiation levels were not associated with psychological distress in non-evacuee community residents. Rather, fear/anxiety after the nuclear power plant accident may be a determinant of psychological distress, mediated by radiation anxiety.

Phosphoinositides (PIs) play important roles in the structure and function of the brain. Associations between PIs and the pathophysiology of schizophrenia have been studied. However, the significance of the PI metabolic pathway in the pathology of schizophrenia is unknown. We examined the expression of PI signaling-associated proteins in the postmortem brain of schizophrenia patients. Protein expression levels of phosphatidylinositol 4-phosphate 5-kinase type-1 gamma (PIP5K1C), phosphatidylinositol 4-kinase alpha (PIK4CA, also known as PIK4A), phosphatase and tensin homolog deleted from chromosome 10 (PTEN), protein kinase B (Akt), and glycogen synthase kinase 3β (GSK3β) were measured using enzyme-linked immunosorbent assays and multiplex fluorescent bead-based immunoassays of the prefrontal cortex (PFC) of postmortem samples from 23 schizophrenia patients and 47 normal controls. We also examined the association between PIK4CA expression and its genetic variants in the same brain samples. PIK4CA expression was lower, whereas Akt expression was higher, in the PFC of schizophrenia patients than in that of controls; PIP5K1C, PTEN, and GSK3β expression was not different. No single-nucleotide polymorphism significantly affected protein expression. We identified molecules involved in the pathology of schizophrenia via this lipid metabolic pathway. These results suggest that PIK4CA is involved in the mechanism underlying the pathogenesis of schizophrenia and is a potential novel therapeutic target.

BackgroundAfter the 3.11 complex disaster, fear of radioactive contamination and forced evacuation influenced a number of residents to seek psychiatric care.ObjectivesThis study assessed the sequential changes in the number of new outpatients and patients with acute stress disorder (ASD), post-traumatic stress disorder (PTSD), adjustment disorder, and depression after the Fukushima disaster.MethodsWe distributed questionnaires to 77 psychiatric institutions to determine the number of new outpatients between March and June in 2010, 2011, and 2012.FindingsThere were 771, 1000, and 733 new patients in 2010, 2011, and 2012, respectively. We observed a statistically significant increase in new patients with ASD or PTSD and a significant decrease in patients with depression in 2011, which returned to predisaster levels in 2012.ConclusionsThere were time- and disease-dependent changes in the numbers of psychiatric care-seeking individuals after the 3.11 complex disaster in Fukushima.

Abstract Background Mothers living with small children in Fukushima prefecture may experience radiation anxiety and related symptoms after the Fukushima Dai’ich Nuclear Power Plant Accident. A behavioral activation (BA) program was developed to improve their psychosomatic symptoms. The purpose of this randomized controlled trial was to examine the effectiveness of a BA program for improving psychological distress and physical symptoms among mothers with preschool children in Fukushima-prefecture 3 years after the Fukushima Daiichi Nuclear Power Plant accident. Methods Participants were recruited from mothers living with a preschool child(ren) in Fukushima city and surrounding areas though a newspaper advertisement, posters, and flyers. Participants allocated to the intervention group received a newly developed group-based BA program, which consisted of two 90- min lessons with a 1-week interval. Psychological distress and physical symptoms as a primary outcome, and radiation anxiety and positive well-being (liveliness and life satisfaction) as a secondary outcome, were measured at baseline, 1- and 3-month follow-ups. Results Participants were randomly allocated to either an intervention or a control group (18 and 19, respectively). The BA program showed a marginally significant intervention effect on psychological distress (p = 0.051) and physical symptoms (p = 0.07) at 1-month follow-up, while the effect became smaller at 3-month follow-up. The effect sizes at 1-month were medium to large (-0.72 and -0.56, respectively). There was a significant intervention effect on increasing liveliness at 3-month follow-up (p = 0.02); and there were marginally significant effects on life satisfaction at 1- and 3-month follow-ups (both p = 0.09). Conclusions This BA program may be effective for improving psychological distress, physical symptoms, and well-being, at least for a short duration, among mothers with preschool children after the nuclear power plant accident in Fukushima, while a further large-scale study is needed. Trial registration The UMIN Clinical Trials Registry (UMIN-CTR; ID = UMIN000014081 ). Registered 27 May 2014.

This study examined parental recognition of bullying victimization and associated factors among evacuated children after the 2011 Fukushima Daiichi Nuclear Power Plant accident, using a 3-year follow-up data (wave 1: January 2012; wave 2: January 2013; wave 3: February 2014). The sample included the caregivers of 2,616 children in the first–sixth grades of elementary school, who lived in one of the 13 municipalities that were the target areas of the Mental Health and Lifestyle Survey, conducted as part of the Fukushima Mental Health Management Survey. Across 3 years, around 80% of caregivers responded “not true,” 15% responded “somewhat true,” and 5% responded “certainly true” in response to a question about bullying victimization of their children. Being male was significantly associated with the parental recognition of bullying victimization at wave 1 and wave 3. At wave 1, experiencing the nuclear plant explosion was significantly associated with parental recognition of bullying victimization. Moreover, age at wave 3 was negatively associated with parental recognition of bullying victimization. Our findings will be helpful for establishing community- and school-based mental health care for children, parents, and teachers.

To investigate associations between dietary patterns and the risk of impaired kidney function, we analyzed data from 14,732 participants (40–89 years) who completed the baseline diet questionnaire of The Fukushima Health Management Survey in 2011. The incidence of chronic kidney disease (CKD) (estimated glomerular filtration rate (eGFR) 2 or proteinuria (≥1+ by dipstick test)) and annual changes in eGFR were assessed from 2012 to 2015. Three major dietary patterns were identified. The adjusted cumulative incidence ratio of the highest vs. lowest tertile of a vegetable diet scores was 0.90 (95% confidence interval (CI): 0.82, 1.00) for eGFR < 60 mL/min/1.73 m2, 0.68 (95% CI: 0.52, 0.90) for proteinuria, and 0.88 (95% CI: 0.80, 0.97) for CKD (P for trend = 0.031, 0.007, and 0.005, respectively). The incident risk of CKD in the highest tertile of juice diet scores was 18% higher than the lowest tertile. The odds ratio of the highest vs. lowest tertile of vegetable diet scores was 0.85 (95% CI: 0.75, 0.98) in the rapidly decreasing eGFR group (P for trend = 0.009). We did not observe significant associations for the meat dietary pattern. A Japanese vegetable diet could reduce the risk of developing impaired kidney function and CKD.

Cardiometabolic risks were increasing in Fukushima residents after the Great East Japan Earthquake. We examined the association between dietary patterns and cardiometabolic risks in those aged ≥16 years. Dietary patterns were derived by principal component analysis for participants who underwent at least one diet assessment using a short-form food frequency questionnaire during 2011−2013 and a health checkup in 2014 and 2015 (n = 15,409 and 14,999, respectively). In 2014, the adjusted prevalence ratio (PR) and 95% confidence interval (CI) in the highest versus lowest quartile of accumulative mean scores were 0.97 (0.96−0.99) for overweight/obesity, 0.96 (0.95−0.97) for total cholesterol (TC) ≥ 220 mg/dL, 0.96 (0.95−0.98) for low-density lipoprotein cholesterol (LDL-C) ≥ 140 mg/dL, and 0.97 (0.96−0.99) for triglycerides ≥ 150 mg/dL for a vegetable diet and 1.03 (1.01−1.04) for TC ≥ 220 mg/dL and 1.02 (1.01−1.04) for LDL-C ≥ 140 mg/dL for a juice/milk diet. In 2015, we found consistently significant associations for the vegetable and juice/milk diets, and the PR and 95% CI were 0.99 (0.98−1.00) for HDL-C < 40 mg/dL for a meat diet. The continuous promotion of the vegetable pattern diet is necessary to reduce cardiometabolic risks, particularly dyslipidemia, in Japan.

Abstract Objective To assess relationships between the perception of radiation risks and psychological distress among evacuees from the Fukushima nuclear power plant disaster. Methods We analysed cross-sectional data from a survey of evacuees conducted in 2012. Psychological distress was classified as present or absent based on the K6 scale. Respondents recorded their views about the health risks of exposure to ionizing radiation, including immediate, delayed and genetic (inherited) health effects, on a four-point Likert scale. We examined associations between psychological distress and risk perception in logistic regression models. Age, gender, educational attainment, history of mental illness and the consequences of the disaster for employment and living conditions were potential confounders. Findings Out of the 180 604 people who received the questionnaire, we included 59 807 responses in our sample. There were 8717 respondents reporting psychological distress. Respondents who believed that radiation exposure was very likely to cause health effects were significantly more likely to be psychologically distressed than other respondents: odds ratio (OR) 1.64 (99.9% confidence interval, CI: 1.42-1.89) for immediate effects; OR: 1.48 (99.9% CI: 1.32-1.67) for delayed effects and OR: 2.17 (99.9% CI: 1.94-2.42) for genetic (inherited) effects. Similar results were obtained after controlling for individual characteristics and disaster-related stressors. Conclusion Among evacuees of the Fukushima nuclear disaster, concern about radiation risks was associated with psychological distress.

Patients with non-alcoholic fatty liver disease (NAFLD) have impaired health-related quality of life including physical and mental state. Near-infrared spectroscopy (NIRS) is a useful tool for evaluation of brain activity and depressive state. This study aimed to determine the brain activity of female NAFLD patients using NIRS. Cerebral oxygenated hemoglobin (oxy-Hb) concentration during a verbal fluency task (VFT) was measured using NIRS in 24 female NAFLD patients and 15 female healthy controls. The Center for Epidemiologic Studies Depression Scale (CES-D) questionnaire was administered to both groups before NIRS. There was no significant difference in CES-D score between groups. However, the oxy-Hb concentration and number of words during the VFT were less in NAFLD compared to healthy controls. The mean value of oxy-Hb concentration during 0-60 s VFT in the frontal lobe was also smaller in NAFLD patients compared to healthy controls (0.082 ± 0.126 vs. 0.183 ± 0.145, P < 0.001). Cerebral oxygen concentration is poorly reactive in response to VFT in female NAFLD patients. This may indicate an association between decreased brain activity and NAFLD regardless of depression.

Background To shed light on the mental health of evacuees after the accident at Fukushima Daiichi Nuclear Power Station (FDNPS), we evaluate the results of the Fukushima Health Management Survey (FHMS) of the residents at Kawauchi village in Fukushima, which is located less than 30 km from the FDNPS. Methods We conducted the cross-sectional study within the framework of the FHMS. Exposure values were “anorexia,” “subjective feelings about health,” “feelings about sleep satisfaction,” and “bereavement caused by the disaster,” confounding variables were “age” and “sex,” and outcome variables were “K6 points.” We collected data from the FHMS, and employed the Kessler Psychological Distress Scale (K6) and the posttraumatic stress disorder (PTSD) Checklist Stressor-Specific Version (PCL-S) to carry out the research. A total of 13 or greater was the cut-off for identifying serious mental illness using the K6 scale. The study subjects included residents (n = 542) of over 30 years of age from Kawauchi village, and data were used from the period of January 1, 2012 to October 31, 2012. Results A total of 474 residents (87.5%) scored less than 13 points in the K6 and 68 (12.6%) scored 13 points or more. The proportion of elderly residents (over 65 years old) among people with K6 score above the cut-off was higher than that among people with K6 score below the cut-off (44.1 vs 31.0%, p < 0.05). In addition, the proportion of residents with anorexia and mental illness among people with K6 score above the cut-off was higher than among people with K6 score below the cut-off (p < 0.001 and p < 0.05, respectively). The amount of residents who scored 44 points or more in the PCL-S among people with K6 score above the cut-off was also considerably higher than among people with K6 score below the cut-off (79.4 vs 12.9%, p < 0.001). Interestingly, the proportion of residents who scored more than among people with K6 score above the cut-off and the among people with PCL-S score above the cut-off in Kawauchi was higher than in previous studies in other locations. Conclusions These results suggest that there are severe mental health problems, such as depression and PTSD, among adults as a consequence of the accident at the FDNPS. Our study showed that residents who lived in the evacuation zone before the disaster are at high risk psychological distress. To facilitate local residents’ recovery from Fukushima, there is a need to continue providing them with physical and mental support, as well as communication regarding the health risks of radiation.

We investigated the psychometric properties of the Japanese version of the Posttraumatic Stress Disorder Checklist–Stressor Specific Version (PCL-S) using baseline data from the Fukushima Health Management Survey. A total of 26,332 men and 33,516 women aged 16 and above participated in this study. Participants lived in the Fukushima evacuation zone in Japan and experienced the Great East Japan Earthquake and nuclear power plant (NPP) incident. The PCL-S was used to assess participants’ posttraumatic stress disorder (PTSD) symptoms. In addition, we described participants and tested the validity of the PCL-S by administering the Kessler Six-item Screening Scale for Psychological Distress (K6) and assessing education; employment; self-rated health; sleep satisfaction; experiencing the earthquake, tsunami, and NPP incident; and bereavement as a result of the disaster. PCL-S scores exhibited a positively skewed, slightly leptokurtic distribution. Confirmatory factor analysis revealed that the five-factor model was a better fit than were the three- or four-factor models. The PCL-S and its subscales had high Cronbach’s alpha coefficients. The PCL-S scores had weak-to-moderate correlations with history of mental illness, bereavement, experiencing the tsunami, experiencing the NPP incident, self-rated health, and sleep satisfaction, as well as a strong correlation with psychological distress. There were significant gender and age differences in PCL-S scores. Overall, this study confirmed the psychometric properties of the PCL-S, including the score distribution, factor structure, reliability, validity, and gender and age differences. Thus, the Japanese version of the PCL-S would be a useful instrument for assessing the PTSD symptoms of community dwellers who have experienced traumatic events.

Following the Great East Japan Earthquake on March 11, 2011, the nuclear disaster at the Fukushima Daiichi Nuclear Power Plant has continued to affect the mental health status of residents in the evacuation zone. To examine the mental health status of evacuee after the nuclear accident, we conducted the Mental Health and Lifestyle Survey as part of the ongoing Fukushima Health Management Survey.We measured mental health status using the Kessler 6-item psychological distress scale (K6) in a total of 73,569 (response rate: 40.7%) evacuees aged 15 and over who lived in the evacuation zone in Fukushima Prefecture. We then dichotomized responders using a 12/13 cutoff on the K6, and compared the proportion of K6 scores ≥13 and ≤12 in each risk factor including demographic information, socioeconomic variables, and disaster-related variables. We also performed bivariate analyses between mental health status and possible risk factors using the chi-square test. Furthermore, we performed multivariate regression analysis using modified Poisson regression models.The median K6 score was 5 (interquartile range: 1-10). The number of psychological distress was 8,717 (14.6%). We found that significant differences in the prevalence of psychological distress by almost all survey items, including disaster-related risk factors, most of which were also associated with increased Prevalence ratios (PRs). Additionally, we found that psychological distress in each evacuation zone was significantly positively associated with the radiation levels in their environment (r = 0.768, p = 0.002).The earthquake, tsunami and subsequent nuclear accident likely caused severe psychological distress among residents in the evacuation zone in Fukushima Prefecture. The close association between psychological distress and the radiation levels shows that the nuclear accident seriously influenced the mental health of the residents, which might be exacerbated by increased risk perception. To provide prompt and appropriate support, continued psychosocial intervention for evacuees is strongly recommended.

The mismatch negativity (MMN) provides a correlate of automatic auditory discrimination in human auditory cortex that is elicited in response to violation of any acoustic regularity. Recently, deviance-related responses were found at much earlier cortical processing stages as reflected by the middle latency response (MLR) of the auditory evoked potential, and even at the level of the auditory brainstem as reflected by the frequency following response (FFR). However, no study has reported deviance-related responses in the FFR, MLR and long latency response (LLR) concurrently in a single recording protocol. Amplitude-modulated (AM) sounds were presented to healthy human participants in a frequency oddball paradigm to investigate deviance-related responses along the auditory hierarchy in the ranges of FFR, MLR and LLR. AM frequency deviants modulated the FFR, the Na and Nb components of the MLR, and the LLR eliciting the MMN. These findings demonstrate that it is possible to elicit deviance-related responses at three different levels (FFR, MLR and LLR) in one single recording protocol, highlight the involvement of the whole auditory hierarchy in deviance detection and have implications for cognitive and clinical auditory neuroscience. Moreover, the present protocol provides a new research tool into clinical neuroscience so that the functional integrity of the auditory novelty system can now be tested as a whole in a range of clinical populations where the MMN was previously shown to be defective.