Post-Disaster Community Transition of Psychiatric Inpatients: Lessons from the Fukushima Nuclear Accident.

This study sought to explore factors related to community transition after the mandatory evacuation of psychiatric inpatients to other hospitals owing to the Fukushima Daiichi Nuclear Power Plant accident. A retrospective cohort design was adopted and 391 psychiatric patients were examined. Univariate and multivariate analyses were conducted to confirm the association between the achievement or non-achievement of discharge to community living and their backgrounds (age, gender, evacuation destination, psychiatric diagnoses, and physical complications). Multivariate analysis indicated that patients with psychiatric diagnoses of schizophrenia, schizotypal, and delusional disorders (International Statistical Classification of Diseases and Related Health Problems 10th revision, F20-29), and those with physical diagnoses of the circulatory (I00-95) and digestive (K00-93) systems showed a significant association with the non-attainment of community transition. From these results, we hypothesized that difficulties in the management of medication during and immediately after the extremely chaotic settings of evacuation could have negative effects on the community transitions. Furthermore, another possible concern was that individuals' persistent psychotic status before the accident had been carried over to the destination hospitals. Therefore, pre-disaster daily cooperation across hospitals and challenges for vulnerable psychiatric patients' future community lives are also essential.

Real-Time Prediction of Medical Demand and Mental Health Status in Ukraine under Russian Invasion Using Tweet Analysis.

Russia's invasion of Ukraine (February 24, 2022) has begun and there are concerns about the impact on health care supply and mental health. This study analyzed tweets in the Ukrainian language to capture the medical needs and mental health conditions in wartime Ukraine by focusing on ostensibly relevant words. The number of tweets containing the keywords and their overall proportion was compared before and after the Russian invasion of Ukraine. The survey period was divided into four phases-the pre-2022 Russian invasion, acute phase (4 weeks), subacute phase (12 weeks), and the chronic phase (8 weeks) up to August 10, 2022. The analysis targeted tweets sent in Ukrainian. The tweets were screened using a set of six classes with 75 key groups and 303 Ukrainian (204 original Japanese) keywords. Overall, 98,526,440 tweets were analyzed, with a pre-invasion and post-onset average of 1,096,976 and 3,328,243 tweets/week (a 3.0-fold increase), respectively. Of these, 3,197,443 tweets contained the keywords, with a pre-invasion and invasion average of 26,241 and 114,640 tweets/week (a 4.4-fold increase), respectively. The post-onset phase witnessed a considerable increase in all classes-medical services, treatment, medical resources, medical situations, and special situations-but not in the symptom class. Keywords related to psychological distress and anxiety immediately increased during the acute phase; those related to depression and post-traumatic stress reactions continued increasing as the invasion persisted, which may have reflected the mental state of those impacted. Analyzing tweets is useful for predicting people's real-time physical and mental health needs during wartime.

Mental Health Problems among University Students under the Prolonged COVID-19 Pandemic in Japan: A Repeated Cross-Sectional Survey.

Numerous studies have investigated the impact of the coronavirus disease 2019 (COVID-19) pandemic on mental health among university students within a year of its onset, but few have examined the impact of a prolonged pandemic on university life. This study aimed to evaluate the impact of the COVID-19 pandemic on the mental health of students in a large university community. Online questionnaire surveys were conducted on students from March 24 to April 14 (first survey, n = 3,357) and December 2-23, 2021 (second survey, n = 2,604). The questionnaires included items on demographic data, living conditions, and mental health status as measured using the Patient Health Questionnaire-9 for depressive symptoms and the Generalized Anxiety Disorder-7 scale for anxiety symptoms. The results showed that, compared with undergraduate students, graduate students, except those in Medicine, Dentistry, and Pharmaceutical Science courses, had more anxiety symptoms. Furthermore, among undergraduate students, depressive and anxiety symptoms were significantly higher in fourth- than in first-year students. Logistic regression analyses of data from both surveys revealed the seven risk factors associated with depressive or anxiety symptoms that affected the mental health of university students throughout the COVID-19 pandemic: 1) female or nonbinary gender, 2) graduate student, 3) quarantine experience due to COVID-19, 4) isolation from friends and acquaintances, 5) disorganized pattern of daily life, 6) worse financial situation, and 7) no availability of consultations regarding health, life, and finances. These findings suggest that mental health measures for university students need to be designed specific to each course.

Elevation of EGR1/zif268, a Neural Activity Marker, in the Auditory Cortex of Patients with Schizophrenia and its Animal Model.

The family of epidermal growth factor (EGF) including neuregulin-1 are implicated in the neuropathology of schizophrenia. We established a rat model of schizophrenia by exposing perinatal rats to EGF and reported that the auditory pathophysiological traits of this model such as prepulse inhibition, auditory steady-state response, and mismatch negativity are relevant to those of schizophrenia. We assessed the activation status of the auditory cortex in this model, as well as that in patients with schizophrenia, by monitoring the three neural activity-induced proteins: EGR1 (zif268), c-fos, and Arc. Among the activity markers, protein levels of EGR1 were significantly higher at the adult stage in EGF model rats than those in control rats. The group difference was observed despite an EGF model rat and a control rat being housed together, ruling out the contribution of rat vocalization effects. These changes in EGR1 levels were seen to be specific to the auditory cortex of this model. The increase in EGR1 levels were detectable at the juvenile stage and continued until old ages but displayed a peak immediately after puberty, whereas c-fos and Arc levels were nearly indistinguishable between groups at all ages with an exception of Arc decrease at the juvenile stage. A similar increase in EGR1 levels was observed in the postmortem superior temporal cortex of patients with schizophrenia. The commonality of the EGR1 increase indicates that the EGR1 elevation in the auditory cortex might be one of the molecular signatures of this animal model and schizophrenia associating with hallucination.

Review of Mental Health Consequences of the Great East Japan Earthquake through Long-Term Epidemiological Studies: The Shichigahama Health Promotion Project.

After the Great East Japan Earthquake, Tohoku University began to provide mental health services during the acute phase of the disaster in cooperation with Shichigahama Town, one of the municipalities located in the coastal area of the Miyagi Prefecture that was severely damaged by the earthquake and tsunami; it continued to be providing long-term mental health activities, incorporating annual surveys for affected residents in the town for 10 years. Ten years of combination of surveys and outreach activities first depicted detailed longitudinal alterations in the mental health conditions of communities affected by a catastrophe. While posttraumatic stress reaction had recovered year by year after the year following the Great East Japan Earthquake, recovery from psychological distress retreated between 2014 and 2017, probably due to the relocation from temporal to eternal housing conditions. The annual cycles of assessment and provision of mental health support and promotion activities continued for 10 years can be an initial model for evidence-based, long-term post-disaster mental health and psychosocial support for the affected communities. Data regarding subsequent disasters should be collected in comparable ways, in order to improve the accuracy and usefulness of the accumulated data for planning and providing evidence-based post-disaster mental health and psychosocial support.

Lessons learned from psychosocial support and mental health surveys during the 10 years since the Great East Japan Earthquake: Establishing evidence-based disaster psychiatry.

Post-disaster mental health and psychosocial support have drawn attention in Japan after the 1995 Great Hanshin-Awaji Earthquake, with mental health care centers for the affected communities being organized. After the catastrophe, a reconstruction budget was allocated to organize mental health care centers to provide psychosocial support for communities affected by the 2007 Chuetsu offshore earthquake, the 2011 Great East Japan Earthquake, and the 2016 Kumamoto Earthquake. There were several major improvements in post-disaster mental health measures after the Great East Japan Earthquake. The Disaster Psychiatric Assistance Team system was organized after the earthquake to orchestrate disaster response related to the psychiatric health system and mental health of the affected communities. Special mental health care efforts were drawn to the communities affected by the nuclear power plant accident through Chemical, Biological, Radiological, Nuclear, and high yield Explosives, being succeeded by measures against the coronavirus pandemic. As another new movement after the Great East Japan Earthquake, the number of surveys involving communities affected by disasters has soared. More than 10 times the number of scientific publications were made in English during the decade following the Great East Japan Earthquake, compared with the previous decades. In this review, we examined the results and issues acquired in the 10 years since the Great East Japan Earthquake, proposing evidence-based disaster psychiatry as the direction of future mental health measures related to emergency preparedness and response.

Evidence for Altered Phosphoinositide Signaling-Associated Molecules in the Postmortem Prefrontal Cortex of Patients with Schizophrenia.

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 3ß (GSK3ß) 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 GSK3ß 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.

Effects of the Great East Japan Earthquake and the Fukushima Daiichi Nuclear Power Plant accident on behavioural and psychological symptoms of dementia among patients.

BACKGROUND: The Great East Japan Earthquake triggered accidents at the Fukushima Daiichi Nuclear Power Plant, becoming the first complex disaster that included both a natural and a nuclear power disaster. This study examines how complex disasters affect patients with dementia. METHODS: Participants included the 331 people diagnosed with dementia out of the 2482 new patients (between January 2008 and December 2015) at a psychiatric hospital located in the indoor sheltering zones nearby mandatory evacuation zones. Medical records were retrospectively examined to identify the number of new patients with dementia, the severity, their chief complaints, and the behavioural and psychological symptoms of dementia (BPSD) types. BPSD were classified into the hyperactive BPSD group and the hypoactive BPSD group. The hyperactive BPSD group was further subdivided into the hyperactivity-impulsivity-irritability-disinhibition-aggression-agitation group, which exhibited agitation, disinhibition, and irritability, and the psychosis group, which exhibited delusions and hallucinations. The hypoactive BPSD group included depression, inactivity, apathy, and anxiety. Results were divided into the period before the complex disaster (2008-2010) and after (2012-2015) and were compared. In addition, the post-complex-disaster period was subdivided into the early phase (2012-2013) and the late phase (2014-2015). RESULTS: The proportion of new patients with dementia increased significantly after the disaster. Although there was no change in patients' age and the disease's severity, the proportion of patients whose chief complaint was BPSD increased significantly after the disaster. Furthermore, there was a significant increase in the hyperactivity-impulsivity-irritability-disinhibition-aggression-agitation group in the early post-complex-disaster phase and a significant increase in the psychosis group in the late post-complex-disaster phase. CONCLUSION: This complex disaster caused increased consultations from patients with dementia and increased BPSD. Additionally, it increased participants' symptoms of agitation and irritability in the early post-complex-disaster phase and the proportion of hallucinations and delusions in the late post-complex-disaster phase.

Does Treatment Response With Antidementia Drugs After 6 Months in Alzheimer's Disease Predict Long-term Treatment Outcome?

BACKGROUND: Alzheimer's disease (AD) is a chronic, progressive disorder that causes declines in cognitive and physical functions. This condition places severe burdens on families and caregivers. Delaying progressive declines in cognitive function and reducing their burden are thus important. Relationships between early treatment response and subsequent outcomes of schizophrenia and major depressive disorder have been reported. We thus aimed to investigate the relationships between treatment response to antidementia drugs in AD after 6 months (M) and subsequent outcomes. METHODS: Eligible individuals comprised 194 patients diagnosed with presumed AD. Of these, 110 patients who received antidementia drugs for the first time and were assessed using the Mini-Mental State Examination (MMSE) at 6 M, 12 M, and 24 M were categorized as responders (n = 84) or nonresponders (n = 26). Responders were defined as showing a change in MMSE after 6 M the same as or lower than that in the natural course according to previously reported data. RESULTS: No significant differences in baseline characteristics (age, sex, education, or comorbidities) were seen between groups. Mean MMSE score at baseline was significantly lower in responders (18.0) than in nonresponders (20.7; P = 0.008). Mean change from baseline MMSE was significantly smaller in responders than in nonresponders at both 12 M (-0.46 vs -2.5; P = 0.04) and 24 M (-0.78 vs -4.4; P = 0.001). CONCLUSIONS: Treatment response with antidementia drugs after 6 M predicted better outcomes at 12 M and 24 M. Treatment response should be assessed every 6 M, and treatment should be reconsidered accordingly.

Serotonin/5-HT1A Signaling in the Neurovascular Unit Regulates Endothelial CLDN5 Expression.

We previously reported that site-selective claudin-5 (CLDN5) breakdown and protein kinase A (PKA) activation are observed in brain microvessels of schizophrenia, but the underlying molecular basis remains unknown. The 5-HT1 receptors decline the intracellular cAMP levels and inactivate the major downstream PKA, and the 5-HT1A receptor is a promising target for schizophrenia. Therefore, we elucidated the involvement of serotonin/5-HT1A signaling in the endothelial CLDN5 expression. We demonstrate, by immunohistochemistry using post-mortem human brain tissue, that the 5-HT1A receptor is expressed in brain microvascular endothelial cells (BMVECs) and mural cells of the normal prefrontal cortex (PFC) gray matter. We also show that PKA is aberrantly activated not only in BMVECs but also in mural cells of the schizophrenic PFC. We subsequently revealed that the endothelial cell-pericyte tube-like structure was formed in a novel two-dimensional co-culture of human primary BMVECs and a human brain-derived pericyte cell line, in both of which the 5-HT1A receptor was expressed. Furthermore, we disclose that the serotonin/5-HT1A signaling enhances endothelial CLDN5 expression in BMVECs under two-dimensional co-culture conditions. Our findings provide novel insights into the physiological and pathological significance of serotonin/5-HT1A signaling in the region-specific regulation of the blood-brain barrier.

The Relationship between Mismatch Negativity and the COMTVal108/158Met Genotype in Schizophrenia.

Mismatch negativity (MMN) is a component of auditory event-related potentials that reflects automatic change detection in the brain, showing qualities of endophenotypes in schizophrenia. MMN deficiency is one of the robust findings in patients, and it reflects both cognitive and functional decline. Catechol-o-methyltransferase (COMT) is a key enzyme involved in regulating dopamine transmission within the prefrontal cortex. A preliminary study suggested that the COMTVal108/158Met genotype (rs4680) is related to cognitive function in schizophrenia. Both the COMTVal108/158Met genotype and MMN are related to cognitive function, but no studies have reported on the relationship between MMN and the COMTVal108/158Met genotype in schizophrenia. This study therefore examined the relationship between COMTVal108/158Met genotype and MMN. The duration of MMN was measured, and the COMTVal108/158Met polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in 49 Japanese schizophrenia patients (Val/Val, n = 21; Met carriers, n = 28). Amplitude and latency of MMN were compared between Val/Val and Met carriers.

Minimal amount of tissue-based pH measurement to improve quality control in neuropsychiatric post-mortem brain studies.

AIM: Tissue pH and RNA integrity are crucial quality-control indicators of human post-mortem brain tissues in the identification of the pathogeneses of neuropsychiatric disorders, but pH has not been measured as often due to limitations in the amount of tissue available. This study was designed to develop and validate a protocol for tissue pH evaluation using a minimal amount of human post-mortem tissues. METHODS: A procedure that included a proper ratio of brain tissue weight to water for homogenization and the duration of homogenization was designed based on preliminary experiments using mouse brain tissues. The minimal (10 mg) and typical (100 mg) amounts of post-mortem brain tissue from 52 subjects were homogenized in 5 volumes (50 µL/10 mg tissue) and 10 volumes (1000 µL/100 mg tissue) of nuclease-free water and subjected to pH measurements using an InLab Ultra micro pH electrode. RESULTS: The pH values based on the new protocol using a minimal amount of tissue significantly correlated with measurements of the standard protocol (r2 = 0.86). The correlation coefficients of the pH values between gray and white matter of the same brain region, and the values between different brain regions were 0.73 and 0.54, respectively. CONCLUSION: The proposed protocol used one-tenth of the tissue amount of current standard protocol and enabled us to evaluate the exact quality of post-mortem brain tissue subjected to subsequent analyses. The application of this protocol may improve the detection of biological phenomena of interest in post-mortem brain studies by diminishing confounding factors.

Mental disorders that exacerbated due to the Fukushima disaster, a complex radioactive contamination disaster.

AIM: The Fukushima disaster was caused by an earthquake that occurred on 11 March 2011. Following the serious damage caused by the earthquake and the subsequent tsunami, radioactive contamination occurred because of the meltdown accident at the Fukushima nuclear power plant. We investigated what mental disorders were likely to become exacerbated under these conditions. METHODS: We surveyed psychiatric outpatients at Fukushima Medical University Hospital for 1 month (31 days) from the day of the earthquake (March­April 2011). RESULTS: The survey revealed that bipolar I disorder was most likely to become exacerbated under the conditions and that the exacerbation exhibited was more likely to involve manic switches than depression. CONCLUSION: On the basis of the results of our study, particular care must be taken to follow up bipolar I disorder patients after a natural disaster. Our results also suggested the possible origin of bipolar I disorder.

Marked alteration of phosphoinositide signaling-associated molecules in postmortem prefrontal cortex with bipolar disorder.

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 3ß (GSK3ß), 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 GSK3ß were measured using enzyme-linked immunosorbent assays and multiplex fluorescent bead-based immunoassays in the prefrontal cortex (PFC). Specifically, PTEN, Akt1, GSK3ß, 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 GSK3ß 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/GSK3ß and its upstream regulator PTEN are considerably altered.

Availability of individual proteins for quantitative analysis in postmortem brains preserved in two different brain banks.

AIM: Postmortem brain research is necessary for elucidating the pathology of schizophrenia; an increasing number of studies require a combination of suitable tissue samples preserved at multiple brain banks. In this study, we examined whether a comparative study of protein expression levels can be conducted using postmortem brain samples preserved in different facilities. METHODS: We compared the demographic factors of postmortem brain samples preserved in two institutions and measured and compared the expression levels of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and glial fibrillary acidic protein (GFAP) in the prefrontal cortex and superior temporal gyrus. GAPDH is generally used as a loading control for western blotting, and GFAP is considered as an astrocyte marker in the brain. RESULTS: We found significant differences between the two institutions in postmortem interval, age at death, and preservation time. To reduce the effects of these differences on our measurements, the parameters were set as covariates in our analyses of covariance. Subsequently, no differences in GAPDH and GFAP expression were found between institutions. CONCLUSIONS: When studies are conducted using brain samples preserved in different brain banks, differences in demographic factors should be carefully considered and taken into account by statistical methods to minimize their impact as much as possible. Since there was no significant difference in the protein expression levels of GAPDH and GFAP in either region between the two institutions that preserved the postmortem brains, we concluded that it is possible to perform protein quantitative analysis assuming that there is no effect of difference between two institutions.

Ethnicity-dependent effect of rs1799971 polymorphism on OPRM1 expression in the postmortem brain and responsiveness to antipsychotics.

Schizophrenia is associated with aberration of inhibitory neurons. Although the mu-opioid receptor (MOR) is an essential modulator of inhibitory neurons, the effect of rs1799971 polymorphism in the MOR gene on risk of schizophrenia is controversial. Moreover, the disturbance of opioids systems in patients with schizophrenia has not been fully examined. We firstly conducted preliminary meta-analyses integrating Asian and European populations separately over 12,000 subjects to assess the effect of rs1799971 on risk of schizophrenia. Based on the above result, we also investigated the effect on the expression levels of MOR mRNA in the prefrontal cortex (PFC) and caudate nucleus of 41 postmortem brains. In addition, we determined whether these levels were related to antemortem schizophrenia symptoms and pharmacotherapeutic effects. The rs1799971 G-allele reduced the risk of schizophrenia in Asian populations (OR: 0.56, 95%CI: 0.32-0.98, p = 0.042) but increased it in European populations (OR: 1.66, 95%CI: 1.08-2.56, p = 0.022). It decreased MOR mRNA levels in PFC in the Japanese population (p = 0.031). Increased MOR mRNA level in PFC correlated with higher total score of antemortem schizophrenia symptoms (p = 0.017). Furthermore, the pharmacotherapeutic effect of first-generation antipsychotics was higher for genotype AA than AG/GG of rs1799971 (p = 0.036). The rs1799971 affects risk of schizophrenia and MOR mRNA expression and the effect varies according to ethnicity. Overexpression of MOR might induce severe schizophrenia symptoms. Therefore, MOR modulation may be the key clue for treating antipsychotics-resistant schizophrenia, and genotyping rs1799971 may provide a better pharmacotherapeutic strategy.

The influence of tissue pH and RNA integrity number on gene expression of human postmortem brain.

Background: Evaluating 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. Methods: We 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. Results: We 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. Conclusion: The 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.

Post-evacuation return of psychiatric hospital inpatients evacuated to hospitals outside the Fukushima prefecture after the nuclear accident: A Retrospective Cohort Study.

BACKGROUND: Post-evacuation return after mandatory hospital evacuation due to complicated disasters is often overlooked and not well-discussed. AIMS: In this study, we explored the factors which are related to the ease or difficulty of the post-evacuation return to Fukushima prefecture of psychiatric inpatients who had been evacuated to hospitals outside the prefecture because of the Great East Japan Earthquake (GEJE) and subsequent Fukushima Daiichi Nuclear Power Plant (FDNPP) accident. METHOD: This retrospective cohort study included evacuated psychiatric hospital inpatients who were registered in the Matching Project for Community Transition (MPCT) and had been traced until July 31, 2019. A total of 531 patients were included for the analyses. Univariable and multivariable analysis were conducted to detect the patients' traits including their psychiatric/physical backgrounds which were associated with their outcome - the time from GEJE to the date of return to Fukushima. RESULTS: Over half of the patients returned to Fukushima. In the multivariable analysis, the patients' gender (male), age (older), and psychiatric diagnoses of schizophrenia, schizotypal and delusional disorders (ICD-10, F20-29) showed lower hazard ratio (HR) and statistically significant association with the difficulties of post-evacuation return. Meanwhile, disorders of psychological development (F80-89), diseases of the nervous (G00-99, except G40-41) and genitourinary (N00-99) systems showed higher HR and statistically significant association with the ease of return. CONCLUSIONS: The specific characteristics of the psychiatric inpatients including their psychiatric and physical status are associated with their post-evacuation return to their hometown. These results indicated that the evacuated hospitals' practitioners and staffs from the MPCT understood the necessity of the earlier return of inpatients to their hometown. Moreover, clinicians should pay more attention to some symptoms unique to psychiatric patients which contributed to their difficulties in returning safely or expressing their hope to return.

Evidence for increased DNA damage repair in the postmortem brain of the high stress-response group of schizophrenia.

Background: Schizophrenia (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. Methods: We selected the following stress-responsive molecules: interleukin (IL) -1ß, 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. Results: We 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. Conclusion: Our 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.