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.

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. 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. 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. 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).

Schizophrenia is one of the major psychiatric disorders, and lipids have focused on the important roles in this disorder. In fact, lipids related to various functions in the brain. Previous studies have indicated that phospholipids, particularly ones containing polyunsaturated fatty acyl residues, are deficient in postmortem brains from patients with schizophrenia. However, due to the difficulties in handling human postmortem brains, particularly the large size and complex structures of the human brain, there is little agreement regarding the qualitative and quantitative abnormalities of phospholipids in brains from patients with schizophrenia, particularly if corresponding brain regions are not used. In this study, to overcome these problems, we employed matrix-assisted laser desorption/ionization imaging mass spectrometry (IMS), enabling direct microregion analysis of phospholipids in the postmortem brain of a patient with schizophrenia via brain sections prepared on glass slides. With integration of traditional histochemical examination, we could analyze regions of interest in the brain at the micrometric level. We found abnormal phospholipid distributions within internal brain structures, namely, the frontal cortex and occipital cortex. IMS revealed abnormal distributions of phosphatidylcholine molecular species particularly in the cortical layer of frontal cortex region. In addition, the combined use of liquid chromatography/electrospray ionization tandem mass spectrometry strengthened the capability for identification of numerous lipid molecular species. Our results are expected to further elucidate various metabolic processes in the neural system.