Mamoru TOCHIGI (栃木 衛)

BACKGROUND: The influence of media reporting on suicide and suicide attempts (SA) has been rigorously studied. Previous studies focused on characteristics like celebrity status, sex and age of suicide decedents, which may facilitate suicide and SA occurrence. These studies have informed guidelines for responsible media reporting. However, the nuanced effects on different sex and age groups of suicidal individuals remain less understood. METHODS: This study examined the association between the characteristics of initial suicide reports in four major newspapers and the differences in admission numbers (Δs) of SA patients across sex and age groups during pre- and post-article release one-week periods. Data from an Emergency and Critical Care Center from 2012 to 2019 were obtained through a review of medical records. Nonparametric MANOVAs were employed to investigate Δs for sex and age groups of SA patients in relation to sex and age of suicide decedents, incident types, and methods. Significant differences were evaluated using Wilcoxon tests. RESULTS: A total of 1,205 articles on 676 suicide incidents and 1,081 SA admissions were analyzed. MANOVAs revealed a significant association between the Δs and the reported suicide methods. Δ for females was positively associated with reports of gas poisoning and other infrequently reported methods, whereas Δ for males was negatively associated with gas poisoning. Δ for younger patients was positively associated with infrequently reported methods and negatively with firearm discharge. No significant associations were found between Δ and sex and age of decedents or incident types. DISCUSSION: This study demonstrates a differential impact of suicide news articles reporting gas poisoning, infrequently reported suicide methods, and firearm discharge, on SA patient admissions across sex and age groups. These differences may arise from variations in emotional responses to the suicide methods, which can be understood in both psychological and socio-cultural contexts. Further research is needed to clarify the determinants of differential influences to more effectively address and mitigate the risks of suicide and SAs.

BACKGROUND: We aimed to determine the similarities and differences in the roles of genic and regulatory copy number variations (CNVs) in bipolar disorder (BD), schizophrenia (SCZ), and autism spectrum disorder (ASD). METHODS: Based on high-resolution CNV data from 8708 Japanese samples, we performed to our knowledge the largest cross-disorder analysis of genic and regulatory CNVs in BD, SCZ, and ASD. RESULTS: In genic CNVs, we found an increased burden of smaller (<100 kb) exonic deletions in BD, which contrasted with the highest burden of larger (>500 kb) exonic CNVs in SCZ/ASD. Pathogenic CNVs linked to neurodevelopmental disorders were significantly associated with the risk for each disorder, but BD and SCZ/ASD differed in terms of the effect size (smaller in BD) and subtype distribution of CNVs linked to neurodevelopmental disorders. We identified 3 synaptic genes (DLG2, PCDH15, and ASTN2) as risk factors for BD. Whereas gene set analysis showed that BD-associated pathways were restricted to chromatin biology, SCZ and ASD involved more extensive and similar pathways. Nevertheless, a correlation analysis of gene set results indicated weak but significant pathway similarities between BD and SCZ or ASD (r = 0.25-0.31). In SCZ and ASD, but not BD, CNVs were significantly enriched in enhancers and promoters in brain tissue. CONCLUSIONS: BD and SCZ/ASD differ in terms of CNV burden, characteristics of CNVs linked to neurodevelopmental disorders, and regulatory CNVs. On the other hand, they have shared molecular mechanisms, including chromatin biology. The BD risk genes identified here could provide insight into the pathogenesis of BD.

Recent evidence has documented the potential roles of histone-modifying enzymes in autism-spectrum disorder (ASD). Aberrant histone H3 lysine 9 (H3K9) dimethylation resulting from genetic variants in histone methyltransferases is known for neurodevelopmental and behavioral anomalies. However, a systematic examination of H3K9 methylation dynamics in ASD is lacking. Here we resequenced nine genes for histone methyltransferases and demethylases involved in H3K9 methylation in individuals with ASD and healthy controls using targeted next-generation sequencing. We identified a novel rare variant (A211S) in the SUV39H2, which was predicted to be deleterious. The variant showed strongly reduced histone methyltransferase activity in vitro. In silico analysis showed that the variant destabilizes the hydrophobic core and allosterically affects the enzyme activity. The Suv39h2-KO mice displayed hyperactivity and reduced behavioral flexibility in learning the tasks that required complex behavioral adaptation, which is relevant for ASD. The Suv39h2 deficit evoked an elevated expression of a subset of protocadherin β (Pcdhb) cluster genes in the embryonic brain, which is attributable to the loss of H3K9 trimethylation (me3) at the gene promoters. Reduced H3K9me3 persisted in the cerebellum of Suv39h2-deficient mice to an adult stage. Congruently, reduced expression of SUV39H1 and SUV39H2 in the postmortem brain samples of ASD individuals was observed, underscoring the role of H3K9me3 deficiency in ASD etiology. The present study provides direct evidence for the role of SUV39H2 in ASD and suggests a molecular cascade of SUV39H2 dysfunction leading to H3K9me3 deficiency followed by an untimely, elevated expression of Pcdhb cluster genes during early neurodevelopment.

INTRODUCTION: Panic disorder (PD) has many comorbidities such as depression, bipolar disorder (BPD), and agoraphobia (AG). PD is a moderately heritable anxiety disorder whose pathogenesis is not well understood. Recently, a tri-allelic serotonin transporter (5-HTTLPR/rs25531) polymorphism was reported to be more sensitive to personality traits compared to the bi-allelic 5-HTTLPR polymorphism. We hypothesized that the 5-HTTLPR/rs25531 polymorphism may lead to a pathological anxious state depending on the presence or absence of a comorbidity in PD. METHODS: In this study, we investigated the relationship between comorbidities in PD and tri-allelic 5-HTTLPR polymorphisms. A total of 515 patients with PD (148 males, 367 females) were genotyped, and the Revised NEO Personality Inventory as well as anxiety-related psychological tests were administered. Depression, BPD, and AG were diagnosed as comorbidities. RESULTS: For the tri-allele 5-HTTLPR genotype, a significant interaction effect was found between openness to experience and comorbid depression. Examination of the interaction between AG and the tri-allelic 5-HTTLPR genotype revealed that L' allele carriers are associated with higher trait anxiety than the S'S' genotype group in PD without AG. CONCLUSION: Some anxiety and personality traits can be characterized by the tri-allelic gene effect of 5-HTTLPR. These results suggest that tri-allelic 5-HTTLPR genotypes have genetic effects on the presence of comorbidities of PD.

OBJECTIVE: To investigate the utility of the voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD). METHODS: Clinical data from patients who underwent screening for dementia using VSRAD and the Japanese version of COGNISTAT, the Neurobehavioral Cognitive Status Examination, were retrospectively investigated to specify the domains of cognitive function that correlate with the statistical mean value of positive Z-scores in the target volume-of-interest (VOI). A receiver operating characteristic (ROC) curve was constructed to assess the mean value of positive Z-scores in discriminating patients with AD. RESULTS: A total of 72 patients were included (18 male and 54 female; 15 patients with AD). The mean value of positive Z-scores in the target VOI was significantly correlated with standardized COGNISTAT scores for Orientation and Memory in all patients (r = –0.35 and –0.38, respectively). ROC curve analysis revealed that a cut-off of 1.57 for mean value of positive Z-scores in the target VOI provided 69.4% accuracy in discriminating patients with AD, with a sensitivity of 0.80 and specificity of 0.67. CONCLUSIONS: The results evinced the value of VSRAD in diagnosing AD. The degree of atrophy represented by the target VOI may reflect impairments in Orientation and Memory, which are early stage symptoms observed in AD.