Takayuki Kannon

OBJECTIVE: Emerging evidence suggests that low-grade systemic inflammation contributes to depressive symptoms; however, population-based longitudinal evidence, particularly from community samples, remains limited. This study examined the associations between serum cytokine levels and depressive symptoms among community-dwelling adults in Japan. PARTICIPANTS AND METHODS: Participants were drawn from the Shika Study cohort (N = 182; 98 men, 84 women; mean age: 62.2 ± 9.34 years for men, 60.9 ± 9.49 for women). They provided blood samples in 2017 and completed the Japanese versions of the Center for Epidemiologic Studies Depression Scale (CES-D) in 2017 and its revised version (CESD-R) in 2019. Serum TNFα, IL-6, IL-10 and IL-17A were quantified using a multiplex human immunoassay. RESULTS: Among men, serum IL-6 levels were positively associated with CES-D scores in 2017 after adjustment for age, visceral adiposity, smoking, and alcohol consumption (standardised regression coefficient (β) = 0.25, p = 0.024). Baseline TNF-α was significantly associated with higher CES-D-R scores in 2019 (β = 0.23, p = 0.026), whereas IL-17A showed only a non-significant trend (β = 0.13, p = 0.231). No significant associations were observed among women or for IL-10. CONCLUSION: In this exploratory community-based study, higher IL-6 levels were modestly associated with concurrent depressive symptoms in men, and baseline TNFα showed a similarly modest association with depressive symptoms two years later as measured by the CESD-R. IL-17A showed a tentative trend that requires replication. These findings suggest possible sex-specific links between peripheral inflammation and depressive symptoms, but the results should be interpreted as hypothesis generating.

PURPOSE: This study investigated the association of polygenic risk scores (PRS) and lifestyle factors with type 2 diabetes mellitus development in Japanese populations and evaluated whether PRS can improve diabetes risk prediction beyond traditional risk factors. METHODS: We conducted a cross-sectional and a longitudinal study using the Shika resident cohort (n = 895) and the Toshiba worker cohort (n = 7,019), respectively. Participants were categorized into low, intermediate, and high genetic risk groups using PRS constructed with genome-wide association study data from East Asian populations. We defined diabetes based on hemoglobin A1c, fasting blood glucose, self-reported diagnosis, or medication use. The associations of PRS and lifestyle factors with diabetes development were analyzed using multivariate logistic regression and Cox proportional hazards models. RESULTS: Higher PRS were associated with increased diabetes risk in both cohorts (resident cohort: odds ratio 4.51, 95% confidence interval [CI] 2.53-8.04; worker cohort: hazard ratio 1.82, 95% CI 1.48-2.24 for high vs. low PRS), which remained consistent across age, body mass index, and comorbidities. Regular exercise, absence of hypertension, and absence of dyslipidemia were associated with lower diabetes risk, particularly in the high PRS group. The addition of PRS to conventional prediction models improved the discrimination of diabetes risk. MAIN CONCLUSIONS: PRS are associated with diabetes risk in Japanese general populations, independent of traditional risk factors. Nonetheless, healthy lifestyle habits may reduce diabetes risk even among genetically susceptible individuals, which support the utility of PRS for personalized diabetes risk assessment and prevention strategies.

BACKGROUND: Oxytocin (OXT) signaling through the oxytocin receptor (OXTR) produces stress-relieving effects and modulates alcohol reward and sucrose preference in animal models. These findings suggest the therapeutic potential of OXT for alcohol use disorder (AUD) and liver steatosis. However, human genetic evidence linking OXT signaling to these cravings remains scarce. OBJECTIVE: This study examined the association between the OXTR rs53576 polymorphism and habitual intake of alcohol and sucrose in a general population, with a further focus on related liver pathology. METHODS: A cross-sectional analysis was conducted using data from the Shika study, comprising 696 participants with complete information on both single-nucleotide polymorphisms (SNPs) and dietary intake, assessed using the Brief Dietary History Questionnaire (BDHQ). We examined the association of the rs53576 SNP with alcohol and sucrose consumption, as well as with clinical outcomes related to these dietary factors, including liver enzyme levels and liver steatosis. RESULTS: Among individuals with regular alcohol consumption, those with the rs53576 G/G genotype (under a recessive model) exhibited significantly lower alcohol intake (p = 0.002) and higher sucrose intake (p = 0.004) compared to A allele carriers. An association between rs53576 and aspartate aminotransferase (AST) levels, an indicator of alcoholic liver disease (ALD), further supported the relationship between this genotype and alcohol intake. Sex-stratified analysis revealed that the G/G genotype was linked to a greater prevalence of liver steatosis in women, but not in men. Mediation analysis indicated that this association in women was driven by a direct effect independent of sucrose intake volume. CONCLUSIONS: These findings indicate that the OXTR rs53576 polymorphism is associated with distinct alcohol and sucrose intake patterns and susceptibility to liver steatosis, supporting the potential for genotype-informed nutritional interventions aimed at reducing the risk of AUD, ALD, and metabolic dysfunction-associated steatotic liver disease (MASLD). CLINICAL TRIALS REGISTRATION NUMBER AND WEBSITE WHERE IT WAS OBTAINED: This study was approved by the Ethics Committee for Human Studies at Kanazawa University Hospital (1491, 2016-376) and performed following the principles outlined in the Declaration of Helsinki. Network Clinical Trials Registry (UMIN-CTR) under the registration number UMIN000024915. The detailed trial information is available at the following URL: https://center6.umin.ac.jp/cgi-open-bin/icdr/ctr_his_list.cgi?recptno=R000028662.

Although recent studies have reported the association between toxins produced by certain gut microbiota and elevated blood pressure, the relationship between oral frailty (OF) and gut microbiota has rarely been investigated. The purpose of this study was to epidemiologically investigate the relationship between the combination of OF and specific gut microbiota on hypertension in the residents of Shika Town, Ishikawa Prefecture, Japan. A total of 322 residents aged ⩾ 50 years in Shika Town agreed to participate and met the criteria. The OF was evaluated difficulty in chewing and swallowing, oral dryness, number of remaining teeth, and frequency of tooth brushing. Blood pressure was measured using an automatic digital blood pressure meter. Next-generation sequencing was used to analyze the gut microbiota. A two-way analysis of covariance revealed a significant interaction between the two OF groups and the two hypertension groups on Megamonas. The binomial logistic regression analysis stratified by OF revealed a positive correlation between Megamonas and hypertension (OR 1.317; P = 0.023). This cross-sectional epidemiological study of the local residents revealed that the abundance of Megamonas in the OF group was significantly higher in the hypertension group than in the normotension group; however, no such relationship was observed in the non-OF group.

Brain asymmetry is a fundamental feature of neural organization. However, the molecular basis of hippocampal lateralization in response to environmental stimuli remains poorly understood. Here, we examined the transcriptomic profiles of the left and right hippocampal CA1 regions in rats reared under isolated or enriched housing conditions to elucidate hemisphere-specific responses and shared molecular adaptations. RNA-sequencing analysis revealed lateralized differences in the number and identity of differentially expressed genes, accompanied by distinct biological themes, as indicated by overrepresentation and gene set enrichment analysis. The left CA1 region was prominently engaged in pathways related to synaptic organization and mitochondrial function, whereas the right CA1 region exhibited enrichment in transcriptional regulation and RNA metabolic processes. Despite these asymmetries, co-expression and protein–protein interaction network analyses revealed shared molecular architectures. Immediate early genes formed consistent central hubs across both hemispheres, and a common Mecp2–Grin2b–Cdkl5–Tet3 protein interaction cluster was identified as a potential integrative regulatory module. Additional enrichment analysis of differentially expressed genes shared between hemispheres further highlighted conserved responses, particularly in synaptic plasticity and cell–cell communication. Together, these findings demonstrate that the left and right CA1 regions employ distinct yet partially convergent transcriptional programs to adapt to environmental stimuli. This coordinated molecular asymmetry provides novel insights into hippocampal lateralization and its role in experience-dependent brain plasticity.