Yukiko Tomioka, Masahito Nakataki, Hidehiro Umehara, Tomohiro Yoshida, Hiroya Matsuda, Yui Matsumoto, Mariko Aoki, Yuri Yoshida, Yuichiroh Kamiyama, Tomohiko Nakayama, Naoki Yamada and Shusuke Numata : DNMT gene expression in peripheral leukocytes in schizophrenia and correlations with one-carbon metabolites: folate, total homocysteine, and vitamin B6., Frontiers in Psychiatry, 16, 2026.
(Summary)
Previous studies have identified alterations in one-carbon metabolism (OCM), including DNA methylation abnormalities, in individuals with schizophrenia. However, the precise etiology of this disorder remains unclear. In the present study, we examined variations in the expression of DNMT1 and DNMT3a-genes implicated in DNA methylation-using peripheral blood leukocytes from Japanese patients with chronic schizophrenia and healthy controls. Additionally, using our previously acquired data, we explored the association between OCM-related factors and DNMT expression levels.Expression levels of DNMT1 and DNMT3a in 215 patients with chronic schizophrenia and 210 healthy controls were quantified using real-time PCR. The Mann-Whitney U test was used to compare the differences between two independent groups. Furthermore, Spearman's correlation analysis was conducted to investigate the relationships between DNMT genes` expression levels and OCM-related metabolites (blood folate, vitamin B6, and total homocysteine).The expression levels of DNMT1 and DNMT3a in peripheral leukocytes were significantly elevated in patients with chronic schizophrenia compared with controls (p = 1.4 × 10-6 and 2.9 × 10-3, respectively). DNMT1 mRNA expression levels exhibited a weak negative correlation with folate exclusively in the aggregated cohort (N = 425) (ρ = -0.16, adjusted q = 5.0 × 10-3), and DNMT3a mRNA expression levels showed a weak negative correlation with vitamin B6 alone in the combined group (ρ = -0.12, adjusted q = 0.03).These findings suggest a potential correlation between nutritional status and elevated expression of DNMT1 and DNMT3a in schizophrenia. Our findings contribute to the understanding of the epigenetic mechanisms associated with schizophrenia and highlight the need for further investigation of the relationships among gene expression, nutritional status, and psychiatric manifestations.
Toshiyuki Shirai, Satoshi Okazaki, Takaki Tanifuji, Shusuke Numata, Tomohiko Nakayama, Tomohiro Yoshida, Kentaro Mouri, Ikuo Otsuka, Noboru Hiroi and Akitoyo Hishimoto : Meta-analyses of epigenetic age acceleration and GrimAge components of schizophrenia or first-episode psychosis., Schizophrenia, 10, 1, 108, 2024.
(Summary)
Schizophrenia is a common chronic psychiatric disorder that causes age-related dysfunction. The life expectancy in patients with schizophrenia is 10 years shorter than that in the general population because of the higher risk of other diseases, such as cardiovascular diseases. Aging studies based on DNA methylation status have received considerable attention. Several epigenetic age accelerations and predicted values of aging-related proteins (GrimAge and GrimAge2 components) have been analyzed in multiple diseases. However, no studies have investigated up to GrimAge and GrimAge2 components between patients with schizophrenia and controls. Therefore, we aimed to conduct multiple regression analyses to investigate the association between schizophrenia and epigenetic age accelerations and GrimAge and GrimAge2 components in seven cohorts. Furthermore, we included patients with first-episode psychosis whose illness duration was often shorter than schizophrenia in our analysis. We integrated these results with meta-analyses, noting the acceleration of GrimAge, GrimAge2, and DunedinPACE, and increase in adrenomedullin, beta-2 microglobulin, cystatin C, and plasminogen activation inhibitor-1 levels, in patients with schizophrenia or first-episode psychosis. These results corroborated the finding that patients with schizophrenia had an increased risk of diabetes, cardiovascular disease, and cognitive dysfunction from a biological perspective. Patients with schizophrenia and first-episode psychosis showed differences in the results when compared with controls. Such analyses may lead to the development of novel therapeutic targets to patients with schizophrenia or relevant diseases from the perspective of aging in the future.
Tomoya Takeda, Hidehiro Umehara, Yui Matsumoto, Tomohiro Yoshida, Masahito Nakataki and Shusuke Numata : Schizophrenia and cognitive dysfunction., The Journal of Medical Investigation : JMI, 71, 3.4, 205-209, 2024.
(Summary)
Schizophrenia is a psychiatric disorder with cognitive dysfunction as a core symptom along with positive and negative symptoms. Cognitive dysfunction in schizophrenia can be broadly classified into neurocognitive and social cognitive deficits, with these deficits significantly influencing social functioning. Therapeutic interventions aiming to enhance neurocognition and social cognition have been developed. In this review, we describe the characteristics of cognitive dysfunction in patients with schizophrenia, its relationship to social function, and intervention strategies. J. Med. Invest. 71 : 205-209, August, 2024.