Epigenetic clock analysis in methamphetamine dependence.

Methamphetamine (MA) is used worldwide and causes serious public health and social problems. MA affects the central nervous, cardiac, and immune systems, which causes neuropsychiatric and cardiovascular diseases and infection. Epigenetic changes, including DNA methylation (DNAm), are associated with various clinical phenotypes of MA abuse. DNAm is related to biological aging and health risks; hence, we aimed to assess the changes in biological aging in MA dependence using the DNAm age and DNA methylation-based telomere length (DNAmTL). We used five measures of DNAm age (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, and GrimAge), DNAmTL, and DNAm-based age-predictive factors (plasma proteins and blood cell composition). We compared patients with MA dependence and healthy controls (n = 24 each) using the DNAm profiles obtained from whole-blood samples. Patients with MA dependence showed significant acceleration in PhenoAge and GrimAge, as well as a trend for significant acceleration in DNAmTL. Following adjustment for confounding factors, MA dependence was significantly associated with accelerations in PhenoAge, GrimAge, and DNAmTL, as well as alterations in DNAm-based age-predictive factors (beta-2-microglobulin, granulocytes, and naive cluster of differentiation 4+ T cells). Our results suggested an acceleration of biological aging and specific changes in the DNAm of age- predictive factors in MA dependence.

Accelerated epigenetic age and shortened telomere length based on DNA methylation in Nicolaides-Baraitser syndrome.

BACKGROUND: Nicolaides-Baraitser syndrome (NCBRS) is a rare disorder characterized by neurodevelopmental delays, seizures, and diverse physical characteristics. The DNA methylation (DNAm) profile in NCBRS is significantly different. DNAm is linked to the biological aging of cells and the health risks associated with biological aging. In this study, we examined changes in biological ages in NCBRS to provide insights into the prognosis and health risks of NCBRS. METHODS: We used a publicly available dataset to examine biological aging in NCBRS using DNAm-based epigenetic ages, such as PhenoAge and GrimAge, as well as DNAm-based estimator of telomere length (DNAmTL). We investigated 12 cases, clinically diagnosed as NCBRS, and 27 controls. RESULTS: Compared to controls, NCBRS cases exhibited significantly accelerated PhenoAge and GrimAge as well as significantly shortened DNAmTL. CONCLUSION: These results suggest an acceleration of biological aging in NCBRS and provide insights into the prognosis and health risks of NCBRS.

Psychological symptoms and related risk factors among healthcare workers and medical students during the early phase of the COVID-19 pandemic in Japan.

Aim: The aim of this study was to investigate the mental health status of healthcare workers and medical students during the early phase of the COVID-19 pandemic. Methods: An online questionnaire was administered to 637 students and 3189 healthcare workers from May to July, 2020. The patient healthcare questionnaire-9 (PHQ-9) and state anxiety (A-State) of the state-trait anxiety inventory-form (STAI) were used to assess depression and anxiety symptoms, respectively. Individuals were categorized into severe (15 or higher) depression and severe (50-51 or higher) anxiety groups. Results: Healthcare workers and those taking care of COVID-19 patients had a higher risk of severe depression (PHQ-9 scores >15) than other comparison groups. Students and men also had a higher risk of severe anxiety (STAI > 50-51). Multivariable logistic regression analysis showed that healthcare workers had a fivefold higher risk of developing severe depression symptoms (adjusted odds ratio [OR] = 4.99, confidence interval [CI] 2.24-5.97, P-value < 0.001) and those taking care of COVID-19 patients had 2.8-fold higher risk of developing severe depression symptoms (OR 2.75, CI 1.36-5.53, P-value = 0.005). Conclusion: Both medical students and healthcare workers have been experiencing depression and anxiety symptoms during the first wave of the pandemic. Our findings showed a high rate of severe anxiety symptoms in medical students and a high rate of severe depression symptoms in healthcare workers. Those who treated COVID-19 patients were at greater risk of developing major depressive disorder than those who treated non-COVID-19 patients.

Searching for biomarkers in schizophrenia and psychosis: Case-control study using capillary electrophoresis and liquid chromatography time-of-flight mass spectrometry and systematic review for biofluid metabolites.

Metabolomics has been attracting attention in recent years as an objective method for diagnosing schizophrenia. In this study, we analyzed 378 metabolites in the serum of schizophrenia patients using capillary electrophoresis- and liquid chromatography-time-of-flight mass spectrometry. Using multivariate analysis with the orthogonal partial least squares method, we observed significantly higher levels of alanine, glutamate, lactic acid, ornithine, and serine and significantly lower levels of urea, in patients with chronic schizophrenia compared to healthy controls. Additionally, levels of fatty acids (15:0), (17:0), and (19:1), cis-11-eicosenoic acid, and thyroxine were significantly higher in patients with acute psychosis than in those in remission. Moreover, we conducted a systematic review of comprehensive metabolomics studies on schizophrenia over the last 20 years and observed consistent trends of increase in some metabolites such as glutamate and glucose, and decrease in citrate in schizophrenia patients across several studies. Hence, we provide substantial evidence for metabolic biomarkers in schizophrenia patients through our metabolomics study.

Association of Two Variable Number of Tandem Repeats in the Monoamine Oxidase A Gene Promoter with Schizophrenia.

BACKGROUND: Monoamine oxidase-A (MAO-A) decomposes dopamine and serotonin, and decreased MAO-A expression increases monoamine levels and is related to the pathophysiology of schizophrenia. Previous studies have reported that variable number of tandem repeats (VNTR), namely, upstream (u)VNTR, and some single nucleotide polymorphisms (SNPs) in the MAOA gene are associated with schizophrenia. METHODS: We investigated the two VNTRs and their related SNPs (rs6323 and rs1137070) in the MAOA gene promoter in 859 patients with schizophrenia and 826 healthy controls. Distal (d)VNTR and uVNTR were genotyped with fluorescence-based fragment polymerase chain reaction assays, and rs6323 and rs1137070 with TaqMan SNP genotyping assays. RESULTS: Neither the genotype nor allelic frequency of the VNTRs or SNPs showed significant differences between the schizophrenia and control groups. On the other hand, analysis of the dVNTR-uVNTR-rs6323-rs1137070 haplotype showed significant association for nine repeats (9R)-3R-T-C in female patients (corrected p = 0.0006, odds ratio [confidence interval] = 2.17 [1.446-3.257]). CONCLUSION: Our findings provide novel evidence that MAOA gene polymorphisms are associated with an increased risk of developing schizophrenia in females.

Epigenetic Clock Analysis in Children With Fetal Alcohol Spectrum Disorder.

BACKGROUND: Fetal alcohol spectrum disorder (FASD) is characterized by severe clinical impairment, considerable social burden, and high mortality and morbidity, which are due to various malformations, sepsis, and cancer. As >50% of deaths from FASD occur during the first year of life, we hypothesized that there is the acceleration of biological aging in FASD. Several recent studies have established genome-wide DNA methylation (DNAm) profiles as "epigenetic clocks" that can estimate biological aging, and FASD has been associated with differential DNAm patterns. Therefore, we tested this hypothesis using epigenetic clocks. METHODS: We investigated 5 DNAm-based measures of epigenetic age (HorvathAge, HannumAge, SkinBloodAge, PhenoAge, and GrimAge) and telomere length (DNAmTL) using 4 independent publicly available DNAm datasets; 2 datasets were derived from buccal epithelium, and the other 2 datasets were derived from peripheral blood. RESULTS: Compared with controls, children with FASD exhibited an acceleration of GrimAge in 1 buccal and 2 blood datasets. No significant difference was found in other DNAm ages and DNAmTL. Meta-analyses showed a significant acceleration of GrimAge in the blood samples but not in the buccal samples. CONCLUSIONS: This study provides novel evidence regarding accelerated epigenetic aging in children with FASD.

Chemokine alterations in the postmortem brains of suicide completers.

Suicide is a major health problem in the modern world. However, its physiological mechanisms have not been well elucidated yet. Immunological disturbances have been reported in psychiatric disorders such as major depressive disorder (MDD), bipolar disorder (BP), and schizophrenia. Some studies have also suggested an association between immunological alterations especially neuroinflammation, and suicide. Chemokines play important roles in inflammation, and studies investigating chemokines in psychiatric diseases such as schizophrenia, MDD, and BP have reported chemokine dysregulations. However, there have been very few studies on the association between chemokines and suicide. We studied chemokine alterations in the postmortem brains of suicide completers and compared them to those of controls. We obtained brain tissue samples of the dorsolateral prefrontal cortex from 16 suicide completers and 23 controls. We examined the concentrations of chemokines and related substances in the brain tissue from these two groups using the Bio-Plex Pro™ Human Chemokine Panel 40-Plex. We performed multiple regression analysis with covariates. The levels of CCL1, CCL8, CCL13, CCL15, CCL17, CCL19, CCL20, CXCL11, and IL-10 were significantly decreased, whereas the IL-16 levels were significantly increased in the suicide completers after adjustment with the Benjamini-Hochberg method to control for type Ⅰ errors (Q < 0.05). The observed chemokine alterations might suggest the presence of suicide-specific immunological mechanisms.