Epigenome-wide association study on methamphetamine dependence.

Repeated abuse of methamphetamine (METH) can cause dependence, repeated relapse of psychotic symptoms, compulsive drug-seeking behaviour, and various neurological symptoms. These long-term biological changes may be associated with epigenetic mechanisms; however, the association between METH use and epigenetic mechanisms has been poorly investigated. Thus, we performed an epigenome-wide association study of METH dependence using genomic DNA extracted from the blood samples of 24 patients with METH dependence and 24 normal controls. All participants were of Japanese descent. We tested the association between METH dependence and DNA methylation using linear regression analysis. We found epigenome-wide significant associations at four CpG sites, one of which occurred in the CNOT1 gene and another in the PUM1 gene. We especially noted the CNOT1 and PUM1 genes as well as several other genes that indicated some degree of association with METH dependence. Among the relatively enriched Gene Ontology terms, we were interested in terms of mRNA metabolism, respirasome, and excitatory extracellular ligand-gated ion channel activity. Among the relatively enriched Kyoto Encyclopedia of Genes and Genome pathways, we noted pathways of several neurological diseases. Our results indicate that genetic changes akin to those in other psychiatric or neurodegenerative disorders may also occur via epigenetic mechanisms in patients with METH dependence.

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.

Retrospective analysis of heroin detoxification with buprenorphine in a psychiatric hospital in Japan.

AIM: We assessed the efficacy of buprenorphine replacement taper therapy in a psychiatric hospital in Japan. METHODS: Based on the medical records, a retrospective analysis was performed to evaluate the outcomes of buprenorphine replacement taper therapy in 106 subjects with heroin dependence. RESULTS: We found that replacement and taper therapy with buprenorphine could significantly reduce withdrawal symptoms during detoxification. In addition, the completion rate of detoxification was significantly improved and the length of hospital stay was significantly reduced relative to those who received conventional treatment without buprenorphine. However, the readmission rate increased after the introduction of detoxication therapy with buprenorphine. CONCLUSION: The present findings suggest not only the efficacy and safety of buprenorphine replacement and taper therapy, but also the requirement for maintenance therapy for individuals with heroin dependence.