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Frontiers in Pharmacology 2020Epimutations secondary to gene-environment interactions have a key role in the pathophysiology of major psychiatric disorders. and evidence suggest that mood...
BACKGROUND
Epimutations secondary to gene-environment interactions have a key role in the pathophysiology of major psychiatric disorders. and evidence suggest that mood stabilizers can potentially reverse epigenetic deregulations found in patients with schizophrenia or mood disorders through mechanisms that are not yet fully understood. However, their activity on epigenetic processes has made them a research target for therapeutic approaches.
METHODS
We conducted a comprehensive literature search of PubMed and EMBASE for studies investigating the specific epigenetic changes induced by non-antipsychotic mood stabilizers (valproate, lithium, lamotrigine, and carbamazepine) in animal models, human cell lines, or patients with schizophrenia, bipolar disorder, or major depressive disorder. Each paper was reviewed for the nature of research, the species and tissue examined, sample size, mood stabilizer, targeted gene, epigenetic changes found, and associated psychiatric disorder. Every article was appraised for quality using a modified published process and those who met a quality score of moderate or high were included.
RESULTS
A total of 2,429 records were identified; 1,956 records remained after duplicates were removed and were screened title, abstract and keywords; 129 records were selected for full-text screening and a remaining of 38 articles were included in the qualitative synthesis. Valproate and lithium were found to induce broader epigenetic changes through different mechanisms, mainly DNA demethylation and histones acetylation. There was less literature and hence smaller effects attributable to lamotrigine and carbamazepine could be associated overall with the small number of studies on these agents. Findings were congruent across sample types.
CONCLUSIONS
An advanced understanding of the specific epigenetic changes induced by classic mood stabilizers in patients with major psychiatric disorders will facilitate personalized interventions. Further related drug discovery should target the induction of selective chromatin remodeling and gene-specific expression effects.
PubMed: 32390836
DOI: 10.3389/fphar.2020.00467 -
European Cardiology Jul 2019Acute coronary syndrome (ACS) is characterised by increased effector cells and decreased regulatory T-cells (Tregs). Statins have been shown to be clinically beneficial... (Review)
Review
The Effect of Statins on the Functionality of CD4+CD25+FOXP3+ Regulatory T-cells in Acute Coronary Syndrome: A Systematic Review and Meta-analysis of Randomised Controlled Trials in Asian Populations.
Acute coronary syndrome (ACS) is characterised by increased effector cells and decreased regulatory T-cells (Tregs). Statins have been shown to be clinically beneficial in ACS patients. This effect could be mediated via the induction of Tregs in ACS patients. The aim of this systemic review and meta-analysis was to evaluate whether statin therapy enhances the frequency of Tregs determined by CD4+CD25+FOXP3+ in this subset of patients. A comprehensive search of PubMed and Embase was performed. Studies were restricted to randomised controlled trials that quantified CD4+CD25+FOXP3+ cell frequency by flow cytometric analysis before and after statin treatment in adults diagnosed with ACS. A minimum of at least two of the conventional markers to identify Tregs was compulsory. Four randomised controlled trials studies (439 participants) were included, all with low-to-moderate risk of bias. Pooled data showed a significant increase in Treg frequency after statin therapy in ACS patients. A further meta-regression and subgroup analysis also showed a negative dose-related effect, and a statin type-related effect (rosuvastatin versus atorvastatin), respectively. The results confirmed that statins positively alter the frequency of Tregs, which may indicate a potential mechanism of their therapeutic effect. However, there was a risk of information bias due to the markers used to identify Tregs, which was not fully explored, therefore, further randomised controlled trials should utilise markers of Tregs, such as the FOXP3 locus (Treg-specific demethylated region), for identification.
PubMed: 31360235
DOI: 10.15420/ecr.2019.9.2