epigenetics & major depression

BACKGROUND: Intergenerational transmission of trauma is a major focus of international research. Epigenetic, complex-trauma, and intergenerational abuse pattern transmission theoretical explanations all have existing empirical support. Three-D theory argues that in addition to trauma victimization severity, victimization invasiveness and exploitativeness have important independent effects. Moreover, 3-D theory claims that a positive 3-way interaction occurs between trauma victimization invasiveness, exploitativeness, and severity...

The presence of alien species represents a major cause of habitat degradation and biodiversity loss worldwide, constituting a critical environmental challenge of our time. Despite sometimes experiencing reduced propagule pressure, leading to a reduced genetic diversity and an increased chance of inbreeding depression, alien invaders are often able to thrive in the habitats of introduction, giving rise to the so-called "genetic paradox" of biological invasions. The adaptation of alien species to the new habitats is therefore a complex aspect of biological invasions, encompassing genetic, epigenetic, and ecological processes...

This review aims to explore the intricate relationship among epigenetic mechanisms, stress, and affective disorders, focusing on how early life experiences and coping mechanisms contribute to susceptibility to mood disorders. Epigenetic factors play a crucial role in regulating gene expression without altering the DNA (deoxyribonucleic acid) sequence, and recent research has revealed associations between epigenetic changes and maladaptive responses to stress or psychiatric disorders. A scoping review of 33 studies employing the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Statement) guidelines investigates the role of stress-induced epigenetic mechanisms and coping strategies in affective disorder occurrence, development, and progression...

Naked mole-rats, Heterocephalus glaber, are champion hypoxia-tolerant rodents that live under low oxygen conditions in their subterranean burrows. Detrimental effects of low oxygen can be mitigated through metabolic rate depression (MRD), metabolic reorganization, and global downregulation of nonessential cellular processes. Recent research has progressively implicated epigenetic modifications - rapid, reversible changes to gene expression that do not alter the DNA sequence itself - as major players in implementing and maintaining MRD...

Genes involved in the hypothalamic-pituitary-adrenal axis may be a robust biomarker of psychiatric disorders. Genetic polymorphisms of the SKA2 gene are associated with several behavioral disorders. In this study, we embarked on a systematic search of all possible reports of genetic association with SKA2 and affective disorder, post-traumatic stress disorder, and suicide behavior; the functional consequences of nsSNPs were explored through computational tools with an in silico analysis. Eight eligible articles were included...

BACKGROUND: Epigenetic modifications, such as DNA methylation, contribute to the pathophysiology of major depressive disorder (MDD). This study aimed to identify novel MDD-associated epigenetic loci using DNA methylation profiles and explore the correlations between epigenetic loci and cortical thickness changes in patients with MDD. METHODS: A total of 350 patients with MDD and 161 healthy controls (HCs) were included in the epigenome-wide association studies (EWAS)...

Depression is highly prevalent globally, however, currently available medications face challenges such as low response rates and short duration of efficacy. Additionally, depression mostly accompany other psychiatric disorders, further progressing to major depressive disorder without long-term effective management. Thus, sustained antidepressant strategies are urgently needed. Recently, ketamine and psilocybin gained attention as potential sustained antidepressants. Review of recent studies highlights that synaptic plasticity changes as key events of downstream long-lasting changes in sustained antidepressant effect...

Major Depressive Disorder (MDD) is a global health concern, affecting over 250 million individuals worldwide. In recent years, the gut-brain axis has emerged as a promising field for understanding the pathophysiology of MDD. Microbial metabolites, such as Short-Chain Fatty Acids (SCFAs) - acetate, butyrate, and propionate -, have gained attention for their potential to influence epigenetic modifications within the host brain. However, the precise mechanisms through which these metabolites participate in MDD pathophysiology remain elusive...

Major depressive disorder (MDD) is associated with interoceptive processing dysfunctions, but the molecular mechanisms underlying this dysfunction are poorly understood. This study combined brain neuronal-enriched extracellular vesicle (NEEV) technology and serum markers of inflammation and metabolism with Functional Magnetic Resonance Imaging (fMRI) to identify the contribution of gene regulatory pathways, in particular micro-RNA (miR) 93, to interoceptive dysfunction in MDD. Individuals with MDD (n = 41) and healthy comparisons (HC; n = 35) provided blood samples and completed an interoceptive attention task during fMRI...

BACKGROUND: Recent developments in metabolomics, transcriptomic and epigenetics open up new horizons regarding the pharmacological understanding of phytocannabinoids as neuromodulators in treating anxiety, depression, epilepsy, Alzheimer's, Parkinson's disease and autism. METHODS: The present review is an extensive search in public databases, such as Google Scholar, Scopus, the Web of Science, and PubMed, to collect all the literature about the neurobiological roles of cannabis extract, cannabidiol, 9-tetrahydrocannabinol specially focused on metabolomics, transcriptomic, epigenetic, mechanism of action, in different cell lines, induced animal models and clinical trials...

Despite the hardships of major depressive disorder (MDD), biomarkers for the diagnosis and pharmacological management of this condition are lacking. MicroRNAs are epigenetic mechanisms that could provide promising MDD biomarkers. Our aim was to summarize the findings and provide validation for the selection and use of specific microRNAs as biomarkers in the diagnosis and treatment of MDD. A systematic review was conducted using the PubMed/Medline, Cochrane, PsycINFO, Embase, and LILACS databases from March 2022 to November 2023, with clusters of terms based on "microRNA" and "antidepressant"...

Major depressive disorder (MDD) is a debilitating and prevalent mental disorder with a high disease burden. Despite a wide array of different treatment options, many patients do not respond to initial treatment attempts. Selection of the most appropriate treatment remains a significant clinical challenge in psychiatry, highlighting the need for the development of biomarkers with predictive utility. Recently, the epigenetic modification DNA methylation (DNAm) has emerged to be of great interest as a potential predictor of MDD treatment outcomes...

For the first time after many decades, many new antidepressants have been approved and many more are under various stages of development and will soon be available in the market. The new drugs present a range of new mechanisms of action with benefits in terms of speed of action, tolerability and range of treatable disorders. Neurosteroids have been recently approved and their rapid benefit may extend from postpartum depression to anxious depression and bipolar depression, dextromethorphan and bupropion combination may prove useful in major depression but also in treatment resistant depression, dextromethadone is a possible augmentation in partial antidepressant response, psychedelic drugs have the potential of long lasting benefits after a single administration, though are still experimental treatments...

Epigenetic regulation of gene expression is involved in the progression of mental disorders, including deviant behavior, brain developmental, and personality disorders. The large number of genes has been studied for their activity association with stress and depression; however, the obtained results for the majority of these genes are contradictory. The aim of our study was to investigate the possible contribution of methylation level changes to the development of personality disorders and deviant behavior...

BACKGROUND: Given the inconsistencies in current studies regarding the impact of FKBP5 gene polymorphisms on depression, arising from variations in study methods, subjects, and treatment strategies, this paper provides a comprehensive review of the relationship between FKBP5 gene polymorphisms and genetic susceptibility to depression, as well as their influence on response to antidepressant treatment. METHODS: Electronic databases were searched up to April 11, 2023, for all literature in English and Chinese on depression, FKBP5 gene polymorphisms, and antidepressant treatment...

The serotonin 1A receptor has been linked to both the pathophysiology of major depressive disorder (MDD) and the antidepressant action of serotonin reuptake inhibitors. Most PET studies of the serotonin 1A receptor in MDD used the receptor antagonist radioligand, [carbonyl- 11 C]WAY100635; however the interpretation of the combined results has been contentious owing to reports of higher or lower binding in MDD with different outcome measures. The reasons for these divergent results originate from several sources, including properties of the radiotracer itself, which complicate its quantification and interpretation; as well as from previously reported differences between MDD and healthy volunteers in both reference tissue binding and plasma free fraction, which are typically assumed not to differ...

Various studies have indicated that the prevalence of depression is almost twice as high among women as among men. A major factor associated with the development of depression and other affective disorders are adverse and psychologically traumatic life events that contribute to changes in the neuroendocrine system, altering the capacity to adapt to stress. These changes are involved in the pathogenesis of mental disorders, along with genetic and other factors, and are to a significant degree regulated by gender dependent mechanisms...

Depression is linked to stress which leaves traces in the epigenetic signature of genes. The oxytocin system is implicated in allostatic processes promoting adaption to environmental stressors. Interactions of the oxytocin system with the environment, e.g., methylation of the gene coding for oxytocin (OXT), are candidates for the investigation of the biological underpinnings of depression. Recently, we found hypomethylation of OXT in patients with Major Depressive Disorder (MDD) compared to healthy controls (HC)...

Mood disorders, including major depressive disorder and bipolar disorder, are highly prevalent and stand among the leading causes of disability. Despite the largely elusive nature of the molecular mechanisms underpinning these disorders, two pivotal contributors-mitochondrial dysfunctions and epigenetic alterations-have emerged as significant players in their pathogenesis. This state-of-the-art review aims to present existing data on epigenetic alterations in the mitochondrial genome in mood disorders, laying the groundwork for future research into their pathogenesis...

BACKGROUND: Military sexual trauma (MST) is a prevalent issue within the U.S. military. Victims are more likely to develop comorbid diseases such as posttraumatic stress disorder (PTSD) and major depressive disorder (MDD). Nonetheless, not everyone who suffers from MST develops PTSD and/or MDD. DNA methylation, which can regulate gene expression, might give us insight into the molecular mechanisms behind this discrepancy. Therefore, we sought to identify genomic loci and enriched biological pathways that differ between patients with and without MST, PTSD, and MDD...