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Epigenetics major depression

Hilde de Kluiver, Jacobine E Buizer-Voskamp, Conor V Dolan, Dorret I Boomsma
We review the hypotheses concerning the association between the paternal age at childbearing and childhood psychiatric disorders (autism spectrum- and attention deficit/hyperactive disorder) and adult disorders (schizophrenia, bipolar-, obsessive-compulsive-, and major depressive disorder) based on epidemiological studies. Several hypotheses have been proposed to explain the paternal age effect. We discuss the four main-not mutually exclusive-hypotheses. These are the de novo mutation hypothesis, the hypothesis concerning epigenetic alterations, the selection into late fatherhood hypothesis, and the environmental resource hypothesis...
October 22, 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
E Rizos, N Siafakas, E Skourti, C Papageorgiou, J Tsoporis, T H Parker, D I Christodoulou, D A Spandidos, E Katsantoni, V Zoumpourlis
Schizophrenia (SZ) and cancer (Ca) have a broad spectrum of clinical phenotypes and a complex biological background, implicating a large number of genetic and epigenetic factors. SZ is a chronic neurodevelopmental disorder signified by an increase in the expression of apoptotic molecular signals, whereas Ca is conversely characterized by an increase in appropriate molecular signaling that stimulates uncontrolled cell proliferation. The rather low risk of developing Ca in patients suffering from SZ is a hypothesis that is still under debate...
October 14, 2016: Molecular Medicine Reports
Stefania Prendes-Alvarez, Charles B Nemeroff
Personalized or precision medicine is a medical discipline that proposes tailoring health care to each individual by integrating data from their genetic makeup, epigenetic modifications, other biomarkers, clinical symptoms and environmental exposures. Currently, patients typically present for treatment of mood disorders relatively late in the disease course and this is of great concern both because delay in attaining remission reduces the success of subsequent treatment and depressive episodes have negative cumulative effects on the brain and body...
October 13, 2016: Neuroscience Letters
Salil Saurav Pathak, Swati Maitra, Sumana Chakravarty, Arvind Kumar
Major depressive disorder (MDD) is debilitating mental illness and is one of the leading contributors to global burden of disease, but unfortunately newer and better drugs are not forthcoming. The reason is lack of complete understanding of molecular mechanisms underlying the development of this disorder. Recent research shows dysregulation in epigenetic regulatory mechanisms, particularly the transcriptionally repressive di- and tri-methylation of histone 3 lysine 9 (H3K9me2/me3) in nucleus accumbens (NAc), a critical region of the reward pathway involved in the development of anhedonia, the hallmark of depression...
October 6, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
S Jha, B E Dong, Y Xue, D F Delotterie, M G Vail, K Sakata
Reduced promoter IV-driven expression of brain-derived neurotrophic factor (BDNF) is implicated in stress and major depression. We previously reported that defective promoter IV (KIV) caused depression-like behavior in young adult mice, which was reversed more effectively by enriched environment treatment (EET) than antidepressants. The effects of promoter IV-BDNF deficiency and EET over the life stages remain unknown. Since early-life development (ED) involves dynamic epigenetic processes, we hypothesized that EET during ED would provide maximum antidepressive effects that would persist later in life due to enhanced, long-lasting BDNF induction...
2016: Translational Psychiatry
G Brand, B Schaal
Research on sensorial interactions with psychiatric diseases and particularly with the depressive syndrome has mainly focused on visual or auditory processes and much less on olfaction. The depressive illness is one of the most frequent psychiatric diagnoses in the community, with approximately one in five women and one in eight men experiencing a major depressive episode during their lifetime. Although genetic, epigenetic, neuroanatomical, neurochemical, neuroendocrinological and neuroimmunological changes can be detected during depression, the etiology of depression remains partly unclear...
September 9, 2016: L'Encéphale
Chiara Fabbri, Ladislav Hosak, Rainald Mössner, Ina Giegling, Laura Mandelli, Frank Bellivier, Stephan Claes, David A Collier, Alejo Corrales, Lynn E Delisi, Carla Gallo, Michael Gill, James L Kennedy, Marion Leboyer, Amanda Lisoway, Wolfgang Maier, Miguel Marquez, Isabelle Massat, Ole Mors, Pierandrea Muglia, Markus M Nöthen, Michael C O'Donovan, Jorge Ospina-Duque, Peter Propping, Yongyong Shi, David St Clair, Florence Thibaut, Sven Cichon, Julien Mendlewicz, Dan Rujescu, Alessandro Serretti
Major depressive disorder (MDD) is a heritable disease with a heavy personal and socio-economic burden. Antidepressants of different classes are prescribed to treat MDD, but reliable and reproducible markers of efficacy are not available for clinical use. Further complicating treatment, the diagnosis of MDD is not guided by objective criteria, resulting in the risk of under- or overtreatment. A number of markers of MDD and antidepressant response have been investigated at the genetic, epigenetic, gene expression and protein levels...
September 7, 2016: World Journal of Biological Psychiatry
Nataša Karas Kuželički
Preclinical Research S-adenosyl methionine (SAM) is a major methyl donor and as such exerts its influence on CNS function through methylation reactions, such as methylation of several catecholamine moiety-containing neurotransmitters, epigenetic changes through methylation of DNA, RNA, RNA-binding proteins and histones, and phospholipid methylation. Based on available evidence, SAM is currently recommended as a next-step (second-line) treatment option following inadequate treatment response to a first-line antidepressant...
September 4, 2016: Drug Development Research
Bhaskar Roy, Michael Dunbar, Richard C Shelton, Yogesh Dwivedi
Major depressive disorder (MDD) is predicted to be the second leading cause of global disease burden by 2030. A large number of MDD patients do not respond to the currently available medication because of its poorly understood etiology. Recently, studies of microRNAs (miRNAs), which act as a molecular switch of gene expression, have shown promise in identifying a molecular network that could provide significant clues to various psychiatric illnesses. Using an in vitro system, a rodent depression model, and a human postmortem brain, we investigated the role of a brain-enriched, neuron-specific miRNA, miR-124-3p, whose expression is highly dysregulated in stressed rodents, and identified a set of target genes involved in stress response and neural plasticity...
October 5, 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Roger Negrete, María Salud García Gutiérrez, Jorge Manzanares, Rafael Maldonado
Joint pain is a major clinical problem mainly associated to osteoarthritis, and characterized by articular cartilage degradation resulting in a complex chronic pain state that includes nociceptive, emotional and cognitive manifestations. Memory impairment, depressive- and anxiety-like symptoms have been reported to be associated with chronic pain, leading to a decrease of life quality. In this study, we evaluated the involvement of the endogenous dynorphin/kappa opioid receptor (KOR) system on the nociceptive, emotional, cognitive, neurochemical and epigenetic manifestations of joint pain...
August 24, 2016: Neuropharmacology
Kathleen Saavedra, Ana María Molina-Márquez, Nicolás Saavedra, Tomás Zambrano, Luis A Salazar
Major depressive disorder (MDD) is a chronic disease whose neurological basis and pathophysiology remain poorly understood. Initially, it was proposed that genetic variations were responsible for the development of this disease. Nevertheless, several studies within the last decade have provided evidence suggesting that environmental factors play an important role in MDD pathophysiology. Alterations in epigenetics mechanism, such as DNA methylation, histone modification and microRNA expression could favor MDD advance in response to stressful experiences and environmental factors...
2016: International Journal of Molecular Sciences
Corina Nagy, Susana G Torres-Platas, Naguib Mechawar, Gustavo Turecki
BACKGROUND: Major depressive disorder (MDD) has been associated with dysfunctional astrocytic networks. The underlying causes, extent, and consequences of such dysfunctions remain to be characterized. Astrocyte-astrocyte communication occurs principally through gap junction channels primarily formed by connexin 30 and 43 (CX30 and CX43). We previously reported decreased connexin expression in the prefrontal cortex (PFC) of depressed suicides. In the present study, we investigated whether these changes are mediated by epigenetic regulation, and expanded gene expression quantifications to other cortical and subcortical regions to assess the regional distribution of connexion disruptions in depressed suicides...
August 11, 2016: International Journal of Neuropsychopharmacology
Cristiana Cruceanu, Elena Kutsarova, Elizabeth S Chen, David R Checknita, Corina Nagy, Juan Pablo Lopez, Martin Alda, Guy A Rouleau, Gustavo Turecki
BACKGROUND: The Synapsins (SYN1, SYN2, and SYN3) are important players in the adult brain, given their involvement in synaptic transmission and plasticity, as well as in the developing brain through roles in axon outgrowth and synaptogenesis. We and others previously reported gene expression dysregulation, both as increases and decreases, of Synapsins in mood disorders, but little is known about the regulatory mechanisms leading to these differences. Thus, we proposed to study DNA methylation at theses genes' promoter regions, under the assumption that altered epigenetic marks at key regulatory sites would be the cause of gene expression changes and thus part of the mood disorder etiology...
2016: BMC Psychiatry
K Malki, E Koritskaya, F Harris, K Bryson, M Herbster, M G Tosto
Although monozygotic (MZ) twins share the majority of their genetic makeup, they can be phenotypically discordant on several traits and diseases. DNA methylation is an epigenetic mechanism that can be influenced by genetic, environmental and stochastic events and may have an important impact on individual variability. In this study we explored epigenetic differences in peripheral blood samples in three MZ twin studies on major depressive disorder (MDD). Epigenetic data for twin pairs were collected as part of a previous study using 8...
2016: Translational Psychiatry
Juan Ausió
Methyl CpG binding protein 2 (MeCP2) is a highly abundant chromosomal protein within the brain. It is hence not surprising that perturbations in its genome-wide distribution, and at particular loci within this tissue, can result in widespread neurological disorders that transcend the early implications of this protein in Rett syndrome (RTT). Yet, the details of its role and involvement in chromatin organization are still poorly understood. This paper focuses on what is known to date about all of this with special emphasis on the relation to different epigenetic modifications (DNA methylation, histone acetylation/ubiquitination, MeCP2 phosphorylation and miRNA)...
2016: Clinical Epigenetics
Silja McIlwrick, Alexandra Rechenberg, Mariana Matthes, Jessica Burgstaller, Thomas Schwarzbauer, Alon Chen, Chadi Touma
A dysregulation of the hypothalamus-pituitary-adrenocortical (HPA) axis and the experience of early-life adversity are both well-established risk factors for the development of affective disorders, such as major depression. However, little is known about the interaction of these two factors in shaping endophenotypes of the disease. Here, we studied the gene-environment interaction of a genetic predisposition for HPA axis dysregulation with early-life stress (ELS), assessing the short-, as well as the long-lasting consequences on emotional behavior, neuroendocrine functions and gene expression profiles...
August 2016: Psychoneuroendocrinology
Carlos Osório, Thomas Probert, Edgar Jones, Allan H Young, Ian Robbins
There is significant variation in the way individuals react and respond to extreme stress and adversity. While some individuals develop psychiatric conditions such as Post-Traumatic Stress Disorder (PTSD) or Major Depressive Disorder (MDD), others, recover from stressful experiences without displaying significant symptoms of psychological ill-health, demonstrating stress-resilience. To understand why some individuals exhibit characteristics of a resilient profile, the interplay between neurochemical, genetic and epigenetic processes over time needs to be explained...
April 21, 2016: Behavioral Medicine
Elsa M Meylan, Olivier Halfon, Pierre J Magistretti, Jean-René Cardinaux
Major depression is a highly complex disabling psychiatric disorder affecting millions of people worldwide. Despite the availability of several classes of antidepressants, a substantial percentage of patients are unresponsive to these medications. A better understanding of the neurobiology of depression and the mechanisms underlying antidepressant response is thus critically needed. We previously reported that mice lacking CREB-regulated transcription coactivator 1 (CRTC1) exhibit a depressive-like phenotype and a blunted antidepressant response to the selective serotonin reuptake inhibitor fluoxetine...
August 2016: Neuropharmacology
Charles B Nemeroff
In the past two decades, much evidence has accumulated unequivocally demonstrating that child abuse and neglect is associated with a marked increase in risk for major psychiatric disorders (major depression, bipolar disorder, post-traumatic stress disorder [PTSD], substance and alcohol abuse, and others) and medical disorders (cardiovascular disease, diabetes, irritable bowel syndrome, asthma, and others). Moreover, the course of psychiatric disorders in individuals exposed to childhood maltreatment is more severe...
March 2, 2016: Neuron
Chun-Lin Su, Chun-Wei Su, Ya-Hsin Hsiao, Po-Wu Gean
Major depressive disorder (MDD), one of the most common mental disorders, is a significant risk factor for suicide and causes a low quality of life for many people. However, the causes and underlying mechanism of depression remain elusive. In the current work, we investigated epigenetic regulation of BDNF in the learned helplessness-induced animal model of depression. Mice were exposed to inescapable stress and divided into learned helplessness (LH) and resilient (LH-R) groups depending on the number they failed to escape...
May 2016: Journal of Psychiatric Research
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