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major depression & suicide & epigenetics

Qingzhong Wang, Bhaskar Roy, Gustavo Turecki, Richard C Shelton, Yogesh Dwivedi
OBJECTIVE: Proinflammatory cytokines have recently received considerable attention for their role in suicidal behavior; however, how the expression of cytokine genes is regulated is not clearly known. The authors examined underlying mechanisms of critical cytokine gene tumor necrosis factor-alpha (TNF-α) dysregulation in the brains of individuals who died by suicide. METHOD: TNF-α expression was examined in the dorsolateral prefrontal cortex of the postmortem brains of persons with and without major depressive disorder who died by suicide and of persons with major depressive disorder who died of causes other than suicide...
March 1, 2018: American Journal of Psychiatry
Pierre-Eric Lutz, Jeffrey A Gross, Sabine K Dhir, Gilles Maussion, Jennie Yang, Alexandre Bramoulle, Michael J Meaney, Gustavo Turecki
BACKGROUND: Experiences of abuse and neglect during childhood are major predictors of the emergence of depressive and suicidal behaviors throughout life. The underlying biological mechanisms, however, remain poorly understood. Here, we focused on the opioid system as a potential brain substrate mediating these effects. METHODS: Postmortem samples from three brain structures regulating social bonds and emotions were analyzed. Groups were constituted of depressed individuals who died by suicide, with or without a history of severe child abuse, and of psychiatrically healthy control subjects...
July 27, 2017: Biological Psychiatry
Bhaskar Roy, Richard C Shelton, Yogesh Dwivedi
Stress plays an important role in major depressive disorder (MDD) and is one of the state dependent factors in suicidal behavior. A dysfunctional hypothalamic-pituitary-adrenal axis is a common feature in this disorder. The involvement of environmental factors has added additional complexity to understanding depression or suicidal behavior. In this regard, epigenetic regulation has been considered a mechanistic interface between environmental stress stimuli and altered functioning of underlying gene network that may increase susceptibility to depression or suicidal behavior...
June 2017: Journal of Psychiatric Research
T M Murphy, B Crawford, E L Dempster, E Hannon, J Burrage, G Turecki, Z Kaminsky, J Mill
Major depressive disorder (MDD) represents a major social and economic health issue and constitutes a major risk factor for suicide. The molecular pathology of suicidal depression remains poorly understood, although it has been hypothesised that regulatory genomic processes are involved in the pathology of both MDD and suicidality. In this study, genome-wide patterns of DNA methylation were assessed in depressed suicide completers (n=20) and compared with non-psychiatric, sudden-death controls (n=20) using tissue from two cortical brain regions (Brodmann Area 11 (BA11) and Brodmann Area 25 (BA25))...
January 3, 2017: Translational Psychiatry
Swapnali Barde, Joelle Rüegg, Josée Prud'homme, Tomas J Ekström, Miklos Palkovits, Gustavo Turecki, Gyorgy Bagdy, Robert Ihnatko, Elvar Theodorsson, Gabriella Juhasz, Rochellys Diaz-Heijtz, Naguib Mechawar, Tomas G M Hökfelt
Major depressive disorder (MDD) is a substantial burden to patients, families, and society, but many patients cannot be treated adequately. Rodent experiments suggest that the neuropeptide galanin (GAL) and its three G protein-coupled receptors, GAL1-3, are involved in mood regulation. To explore the translational potential of these results, we assessed the transcript levels (by quantitative PCR), DNA methylation status (by bisulfite pyrosequencing), and GAL peptide by RIA of the GAL system in postmortem brains from depressed persons who had committed suicide and controls...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
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...
December 2016: Molecular Medicine Reports
Corina Nagy, Susana G Torres-Platas, Naguib Mechawar, Gustavo Turecki
Background: Major depressive disorder 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 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...
January 1, 2017: International Journal of Neuropsychopharmacology
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
Fatemeh Haghighi, Hanga Galfalvy, Sean Chen, Yung-Yu Huang, Thomas B Cooper, Ainsley K Burke, Maria A Oquendo, J John Mann, M Elizabeth Sublette
Polyunsaturated fatty acid (PUFA) status has been associated with neuropsychiatric disorders, including depression and risk of suicide. Long-chain PUFAs (LC-PUFAs) are obtained in the diet or produced by sequential desaturation and elongation of shorter-chain precursor fatty acids linoleic acid (LA, 18:2n-6) and α-linolenic acid (ALA, 18:3n-3). We compared DNA methylation patterns in genes involved in LC-PUFA biosynthesis in major depressive disorder (MDD) with (n = 22) and without (n = 39) history of suicide attempt, and age- and sex-matched healthy volunteers (n = 59)...
2015: Frontiers in Neurology
Fatemeh Haghighi, Yurong Xin, Benjamin Chanrion, Anne H O'Donnell, Yongchao Ge, Andrew J Dwork, Victoria Arango, J John Mann
Clinical studies find that childhood adversity and stressful life events in adulthood increase the risk for major depression and for suicide. The predispositions to either major depression or suicide are thought to depend on genetic risk factors or epigenetic effects. We investigated DNA methylation signatures postmortem in brains of suicides with diagnosis of major depressive disorder. DNA methylation levels were determined at single C-phosphate-G (CpG) resolution sites within ventral prefrontal cortex of 53 suicides and nonpsychiatric controls, aged 16 to 89 years...
September 2014: Dialogues in Clinical Neuroscience
Emma L Dempster, Chloe C Y Wong, Kathryn J Lester, Joe Burrage, Alice M Gregory, Jonathan Mill, Thalia C Eley
BACKGROUND: Adolescent depression is a common neuropsychiatric disorder that often continues into adulthood and is associated with a wide range of poor outcomes including suicide. Although numerous studies have looked at genetic markers associated with depression, the role of epigenetic variation remains relatively unexplored. METHODS: Monozygotic (MZ) twins were selected from an adolescent twin study designed to investigate the interplay of genetic and environmental factors in the development of emotional and behavioral difficulties...
December 15, 2014: Biological Psychiatry
Kyoung-Sae Na, Hun Soo Chang, Eunsoo Won, Kyu-Man Han, Sunyoung Choi, Woo Suk Tae, Ho-Kyoung Yoon, Yong-Ku Kim, Sook-Haeng Joe, In-Kwa Jung, Min-Soo Lee, Byung-Joo Ham
BACKGROUND: DNA methylation in the promoter region of the glucocorticoid receptor gene (NR3C1) is closely associated with childhood adversity and suicide. However, few studies have examined NR3C1 methylation in relation to major depressive disorder (MDD) and hippocampal subfield volumes. We investigated the possible association between NR3C1 methylation and structural brain alterations in MDD in comparison with healthy controls. METHODS: We compared the degree of NR3C1 promoter methylation in the peripheral blood of non-psychotic outpatients with MDD and that of healthy controls...
2014: PloS One
Pavo Filaković, Anamarija Petek Erić
The psychopathological dynamics in suicidality overcomes actual diagnostic distribution therefore pharmacotherapy has restricted role in overall prevention of suicidal behaviour among mentally ill and is demanding for clinician. This role is achieved through reduction and alleviation of suicidal risk with rational and individual pharmacotherapeutic approach emphasising effective, safe and tolerable treatment. The genetic and epigenetic factors, dysfunction of neurotransmitter, neuroendocrine system and stress response system has been determining for neurobiology of suicidality...
September 2013: Collegium Antropologicum
Hee-Ju Kang, Jae-Min Kim, Ju-Yeon Lee, Seon-Young Kim, Kyung-Yeol Bae, Sung-Wan Kim, Il-Seon Shin, Hye-Ran Kim, Myung-Geun Shin, Jin-Sang Yoon
INTRODUCTION: Suicide is a major health problem, and depression is a major psychiatric cause of suicide. Suicide is influenced by the multifactorial interaction of many risk factors. Therefore, epigenetic research may lead to understandings that are applicable to suicide. This study investigated whether epigenetic changes are associated with suicidal behavior and evaluated the treatment outcome of suicidal ideation in depressive patients. METHODS: In 108 patients with major depression, the promoter methylation of the gene encoding brain-derived neurotrophic factor (BDNF) was measured...
November 2013: Journal of Affective Disorders
Martin H Teicher, Jacqueline A Samson
OBJECTIVE: Childhood maltreatment increases risk for psychopathology. For some highly prevalent disorders (major depression, substance abuse, anxiety disorders, and posttraumatic stress disorder) a substantial subset of individuals have a history of maltreatment and a substantial subset do not. The authors examined the evidence to assess whether those with a history of maltreatment represent a clinically and biologically distinct subtype. METHOD: The authors reviewed the literature on maltreatment as a risk factor for these disorders and on the clinical differences between individuals with and without a history of maltreatment who share the same diagnoses...
October 2013: American Journal of Psychiatry
Milica Pjevac, Peter Pregelj
It is known that suicidal behaviour has multiple causes. If triggers could be mainly attributed to environmental factors, predisposition could be associated with early stressors on one side such as childhood adversities and genetic predisposition. No convincing animal model of suicide has been produced to date. The study of endophenotypes has been proposed as a good strategy to overcome the methodological difficulties. However, research in suicidal behaviours using endophenotypes entrails important methodological problems...
October 2012: Psychiatria Danubina
Gabriele Masi, Paola Brovedani
Depression is a prevalent, highly debilitating mental disorder affecting up to 15% of the population at least once in their lifetime, with huge costs for society. Neurobiological mechanisms of depression are still not well known, although there is consensus about interplay between genetic and environmental factors. Antidepressant medications are frequently used in depression, but at least 50% of patients are poor responders, even to more recently discovered medications. Furthermore, clinical response only occurs following weeks to months of treatment and only chronic treatment is effective, suggesting that actions beyond the rapidly occurring effect of enhancing monoaminergic systems, such as adaptation of these systems, are responsible for the effects of antidepressants...
November 1, 2011: CNS Drugs
Anita E Autry, Lisa M Monteggia
No abstract text is available yet for this article.
November 1, 2009: Biological Psychiatry
Yogesh Dwivedi
Depression and suicidal behavior have recently been shown to be associated with disturbances in structural and synaptic plasticity. Brain-derived neurotrophic factor (BDNF), one of the major neurotrophic factors, plays an important role in the maintenance and survival of neurons and in synaptic plasticity. Several lines of evidence suggest that BDNF is involved in depression, such that the expression of BDNF is decreased in depressed patients. In addition, antidepressants up-regulate the expression of BDNF...
2009: Neuropsychiatric Disease and Treatment
Timothy A Klempan, Carl Ernst, Vesselina Deleva, Benoit Labonte, Gustavo Turecki
BACKGROUND: A number of studies have suggested deficits in myelination and glial gene expression in different psychiatric disorders. We examined the brain expression and genetic/epigenetic regulation of QKI, an oligodendrocyte-specific RNA binding protein important for cell development and myelination. METHODS: The microarray-based expression of QKI was evaluated in cortical and subcortical brain regions from suicide victims with a diagnosis of major depression (n = 16) and control subjects (n = 13)...
November 1, 2009: Biological Psychiatry
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