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Bipolar, depression, epigenetics

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
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
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
Seher Karsli-Ceppioglu
Preclinical Research Epigenetic mechanisms refer covalent modification of DNA and histone proteins that control transcriptional regulation of gene expression. Epigenetic regulation is involved in the development of the nervous system and plays an important role in the pathophysiology of psychiatric disorders, including depression, bipolar disorder, and schizophrenia. Epigenetic drugs, including histone deacetylation and DNA methylation inhibitors have received increased attention for the management of psychiatric diseases...
September 4, 2016: Drug Development Research
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
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
J W Wiley, G A Higgins, B D Athey
BACKGROUND: Chronic psychological stress is associated with enhanced abdominal pain and altered intestinal barrier function that may result from a perturbation in the hypothalamic-pituitary-adrenal (HPA) axis. The glucocorticoid receptor (GR) exploits diverse mechanisms to activate or suppress congeneric gene expression, with regulatory variation associated with stress-related disorders in psychiatry and gastroenterology. PURPOSE: During acute and chronic stress, corticotropin-releasing hormone drives secretion of adrenocorticotropic hormone from the pituitary, ultimately leading to the release of cortisol (human) and corticosterone (rodent) from the adrenal glands...
January 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
S Dimitrakopoulos, G Konstantakopoulos
The treatment of bipolar disorder is a current challenge for clinicians and despite progress in psychopharmacology, options remain limited and results are often unsatisfactory. Current research focuses on finding new pharmaceutical agents for all phases of bipolar disorder, i.e. mania, bipolar depression and maintenance. Particularly, relapse prevention and longterm stabilization is a major therapeutic target. Combination treatment and polypharmacy are the most common choices concerning relapse prevention. Furthermore, during maintenance phase patients often experience residual mood symptoms, cognitive deficits and functional decline, which altogether illustrate the inadequate effectiveness of existing treatments and the need for new, targeted, effective and safe treatments for bipolar disorder...
July 2015: Psychiatrikē, Psychiatriki
Eric J Nestler, Catherine J Peña, Marija Kundakovic, Amanda Mitchell, Schahram Akbarian
Psychiatric disorders are complex multifactorial illnesses involving chronic alterations in neural circuit structure and function as well as likely abnormalities in glial cells. While genetic factors are important in the etiology of most mental disorders, the relatively high rates of discordance among identical twins, particularly for depression and other stress-related syndromes, clearly indicate the importance of additional mechanisms. Environmental factors such as stress are known to play a role in the onset of these illnesses...
October 2016: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
Hamid M Abdolmaleky, Sara Pajouhanfar, Masoomeh Faghankhani, Mohammad Taghi Joghataei, Ashraf Mostafavi, Sam Thiagalingam
Due to the lack of genetic association between individual genes and schizophrenia (SCZ) pathogenesis, the current consensus is to consider both genetic and epigenetic alterations. Here, we report the examination of DNA methylation status of DTNBP1 promoter region, one of the most credible candidate genes affected in SCZ, assayed in saliva and post-mortem brain samples. The Illumina DNA methylation profiling and bisulfite sequencing of representative samples were used to identify methylation status of the DTNBP1 promoter region...
December 2015: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Douglas S Lehrer, Michele T Pato, Ramzi W Nahhas, Brian R Miller, Dolores Malaspina, Peter F Buckley, Janet L Sobell, Julie Walsh-Messinger, Genomic Psychiatry Cohort Consortium, Carlos N Pato
Advanced paternal age (APA) is a risk factor for schizophrenia (Sz) and bipolar disorder (BP). Putative mechanisms include heritable genetic factors, de novo mutations, and epigenetic mechanisms. Few studies have explored phenotypic features associated with APA. The Genomic Psychiatry Cohort established a clinically characterized repository of genomic samples from subjects with a Sz-BP diagnosis or unaffected controls, 12,975 with parental age information. We estimated relative risk ratios for Sz, schizoaffective depressed and bipolar types (SA-D, SA-B), and BP with and without history of psychotic features (PF) relative to the control group, comparing each paternal age group to the reference group 20-24 years...
June 2016: American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics
Angela Heinrich, Arlette F Buchmann, Katrin Zohsel, Helene Dukal, Josef Frank, Jens Treutlein, Vanessa Nieratschker, Stephanie H Witt, Daniel Brandeis, Martin H Schmidt, Günter Esser, Tobias Banaschewski, Manfred Laucht, Marcella Rietschel
Epigenetic modulations are a hypothesized link between environmental factors and the development of psychiatric disorders. Research has suggested that patients with depression or bipolar disorder exhibit higher methylation levels in the glucocorticoid receptor gene NR3C1. We aimed to investigate whether NR3C1 methylation changes are similarly associated with externalizing disorders such as aggressive behavior and conduct disorder. NR3C1 exon 1F methylation was analyzed in young adults with a lifetime diagnosis of an externalizing disorder (N = 68) or a depressive disorder (N = 27) and healthy controls (N = 124) from the Mannheim Study of Children at Risk...
September 2015: Behavior Genetics
Gregor Hasler, Andreas Wolf
In bipolar disorders, there are unclear diagnostic boundaries with unipolar depression and schizophrenia, inconsistency of treatment guidelines, relatively long trial-and-error phases of treatment optimization, and increasing use of complex combination therapies lacking empirical evidence. These suggest that the current definition of bipolar disorders based on clinical symptoms reflects a clinically and etiologically heterogeneous entity. Stratification of treatments for bipolar disorders based on biomarkers and improved clinical markers are greatly needed to increase the efficacy of currently available treatments and improve the chances of developing novel therapeutic approaches...
March 2015: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
R P Rajkumar
Anticipation is a phenomenon in which successive generations within a family experience an earlier age of onset and a more severe form of a given illness. It has been observed in various neurological and psychiatric conditions, including bipolar disorder. The molecular basis of anticipation involves trinucleotide repeat expansions in genes, but this has not been conclusively demonstrated in bipolar disorder. The histories of 3 father-son pairs are presented. In each pair, the son presented with an early-onset bipolar disorder, and the father developed severe depression after the age of 50 years...
December 2014: East Asian Archives of Psychiatry: Official Journal of the Hong Kong College of Psychiatrists
Marija Kundakovic, Kathryn Gudsnuk, Julie B Herbstman, Deliang Tang, Frederica P Perera, Frances A Champagne
Early-life adversity increases the risk for psychopathology in later life. The underlying mechanism(s) is unknown, but epigenetic variation represents a plausible candidate. Early-life exposures can disrupt epigenetic programming in the brain, with lasting consequences for gene expression and behavior. This evidence is primarily derived from animal studies, with limited study in humans due to inaccessibility of the target brain tissue. In humans, although there is evidence for DNA methylation changes in the peripheral blood of psychiatric patients, a fundamental question remains as to whether epigenetic markers in the blood can predict epigenetic changes occurring in the brain...
June 2, 2015: Proceedings of the National Academy of Sciences of the United States of America
Miranda M Darby, Sarven Sabunciyan
Repetitive elements, which are relics of previous transposition events, constitute a large proportion of the human genome. The ability of transposons to gives rise to new DNA combinations has clearly provided an evolutionary advantage to their hosts. Transposons have shaped our genomes by giving rise to novel coding sequences, alternative gene promoters, conserved noncoding elements, and gene networks. Despite its benefits, the process of transposition can also create deleterious DNA combinations, and a growing number of human diseases are being linked to abnormal repetitive element activity...
2014: Advances in Genetics
Laura Carlberg, Janine Scheibelreiter, Melanie R Hassler, Monika Schloegelhofer, Michaela Schmoeger, Birgit Ludwig, Siegfried Kasper, Harald Aschauer, Gerda Egger, Alexandra Schosser
BACKGROUND: Alterations of brain-derived neurotrophic factor (BDNF) DNA methylation at specific BDNF promoters and corresponding gene expressions are associated with pathology and the response to antidepressant (AD) therapy in affective disorders such as major depressive disorder (MDD) and bipolar disorder (BD). METHODS: Genomic DNA was derived from peripheral blood mononuclear cells (PBMCs) and was bisulfite converted. Percentage of methylated reference (PMR) was calculated based on results from quantitative real-time PCR following the MethyLight protocol...
October 2014: Journal of Affective Disorders
Bernardo Dell'Osso, Claudio D'Addario, Maria Carlotta Palazzo, Beatrice Benatti, Giulia Camuri, Daniela Galimberti, Chiara Fenoglio, Elio Scarpini, Andrea Di Francesco, Mauro Maccarrone, A Carlo Altamura
BACKGROUND: The brain derived neurotrophic factor (BDNF) gene and its epigenetic regulation have been repeatedly implicated in the pathophysiology of mood disorders. Following previous investigation in the field, we further investigated differences in BDNF promoter gene methylation in patients with mood disorders, comparing unipolar and bipolar subjects, on the basis of illness phase, gender, age and psychotropic prescription. METHODS: 154 patients (43 MDD; 61 BD I; 50 BD II), on stable pharmacological treatment, and 44 age-matched, healthy controls were recruited...
September 2014: Journal of Affective Disorders
Andrea Schmitt, Berend Malchow, Alkomiet Hasan, Peter Falkai
During the last decades, schizophrenia has been regarded as a developmental disorder. The neurodevelopmental hypothesis proposes schizophrenia to be related to genetic and environmental factors leading to abnormal brain development during the pre- or postnatal period. First disease symptoms appear in early adulthood during the synaptic pruning and myelination process. Meta-analyses of structural MRI studies revealing hippocampal volume deficits in first-episode patients and in the longitudinal disease course confirm this hypothesis...
2014: Frontiers in Neuroscience
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