Depressive Disorder, Major

Publication Title: 
PloS One

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.

Author(s): 
Na, Kyoung-Sae
Chang, Hun Soo
Won, Eunsoo
Han, Kyu-Man
Choi, Sunyoung
Tae, Woo Suk
Yoon, Ho-Kyoung
Kim, Yong-Ku
Joe, Sook-Haeng
Jung, In-Kwa
Lee, Min-Soo
Ham, Byung-Joo
Publication Title: 
Biological Psychiatry

BACKGROUND: Enhanced glucocorticoid receptor (GR) sensitivity is present in people with posttraumatic stress disorder (PTSD), but the molecular mechanisms of GR sensitivity are not understood. Epigenetic factors have emerged as one potential mechanism that account for how trauma exposure leads to sustained PTSD symptoms given that PTSD develops in only a subset of trauma survivors.

Author(s): 
Yehuda, Rachel
Flory, Janine D.
Bierer, Linda M.
Henn-Haase, Clare
Lehrner, Amy
Desarnaud, Frank
Makotkine, Iouri
Daskalakis, Nikolaos P.
Marmar, Charles R.
Meaney, Michael J.
Publication Title: 
The International Journal of Neuropsychopharmacology

Variation in the serotonin transporter gene (5-HTT; SERT; SLC6A4) has been suggested to pharmacogenetically drive interindividual differences in antidepressant treatment response. In the present analysis, a 'pharmaco-epigenetic' approach was applied by investigating the influence of DNA methylation patterns in the 5-HTT transcriptional control region on antidepressant treatment response.

Author(s): 
Domschke, Katharina
Tidow, Nicola
Schwarte, Kathrin
Deckert, J¸rgen
Lesch, Klaus-Peter
Arolt, Volker
Zwanzger, Peter
Baune, Bernhard T.
Publication Title: 
Genome Biology

BACKGROUND: Although genetic variation is believed to contribute to an individual's susceptibility to major depressive disorder, genome-wide association studies have not yet identified associations that could explain the full etiology of the disease. Epigenetics is increasingly believed to play a major role in the development of common clinical phenotypes, including major depressive disorder. RESULTS: Genome-wide MeDIP-Sequencing was carried out on a total of 50 monozygotic twin pairs from the UK and Australia that are discordant for depression.

Author(s): 
Davies, Matthew N.
Krause, Lutz
Bell, Jordana T.
Gao, Fei
Ward, Kirsten J.
Wu, Honglong
Lu, Hanlin
Liu, Yuan
Tsai, Pei-Chein
Collier, David A.
Murphy, Therese
Dempster, Emma
Mill, Jonathan
UK Brain Expression Consortium
Battle, Alexis
Mostafavi, Sara
Zhu, Xiaowei
Henders, Anjali
Byrne, Enda
Wray, Naomi R.
Martin, Nicholas G.
Spector, Tim D.
Wang, Jun
Publication Title: 
Journal of Affective Disorders

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.

Author(s): 
Carlberg, Laura
Scheibelreiter, Janine
Hassler, Melanie R.
Schloegelhofer, Monika
Schmoeger, Michaela
Ludwig, Birgit
Kasper, Siegfried
Aschauer, Harald
Egger, Gerda
Schosser, Alexandra
Publication Title: 
Biological Psychiatry

BACKGROUND: Major depressive disorder (MDD) exhibits numerous clinical and molecular features that are consistent with putative epigenetic misregulation. Despite growing interest in epigenetic studies of psychiatric diseases, the methodologies guiding such studies have not been well defined. METHODS: We performed DNA modification analysis in white blood cells from monozygotic twins discordant for MDD, in brain prefrontal cortex, and germline (sperm) samples from affected individuals and control subjects (total N = 304) using 8.1K CpG island microarrays and fine mapping.

Author(s): 
Oh, Gabriel
Wang, Sun-Chong
Pal, Mrinal
Chen, Zheng Fei
Khare, Tarang
Tochigi, Mamoru
Ng, Catherine
Yang, Yeqing A.
Kwan, Andrew
Kaminsky, Zachary A.
Mill, Jonathan
Gunasinghe, Cerisse
Tackett, Jennifer L.
Gottesman, Irving I.
Willemsen, Gonneke
de Geus, Eco J. C.
Vink, Jacqueline M.
Slagboom, P. Eline
Wray, Naomi R.
Heath, Andrew C.
Montgomery, Grant W.
Turecki, Gustavo
Martin, Nicholas G.
Boomsma, Dorret I.
McGuffin, Peter
Kustra, Rafal
Petronis, Art
Publication Title: 
Translational Psychiatry

Early life stress (ELS) is associated with increased vulnerability for diseases in later life, including psychiatric disorders. Animal models and human studies suggest that this effect is mediated by epigenetic mechanisms. In humans, epigenetic studies to investigate the influence of ELS on psychiatric phenotypes are limited by the inaccessibility of living brain tissue.

Author(s): 
Nieratschker, V.
Massart, R.
Gilles, M.
Luoni, A.
Suderman, M. J.
Krumm, B.
Meier, S.
Witt, S. H.
Nˆthen, M. M.
Suomi, S. J.
Peus, V.
Scharnholz, B.
Dukal, H.
Hohmeyer, C.
Wolf, I. a.-C.
Cirulli, F.
Gass, P.
S¸tterlin, M. W.
Filsinger, B.
Laucht, M.
Riva, M. A.
Rietschel, M.
Deuschle, M.
Szyf, M.
Publication Title: 
The American Journal of Psychiatry

OBJECTIVE: The authors compared the effectiveness of fluoxetine and desipramine treatment in a prospective double-blind pharmacogenetics study in first-generation Mexican Americans and examined the role of whole-exome functional gene variations in the patients' antidepressant response. METHOD: A total of 232 Mexican Americans who met DSM-IV criteria for major depressive disorder were randomly assigned to receive 8 weeks of double-blind treatment with desipramine (50-200 mg/day) or fluoxetine (10-40 mg/day) after a 1-week placebo lead-in period.

Author(s): 
Wong, Ma-Li
Dong, Chuanhui
Flores, Deborah L.
Ehrhart-Bornstein, Monika
Bornstein, Stefan
Arcos-Burgos, Mauricio
Licinio, Julio
Publication Title: 
Progress in Molecular Biology and Translational Science

Major depressive disorder (MDD) is a leading cause of disability worldwide and is associated with poor psychological, medical, and socioeconomic outcomes. Although much has been learned about the etiology and treatment options of MDD over the past decade, there remain unanswered questions that pose challenges to improving acute and chronic outcomes for those with MDD. MDD is a clinically heterogeneous disorder.

Author(s): 
Lolak, Sermsak
Suwannarat, Pim
Lipsky, Robert H.
Publication Title: 
Journal of Affective Disorders

Considerable evidence suggests a crucial role for the epigenetic regulation of brain-derived neurotrophic factor (BDNF) in the pathophysiology of major depressive disorder (MDD). However, the relationship between BDNF DNA methylation and white matter (WM) integrity in MDD has not yet been investigated. In the current study, we examined the association between the DNA methylation status of the BDNF promoter region and WM integrity in MDD.

Author(s): 
Choi, Sunyoung
Han, Kyu-Man
Won, Eunsoo
Yoon, Bong-June
Lee, Min-Soo
Ham, Byung-Joo

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