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Major Depressive Disorder SLC6A4

J H Piel, T A Lett, C Wackerhagen, M M Plichta, S Mohnke, O Grimm, N Romanczuk-Seiferth, F Degenhardt, H Tost, S Witt, M Nöthen, M Rietschel, A Heinz, A Meyer-Lindenberg, H Walter, S Erk
Major depressive disorder (MDD) is characterized by low mood for at least two weeks. Impaired emotion regulation has been suggested to be the consequence of dysfunctional serotonergic regulation of limbic and prefrontal regions, especially the amygdala, the anterior cingulate cortex (ACC) and the prefrontal cortex (PFC). The impact of genetic variation on brain function can be investigated with intermediate phenotypes. A suggested intermediate phenotype of MDD is emotion recognition: The 5-HTTLPR polymorphism of SLC6A4 as well as other serotonergic genes have been associated with amygdala and prefrontal function during emotion recognition...
March 2018: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Ali Bozorgmehr, Fatemeh Alizadeh, Sattar Norouzi Ofogh, Mohammad Reza Abdollahzadeh Hamzekalayi, Sara Herati, Atefeh Moradkhani, Ali Shahbazi, Mohammad Ghadirivasfi
BACKGROUND: Available sources indicate that the risk of suicide in people with major depression is higher than other psychiatric disorders. Although it seems that these two conditions may have a shared cause in some cases, no studies have been conducted to identify a common basis for them. METHODS: In this study, following an extensive review of literature, we found almost all the genes that are involved in major depression and suicidal behavior, and we isolated genes shared between the two conditions...
January 8, 2018: Journal of Affective Disorders
Roy Otten, Carmen S van der Zwaluw, Rutger C Engels
Alcohol abuse often co-exists with a major depressive disorder. In order to understand the development of this comorbidity, it is important to concentrate on the preceding process. It has been suggested that the link between alcohol use and depressive symptoms is a result of an interaction with genetic factors. The aim of this study was to longitudinally examine the effect of the 5-HTTLPR genotype on the association between depressive symptoms and alcohol use in a Dutch community sample. Following a stepwise approach, bivariate correlations, longitudinal regression analyses, and latent growth curve analyses were separately conducted for 316 males and 321 females...
February 2018: Alcohol
Ilona Schneider, Harald Kugel, Ronny Redlich, Dominik Grotegerd, Christian Bürger, Paul-Christian Bürkner, Nils Opel, Katharina Dohm, Dario Zaremba, Susanne Meinert, Nina Schröder, Anna Milena Straßburg, Kathrin Schwarte, Christiane Schettler, Oliver Ambrée, Stephan Rust, Katharina Domschke, Volker Arolt, Walter Heindel, Bernhard T Baune, Weiqi Zhang, Udo Dannlowski, Christa Hohoff
DNA methylation profiles of the serotonin transporter gene (SLC6A4) have been shown to alter SLC6A4 expression, drive antidepressant treatment response and modify brain functions. This study investigated whether methylation of an AluJb element in the SLC6A4 promotor was associated with major depressive disorder (MDD), amygdala reactivity to emotional faces, 5-HTTLPR/rs25531 polymorphism, and recent stress. MDD patients (n=122) and healthy controls (HC, n=176) underwent fMRI during an emotional face-matching task...
November 7, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Azmeraw T Amare, Klaus Oliver Schubert, Bernhard T Baune
Personalized medicine (personalized psychiatry in a specific setting) is a new model towards individualized care, in which knowledge from genomics and other omic pillars (microbiome, epigenomes, proteome, and metabolome) will be combined with clinical data to guide efforts to new drug development and targeted prescription of the existing treatment options. In this review, we summarize pharmacogenomic studies in mood disorders that may lay the foundation towards personalized psychiatry. In addition, we have discussed the possible strategies to integrate data from omic pillars as a future path to personalized psychiatry...
September 2017: EPMA Journal
Dongmei Chen, Lin Meng, Fei Pei, Yang Zheng, Jiyan Leng
As one of the most common psychiatric disorders, depression has been a major public health problem. Growing evidence suggests that epigenetic modification is essential in biological processes of depression. Recently, DNA methylation has been regarded as a potential link between environment and depression. In this review, we reviewed current studies of the association between DNA methylation and depression. The association between DNA methylation of seven genes, including BDNF, SLC6A4, NR3C1, 5-HTR (1A, 2A, and 3A), FKBP5, MAO-A and OXTR, and depression were reviewed in this study...
September 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
(no author information available yet)
BACKGROUND: A large proportion of the Ontario population lives with a diagnosed mental illness. Nearly 5% of Ontarians have major depressive disorder, and another 5% have another type of depressive disorder, bipolar disorder, schizophrenia, anxiety, or some other disorder not otherwise specified. Medications are commonly used to treat mental illness, but choosing the right medication for each patient is challenging, and more than 40% of patients discontinue their medication within 90 days because of adverse effects or lack of response...
2017: Ontario Health Technology Assessment Series
Kimberly Peterson, Eric Dieperink, Johanna Anderson, Erin Boundy, Lauren Ferguson, Mark Helfand
OBJECTIVE: This study aims to conduct an evidence review of the effectiveness, harms, and cost-effectiveness of pharmacogenomics-guided antidepressant treatment for major depressive disorder. METHODS: We searched MEDLINE®, the Cochrane Central Registry of Controlled Trials, and PsycINFO through February 2017. We used prespecified criteria to select studies, abstract data, and rate internal validity and strength of the evidence (PROSPERO number CRD42016036358). RESULTS: We included two randomized trials (RCT), five controlled cohort studies, and six modeling studies of mostly women in their mid-40s with few comorbidities...
June 2017: Psychopharmacology
Shin-Ya Watanabe, Shusuke Numata, Jun-Ichi Iga, Makoto Kinoshita, Hidehiro Umehara, Kazuo Ishii, Tetsuro Ohmori
PURPOSE: Recently, we could distinguished patients with major depressive disorder (MDD) from nonpsychiatric controls with high accuracy using a panel of five gene expression markers (ARHGAP24, HDAC5, PDGFC, PRNP, and SLC6A4) in leukocyte. In the present study, we examined whether this biological test is able to discriminate patients with MDD from those without MDD, including those with schizophrenia and bipolar disorder. PATIENTS AND METHODS: We measured messenger ribonucleic acid expression levels of the aforementioned five genes in peripheral leukocytes in 17 patients with schizophrenia and 36 patients with bipolar disorder using quantitative real-time polymerase chain reaction (PCR), and we combined these expression data with our previous expression data of 25 patients with MDD and 25 controls...
2017: Neuropsychiatric Disease and Treatment
Victoria S Marshe, Malgorzata Maciukiewicz, Soham Rej, Arun K Tiwari, Etienne Sibille, Daniel M Blumberger, Jordan F Karp, Eric J Lenze, Charles F Reynolds, James L Kennedy, Benoit H Mulsant, Daniel J Müller
OBJECTIVE: The primary objective of this study was to investigate five putatively functional variants of the norepinephrine transporter (SLC6A2, NET) and serotonin transporter (SLC6A4, SERT) genes and remission in depressed older adults treated with venlafaxine. A secondary objective was to analyze 17 other variants in serotonergic system genes (HTR1A, HTR2A, HTR1B, HTR2C, TPH1, TPH2) potentially involved in the mechanism of action of venlafaxine. METHOD: The sample included 350 adults age 60 or older with DSM-IV-defined major depressive disorder and a score of at least 15 on the Montgomery-Åsberg Depression Rating Scale (MADRS)...
May 1, 2017: American Journal of Psychiatry
Amanda J Lisoway, Clement C Zai, Arun K Tiwari, James L Kennedy
Antidepressant medications are the most common treatment for major depression and related disorders. Pharmacogenetic studies have demonstrated that response to these medications is associated with genetic variation. While these studies have been invaluable they have yet to explain why a significant number of patients do not respond to their initial medication. The epigenetic modification known as DNA methylation has recently been studied in the context of antidepressant treatment response. As such, the purpose of this article is to review the advances made in the relatively new field of pharmaco-epigenetics of antidepressant response...
January 4, 2017: Neuroscience Letters
Jelena Bakusic, Wilmar Schaufeli, Stephan Claes, Lode Godderis
Despite that burnout presents a serious burden for modern society, there are no diagnostic criteria. Additional difficulty is the differential diagnosis with depression. Consequently, there is a need to dispose of a burnout biomarker. Epigenetic studies suggest that DNA methylation is a possible mediator linking individual response to stress and psychopathology and could be considered as a potential biomarker of stress-related mental disorders. Thus, the aim of this review is to provide an overview of DNA methylation mechanisms in stress, burnout and depression...
January 2017: Journal of Psychosomatic Research
Shitao Rao, Cherry She Ting Leung, Macro Hb Lam, Yun Kwok Wing, Mary Miu Yee Waye, Stephen Kwok Wing Tsui
BACKGROUND: To date almost 200 genes were found to be associated with major depressive disorder (MDD) or suicide attempts (SA), but very few genes were reported for their molecular mechanisms. This study aimed to find out whether there were common or rare variants in three candidate genes altering the risk for MDD and SA in Chinese. METHODS: Three candidate genes (HOMER1, SLC6A4 and TEF) were chosen for resequencing analysis and association studies as they were reported to be involved in the etiology of MDD and SA...
March 1, 2017: Gene
Marta Ramos, Cecilia Berrogain, Julia Concha, Laura Lomba, Cristina Belén García, Mª Pilar Ribate
The World Health Organization (WHO) predicts that major depressive disorder (MDD) will be the second leading cause of death and disability by 2020. Nowadays, approximately 60-70% of patients with this disorder have shown the lack of effectiveness and tolerability of the therapy with antidepressants. The US Food and Drug Administration (FDA) and the European Medicine Agency (EMA) are including pharmacogenetic information in the labeling of several antidepressants. The presence of this information represents the relevance of genetic polymorphisms in drug response...
December 1, 2016: Drug Metabolism and Personalized Therapy
Laura R Stroud, George D Papandonatos, Stephanie H Parade, Amy L Salisbury, Maureen G Phipps, Barry M Lester, James F Padbury, Carmen J Marsit
OBJECTIVES: Extending prior studies of prenatal adversity and depressive symptoms, we tested associations between maternal prenatal major depressive disorder (MDD) and infant cortisol regulation. Based on prior findings by our group, we also tested placenta glucocorticoid (HSD11B2 methylation) and serotonin (SLC6A4 gene expression) signaling as moderators of links between prenatal MDD and infant cortisol. METHODS: Participants were 153 mother-infant pairs from a low-income, diverse sample (M [SD] age = 26 [6] years)...
November 2016: Psychosomatic Medicine
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...
February 2017: World Journal of Biological Psychiatry
E Won, S Choi, J Kang, A Kim, K-M Han, H S Chang, W S Tae, K R Son, S-H Joe, M-S Lee, B-J Ham
Previous evidence suggests that the serotonin transporter gene (SLC6A4) is associated with the structure of brain regions that are critically involved in dysfunctional limbic-cortical network activity associated with major depressive disorder (MDD). Diffusion tensor imaging (DTI) and tract-based spatial statistics were used to investigate changes in white matter integrity in patients with MDD compared with healthy controls. A possible association between structural alterations in white matter tracts and DNA methylation of the SLC6A4 promoter region was also assessed...
August 9, 2016: Translational Psychiatry
Aarthi Manoharan, Deepak Gopal Shewade, Ravi Philip Rajkumar, Surendiran Adithan
PURPOSE: Up to 30-40 % of the major depressive disorder patients do not respond sufficiently to antidepressant treatment. Genetic variations in the serotonin transporter gene have been implicated in modulating treatment response to selective serotonin reuptake inhibitors, and this association is influenced by ethnicity. We investigated the influence of serotonin transporter gene variants 5-HTTLPR and rs25531 in Indian population on fluoxetine response. METHODS: One hundred and two major depressive disorder patients were started on fluoxetine treatment and after 6 weeks, classified as responders (n = 56) and non-responders (n = 46) using Hamilton depression rating scale and genotyped...
October 2016: European Journal of Clinical Pharmacology
C H Ng, C Bousman, D J Smith, N Dowling, K Byron, J King, J Sarris
No studies to date have evaluated SLC6A2 and SLC6A4 genetic polymorphisms influencing antidepressant response to desvenlafaxine. We conducted an 8-week, open-label, prospective pilot study in 35 patients with major depressive disorder to assess the effects of genetic variations in SLC6A2 and SLC6A4 on both efficacy and side effect profile of desvenlafaxine. Results revealed that homozygotes for the SLC6A4 HTTLPR S allele showed a 33% HDRS reduction compared to a 58% reduction for L allele carriers (p=0.037)...
September 2016: Pharmacopsychiatry
Arielle Y Zahavi, Mark A Sabbagh, Dustin Washburn, Raegan Mazurka, R Michael Bagby, John Strauss, James L Kennedy, Arun Ravindran, Kate L Harkness
Theory of mind-the ability to decode and reason about others' mental states-is a universal human skill and forms the basis of social cognition. Theory of mind accuracy is impaired in clinical conditions evidencing social impairment, including major depressive disorder. The current study is a preliminary investigation of the association of polymorphisms of the serotonin transporter (SLC6A4), dopamine transporter (DAT1), dopamine receptor D4 (DRD4), and catechol-O-methyl transferase (COMT) genes with theory of mind decoding in a sample of adults with major depression...
2016: PloS One
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