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proteome, antidepressant

Christoph W Turck, Paul C Guest, Giuseppina Maccarrone, Marcus Ising, Stefan Kloiber, Susanne Lucae, Florian Holsboer, Daniel Martins-de-Souza
The current inability of clinical psychiatry to objectively select the most appropriate treatment is a major factor contributing to the severity and clinical burden of major depressive disorder (MDD). Here, we have attempted to identify plasma protein signatures in 39 MDD patients to predict response over a 6-week treatment period with antidepressants. LC-MS/MS analysis showed that differences in the levels of 29 proteins at baseline were found in the group with a favorable treatment outcome. Most of these proteins were components of metabolism or immune response pathways as well as multiple components of the coagulation cascade...
2017: Frontiers in Molecular Neuroscience
Indira Mendez-David, Céline Boursier, Valérie Domergue, Romain Colle, Bruno Falissard, Emmanuelle Corruble, Alain M Gardier, Jean-Philippe Guilloux, Denis J David
The incorporation of peripheral biomarkers in the treatment of major depressive disorders (MDD) could improve the efficiency of treatments and increase remission rate. Peripheral blood mononuclear cells (PBMCs) represent an attractive biological substrate allowing the identification of a drug response signature. Using a proteomic approach with high-resolution mass spectrometry, the present study aimed to identify a biosignature of antidepressant response (fluoxetine, a Selective Serotonin Reuptake Inhibitor) in PBMCs in a mouse model of anxiety/depression...
2017: Frontiers in Cellular Neuroscience
Bharathi S Gadad, Manish K Jha, Andrew Czysz, Jennifer L Furman, Taryn L Mayes, Michael P Emslie, Madhukar H Trivedi
BACKGROUND: In recent years, we have accomplished a deeper understanding about the pathophysiology of major depressive disorder (MDD). Nevertheless, this improved comprehension has not translated to improved treatment outcome, as identification of specific biologic markers of disease may still be crucial to facilitate a more rapid, successful treatment. Ongoing research explores the importance of screening biomarkers using neuroimaging, neurophysiology, genomics, proteomics, and metabolomics measures...
July 5, 2017: Journal of Affective Disorders
Bharathi S Gadad, Manish K Jha, Bruce D Grannemann, Taryn L Mayes, Madhukar H Trivedi
Animal and human studies suggest an association between depression and aberrant immune response. Further, common inflammatory markers may change during the course of antidepressant treatment in patients. The objective of this study was to evaluate changes in inflammatory markers and clinical outcomes from subjects enrolled in the Combining Medications to Enhance Depression Outcome (CO-MED) trial. At baseline and week 12 (treatment completion), plasma samples of 102 participants were analyzed via a multiplex assay comprised of inflammatory markers using a 27-plex standard assay panel plus a 4-plex human acute phase xMAP technology based platform...
May 26, 2017: Journal of Psychiatric Research
Thomas Frodl
Major depressive disorder is one of the leading causes of disability in the world since depression is highly frequent and causes a strong burden. In order to reduce the duration of depressive episodes, clinicians would need to choose the most effective therapy for each individual right away. A prerequisite for this would be to have biomarkers at hand that would predict which individual would benefit from which kind of therapy (for example, pharmacotherapy or psychotherapy) or even from which kind of antidepressant class...
2017: F1000Research
Katarzyna Głombik, Aneta Stachowicz, Ewa Trojan, Rafał Olszanecki, Joanna Ślusarczyk, Maciej Suski, Katarzyna Chamera, Bogusława Budziszewska, Władysław Lasoń, Agnieszka Basta-Kaim
Several lines of evidence indicate that adverse experience in early life may be a triggering factor for disturbances in the brain mitochondrial proteins and lead to the development of depression in adulthood. On the other hand, little is known about the impact of chronic administration of various antidepressant drugs on the brain mitochondria, as a target for the pharmacotherapy of depression. The purpose of our study was to compare the impact of chronic treatment with two antidepressant drugs with different mechanisms of action, a tricyclic antidepressant (TCA), imipramine, and an antidepressant of the selective serotonin reuptake inhibitor (SSRI) class, fluoxetine, on the mitochondria-enriched subproteome profile in the hippocampus of 3-month-old male rats following a prenatal stress procedure (an animal model of depression)...
May 17, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
D I Park, C Dournes, I Sillaber, M Ising, J M Asara, C Webhofer, M D Filiou, M B Müller, C W Turck
The aim of this study was to identify molecular pathways related to antidepressant response. We administered paroxetine to the DBA/2J mice for 28 days. Following the treatment, the mice were grouped into responders or non-responders depending on the time they spent immobile in the forced swim test. Hippocampal metabolomics and proteomics analyses revealed that chronic paroxetine treatment affects glutamate-related metabolite and protein levels differentially in the two groups. We found significant differences in the expression of N-methyl-d-aspartate receptor and neuronal nitric oxide synthase proteins between the two groups, without any significant alterations in the respective transcript levels...
April 4, 2017: Translational Psychiatry
Uhna Sung, Francesca Binda, Valentina Savchenko, William A Owens, Lynette C Daws
The antidepressant-sensitive norepinephrine (NE) transporter (NET) inactivates NE released during central and peripheral neuronal activity by transport into presynaptic cells. Altered NE clearance due to dysfunction of NET has been associated with the development of mental illness and cardiovascular diseases. NET activity in vivo is influenced by stress, neuronal activity, hormones and drugs. We investigated the mechanisms of Ca(2+) regulation of NET and found that Ca(2+) influenced both Vmax and Km for NE transport into cortical synaptosomes...
October 2017: Journal of Chemical Neuroanatomy
Dong Ik Park, Carine Dournes, Inge Sillaber, Manfred Uhr, John M Asara, Nils C Gassen, Theo Rein, Marcus Ising, Christian Webhofer, Michaela D Filiou, Marianne B Müller, Christoph W Turck
Selective Serotonin Reuptake Inhibitors (SSRIs) are commonly used drugs for the treatment of psychiatric diseases including major depressive disorder (MDD). For unknown reasons a substantial number of patients do not show any improvement during or after SSRI treatment. We treated DBA/2J mice for 28 days with paroxetine and assessed their behavioral response with the forced swim test (FST). Paroxetine-treated long-time floating (PLF) and paroxetine-treated short-time floating (PSF) groups were stratified as proxies for drug non-responder and responder mice, respectively...
October 12, 2016: Scientific Reports
Lucia Carboni, Thanh-Phuong Nguyen, Laura Caberlotto
PURPOSE: The pathophysiological basis of major depression is incompletely understood. Recently, numerous proteomic studies have been performed in rodent models of depression to investigate the molecular underpinnings of depressive-like behaviours with an unbiased approach. The objective of the study is to integrate the results of these proteomic studies in depression models to shed light on the most relevant molecular pathways involved in the disease. EXPERIMENTAL DESIGN: Network analysis is performed integrating preexisting proteomic data from rodent models of depression...
December 2016: Proteomics. Clinical Applications
Yongtao Yang, Jin Chen, Chengyu Liu, Liang Fang, Zhao Liu, Jing Guo, Ke Cheng, Chanjuan Zhou, Yuan Zhan, Narayan D Melgiri, Liang Zhang, Jiaju Zhong, Jianjun Chen, Chenglong Rao, Peng Xie
Although an association between major depressive disorder (MDD) and suicide exists, most depressed patients never attempt suicide. An improved understanding of the factors contributing to suicidal risk in MDD can provide direction for suicide predictor development. In MDD suicide attempters (MDD-SA), MDD non-attempters (MDD-NA), and healthy controls (HC) (n = 12 each group), complementary plasma proteomics identified 45 differential proteins mapped to coagulation and inflammation, 25 of which underwent Western blotting...
September 8, 2016: Scientific Reports
Helena Kaihola, Fatma G Yaldir, Julius Hreinsson, Katarina Hörnaeus, Jonas Bergquist, Jocelien D A Olivier, Helena Åkerud, Inger Sundström-Poromaa
The use of antidepressant treatment during pregnancy is increasing, and selective serotonin reuptake inhibitors (SSRIs) are the most widely prescribed antidepressants in pregnant women. Serotonin plays a role in embryogenesis, and serotonin transporters are expressed in two-cell mouse embryos. Thus, the aim of the present study was to evaluate whether fluoxetine, one of the most prescribed SSRI antidepressant world-wide, exposure influences the timing of different embryo developmental stages, and furthermore, to analyze what protein, and protein networks, are affected by fluoxetine in the early embryo development...
2016: Frontiers in Cellular Neuroscience
Barbara Gellén, Katalin Völgyi, Balázs András Györffy, Zsuzsa Darula, Éva Hunyadi-Gulyás, Péter Baracskay, András Czurkó, István Hernádi, Gábor Juhász, Árpád Dobolyi, Katalin Adrienna Kékesi
Neonatal rodents chronically treated with the tricyclic antidepressant clomipramine show depression-like behavior, which persists throughout adulthood. Therefore, this animal model is suitable to investigate the pathomechanism of depression, which is still largely unknown at the molecular level beyond monoaminergic dysfunctions. Here, we describe protein level changes in the prefrontal cortex of neonatally clomipramine-treated adult rats correlating with behavioral abnormalities. Clomipramine was administered to rat pups twice daily between postnatal days 8-21, while controls received saline injections...
February 5, 2017: Journal of Proteomics
Raymond W Lam, Roumen Milev, Susan Rotzinger, Ana C Andreazza, Pierre Blier, Colleen Brenner, Zafiris J Daskalakis, Moyez Dharsee, Jonathan Downar, Kenneth R Evans, Faranak Farzan, Jane A Foster, Benicio N Frey, Joseph Geraci, Peter Giacobbe, Harriet E Feilotter, Geoffrey B Hall, Kate L Harkness, Stefanie Hassel, Zahinoor Ismail, Francesco Leri, Mario Liotti, Glenda M MacQueen, Mary Pat McAndrews, Luciano Minuzzi, Daniel J Müller, Sagar V Parikh, Franca M Placenza, Lena C Quilty, Arun V Ravindran, Tim V Salomons, Claudio N Soares, Stephen C Strother, Gustavo Turecki, Anthony L Vaccarino, Fidel Vila-Rodriguez, Sidney H Kennedy
BACKGROUND: Major Depressive Disorder (MDD) is among the most prevalent and disabling medical conditions worldwide. Identification of clinical and biological markers ("biomarkers") of treatment response could personalize clinical decisions and lead to better outcomes. This paper describes the aims, design, and methods of a discovery study of biomarkers in antidepressant treatment response, conducted by the Canadian Biomarker Integration Network in Depression (CAN-BIND). The CAN-BIND research program investigates and identifies biomarkers that help to predict outcomes in patients with MDD treated with antidepressant medication...
April 16, 2016: BMC Psychiatry
M J Bebianno, S Sroda, T Gomes, P Chan, E Bonnafe, H Budzinski, F Geret
The increase use of pharmaceutical compounds in veterinary practice and human population results in the ubiquitous presence of these compounds in aquatic ecosystems. Because pharmaceuticals are highly bioactive, there is concern about their toxicological effects in aquatic organisms. Therefore, the aim of this study was to assess the effects of an effluent from a psychiatric hospital (containing a complex mixture of 25 pharmaceutical compounds from eleven therapeutic classes) on the freshwater clam Corbicula fluminea using a proteomic approach...
March 2016: Environmental Science and Pollution Research International
L Ruiz-Perera, M Muniz, G Vierci, N Bornia, L Baroncelli, A Sale, F M Rossi
The scarce functional recovery of the adult CNS following injuries or diseases is largely due to its reduced potential for plasticity, the ability to reorganize neural connections as a function of experience. Recently, some new strategies restoring high levels of plasticity in the adult brain have been identified, especially in the paradigmatic model of the visual system. A chronic treatment with the anti-depressant fluoxetine reinstates plasticity in the adult rat primary visual cortex, inducing recovery of vision in amblyopic animals...
2015: Scientific Reports
M Bot, M K Chan, R Jansen, F Lamers, N Vogelzangs, J Steiner, F M Leweke, M Rothermundt, J Cooper, S Bahn, B W J H Penninx
Much has still to be learned about the molecular mechanisms of depression. This study aims to gain insight into contributing mechanisms by identifying serum proteins related to major depressive disorder (MDD) in a large psychiatric cohort study. Our sample consisted of 1589 participants of the Netherlands Study of Depression and Anxiety, comprising 687 individuals with current MDD (cMDD), 482 individuals with remitted MDD (rMDD) and 420 controls. We studied the relationship between MDD status and the levels of 171 serum proteins detected on a multi-analyte profiling platform using adjusted linear regression models...
July 14, 2015: Translational Psychiatry
Mark J Niciu, Daniel C Mathews, Dawn F Ionescu, Erica M Richards, Maura L Furey, Peixiong Yuan, Allison C Nugent, Ioline D Henter, Rodrigo Machado-Vieira, Carlos A Zarate
BACKGROUND: Recently, surrogate neurobiological biomarkers that correlate with target engagement and therapeutic response have been developed and tested in early phase studies of mood disorders. OBJECTIVE: The identification of biomarkers could help develop personalized psychiatric treatments that may impact public health. METHODS: These biomarkers, which are associated with clinical response post-treatment, can be directly validated using multimodal approaches including genetic tools, proteomics/metabolomics, peripheral measures, neuroimaging, biostatistical predictors, and clinical predictors...
2014: Revista de Psiquiatria Clínica
Michael Maes, Gabriel Nowak, Javier R Caso, Juan Carlos Leza, Cai Song, Marta Kubera, Hans Klein, Piotr Galecki, Cristiano Noto, Enrico Glaab, Rudi Balling, Michael Berk
Meta-analyses confirm that depression is accompanied by signs of inflammation including increased levels of acute phase proteins, e.g., C-reactive protein, and pro-inflammatory cytokines, e.g., interleukin-6. Supporting the translational significance of this, a meta-analysis showed that anti-inflammatory drugs may have antidepressant effects. Here, we argue that inflammation and depression research needs to get onto a new track. Firstly, the choice of inflammatory biomarkers in depression research was often too selective and did not consider the broader pathways...
July 2016: Molecular Neurobiology
Lin Ge, Ming-Ming Zhu, Jing-Yu Yang, Fang Wang, Rong Zhang, Jing-Hai Zhang, Jing Shen, Hui-Fang Tian, Chun-Fu Wu
Depression is a complex psychiatric disorder, and its etiology and pathophysiology are not completely understood. Depression involves changes in many biogenic amine, neuropeptide, and oxidative systems, as well as alterations in neuroendocrine function and immune-inflammatory pathways. Oleamide is a fatty amide which exhibits pharmacological effects leading to hypnosis, sedation, and anti-anxiety effects. In the present study, the chronic mild stress (CMS) model was used to investigate the antidepressant-like activity of oleamide...
April 2015: Pharmacology, Biochemistry, and Behavior
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