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Serotonin depression

Laura Orsolini, Carmine Tomasetti, Alessandro Valchera, Felice Iasevoli, Elisabetta Filomena Buonaguro, Michele Fornaro, Annastasia L C Fiengo, Giovanni Martinotti, Federica Vellante, Ilaria Matarazzo, Roberta Vecchiotti, Giampaolo Perna, Marco Di Nicola, Alessandro Carano, Andrea de Bartolomeis, Massimo Di Giannantonio, Andrea de Bartolomeis, Domenico De Berardis
BACKGROUND: Vortioxetine (VRX) is a multimodal antidepressant that acts as serotonin (5¬HT) transporter inhibitor as well as 5¬HT3A and 5¬HT7 receptors antagonist, 5¬HT1A and 5¬HT1B receptors partial agonist. It was recently approved in the US and the EU for the treatment of adult patients with Major Depressive Disorder (MDD). OBJECTIVE: The present article aims at systematically reviewing findings of the published and unpublished research on the pharmacological properties, efficacy, safety and tolerability of oral VRX in the treatment of major depressive disorder (MDD)...
October 25, 2016: CNS & Neurological Disorders Drug Targets
Lori L Davis, Ai Ota, Pamela Perry, Kana Tsuneyoshi, Emmanuelle Weiller, Ross A Baker
BACKGROUND: Major depressive disorder (MDD) with concurrent anxiety symptoms may signal a difficult-to-treat patient. Brexpiprazole is a serotonin-dopamine activity modulator: a partial agonist at 5-HT1A and dopamine D2 receptors at similar potency, and an antagonist at 5-HT2A and noradrenaline alpha1B/2C receptors. The objective of this Phase IIIb study was to explore effectiveness, safety, and tolerability of brexpiprazole adjunctive to antidepressant (ADT) monotherapy in patients with MDD and anxiety symptoms (NCT02013531)...
October 2016: Brain and Behavior
Paula Honório de Melo Martimiano, André de Sa Braga Oliveira, Véronique Ferchaud-Roucher, Mikaël Croyal, Audrey Aguesse, Isabelle Grit, Khadija Ouguerram, Sandra Lopes de Souza, Bertrand Kaeffer, Francisco Bolaños-Jiménez
Early malnutrition is a risk factor for depression and schizophrenia. Since the offspring of malnourished dams exhibit increased brain levels of serotonin (5-HT), a tryptophan-derived neurotransmitter involved in the pathophysiology of these mental disorders, it is believed that the deleterious effects of early malnutrition on brain function are due in large part to altered serotoninergic neurotransmission resulting from impaired tryptophan (Trp) metabolism. However, tryptophan is also metabolized through the kynurenine (KYN) pathway yielding several neuroactive compounds including kynurenic (KA), Qinolinic (QA) and Xanthurenic (XA) acids...
October 25, 2016: Journal of Neurochemistry
Tasuku Hashimoto, Akihiro Shiina, Tadashi Hasegawa, Hiroshi Kimura, Yasunori Oda, Tomihisa Niitsu, Masatomo Ishikawa, Masumi Tachibana, Katsumasa Muneoka, Satoshi Matsuki, Michiko Nakazato, Masaomi Iyo
BACKGROUND: This study aimed to evaluate whether selecting mirtazapine as the first choice for current depressive episode instead of selective serotonin reuptake inhibitors (SSRIs) reduces benzodiazepine use in patients with major depressive disorder (MDD). We concurrently examined the relationship between clinical responses and serum mature brain-derived neurotrophic factor (BDNF) and its precursor, proBDNF. METHODS: We conducted an open-label randomized trial in routine psychiatric practice settings...
2016: Annals of General Psychiatry
Subethini Roopan, Erik Roj Larsen
OBJECTIVE: Depression may be difficult to treat and with comorbid diabetes mellitus (DM) it is an even bigger challenge. This article aims to evaluate antidepressants most suitable for patients with depression and comorbid DM. Design and methods Initially we searched for randomised, controlled double-blind trials of treatment with antidepressants in depressed with DM but there were only a few studies and many of them were small trials. Thus, we decided to include studies that were not only randomised-controlled trials...
October 25, 2016: Acta Neuropsychiatrica
Eliza Pelrine, Sara Diana Pasik, Leyla Bayat, Debora Goldschmiedt, Elizabeth P Bauer
Selective serotonin reuptake inhibitors (SSRIs) are widely prescribed to treat anxiety and depression, yet they paradoxically increase anxiety during initial treatment. Acute administration of these drugs prior to learning can also enhance Pavlovian cued fear conditioning. This potentiation has been previously reported to depend upon the bed nucleus of the stria terminalis (BNST). Here, using temporary inactivation, we confirmed that the BNST is not necessary for the acquisition of cued or contextual fear memory...
October 20, 2016: Neurobiology of Learning and Memory
Aviad Hai, Lili X Cai, Taekwan Lee, Victor S Lelyveld, Alan Jasanoff
Reuptake of neurotransmitters from the brain interstitium shapes chemical signaling processes and is disrupted in several pathologies. Serotonin reuptake in particular is important for mood regulation and is inhibited by first-line drugs for treatment of depression. Here we introduce a molecular-level fMRI technique for micron-scale mapping of serotonin transport in live animals. Intracranial injection of an MRI-detectable serotonin sensor complexed with serotonin, together with serial imaging and compartmental analysis, permits neurotransmitter transport to be quantified as serotonin dissociates from the probe...
October 19, 2016: Neuron
Tae-Kyeong Lee, Joon Ha Park, Ji Hyeon Ahn, Myoung Cheol Shin, Jun Hwi Cho, Eun Joo Bae, Young-Myeong Kim, Moo-Ho Won, Choong-Hyun Lee
Duloxetine (DXT), a serotonin/norepinephrine reuptake inhibitor, is widely used for the treatment of major depressive disorders. In the present study, we investigated the neuroprotective effect of pre-treated DXT in the hippocampal CA1 region following transient global cerebral ischemia. Pre-treatment with 40mg/kg DXT protected pyramidal neurons in the CA1 region from ischemia-reperfusion injury. In addition, pre-treatment with DXT reduced ischemia-induced activations of microglia and astrocytes in the ischemic CA1 region...
November 15, 2016: Journal of the Neurological Sciences
Andrew F Leuchter, Aimee M Hunter, Felipe A Jain, Molly Tartter, Caroline Crump, Ian A Cook
Serotonin modulates brain oscillatory activity, and serotonergic projections to the thalamus and cortex modulate the frequency of prefrontal rhythmic oscillations. Changes in serotonergic tone have been reported to shift oscillations between the combined delta-theta (2.5-8 Hz) and the alpha (8-12 Hz) frequency ranges. Such frequency shifts may constitute a useful biomarker for the effects of selective serotonin reuptake inhibitor (SSRI) medications in Major Depressive Disorder (MDD). We utilized quantitative electroencephalography (qEEG) to measure shifts in prefrontal rhythmic oscillations early in treatment with either the SSRI escitalopram or placebo, and examined the relationship between these changes and remission of depressive symptoms...
October 7, 2016: Journal of Psychiatric Research
Carla Elena Sartori Oliveira, Marcel Henrique Marcondes Sari, Vanessa A Zborowski, Vinicius Costa Prado, Cristina Wayne Nogueira, Gilson Zeni
Depression and pain comorbidity represent a neuropsychiatric condition with substantial socioeconomic impact to society. The commonly used antidepressants and analgesics to treat this comorbidity have shown restricted clinical efficacy. In this way, the aim of this study was to investigate the behavioral, biochemical and neurochemical effects of a p,p'-methoxyl-diphenyl diselenide (OMePhSe)2 supplemented diet on pain-depression dyad induced by reserpine in rats. Adult Wistar rats were fed with 10mg (MeOPhSe)2 per kg of rat chow supplemented diet for 30 days...
October 18, 2016: European Journal of Pharmacology
Vishal Bali, Satabdi Chatterjee, Michael L Johnson, Hua Chen, Ryan M Carnahan, Rajender R Aparasu
OBJECTIVE: This study evaluated the risk of cognitive decline associated with paroxetine use in elderly nursing home patients with depression. METHODS: A retrospective cohort study was conducted using the 2007 to 2010 Medicare Part D claims and minimum data set (MDS) data involving new users of paroxetine and other selective serotonin reuptake inhibitors (SSRIs). The primary outcome was MDS Cognition Scale. The repeated-measures mixed model was used to examine the effect of paroxetine on cognition after controlling for other factors...
October 20, 2016: American Journal of Alzheimer's Disease and Other Dementias
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)...
October 19, 2016: Psychosomatic Medicine
Itai Danovitch, Alexander Joseph Steiner, Anna Kazdan, Matthew Goldenberg, Margaret Haglund, James Mirocha, Katherine Collison, Brigitte Vanle, Jonathan Dang, Waguih William IsHak
OBJECTIVE: Alcohol use disorders (AUDs) are common among persons with major depressive disorder (MDD) and have an adverse impact on course of illness and patient outcomes. The aim of this study was to examine whether AUD adversely impacted patient-centered outcomes in a sample of research subjects evaluated as part of a large clinical trial for depression. The outcomes of interest to this post hoc analysis are quality of life (QOL), functioning, and depressive symptom severity. METHODS: We analyzed 2280 adult MDD outpatient research subjects using data from the Sequenced Treatment Alternatives to Relieve Depression trial...
October 18, 2016: Journal of Addiction Medicine
Kasper D Tidemand, Hans E M Christensen, Niclas Hoeck, Pernille Harris, Jane Boesen, Günther H Peters
Tryptophan hydroxylase 2 (TPH2) catalyses the initial and rate-limiting step in the biosynthesis of serotonin, which is associated with a variety of disorders such as depression, obsessive compulsive disorder, and schizophrenia. Full-length TPH2 is poorly characterized due to low purification quantities caused by its inherent instability. Three truncated variants of human TPH2 (rch TPH2; regulatory and catalytic domain, NΔ47-rch TPH2; truncation of 47 residues in the N terminus of rch TPH2, and ch TPH2; catalytic domain) were expressed, purified, and examined for changes in transition temperature, inactivation rate, and oligomeric state...
October 2016: FEBS Open Bio
A Kenneth MacLeod, Lesley A McLaughlin, Colin J Henderson, C Roland Wolf
Tamoxifen is an oestrogen-receptor (ER) antagonist used in the treatment of breast cancer. It is a pro-drug, converted by several P450 enzymes to a primary metabolite, N-desmethyltamoxifen (NDT), which is then further modified by CYP2D6 to a pharmacologically potent secondary metabolite, 4-hydroxy-N-desmethyltamoxifen (endoxifen). Anti-depressants (ADs), which are often co-prescribed to patients receiving tamoxifen, are also metabolised by CYP2D6 and evidence suggests that a drug-drug interaction (DDI) between these agents adversely affects the outcome of tamoxifen therapy by inhibiting endoxifen formation...
October 18, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Rui Zhang, Yan Bi, Weibo Niu, Xiaoye Huang, Shiqing Chen, Xingwang Li, Xi Wu, Yanfei Cao, Fengping Yang, Lu Wang, Weidong Li, Yifeng Xu, Lin He, Tao Yu, Guang He
Schizophrenia (SZ) and major depressive disorder (MDD) are two common severe mental disorders that have arisen to public awareness in recent years. Serotonin (5-HT) receptors have been implicated in the pathophysiology of psychiatric disorders especially in MDD and SZ. The aim of this study is to explore whether the variants in the 5-HT1A and 5-HT2A gene are susceptible to SZ or MDD in the Chinese Han population. Five SNPs (Single Nucleotide Polymorphisms) (rs1364043, rs10042486, rs6313, rs6311, rs17289304) in these genes were genotyped from 752 SZ patients, 568 MDD patients, and 846 normal controls of Chinese Han origin...
October 15, 2016: Neuroscience Letters
Benedetta Vai, Chiara Bulgarelli, Beata R Godlewska, Philip J Cowen, Francesco Benedetti, Catherine J Harmer
The timely selection of the optimal treatment for depressed patients is critical to improve remission rates. The detection of pre-treatment variables able to predict differential treatment response may provide novel approaches for treatment selection. Selective serotonin reuptake inhibitors (SSRIs) modulate the fronto-limbic functional response and connectivity, an effect preceding the overt clinical antidepressant effects. Here we investigated whether the cortico-limbic connectivity associated with emotional bias measured before SSRI administration predicts the efficacy of antidepressant treatment in MDD patients...
October 15, 2016: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
Katarzyna Kamińska, Karolina Noworyta-Sokołowska, Alexandra Jurczak, Anna Górska, Zofia Rogóż, Krystyna Gołembiowska
BACKGROUND: Schizophrenia is a psychiatric disorder characterized by positive and negative symptoms often accompanied by depression and cognitive deficits. Positive symptoms, like delusions and hallucinations are caused by an excess of dopamine (DA) signaling and are treated with the second generation antipsychotic drugs. Negative symptoms of schizophrenia are represented by social withdrawal, apathy and blunted emotional response. It was demonstrated that co-administration of risperidone and selective serotonin reuptake inhibitors alleviated depressive symptoms and cognitive dysfunction in animal models of schizophrenia...
September 11, 2016: Pharmacological Reports: PR
Roberto Lewis-Fernández, Peter Lam, Susan Lucak, Hanga Galfalvy, Elizabeth Jackson, Jane Fried, Melissa Rosario, Ana Alicia de la Cruz, Arturo Sánchez-Lacay, Samantha Díaz, Franklin Schneier
Major depressive disorder (MDD) and irritable bowel syndrome (IBS) frequently co-occur, yet treating their comorbid presentation is challenging. Low-dose tricyclic antidepressants are efficacious for IBS, but higher doses to treat depressive symptoms present tolerability problems, whereas selective serotonin reuptake inhibitors are more tolerable but show inconsistent efficacy for IBS. If efficacious, serotonin-norepinephrine reuptake inhibitors like duloxetine would provide a useful alternative. We explored efficacy, tolerability, and time to onset of action of duloxetine in comorbid IBS-MDD in an open-label, 12-week trial...
October 17, 2016: Journal of Clinical Psychopharmacology
Stefan Gebhardt, Monika Heinzel-Gutenbrunner, Udo König
BACKGROUND: Pain is a common symptom in patients with depressive disorders, which, if present, worsens the prognosis. However, there is little empirical knowledge of the therapeutic effects of antidepressants on painful physical symptoms of patients with depressive disorders. Furthermore, tricyclic/tetracyclic antidepressants (TCAs) have not yet been included in existing meta-analyses. METHODS: A broad, systematic search of PubMed literature on antidepressant drug treatment of patients with depressive disorders with comorbid pain symptoms was carried out...
October 5, 2016: Journal of Clinical Psychopharmacology
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