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https://www.readbyqxmd.com/read/29163031/microrna-mediated-regulation-of-itgb3-and-chl1-is-implicated-in-ssri-action
#1
Keren Oved, Luba Farberov, Avial Gilam, Ifat Israel, Danielle Haguel, David Gurwitz, Noam Shomron
Background: Selective serotonin reuptake inhibitor (SSRI) antidepressant drugs are the first-line of treatment for major depressive disorder (MDD) but are effective in <70% of patients. Our earlier genome-wide studies indicated that two genes encoding for cell adhesion proteins, close homolog of L1 (CHL1) and integrin beta-3 (ITGB3), and microRNAs, miR-151a-3p and miR-221/222, are implicated in the variable sensitivity and response of human lymphoblastoid cell lines (LCL) from unrelated individuals to SSRI drugs...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/29156999/risk-factors-for-intracranial-lesions-and-mortality-in-older-patients-with-mild-traumatic-brain-injuries
#2
Ma Angustias Ibañez Pérez De La Blanca, Enrique Fernández Mondéjar, Francisco Javier Gómez Jimènez, Jóse María Alonso Morales, Ma Dolores Quijano Lombardo, Juan Luis Viso Rodriguez
PRIMARY OBJECTIVE: To identify risk factors for intracerebral lesion (ICL) in older adults with mild traumatic brain injury (MTBI) and evaluate the influence of comorbidities on outcomes. RESEARCH DESIGN: Prospective cohort study. METHODS AND PROCEDURES: Information was gathered on clinical history/examination, cranial computed tomography, admission Glasgow Coma Scale (GCS) score, analytical and coagulation findings, and mortality at 1 week post-discharge...
November 20, 2017: Brain Injury: [BI]
https://www.readbyqxmd.com/read/29151792/fluoxetine-modulates-sex-steroid-levels-in-vitro
#3
Diana Lupu, Marcus O D Sjödin, Mukesh Varshney, Johan Lindberg, Felicia Loghin, Joëlle Rüegg
Background and aims: Selective serotonin reuptake inhibitors (SSRIs) are antidepressants increasingly prescribed against depression during and after pregnancy. However, these compounds cross the placenta and are found in breast milk, thus reaching, and possibly affecting, the fetus and infant during critical developmental stages. Fluoxetine (FLX), a widely used SSRI, can interfere with estrogen signaling, which is important for the development of female sex organs and certain brain areas, among others...
2017: Clujul Medical (1957)
https://www.readbyqxmd.com/read/29150233/management-of-first-depression-or-generalized-anxiety-disorder-episode-in-adults-in-primary-care-a-systematic-metareview
#4
Damien Driot, Michel Bismuth, Adrien Maurel, Julie Soulie-Albouy, Jordan Birebent, Stéphane Oustric, Julie Dupouy
CONTEXT: General Practitioners (GPs) are the leading antidepressants prescribers in Europe and in France. Difficulties in implementing existing recommendations in daily practice have been described. OBJECTIVE: The objective of this study was to elaborate two algorithms to guide GPs in the patient management for a first major depressive disorder (MDD) or generalized anxiety disorder (GAD) episode in primary care. DATA SOURCES: PubMed, Cochrane, and ISI Web of Science were explored using mainly the following keywords: depressive disorder, anxiety disorders, antidepressive agents or antidepressant...
November 14, 2017: La Presse Médicale
https://www.readbyqxmd.com/read/29146408/paroxetine-blunts-the-corticosterone-response-to-swim-induced-stress-and-increases-depressive-like-behavior-in-a-rat-model-of-postpartum-depression
#5
Agnete Overgaard, Stephanie E Lieblich, Robin Richardson, Liisa A M Galea, Vibe G Frokjaer
Perinatal depression (PND) affects 15% of women. During the perinatal period both stress- and gonadal hormones fluctuate widely. Putatively, these fluctuations are involved in PND disease mechanisms. The serotonin system is sensitive to such hormone fluctuations, and serotonin reuptake inhibitors (SSRIs) are used to treat PND, although treatment is suboptimal and it is not known at which peripartum time-point SSRI treatment may be most efficacious. In this study, we investigate the effect of the SSRI paroxetine (5mg/kgs...
October 31, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/29138029/synthesis-and-antidepressant-activity-of-a-series-of-arylalkanol-and-aralkyl-piperazine-derivatives-targeting-ssri-5-ht1a-5-ht7
#6
Zheng-Song Gu, Ying Xiao, Qing-Wei Zhang, Jian-Qi Li
A series of arylalkanol and aralkyl piperazine derivatives have been synthesized and evaluated for 5-HT reuptake inhibitory abilities and binding affinities at the 5-HT1A/5-HT7 receptors. Antidepressant activities of the compounds in vivo were screened using the forced swimming test (FST). The results indicated that the compound 8j exhibited high affinities for the 5-HT1A/5-HT7 receptors (5-HT1A, ki = 0.84 nM; 5-HT7, ki = 12 nM) coupling with moderate 5-HT reuptake inhibitory activity (RUI, IC50 = 100 nM) and showed a marked antidepressant-like activity in the FST model...
November 6, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/29136336/effect-of-polymorphisms-on-the-pharmacokinetics-pharmacodynamics-and-safety-of-sertraline-in-healthy-volunteers
#7
Miriam Saiz-Rodríguez, Carmen Belmonte, Manuel Román, Dolores Ochoa, Dora Koller, María Talegón, María C Ovejero-Benito, Rosario López-Rodríguez, Teresa Cabaleiro, Francisco Abad-Santos
Sertraline is a selective serotonin reuptake inhibitor (SSRI) widely metabolized in the liver by cytochrome P450 (CYP) enzymes. Besides, it is a P-glycoprotein substrate. Moreover, serotonin transporters and serotonin receptors are involved in its efficacy and safety. The aim of the present study was to evaluate the role of polymorphisms of metabolizing enzymes, transporters and receptors on the pharmacokinetics, pharmacodynamics and tolerability of sertraline in healthy volunteers. Forty-six healthy volunteers (24 men and 22 women) receiving a 100-mg single oral dose of sertraline were genotyped for 17 genetic variants of CYP enzymes (CYP2B6, CYP2C9, CYP2C19, CYP2D6), ATP binding cassette subfamily B member 1 (ABCB1), Solute carrier family 6 member 4 (SLC6A4), 5-Hydroxytryptamine receptor 2A (HTR2A) and 5-Hydroxytryptamine receptor 2C (HTR2C) genes...
November 14, 2017: Basic & Clinical Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29134925/effects-of-ssri-exposure-on-hemorrhagic-complications-and-outcome-following-thrombolysis-in-ischemic-stroke
#8
Schellen Christoph, Ferrari Julia, Lang Wilfried, Sykora Marek
Background Selective serotonin reuptake inhibitors (SSRI) may interfere with platelet function, and pre-stroke SSRI treatment has been associated with increased hematoma volumes and mortality in hemorrhagic stroke patients. The effects of SSRI on the risk of hemorrhagic complications after thrombolysis in ischemic stroke patients are unclear. Aims To examine the effects of pre-stroke SSRI exposure on bleeding complications, functional outcome, and mortality following thrombolysis in ischemic stroke. Methods Data including standard demographic and clinical variables as well as baseline and follow-up stroke severity (measured by National Institutes of Health Stroke Score), functional outcome (measured by modified Rankin Scale) at 3 months, and mortality at 7 and 90 days were extracted from the Virtual International Stroke Trials Archive...
January 1, 2017: International Journal of Stroke: Official Journal of the International Stroke Society
https://www.readbyqxmd.com/read/29131015/therapeutic-response-to-paroxetine-in-major-depressive-disorder-predicted-by-dna-methylation
#9
Naohiro Takeuchi, Shinpei Nonen, Masaki Kato, Masataka Wakeno, Yoshiteru Takekita, Toshihiko Kinoshita, Fumihiko Kugawa
BACKGROUND: Antidepressants have variable therapeutic effects, depending on genetic and environmental factors. Approximately 30% of major depressive disorder (MDD) patients do not respond significantly to antidepressants such as paroxetine, a selective serotonin reuptake inhibitor (SSRI). However, the biological mechanisms behind this phenomenon are mostly unknown. Here, we examined the role of patients' epigenetic background in SSRI efficacy. METHODS: Genome-wide DNA methylation analysis of the peripheral blood of Japanese MDD patients was performed by using the Infinium HumanMethylation450 BeadChip...
November 4, 2017: Neuropsychobiology
https://www.readbyqxmd.com/read/29127269/intracerebral-hemorrhage-and-outcome-after-thrombolysis-in-stroke-patients-using-selective-serotonin-reuptake-inhibitors
#10
Jan F Scheitz, Guillaume Turc, Linda Kujala, Alexandros A Polymeris, Mirjam R Heldner, Thomas P Zonneveld, Hebun Erdur, Sami Curtze, Christopher Traenka, Céline Brenière, Roland Wiest, Andrea Rocco, Gerli Sibolt, Henrik Gensicke, Matthias Endres, Nicolas Martinez-Majander, Yannick Béjot, Paul J Nederkoorn, Catherine Oppenheim, Marcel Arnold, Stefan T Engelter, Daniel Strbian, Christian H Nolte
BACKGROUND AND PURPOSE: Selective serotonin-reuptake inhibitors (SSRIs) impair platelet function and have been linked to a higher risk of spontaneous intracerebral hemorrhage-an association that may be augmented by oral anticoagulants (OAC). We aimed to assess whether preadmission treatment with SSRIs in patients with acute ischemic stroke is associated with post-thrombolysis symptomatic intracerebral hemorrhage (sICH) and functional outcome. METHODS: A multicenter retrospective analysis was conducted in prospective registries of patients treated by thrombolysis within 4...
November 10, 2017: Stroke; a Journal of Cerebral Circulation
https://www.readbyqxmd.com/read/29123931/rapid-ascending-sensorimotor-paralysis-hearing-loss-and-fatal-arrhythmia-in-a-multimorbid-patient-due-to-an-accidental-overdose-of-fluoxetine
#11
Matthew Herrmann, Prissilla Xu, Antonio Liu
Background: Common side effects of selective serotonin reuptake inhibitors (SSRIs) include tachycardia, drowsiness, tremor, nausea, and vomiting. Although SSRIs have less toxic side effects compared to more traditional antidepressants, serious and life threatening cases of SSRI overdose have been reported. We describe a 24-year-old multimorbid female who presented to the emergency department with rapid onset ascending sensorimotor paralysis, complicated by respiratory and cardiac arrest, found to have fatal levels of fluoxetine by toxicological analysis, not taken in a suicidal act...
2017: Case Reports in Neurological Medicine
https://www.readbyqxmd.com/read/29123483/impact-of-vortioxetine-on-synaptic-integration-in-prefrontal-subcortical-circuits-comparisons-with-escitalopram
#12
Shreaya Chakroborty, Thomas R Geisbush, Elena Dale, Alan L Pehrson, Connie Sánchez, Anthony R West
Prefrontal-subcortical circuits support executive functions which often become dysfunctional in psychiatric disorders. Vortioxetine is a multimodal antidepressant that is currently used in the clinic to treat major depressive disorder. Mechanisms of action of vortioxetine include serotonin (5-HT) transporter blockade, 5-HT1A receptor agonism, 5-HT1B receptor partial agonism, and 5-HT1D, 5-HT3, and 5-HT7 receptor antagonism. Vortioxetine facilitates 5-HT transmission in the medial prefrontal cortex (mPFC), however, the impact of this compound on related prefrontal-subcortical circuits is less clear...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29116785/a-positive-allosteric-modulator-of-the-serotonin-5-ht2c-receptor-for-obesity
#13
Javier García-Cárceles, Juan M Decara, Henar Vázquez-Villa, Ramón Rodríguez, Eva Codesido, Jacobo Cruces, José Brea, María I Loza, Francisco Alén, Joaquin Botta, Peter J McCormick, Juan A Ballesteros, Bellinda Benhamú, Fernando Rodríguez de Fonseca, María L López-Rodríguez
The 5-HT2CR agonist lorcaserin, clinically approved for the treatment of obesity, causes important side effects mainly related to subtype selectivity. In the search for 5-HT2CR allosteric modulators as safer antiobesity drugs, a chemical library from Vivia Biotech was screened using ExviTech platform. Structural modifications of identified hit VA240 in synthesized analogues 6-41 afforded compound 11 (N-[(1-benzyl-1H-indol-3-yl)methyl]pyridin-3-amine, VA012), which exhibited dose-dependent enhancement of serotonin efficacy, no significant off-target activities, and low binding competition with serotonin or other orthosteric ligands...
November 17, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29105282/escitalopram-oxalate-induces-apoptosis-in-u-87mg-cells-and-autophagy-in-gbm8401-cells
#14
Vincent Chin-Hung Chen, Yi-Hsien Hsieh, Li-Jeng Chen, Tsai-Ching Hsu, Bor-Show Tzang
Glioblastoma multiforme (GBM) is recognized as a most aggressive brain cancer with the worst prognosis and survival time. Owing to the anatomic location of gliomas, surgically removing the tumour is very difficult and avoiding damage to vital brain regions during radiotherapy is impossible. Therefore, therapeutic strategies for malignant glioma must urgently be improved. Recent studies have demonstrated that selective serotonin reuptake inhibitors (SSRIs) have cytotoxic effect on certain cancers. Considering as a more superior SSRI, escitalopram oxalate exhibits favourable tolerability and causes generally mild and temporary adverse events...
November 3, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/29104538/chronic-treatment-with-fluoxetine-induces-sex-dependent-analgesic-effects-and-modulates-hdac2-and-mglu2-expression-in-female-mice
#15
Magda Zammataro, Sara Merlo, Massimo Barresi, Carmela Parenti, Huijuan Hu, Maria A Sortino, Santina Chiechio
Gender and sex differences in pain recognition and drug responses have been reported in clinical trials and experimental models of pain. Among antidepressants, contradictory results have been observed in patients treated with selective serotonin reuptake inhibitors (SSRIs). This study evaluated sex differences in response to the SSRI fluoxetine after chronic administration in the mouse formalin test. Adult male and female CD1 mice were intraperitoneally injected with fluoxetine (10 mg/kg) for 21 days and subjected to pain assessment...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29102768/brain-derived-neurotrophic-factor-bdnf-and-neurotrophin-3-nt3-levels-in-post-mortem-brain-tissue-from-patients-with-depression-compared-to-healthy-individuals%C3%A2-%C3%A2-a-proof-of-concept-study
#16
A Sheldrick, S Camara, M Ilieva, P Riederer, T M Michel
The neurotrophic factors (NTF) hypothesis of depression was postulated nearly a decade ago and is nowadays widely acknowledged. Previous reports suggest that cerebral concentrations of NTF may be reduced in suicide victims who received minimal or no antidepressant pharmacotherapy. Recent evidence suggests that antidepressant treatment may improve or normalise cerebral concentrations of neurotrophic factors. Therefore, we examined the concentration of brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT3) in different brain regions (cortex, cingulate gyrus, thalamus, hippocampus, putamen and nucleus caudatus) of 21 individuals - 7 patients of which 4 patients with major depressive disorder (MDD) and overall age 86...
July 11, 2017: European Psychiatry: the Journal of the Association of European Psychiatrists
https://www.readbyqxmd.com/read/29102760/partial-inhibition-of-catecholamine-activity-and-enhanced-responsiveness-to-nmda-after-sustained-administration-of-vortioxetine
#17
Mohammad Ebrahimzadeh, Mostafa El Mansari, Pierre Blier
Vortioxetine is a multimodal drug that blocks serotonin (5-HT) reuptake and directly modulates 5-HT receptors. The effects of subacute and long-term administration of vortioxetine on various aspects of catecholamine and glutamate systems were investigated using single-unit extracellular recordings and microiontophoresis in the rat brain. The firing rate of dopamine (DA) neurons was significantly decreased (26%) after 14, but not 4 days of vortioxetine administration (vortioxetine-containing chow, 1.8 g/kg vortioxetine)...
November 13, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/29099547/treating-pediatric-anxiety-initial-use-of-ssris-and-other-antianxiety-prescription-medications
#18
Greta A Bushnell, Scott N Compton, Stacie B Dusetzina, Bradley N Gaynes, M Alan Brookhart, John T Walkup, Moira A Rynn, Til Stürmer
OBJECTIVE: Multiple pharmacotherapies for treating anxiety disorders exist, including selective serotonin reuptake inhibitors (SSRIs), the recommended first-line pharmacotherapy for pediatric anxiety. We sought to describe initial antianxiety medication use in children and estimate how long antianxiety medications were continued. METHODS: In a large commercial claims database, we identified children (3-17 years) initiating prescription antianxiety medication from 2004 to 2014 with a recent anxiety diagnosis (ICD-9-CM = 293...
October 31, 2017: Journal of Clinical Psychiatry
https://www.readbyqxmd.com/read/29097744/alleviative-effects-of-fluoxetine-on-depressive-like-behaviors-by-epigenetic-regulation-of-bdnf-gene-transcription-in-mouse-model-of-post-stroke-depression
#19
Hui-Juan Jin, Lei Pei, Ya-Nan Li, Hui Zheng, Shuai Yang, Yan Wan, Ling Mao, Yuan-Peng Xia, Quan-Wei He, Man Li, Zhen-Yu Yue, Bo Hu
Fluoxetine, one of the selective serotonin reuptake inhibitor (SSRI) antidepressants, has been thought to be effective for treating post-stroke depression (PSD). Recent work has shown that fluoxetine may exert an antidepressive effect through increasing the level of brain-derived neurotrophic factor (BDNF), but the underlying mechanism still remains unclear. In the present study, we successfully established the PSD model using male C57BL/6 J mice by photothrombosis of the left anterior cortex combined with isolatied-housing conditions...
November 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29080976/relationships-of-depressive-behavior-and-sertraline-treatment-with-walking-speed-and-activity-in-older-female-nonhuman-primates
#20
Jamie N Justice, Marnie G Silverstein-Metzler, Beth Uberseder, Susan E Appt, Thomas B Clarkson, Thomas C Register, Stephen B Kritchevsky, Carol A Shively
Depression is the most common mental health problem in aging persons and is a leading risk factor for physical disability, especially in women. Though antidepressant drugs such as serotonin reuptake inhibitors (SSRI) are commonly prescribed, epidemiological evidence reveals mixed effects of long-term antidepressant use on physical function and activity, possibly depending on depressive status. The purpose of this preclinical trial was to determine the relationships of depressive behavior and the potential for an SSRI treatment to modulate walking speed and activity patterns in older adult female cynomolgus monkeys (Macaca fascicularis)...
October 28, 2017: GeroScience
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