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https://www.readbyqxmd.com/read/29045739/assessment-of-ketamine-binding-of-the-serotonin-transporter-in-humans-with-positron-emission-tomography
#1
Marie Spies, Gregory M James, Neydher Berroterán-Infante, Harald Ibeschitz, Georg S Kranz, Jakob Unterholzner, Mathis Godbersen, Gregor Gryglewski, Marius Hienert, Johannes Jungwirth, Verena Pichler, Birgit Reiter, Leo Silberbauer, Dietmar Winkler, Markus Mitterhauser, Thomas Stimpfl, Marcus Hacker, Siegfried Kasper, Rupert Lanzenberger
Background: Comprehensive description of ketamine's molecular binding profile becomes increasingly pressing as use in real life patient cohorts widens. Animal studies attribute a significant role in the substance's antidepressant effects to the serotoninergic system. The serotonin transporter (SERT) is a highly relevant target in this context because it is central to depressive pathophysiology and treatment. This is to our knowledge the first study investigating ketamine's SERT binding in-vivo in humans...
October 16, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29033635/evaluation-of-5-httlpr-gene-polymorphism-and-resilience-components-on-the-development-of-psychopathology-in-adolescent-sexual-abuse-cases
#2
Gresa Çarkaxhiu Bulut, Ayşe Rodopman Arman, İlter Güney, Pınar Gültepe
INTRODUCTION: More than one-fourth adolescents are exposed to unexpected frightening experiences and traumas until adulthood. In this study, we aimed to determine the potential role of serotonin transporter (5-HTT) gene polymorphism regarding resilience factors in the symptom variability of individuals exposed to sexual abuse. METHODS: Adolescents aged 11-17 years, who were admitted to the Marmara University Child Psychiatry Outpatient Clinic Forensic division with sexual abuse experience history, were informed about the research, and volunteers were included in the study...
September 2017: Noro Psikiyatri Arsivi
https://www.readbyqxmd.com/read/29032922/serotonin-transporter-density-in-binge-eating-disorder-and-pathological-gambling-a-pet-study-with-11-c-madam
#3
Joonas Majuri, Juho Joutsa, Jarkko Johansson, Valerie Voon, Riitta Parkkola, Hannu Alho, Eveliina Arponen, Valtteri Kaasinen
Behavioral addictions, such as pathological gambling (PG) and binge eating disorder (BED), appear to be associated with specific changes in brain dopamine and opioid function, but the role of other neurotransmitter systems is less clear. Given the crucial role of serotonin in a number of psychiatric disorders, we aimed to compare brain serotonergic function among individuals with BED, PG and healthy controls. Seven BED patients, 13 PG patients and 16 healthy controls were scanned with high-resolution positron emission tomography (PET) using the serotonin transporter (SERT) tracer [(11)C]MADAM...
October 9, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29030987/nod1-downregulates-intestinal-serotonin-transporter-and-interacts-with-other-pattern-recognition-receptors
#4
Elena Layunta, Eva Latorre, Raquel Forcén, Laura Grasa, Miguel Ángel Plaza, Maykel Arias, Ana I Alcalde, José E Mesonero
Serotonin (5-HT) is an essential gastrointestinal modulator whose effects regulate the intestinal physiology. 5-HT effects depend on extracellular 5-HT bioavailability, which is controlled by the serotonin transporter (SERT) expressed in both the apical and basolateral membranes of enterocytes. SERT is a critical target for regulating 5-HT levels and consequently, modulating the intestinal physiology. The deregulation of innate immune receptors has been extensively studied in inflammatory bowel diseases (IBD), where an exacerbated defense response to commensal microbiota is observed...
October 14, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29030421/serotonin-transporter-gene-polymorphisms-may-be-associated-with-poststroke-neurological-recovery-after-escitalopram-use
#5
Eun-Jae Lee, Mi-Sun Oh, Jong S Kim, Dae-Il Chang, Jong-Ho Park, Jae-Kwan Cha, Ji Hoe Heo, Sung-Il Sohn, Dong-Eog Kim, Hahn Young Kim, Jei Kim, Woo-Keun Seo, Jun Lee, Sang-Won Park, Yun Joong Kim, Byung-Chul Lee
OBJECTIVE: Selective serotonin reuptake inhibitors (SSRIs) putatively improve neurological recovery after stroke. We aimed to investigate whether serotonin transporter (SERT) gene polymorphisms are related to the responsiveness to SSRIs in the poststroke neurological recovery. METHODS: This was a post hoc analysis of the EMOTION study (ClinicalTrials.gov NCT01278498), a randomised, placebo-controlled, double-blind trial examining the efficacy of escitalopram on emotional and neurological disturbances after acute stroke...
October 13, 2017: Journal of Neurology, Neurosurgery, and Psychiatry
https://www.readbyqxmd.com/read/29020405/neuroticism-associates-with-cerebral-in-vivo-serotonin-transporter-binding-differently-in-males-and-females
#6
Lauri Tuominen, Jouko Miettunen, Dara M Cannon, Wayne C Drevets, Vibe G Frokjaer, Jussi Hirvonen, Masanori Ichise, Peter S Jensen, Liisa Keltikangas-Järvinen, Jacqueline M Klaver, Gitte M Knudsen, Akihiro Takano, Tetsuya Suhara, Jarmo Hietala
Background: Neuroticism is a major risk factor for affective disorders. This personality trait has been hypothesized to associate with synaptic availability of the serotonin transporter (5-HTT), which critically controls serotonergic tone in the brain. However, earlier studies linking neuroticism and 5-HTT have failed to produce converging findings. Because sex affects both the serotonergic system and the risk that neuroticism poses to the individual, sex may modify the association between neuroticism and 5-HTT, but this question has not been investigated by previous studies...
August 7, 2017: International Journal of Neuropsychopharmacology
https://www.readbyqxmd.com/read/29018523/comparative-study-of-two-protocols-for-quantitative-image-analysis-of-serotonin-transporter-clustering-in-lymphocytes-a-putative-biomarker-of-therapeutic-efficacy-in-major-depression
#7
Raquel Romay-Tallon, Tania Rivera-Baltanas, Josh Allen, Jose M Olivares, Lisa E Kalynchuk, Hector J Caruncho
BACKGROUND: The pattern of serotonin transporter clustering on the plasma membrane of lymphocytes extracted from human whole blood samples has been identified as a putative biomarker of therapeutic efficacy in major depression. Here we evaluated the possibility of performing a similar analysis using blood smears obtained from rats, and from control human subjects and depression patients. We hypothesized that we could optimize a protocol to make the analysis of serotonin protein clustering in blood smears comparable to the analysis of serotonin protein clustering using isolated lymphocytes...
2017: Biomarker Research
https://www.readbyqxmd.com/read/29016262/association-of-5-httlpr-polymorphism-with-the-nursing-diagnoses-and-the-achievement-of-nursing-outcomes-in-patients-with-major-depression
#8
Margarita Prokofieva, Georgia Karadima, Evmorfia Koukia, Vassiliki Michou, Chrysoula Kyprianidou, Chrysovalantis V Papageorgiou, Evangelos Alexiadis, Pantelis Constantoulakis, Dimitris Dikeos
The aim of this study is to investigate whether a 44-base-pair insertion/deletion polymorphism in the upstream regulatory region of the serotonin transporter gene (5-HTTLPR) is associated with the nursing diagnoses and the achievement of the desired nursing outcomes in inpatients with major depression. Thirty five patients were evaluated. The nursing diagnoses of risk for suicide and imbalanced nutrition are reported less often in homozygotes of the high-expressing gene (LA). Carriers of the low-expressing genes (LG or S) have a worse response to interventions which aim to increase low self-esteem, indicating that they may need more intensive care in order to achieve the desired outcome...
October 2017: Issues in Mental Health Nursing
https://www.readbyqxmd.com/read/28991462/structure-activity-relationship-pharmacological-characterization-and-molecular-modeling-of-non-competitive-inhibitors-of-the-betaine-%C3%AE-aminobutyric-acid-transporter-1-bgt1
#9
Lars Jørgensen, Anas Al-Khawaja, Stefanie Kickinger, Stine Byskov Vogensen, Jonas Skovgaard-Petersen, Emil Rosenthal Jensen, Nrupa Borkar, Rebekka Löffler, Karsten K Madsen, Hans Bräuner-Osborne, Arne Schousboe, Gerhard F Ecker, Petrine Wellendorph, Rasmus Prætorius Clausen
N-(1-Benzyl-4-piperidinyl)-2,4-dichlorobenzamide 5 (BPDBA) is a non-competitive inhibitor of the betaine/GABA transporter 1 (BGT1). We here report the synthesis and structure-activity relationship of 71 analogues. We identify 26m as a more soluble 2,4-Cl substituted 3-pyridine analogue with retained BGT1 activity and an improved off-target profile compared to 5. We performed radioligand-based uptake studies at chimeric constructs between BGT1 and GAT3, experiments with site-directed mutated transporters and computational docking in a BGT1 homology model based on the newly determined X-ray crystal structure of the human serotonin transporter (hSERT)...
October 9, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28983622/novel-insights-into-the-effect-of-paroxetine-administration-in-pilocarpine%C3%A2-induced-chronic-epileptic-rats
#10
Wan-Hui Lin, Xiao-Feng Li, Ming-Xing Lin, Ying Zhou, Hua-Pin Huang
The aim of the present study was to investigate the role of paroxetine intervention in epilepsy, and its association with the expression of serotonin transporter (SERT) and hippocampal apoptosis. Thirty adult male Sprague Dawley rats were divided into control vehicle (n=6) and epileptic (n=24) groups. Status epilepticus (SE) was induced via systemic injection of pilocarpine, and seizure activity was monitored via video electroencephalogram. The epileptic group was then randomly divided into two groups; Four weeks following SE induction, paroxetine (5 mg/kg/day; SE + paroxetine group) or normal saline (SE group) was intraperitoneally injected for 4 weeks...
September 28, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28982335/reduced-serotonin-transporter-levels-and-inflammation-in-the-midbrain-raphe-of-12-month-old-appswe-psen1de9-mice
#11
Athanasios Metaxas, Ramanan Vaitheeswaran, Katrine T Jensen, Camilla Thygesen, Laura Ilkjaer, Sultan Darvesh, Bente Finsen
Background Although mood and sleep disturbances are nearly universal among patients with Alzheimer's disease (AD), brain structures involved in non-cognitive processing remain under characterized in terms of AD pathology. Objectives This study was designed to evaluate hallmarks of AD pathology in the brainstem of the APPswe/PS1dE9 mouse model of familial AD. Methods Fresh-frozen sections from female, 12 month old, transgenic and control B6C3 mice (n=6/genotype) were examined for amyloid burden and neurofibrillary alterations, by using 6E10 immunohistochemistry and the Gallyas silver stain, respectively...
October 4, 2017: Current Alzheimer Research
https://www.readbyqxmd.com/read/28971674/3d-printed-molds-encompassing-carbon-composite-electrodes-to-conduct-multisite-monitoring-in-the-entire-colon
#12
Nirav Patel, Aidan Fagan-Murphy, Derek Covill, Bhavik Anil Patel
The activity of the colon is regulated by chemical signaling, of which serotonin (5-HT) is a key transmitter. Monitoring of mucosal 5-HT overflow has been achieved to date using microelectrodes on a small segment of colonic tissue; however, little is known if such measurements are reflective with regards to 5-HT signaling from the entire colon. This study focused on developing an electrochemical array device that could be utilized to conduct multisite measurements of 5-HT overflow from the entire colon. A 3D printed mold was fabricated that could house 6 multiwall carbon nanotube composite electrodes and provide a fixed distance between the electrodes and the tissue along the entire length of the colon...
October 10, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28969722/the-interaction-between-5-httlpr-genotype-and-ruminative-thinking-on-bmi
#13
Robbie Schepers, C Robert Markus
Negative affect or stress is often found to increase energy intake for high palatable energy-rich foods and hence weight gain. Reduced brain serotonin (5-HT) function is known to increase stress vulnerability and the risk for eating-related disturbances. A short (S) allele polymorphism in the serotonin transporter gene (5-HTTLPR) is associated with a less efficient functioning brain serotonin system and therefore higher stress vulnerability. It has been suggested that this genotype may be directly linked to an increased risk for weight gain and/or obesity...
October 3, 2017: British Journal of Nutrition
https://www.readbyqxmd.com/read/28959218/maternal-sensitivity-buffers-the-association-between-slc6a4-methylation-and-socio-emotional-stress-response-in-3-month-old-full-term-but-not-very-preterm-infants
#14
Livio Provenzi, Monica Fumagalli, Roberto Giorda, Francesco Morandi, Ida Sirgiovanni, Uberto Pozzoli, Fabio Mosca, Renato Borgatti, Rosario Montirosso
BACKGROUND: Very preterm (VPT) infants are hospitalized in Neonatal Intensive Care Units (NICUs) and are exposed to life-saving procedures eliciting pain-related stress. Recent research documented that pain-related stress might result in birth-to-discharge increased methylation of serotonin transporter gene (SLC6A4) in VPT infants, leading to poorer stress regulation at 3 months of age in VPT infants compared to their full-term (FT) counterparts. Maternal sensitivity is thought to support infants' stress response, but its role in moderating the effects of altered SLC6A4 methylation is unknown...
2017: Frontiers in Psychiatry
https://www.readbyqxmd.com/read/28939188/neural-and-psychological-characteristics-of-college-students-with-alcoholic-parents-differ-depending-on-current-alcohol-use
#15
Kathleen A Brown-Rice, Jamie L Scholl, Kelene A Fercho, Kami Pearson, Noah A Kallsen, Gareth E Davies, Erik A Ehli, Seth Olson, Amy Schweinle, Lee A Baugh, Gina L Forster
A significant proportion of college students are adult children of an alcoholic parent (ACoA), which can confer greater risk of depression, poor self-esteem, alcohol and drug problems, and greater levels of college attrition. However, some ACoA are resilient to these negative outcomes. The goal of this study was to better understand the psychobiological factors that distinguish resilient and vulnerable college-aged ACoAs. To do so, scholastic performance and psychological health were measured in ACoA college students not engaged in hazardous alcohol use (resilient) and those currently engaged in hazardous alcohol use (vulnerable)...
September 20, 2017: Progress in Neuro-psychopharmacology & Biological Psychiatry
https://www.readbyqxmd.com/read/28935840/test-retest-reliability-of-the-sert-imaging-agent-11-c-homadam-in-healthy-humans
#16
Vikram Adhikarla, Boadie W Dunlop, Nachwa Jarkas, Mark Goodman, Helen Mayberg, Michael J Owens, Jonathon A Nye
The aim of this study was to measure the test-retest reliability of (11)C-N,N-dimethyl-2-(2'-amino-4'-hydroxymethylphenylthio)benzylamine ([(11)C]HOMADAM) imaging of serotonin transporter (SERT) density in healthy control subjects. Methods: Two female and two male volunteers participated in the study and underwent three [(11)C]HOMADAM Positron Emission Tomography (PET) scans each of 90 min in duration. Time-activity curves were derived from SERT rich structures and fit to two models: 1) a simplified reference tissue model (SRTM) and 2) a multi-linear graphical model (MRTM)...
September 21, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28935838/decreased-pretreatment-amygdalae-serotonin-transporter-binding-in-unipolar-depression-remitters-a-prospective-pet-study
#17
Mala Ananth, Christine DeLorenzo, Jie Yang, J John Mann, Ramin Parsey
Major Depressive Disorder (MDD) is a debilitating condition that affects over 14 million Americans. Remission only occurs in a minority of individuals following first-line antidepressant treatment (~35%); predictors of treatment outcome are therefore needed. Using Positron Emission Tomography (PET) imaging with a radiotracer specific for the serotonin transporter (5-HTT), (11)C-McN5652, we found that patients with MDD who did not achieve remission following 12 months of naturalistic treatment had lower pre-treatment midbrain and amygdala binding compared to healthy volunteers...
September 21, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28921740/5-httlpr-moderates-the-association-between-interdependence-and-brain-responses-to-mortality-threats
#18
Siyang Luo, Dian Yu, Shihui Han
While behavioral research suggests an association between cultural worldview and decreased anxiety of death, the underlying neurobiological mechanisms remain unclear. Using functional MRI, we investigated whether and how the serotonin transporter promoter polymorphism (5-HTTLPR), which has been associated with mental disorders such as anxiety and depression, moderates the associations between a cultural trait (i.e., interdependence) and self-report of death anxiety/depression and between interdependence and brain responses to mortality threats...
September 17, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28914102/5-httlpr-brain-derived-neurotrophic-factor-bdnf-gene-interactions-and-early-adverse-life-events-effect-on-impulsivity-in-suicide-attempters
#19
Luis Jiménez-Treviño, Pilar Alejandra Saiz, Maria Paz García-Portilla, Hilario Blasco-Fontecilla, Vladimir Carli, Miriam Iosue, Isabelle Jaussent, Jorge López-Castroman, Concepcion Vaquero-Lorenzo, Marco Sarchiapone, Enrique Baca-García, Philippe Courtet, Julio Bobes
OBJECTIVES: An expanding body of research suggests that childhood adverse experiences can lead to different negative health outcomes, including attempted suicide. Serotonergic genes such as the promoter region of the serotonin transporter gene (5-HTTLPR) have been associated both with impulsivity in suicide attempts and reactivity to environmental stress exposure. BDNF gene may play an epigenetic role. METHODS: We studied the influence of childhood stressful events and 5-HTTLPR genotype on impulsivity measured by Barratt Impulsivity Scale (BIS-10) in a multicentre sample of 1,655 suicide attempters (69...
September 15, 2017: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/28910072/mapping-the-binding-site-for-escitalopram-and-paroxetine-in-the-human-serotonin-transporter-using-genetically-encoded-photo-cross-linkers
#20
Hafsteinn Rannversson, Jacob Andersen, Benny Bang-Andersen, Kristian Strømgaard
In spite of the important role of the human serotonin transporter (hSERT) in depression treatment, the molecular details of how antidepressant drugs bind are still not completely understood, in particular those related to potential high- and low-affinity binding sites in hSERT. Here, we utilize amber codon suppression in hSERT to encode the photo-cross-linking unnatural amino acid p-azido-l-phenylalanine into the suggested high- and low-affinity binding sites. We then employ UV-induced cross-linking with azF to map the binding site of escitalopram and paroxetine, two prototypical selective serotonin reuptake inhibitors (SSRIs)...
September 26, 2017: ACS Chemical Biology
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