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https://www.readbyqxmd.com/read/28534451/genetic-moderation-of-multiple-pathways-linking-early-cumulative-socioeconomic-adversity-and-young-adults-cardiometabolic-disease-risk
#1
Kandauda A S Wickrama, Tae Kyoung Lee, Catherine Walker O'Neal
Recent research suggests that psychosocial resources and life stressors are mediating pathways explaining socioeconomic variation in young adults' health risks. However, less research has examined both these pathways simultaneously and their genetic moderation. A nationally representative sample of 11,030 respondents with prospective data collected over 13 years from the National Study of Adolescent to Adult Health was examined. First, the association between early cumulative socioeconomic adversity and young adults' (ages 25-34) cardiometabolic disease risk, as measured by 10 biomarkers, through psychosocial resources (educational attainment) and life stressors (accelerated transition to adulthood) was examined...
May 23, 2017: Development and Psychopathology
https://www.readbyqxmd.com/read/28533695/the-triallelic-serotonin-transporter-gene-polymorphism-is-associated-with-depressive-symptoms-in-adults-with-chronic-pain
#2
W Michael Hooten, Cynthia O Townsend, Christopher D Sletten
BACKGROUND: The serotonin (5-HT) transporter-linked polymorphic region (5-HTTLPR) moderates the relationship between stressful life events and depression. Given the high prevalence of depression in chronic pain, the primary aim of this preliminary study was to investigate the associations between the 5-HTTLPR and the severity of depressive symptoms in a cohort of adults with chronic pain. METHODS: Adults with chronic pain who were consecutively admitted to an outpatient pain rehabilitation program and met inclusion criteria were recruited for study participation (n=277)...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/28528967/chronic-fluoxetine-rescues-changes-in-plasma-membrane-density-of-5-ht1a-autoreceptors-and-serotonin-transporters-in-the-olfactory-bulbectomy-rodent-model-of-depression
#3
Mustapha Riad, Antonia Kobert, Laurent Descarries, Sandra Boye, Pierre-Paul Rompré, Jean-Claude Lacaille
Reduced serotonin (5-HT) neurotransmission is postulated to underlie the pathogenesis of depression. The serotonin transporter (SERT) and 5-HT1A auto-receptors act in concert to ensure homeostasis of serotonin (5-HT) neurotransmission and regulation of their cell surface expression represent efficient mechanisms to maintain this homeostasis. Thus, we investigated the changes in the subcellular distribution of SERT and 5-HT1A receptors (5-HT1AR) in the rat olfactory bulbectomy model of depression using immuno-gold labelling and electron microscopy, and examined the effect of chronic treatment with the antidepressant, fluoxetine, a serotonin reuptake inhibitor, on the subcellular distribution of SERT and 5-HT1AR...
May 18, 2017: Neuroscience
https://www.readbyqxmd.com/read/28511918/molecular-imaging-of-serotonin-degeneration-in-mild-cognitive-impairment
#4
Gwenn S Smith, Frederick S Barrett, Jin Hui Joo, Najlla Nassery, Alena Savonenko, Devin J Sodums, Christopher M Marano, Cynthia A Munro, Jason Brandt, Michael A Kraut, Yun Zhou, Dean F Wong, Clifford I Workman
Neuropathological and neuroimaging studies have consistently demonstrated degeneration of monoamine systems, especially the serotonin system, in normal aging and Alzheimer's disease. The evidence for degeneration of the serotonin system in mild cognitive impairment is limited. Thus, the goal of the present study was to measure the serotonin transporter in vivo in mild cognitive impairment and healthy controls. The serotonin transporter is a selective marker of serotonin terminals and of the integrity of serotonin projections to cortical, subcortical and limbic regions, as well as the cell bodies of origin (raphe nuclei)...
May 13, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28504644/direct-reconstruction-of-parametric-images-for-brain-pet-with-event-by-event-motion-correction-evaluation-in-two-tracers-across-count-levels
#5
Mary Germino, Jean-Dominique Gallezot, Jianhua Yan, Richard Carson
Parametric images for dynamic positron emission tomography (PET) are typically generated by an indirect method, i.e., reconstructing a time series of emission images, then fitting a kinetic model to each voxel time activity curve. Alternatively, "direct reconstruction," incorporates the kinetic model into the reconstruction algorithm itself, directly producing parametric images from projection data. Direct reconstruction has been shown to achieve parametric images with lower standard error than the indirect method...
May 15, 2017: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/28501470/possibility-of-predicting-sert-occupancy-from-the-in-vitro-inhibition-constant-for-sert-the-clinically-relevant-plasma-concentration-of-unbound-drugs-and-their-profiles-for-substrates-of-transporters
#6
REVIEW
Masahiro Yahata, Koji Chiba, Takao Watanabe, Yuichi Sugiyama
Accurate prediction of target occupancy facilitates CNS drug development. In this review, we discuss the predictability of serotonin transporter (SERT) occupancy in human brain estimated from in vitro Ki values for human SERT and plasma concentrations of unbound drug (Cu,plasma) as well as the impact of drug transporters in the blood-brain barrier. First, the geometric means of in vitro Ki values were compared with the means of in vivo Ki values (Ki,u,plasma) which were calculated as Cu,plasma values at 50% occupancy of SERT obtained from previous clinical PET/SPECT imaging studies for 6 selective serotonin transporter reuptake inhibitors (SSRIs) and 3 serotonin norepinephrine reuptake inhibitors (SNRIs)...
May 10, 2017: Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28499187/vortioxetine-a-review-of-the-pharmacology-and-clinical-profile-of-the-novel-antidepressant
#7
REVIEW
Magdalena Sowa-Kućma, Patrycja Pańczyszyn-Trzewik, Paulina Misztak, Rafał R Jaeschke, Katherine Sendek, Krzysztof Styczeń, Wojciech Datka, Magdalena Koperny
The aim of this paper was to review the up-to-date evidence base on pharmacology and clinical properties of vortioxetine. Vortioxetine is a novel antidepressant, approved by the US Food and Drug Administration (FDA) for the treatment of major depressive disorder (MDD). Because vortioxetine exhibits both an antidepressant and anxiolytic effect, it may be effective in treating both depressive and anxiety disorders, such as generalized anxiety disorder (GAD). Based on its pharmacodynamics profile and preclinical studies, it is believe that the drug's clinical action is mediated mainly by selective blockade of serotonin reuptake (by inhibiting the serotonin transporter [SERT]) and direct modulation of 5-HT receptors activity (such as 5-HT3, 5-HT7, 5-HT1D and 5-HT1B)...
February 1, 2017: Pharmacological Reports: PR
https://www.readbyqxmd.com/read/28491024/the-serotonin-transporter-and-early-life-stress-translational-perspectives
#8
REVIEW
Danielle J Houwing, Bauke Buwalda, Eddy A van der Zee, Sietse F de Boer, Jocelien D A Olivier
The interaction between the serotonin transporter (SERT) linked polymorphic region (5-HTTLPR) and adverse early life stressing (ELS) events is associated with enhanced stress susceptibility and risk to develop mental disorders like major depression, anxiety, and aggressiveness. In particular, human short allele carriers are at increased risk. This 5-HTTLPR polymorphism is absent in the rodent SERT gene, but heterozygous SERT knockout rodents (SERT(+/-)) show several similarities to the human S-allele carrier, therefore creating an animal model of the human situation...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28486929/ulk1-phosphorylates-sec23a-and-mediates-autophagy-induced-inhibition-of-er-to-golgi-traffic
#9
Wenjia Gan, Caiyun Zhang, Ka Yu Siu, Ayano Satoh, Julian A Tanner, Sidney Yu
BACKGROUND: Autophagy is an inducible autodigestive process that allows cells to recycle proteins and other materials for survival during stress and nutrient deprived conditions. The kinase ULK1 is required to activate this process. ULK1 phosphorylates a number of target proteins and regulates many cellular processes including the early secretory pathway. Recently, ULK1 has been demonstrated to phosphorylate Sec16 and affects the transport of serotonin transporter at the ER exit sites (ERES), but whether ULK1 may affect the transport of other cargo proteins and general secretion has not been fully addressed...
May 10, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28485037/serotonin-axons-in-the-neocortex-of-the-adult-female-mouse-regrow-after-traumatic-brain-injury
#10
Tymoteusz J Kajstura, Sarah E Dougherty, David J Linden
It is widely held that injured neurons in the central nervous system do not undergo axonal regrowth. However, there is mounting evidence that serotonin axons are a notable exception. Serotonin axons undergo long-distance regrowth in the neocortex after amphetamine lesion, and, following a penetrating stab injury, they can regrow from cut ends to traverse the stab rift. Traumatic brain injury (TBI) is clinically prevalent and can lead to pathologies, such as depression, that are related to serotonergic dysfunction...
May 9, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28473438/serotonin-signaling-through-the-5-ht1b-receptor-and-nadph-oxidase-1-in-pulmonary-arterial-hypertension
#11
Katie Y Hood, Kirsty M Mair, Adam P Harvey, Augusto C Montezano, Rhian M Touyz, Margaret R MacLean
OBJECTIVE: Serotonin can induce human pulmonary artery smooth muscle cell (hPASMC) proliferation through reactive oxygen species (ROS), influencing the development of pulmonary arterial hypertension (PAH). We hypothesize that in PASMCs, serotonin induces oxidative stress through NADPH-oxidase-derived ROS generation and reduced Nrf-2 (nuclear factor (erythroid-derived 2)-like 2) antioxidant systems, promoting vascular injury. APPROACH AND RESULTS: HPASMCs from controls and PAH patients, and PASMCs from Nox1(-)(/-) mice, were stimulated with serotonin in the absence/presence of inhibitors of Src kinase, the 5-HT1B receptor, and NADPH oxidase 1 (Nox1)...
May 4, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28467954/-association-between-the-5-httlpr-polymorphism-of-the-serotonin-transporter-gene-and-suicide-a-case-control-pilot-study
#12
Janos Bokor, Xenia Gonda, Peter Dome, Gabor Faludi, Elek Dinya, Andras Laszik
OBJECTIVES: Besides psychological and social effects, biological, biochemical and genetic factors also play a role in the background of suicide. The aim is developing a complex model incorporating all the above factors so that suicide could be predicted and prevented in those at risk. Based on several studies 5-HTTLPR s allele frequency is increased in case of violent completed suicides. The aim of the present study was to validate this association in a sample of completed suicides. METHODS: During autopsy sample DNA samples were obtained for 5-HTTLPR genotyping from 200 subjects deceased due to suicide and 200 controls deceased due to other causes...
March 2017: Neuropsychopharmacologia Hungarica
https://www.readbyqxmd.com/read/28465138/a-polymorphism-in-the-5-flanking-region-of-the-serotonin-transporter-5-htt-gene-affects-fear-related-behaviours-of-adult-domestic-chickens
#13
E Tobias Krause, Joergen B Kjaer, Carolin Lüders, Loc Phi van
The neural serotonin (5-HT)/serotonin transporter (5-HTT) system is involved in the regulation of physiological processes and emotional states. In humans, the short (S) allele in the 5-HTT gene-linked polymorphic region, which decreases 5-HTT expression, has been shown to be associated with behavioural changes including an increased level of anxiety. Also in birds a polymorphism in the 5-HTT gene is described, a deletion (D) has been found to have functional consequences on growth and locomotion. Furthermore, the D-allele leads to an increased 5-HTT expression compared to the wild type (W), a feature which is linked to lower levels of fear in mammalian species...
April 29, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28459713/cardiac-outcomes-after-perinatal-sertraline-exposure-in-mice
#14
Sarah E Haskell, Cecilia Lo, Mitchell E Kent, Timothy M Eggleston, Kenneth A Volk, Benjamin E Reinking, Robert D Roghair
Selective serotonin reuptake inhibitors are prescribed to 6-10% of pregnant women in the United States. Using an intrauterine plus neonatal exposure model to represent exposure throughout human pregnancy, we hypothesized sertraline exposure would impact intracardiac serotonin signaling and lead to small left heart syndrome in the absence of maternal psychopathology. C57BL/6 adult female mice received sertraline (5 mg/kg/d IP) or saline throughout pregnancy to time of delivery. Pups maintained exposure on postnatal days 1-14 to encompass the developmental window analogous to human gestation...
April 25, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28450386/update-on-congenital-heart-disease-and-sudden-infant-perinatal-death-from-history-to-future-trends
#15
REVIEW
Giulia Ottaviani, L Maximilian Buja
During the 20th century, expert pathologists contributed an in-depth characterisation of the anatomical pathology and associated pathophysiology of congenital heart disease (CHD). Starting in the 1970s, the reported CHD birth prevalence has been increasing, owing to advances in diagnostic methods. Over the years, surgical treatments have been associated with an enormous reduction of CHD mortality. Advances also have been made in understanding the developmental biology and molecular pathogenesis of CHD. In developed countries, sudden infant death syndrome (SIDS) is the most frequent form of death during the first year of life, with a death rate of 0...
April 27, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28445860/brephedrone-a-new-psychoactive-substance-seized-in-brazil
#16
Yuri Machado, José Coelho Neto, Paulo Eduardo Nunes Barbosa, Rogério Araújo Lordeiro, Rosemeire Brondi Alves
At the beginning of 2015, sixty-two capsules containing red-brown crystals seized in a historical city in Brazil were sent to this forensic laboratory for drug testing analysis. The material was identified as being Brephedrone, a new psychoactive substance and a bromine synthetic cathinone that is related to serotonin transportation. This substance was analyzed by ATR-FTIR, GC-MS, LC-MS, (1)H, (13)C and 2D NMR. Brephedrone apprehensions have been previously reported in Finland, France and Spain. It was the first detection of this substance in the State of Minas Gerais...
April 15, 2017: Forensic Science International
https://www.readbyqxmd.com/read/28444137/effects-of-serotonin-transporter-gene-variation-on-impulsivity-mediated-by-default-mode-network-a-family-study-of-depression
#17
Jiook Cha, Guia Guffanti, Jay Gingrich, Ardesheer Talati, Priya Wickramaratne, Myrna Weissman, Jonathan Posner
Serotonergic neurotransmission, potentially through effects on the brain's default mode network (DMN), may regulate aspects of attention including impulse control. Indeed, genetic variants of the serotonin transporter (5-HTT) have been implicated in impulsivity and related psychopathology. Yet it remains unclear the mechanism by which the 5-HTT genetic variants contribute to individual variability in impulse control. Here, we tested whether DMN connectivity mediates an association between the 5-HTT genetic variants and impulsivity...
April 21, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/28442777/serotonin-transporter-deficiency-drives-estrogen-dependent-obesity-and-glucose-intolerance
#18
Weibin Zha, Horace T B Ho, Tao Hu, Mary F Hebert, Joanne Wang
Depression and use of antidepressant medications are both associated with increased risk of obesity, potentially attributed to a reduced serotonin transporter (SERT) function. However, how SERT deficiency promotes obesity is unknown. Here, we demonstrated that SERT (-/-) mice display abnormal fat accumulation in both white and brown adipose tissues, glucose intolerance and insulin resistance while exhibiting suppressed aromatase (Cyp19a1) expression and reduced circulating 17β-estradiol levels. 17β-estradiol replacement in SERT (-/-) mice reversed the obesity and glucose intolerance, supporting a role for estrogen in SERT deficiency-associated obesity and glucose intolerance...
April 25, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28434415/does-the-incredible-years-reduce-child-externalizing-problems-through-improved-parenting-the-role-of-child-negative-affectivity-and-serotonin-transporter-linked-polymorphic-region-5-httlpr-genotype
#19
Joyce Weeland, Rabia R Chhangur, Sara R Jaffee, Danielle Van Der Giessen, Walter Matthys, Bram Orobio De Castro, Geertjan Overbeek
In a randomized controlled trial, the Observational Randomized Controlled Trial of Childhood Differential Susceptibility (ORCHIDS study), we tested whether observed parental affect and observed and reported parenting behavior are mechanisms of change underlying the effects of the behavioral parent training program the Incredible Years (IY). Furthermore, we tested whether some children are more susceptible to these change mechanisms because of their temperamental negative affectivity and/or serotonin transporter linked polymorphic region (5-HTTLPR) genotype...
April 24, 2017: Development and Psychopathology
https://www.readbyqxmd.com/read/28431168/identifying-new-susceptibility-genes-on-dopaminergic-and-serotonergic-pathways-for-the-framing-effect-in-decision-making
#20
Xiaoxue Gao, Jinting Liu, Pingyuan Gong, Junhui Wang, Wan Fang, Hongming Yan, Lusha Zhu, Xiaolin Zhou
The framing effect refers the tendency to be risk-averse when options are presented positively but be risk-seeking when the same options are presented negatively during decision-making. This effect has been found to be modulated by the serotonin transporter gene (SLC6A4) and the catechol-o-methyltransferase gene (COMT) polymorphisms, which are on the dopaminergic and serotonergic pathways and which are associated with affective processing. The current study aimed to identify new genetic variations of genes on dopaminergic and serotonergic pathways that may contribute to individual differences in the susceptibility to framing...
April 19, 2017: Social Cognitive and Affective Neuroscience
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