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https://www.readbyqxmd.com/read/29115994/exploring-venlafaxine-pharmacokinetic-variability-with-a-phenotyping-approach-a-multicentric-french-swiss-study-marvel-study
#1
Célia Lloret-Linares, Youssef Daali, Sylvie Chevret, Isabelle Nieto, Fanny Molière, Philippe Courtet, Florence Galtier, Raphaëlle-Marie Richieri, Sophie Morange, Pierre-Michel Llorca, Wissam El-Hage, Thomas Desmidt, Frédéric Haesebaert, Philippe Vignaud, Jerôme Holtzmann, Jean-Luc Cracowski, Marion Leboyer, Antoine Yrondi, Fabienne Calvas, Liova Yon, Philippe Le Corvoisier, Olivier Doumy, Kyle Heron, Damien Montange, Siamak Davani, Julien Déglon, Marie Besson, Jules Desmeules, Emmanuel Haffen, Frank Bellivier
BACKGROUND: It is well known that the standard doses of a given drug may not have equivalent effects in all patients. To date, the management of depression remains mainly empirical and often poorly evaluated. The development of a personalized medicine in psychiatry may reduce treatment failure, intolerance or resistance, and hence the burden and costs of mood depressive disorders. The Geneva Cocktail Phenotypic approach presents several advantages including the "in vivo" measure of different cytochromes and transporter P-gp activities, their simultaneous determination in a single test, avoiding the influence of variability over time on phenotyping results, the administration of low dose substrates, a limited sampling strategy with an analytical method developed on DBS analysis...
November 7, 2017: BMC Pharmacology & Toxicology
https://www.readbyqxmd.com/read/29061424/dopamine-transporter-gene-polymorphism-in-children-with-adhd-a-pilot-study-in-indonesian-samples
#2
Tjhin Wiguna, Raden Irawati Ismail, Noorhana Setyawati Winarsih, Fransiska Kaligis, Anggia Hapsari, Lina Budiyanti, Rini Sekartini, Susan Rahayu, Anthony P S Guerrero
INTRODUCTION: Several studies showed that DAT1 polymorphism closed related with ADHD although the results were not consistently found. Studies in China, South Korea, Japan revealed that 10-repeat allele gave a risk for ADHD. Based on that understanding, this study tried to identify whether the similar polymorphism of DAT1 was also apparent in Indonesian children with ADHD. METHOD: This was a case - control study. Case was 50 Indonesian origin children with ADHD and without any other mental disorders and metal retardation...
October 2017: Asian Journal of Psychiatry
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
#3
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/28963561/drug-enrichment-and-discovery-from-schizophrenia-genome-wide-association-results-an-analysis-and-visualisation-approach
#4
H A Gaspar, G Breen
Using successful genome-wide association results in psychiatry for drug repurposing is an ongoing challenge. Databases collecting drug targets and gene annotations are growing and can be harnessed to shed a new light on psychiatric disorders. We used genome-wide association study (GWAS) summary statistics from the Psychiatric Genetics Consortium (PGC) Schizophrenia working group to build a drug repositioning model for schizophrenia. As sample size increases, schizophrenia GWAS results show increasing enrichment for known antipsychotic drugs, selective calcium channel blockers, and antiepileptics...
September 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28934028/toward-neuroproteomics-in-biological-psychiatry-a-systems-approach-unravels-okadaic-acid-induced-alterations-in-the-neuronal-phosphoproteome
#5
Joana Machado Oliveira, Cristóvão B da Cruz E Silva, Thorsten Müller, Tânia Soares Martins, Marta Cova, Odete A B da Cruz E Silva, Ana Gabriela Henriques
Neuroproteomics is an evolving field of postgenomic medicine, highlighting the convergence of psychiatry/neurology and proteomics, yet compared with neurogenetics, it has received little attention. This study in rat primary neuronal cultures provides an example of a neuroproteomic approach relevant to the study of psychiatric disease pathophysiology, focusing on Alzheimer's disease. In this context, okadaic acid (OA) is routinely used in experimental designs to investigate phosphorylation-mediated events. It is a potent protein phosphatase (PP) inhibitor, particularly of PP1 and PP2A...
September 2017: Omics: a Journal of Integrative Biology
https://www.readbyqxmd.com/read/28894304/quantification-of-brain-cholinergic-denervation-in-alzheimer-s-disease-using-pet-imaging-with-18-f-feobv
#6
M Aghourian, C Legault-Denis, J-P Soucy, P Rosa-Neto, S Gauthier, A Kostikov, P Gravel, M-A Bédard
(18)F-fluoroethoxybenzovesamicol (FEOBV) is a new PET radiotracer that binds to the vesicular acetylcholine transporter. In both animals and healthy humans, FEOBV was found sensitive and reliable to characterize presynaptic cholinergic nerve terminals in the brain. It has been used here for we believe the first time in patients with Alzheimer's disease (AD) to quantify brain cholinergic losses. The sample included 12 participants evenly divided in healthy subjects and patients with AD, all assessed with the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) cognitive scales...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28894302/g%C3%AE-%C3%AE-subunit-activation-promotes-dopamine-efflux-through-the-dopamine-transporter
#7
J Garcia-Olivares, T Baust, S Harris, P Hamilton, A Galli, S G Amara, G E Torres
The dopamine transporter (DAT) is an important regulator of brain dopamine (DA) homeostasis, controlling the intensity and duration of DA signaling. DAT is the target for psychostimulants-like cocaine and amphetamine-and plays an important role in neuropsychiatric disorders, including attention-deficit hyperactivity disorder and drug addiction. Thus, a thorough understanding of the mechanisms that regulate DAT function is necessary for the development of clinical interventions to treat DA-related brain disorders...
September 12, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28829051/dopamine-transporter-and-reward-anticipation-in-a-dimensional-perspective-a-multimodal-brain-imaging-study
#8
Manon Dubol, Christian Trichard, Claire Leroy, Anca-Larisa Sandu, Mehdi Rahim, Bernard Granger, Eleni T Tzavara, Laurent Karila, Jean-Luc Martinot, Eric Artiges
Dopamine function and reward processing are highly interrelated and involve common brain regions afferent to the Nucleus Accumbens, within the mesolimbic pathway. While dopamine function and reward system neural activity are impaired in most psychiatric disorders, it is unknown if alterations in the dopamine system underlie variations in reward processing across a continuum encompassing health and these disorders. We explored the relationship between dopamine function and neural activity during reward anticipation in twenty-seven participants including healthy volunteers and psychiatric patients with schizophrenia, depression or cocaine addiction, using functional Magnetic Resonance Imaging (fMRI) and Positron Emission Tomography (PET) multimodal imaging with a voxel-based statistical approach...
August 22, 2017: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28811687/a-preliminary-study-on-investigation-of-serum-%C3%AE-synuclein-and-tau-protein-levels-in-children-with-attention-deficit-hyperactivity%C3%A2-disorder
#9
Ihsan Cetin, Seref Simsek
Neurodegenerative molecules play an important role in maintaining a supply for synaptic vesicles; and they are also likely to help regulate the dopamine release which is the primary mechanism of action in pharmacological treatments for attention deficit hyperactivity disorder (ADHD). It is suggested that there could be interactions between α-synuclein and tau in cytoskeletal disorganization and synaptic dystrophy. Therefore, we aim to determine the serum levels of neurodegenerative molecules such as α-synuclein and tau in children with ADHD...
July 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28727685/erbb4-signaling-in-dopaminergic-axonal-projections-increases-extracellular-dopamine-levels-and-regulates-spatial-working-memory-behaviors
#10
M Skirzewski, I Karavanova, A Shamir, L Erben, J Garcia-Olivares, J H Shin, D Vullhorst, V A Alvarez, S G Amara, A Buonanno
Genetic variants of Neuregulin 1 (NRG1) and its neuronal tyrosine kinase receptor ErbB4 are associated with risk for schizophrenia, a neurodevelopmental disorder characterized by excitatory/inhibitory imbalance and dopamine (DA) dysfunction. To date, most ErbB4 studies have focused on GABAergic interneurons in the hippocampus and neocortex, particularly fast-spiking parvalbumin-positive (PV+) basket cells. However, NRG has also been shown to modulate DA levels, suggesting a role for ErbB4 signaling in dopaminergic neuron function...
July 20, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28439098/uncoupling-dapk1-from-nmda-receptor-glun2b-subunit-exerts-rapid-antidepressant-like-effects
#11
S-X Li, Y Han, L-Z Xu, K Yuan, R-X Zhang, C-Y Sun, D-F Xu, M Yuan, J-H Deng, S-Q Meng, X-J Gao, Q Wen, L-J Liu, W-L Zhu, Y-X Xue, M Zhao, J Shi, L Lu
Several preclinical studies have reported the rapid antidepressant effects of N-methyl-D-aspartate receptor (NMDAR) antagonists, although the underlying mechanisms are still unclear. Death-associated protein kinase 1 (DAPK1) couples GluN2B subunits at extrasynaptic sites to regulate NMDAR channel conductance. In the present study, we found that chronic unpredictable stress (CUS) induced extracellular glutamate accumulation, accompanied by an increase in the DAPK1-NMDAR interaction, the high expression of DAPK1 and phosphorylated GluN2B at Ser1303, a decrease in phosphorylated DAPK1 at Ser308 and synaptic protein deficits in the rat medial prefrontal cortex (mPFC)...
April 25, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28373689/collaborative-meta-analysis-finds-no-evidence-of-a-strong-interaction-between-stress-and-5-httlpr-genotype-contributing-to-the-development-of-depression
#12
R C Culverhouse, N L Saccone, A C Horton, Y Ma, K J Anstey, T Banaschewski, M Burmeister, S Cohen-Woods, B Etain, H L Fisher, N Goldman, S Guillaume, J Horwood, G Juhasz, K J Lester, L Mandelli, C M Middeldorp, E Olié, S Villafuerte, T M Air, R Araya, L Bowes, R Burns, E M Byrne, C Coffey, W L Coventry, K A B Gawronski, D Glei, A Hatzimanolis, J-J Hottenga, I Jaussent, C Jawahar, C Jennen-Steinmetz, J R Kramer, M Lajnef, K Little, H M Zu Schwabedissen, M Nauck, E Nederhof, P Petschner, W J Peyrot, C Schwahn, G Sinnamon, D Stacey, Y Tian, C Toben, S Van der Auwera, N Wainwright, J-C Wang, G Willemsen, I M Anderson, V Arolt, C Åslund, G Bagdy, B T Baune, F Bellivier, D I Boomsma, P Courtet, U Dannlowski, E J C de Geus, J F W Deakin, S Easteal, T Eley, D M Fergusson, A M Goate, X Gonda, H J Grabe, C Holzman, E O Johnson, M Kennedy, M Laucht, N G Martin, M R Munafò, K W Nilsson, A J Oldehinkel, C A Olsson, J Ormel, C Otte, G C Patton, B W J H Penninx, K Ritchie, M Sarchiapone, J M Scheid, A Serretti, J H Smit, N C Stefanis, P G Surtees, H Völzke, M Weinstein, M Whooley, J I Nurnberger, N Breslau, L J Bierut
The hypothesis that the S allele of the 5-HTTLPR serotonin transporter promoter region is associated with increased risk of depression, but only in individuals exposed to stressful situations, has generated much interest, research and controversy since first proposed in 2003. Multiple meta-analyses combining results from heterogeneous analyses have not settled the issue. To determine the magnitude of the interaction and the conditions under which it might be observed, we performed new analyses on 31 data sets containing 38 802 European ancestry subjects genotyped for 5-HTTLPR and assessed for depression and childhood maltreatment or other stressful life events, and meta-analysed the results...
April 4, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28289283/the-dopamine-hypothesis-of-bipolar-affective-disorder-the-state-of-the-art-and-implications-for-treatment
#13
REVIEW
A H Ashok, T R Marques, S Jauhar, M M Nour, G M Goodwin, A H Young, O D Howes
Bipolar affective disorder is a common neuropsychiatric disorder. Although its neurobiological underpinnings are incompletely understood, the dopamine hypothesis has been a key theory of the pathophysiology of both manic and depressive phases of the illness for over four decades. The increased use of antidopaminergics in the treatment of this disorder and new in vivo neuroimaging and post-mortem studies makes it timely to review this theory. To do this, we conducted a systematic search for post-mortem, pharmacological, functional magnetic resonance and molecular imaging studies of dopamine function in bipolar disorder...
May 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28167616/towards-trans-diagnostic-mechanisms-in-psychiatry-neurobehavioral-profile-of-rats-with-a-loss-of-function-point-mutation-in-the-dopamine-transporter-gene
#14
Valentina Vengeliene, Anton Bespalov, Martin Roßmanith, Sandra Horschitz, Stefan Berger, Ana L Relo, Hamid R Noori, Peggy Schneider, Thomas Enkel, Dusan Bartsch, Miriam Schneider, Berthold Behl, Anita C Hansson, Patrick Schloss, Rainer Spanagel
The research domain criteria (RDoC) matrix has been developed to reorient psychiatric research towards measurable behavioral dimensions and underlying mechanisms. Here, we used a new genetic rat model with a loss-of-function point mutation in the dopamine transporter (DAT) gene (Slc6a3_N157K) to systematically study the RDoC matrix. First, we examined the impact of the Slc6a3_N157K mutation on monoaminergic signaling. We then performed behavioral tests representing each of the five RDoC domains: negative and positive valence systems, cognitive, social and arousal/regulatory systems...
April 1, 2017: Disease Models & Mechanisms
https://www.readbyqxmd.com/read/28044943/forgotten-but-not-gone-new-developments-in-the-understanding-and-treatment-of-tardive-dyskinesia
#15
REVIEW
Jonathan M Meyer
The broad use of atypical antipsychotics was expected to dramatically reduce the prevalence and incidence of tardive dyskinesia (TD), but data show that TD remains an important challenge due the persistent nature of its symptoms and resistance to numerous treatment modalities, including antipsychotic discontinuation. Recent insights on genetic risk factors and new concepts surrounding pathophysiology have spurred interest in the possibility of targeted treatment for TD. As will be reviewed in this article, the number of evidence-based strategies for TD treatment is small: only clonazepam, amantadine, ginkgo biloba extract, and the vesicular monoamine transporter 2 (VMAT2) inhibitor tetrabenazine have compelling data...
December 2016: CNS Spectrums
https://www.readbyqxmd.com/read/28034451/predictors-of-response-to-repetitive-transcranial-magnetic-stimulation-rtms-in-the-treatment-of-major-depressive-disorder
#16
REVIEW
G Beuzon, Q Timour, M Saoud
Repetitive transcranial magnetic stimulation (rTMS), based on the principle of electromagnetic induction, consists of applying series of magnetic impulses to the cerebral cortex so as to modulate neurone activity in a target zone. This technique, still experimental, could prove promising in the field of psychiatry, in particular for the treatment of major depressive disorder. It is important for the clinician to be able to assess the response potential of a given patient to rTMS, and this among other things requires relevant predictive factors to be available...
February 2017: L'Encéphale
https://www.readbyqxmd.com/read/27956747/acute-engagement-of-gq-mediated-signaling-in-the-bed-nucleus-of-the-stria-terminalis-induces-anxiety-like-behavior
#17
C M Mazzone, D Pati, M Michaelides, J DiBerto, J H Fox, G Tipton, C Anderson, K Duffy, J M McKlveen, J A Hardaway, S T Magness, W A Falls, S E Hammack, Z A McElligott, Y L Hurd, T L Kash
The bed nucleus of the stria terminalis (BNST) is a brain region important for regulating anxiety-related behavior in both humans and rodents. Here we used a chemogenetic strategy to investigate how engagement of G protein-coupled receptor (GPCR) signaling cascades in genetically defined GABAergic BNST neurons modulates anxiety-related behavior and downstream circuit function. We saw that stimulation of vesicular γ-aminobutyric acid (GABA) transporter (VGAT)-expressing BNST neurons using hM3Dq, but neither hM4Di nor rM3Ds designer receptors exclusively activated by a designer drug (DREADD), promotes anxiety-like behavior...
December 13, 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/27922607/endocytosis-following-dopamine-d2-receptor-activation-is-critical-for-neuronal-activity-and-dendritic-spine-formation-via-rabex-5-pdgfr%C3%AE-signaling-in-striatopallidal-medium-spiny-neurons
#18
N Shioda, Y Yabuki, Y Wang, M Uchigashima, T Hikida, T Sasaoka, H Mori, M Watanabe, M Sasahara, K Fukunaga
Aberrant dopamine D2 receptor (D2R) activity is associated with neuropsychiatric disorders, making those receptors targets for antipsychotic drugs. Here, we report that novel signaling through the intracellularly localized D2R long isoform (D2LR) elicits extracellular signal-regulated kinase (ERK) activation and dendritic spine formation through Rabex-5/platelet-derived growth factor receptor-β (PDGFRβ)-mediated endocytosis in mouse striatum. We found that D2LR directly binds to and activates Rabex-5, promoting early-endosome formation...
August 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/27843150/the-bacterial-peptidoglycan-sensing-molecule-pglyrp2-modulates-brain-development-and-behavior
#19
T Arentsen, Y Qian, S Gkotzis, T Femenia, T Wang, K Udekwu, H Forssberg, R Diaz Heijtz
Recent studies have revealed that the gut microbiota modulates brain development and behavior, but the underlying mechanisms are still poorly understood. Here, we show that bacterial peptidoglycan (PGN) derived from the commensal gut microbiota can be translocated into the brain and sensed by specific pattern-recognition receptors (PRRs) of the innate immune system. Using expression-profiling techniques, we demonstrate that two families of PRRs that specifically detect PGN (that is, PGN-recognition proteins and NOD-like receptors), and the PGN transporter PepT1 are highly expressed in the developing brain during specific windows of postnatal development in both males and females...
February 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/27816610/forward-psychiatry%C3%A2-%C3%A2-early-intervention-for-mental-health-problems-among-uk-armed-forces-in-afghanistan
#20
N Jones, N T Fear, S Wessely, G Thandi, N Greenberg
BACKGROUND: This observational study examined return to duty (RTD) rates following receipt of early mental health interventions delivered by deployed mental health practitioners. METHOD: In-depth clinical interviews were conducted among 975 UK military personnel referred for mental health assessment whilst deployed in Afghanistan. Socio-demographic, military, operational, clinical and therapy outcomes were recorded in an electronic health record database. Rates and predictors of EVAC were the main outcomes examined using adjusted binary logistic regression analyses...
January 2017: European Psychiatry: the Journal of the Association of European Psychiatrists
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