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https://www.readbyqxmd.com/read/29021832/pharmacogenomics-in-the-treatment-of-mood-disorders-strategies-and-opportunities-for-personalized-psychiatry
#1
REVIEW
Azmeraw T Amare, Klaus Oliver Schubert, Bernhard T Baune
Personalized medicine (personalized psychiatry in a specific setting) is a new model towards individualized care, in which knowledge from genomics and other omic pillars (microbiome, epigenomes, proteome, and metabolome) will be combined with clinical data to guide efforts to new drug development and targeted prescription of the existing treatment options. In this review, we summarize pharmacogenomic studies in mood disorders that may lay the foundation towards personalized psychiatry. In addition, we have discussed the possible strategies to integrate data from omic pillars as a future path to personalized psychiatry...
September 2017: EPMA Journal
https://www.readbyqxmd.com/read/28972592/genetically-driven-brain-serotonin-deficiency-facilitates-panic-like-escape-behavior-in-mice
#2
J Waider, S Popp, M D Lange, R Kern, J F Kolter, J Kobler, N C Donner, K R Lowe, J H Malzbender, C J Brazell, M R Arnold, B Aboagye, A Schmitt-Böhrer, C A Lowry, H C Pape, K P Lesch
Multiple lines of evidence implicate brain serotonin (5-hydroxytryptamine; 5-HT) system dysfunction in the pathophysiology of stressor-related and anxiety disorders. Here we investigate the influence of constitutively deficient 5-HT synthesis on stressor-related anxiety-like behaviors using Tryptophan hydroxylase 2 (Tph2) mutant mice. Functional assessment of c-Fos after associated foot shock, electrophysiological recordings of GABAergic synaptic transmission, differential expression of the Slc6a4 gene in serotonergic neurons were combined with locomotor and anxiety-like measurements in different contextual settings...
October 3, 2017: Translational Psychiatry
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
#3
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/28951738/serotonin-related-gene-variants-in-patients-with-irritable-bowel-syndrome-and-depressive-or-anxiety-disorders
#4
Magdalena Grzesiak, Jan Aleksander Beszłej, Ewa Waszczuk, Marcin Szechiński, Monika Szewczuk-Bogusławska, Dorota Frydecka, Tadeusz Dobosz, Anna Jonkisz, Arleta Lebioda, Małgorzata Małodobra, Agata Mulak
AIM: To assess the association of six polymorphisms in serotonin-related genes with depressive or anxiety disorders in patients with irritable bowel syndrome (IBS). METHODS: The lifetime prevalence of depressive and anxiety disorders was assessed in 95 IBS patients (85% women) using the Munich version of the Composite International Diagnostic Interview (CIDI). IBS was diagnosed according to the Rome III criteria. SCL6A4 HTTLPR polymorphism (rs4795541) was determined using PCR-based method...
2017: Gastroenterology Research and Practice
https://www.readbyqxmd.com/read/28904509/peripheral-slc6a4-gene-expression-in-obsessive-compulsive-disorder-in-the-han-chinese-population
#5
Xuemei Wang, Qing Zhao, Wen Chen, Shunying Yu, Zhen Wang, Zeping Xiao
BACKGROUND: Serotonergic system dysfunction has been implicated in obsessive-compulsive disorder (OCD). This study examined peripheral SLC6A4 gene expression in OCD patients and healthy controls to explore the relationship between SLC6A4 and OCD. METHODS: Participants included 50 first episode OCD patients and 60 age and gender-matched healthy controls. Relative SLC6A4 gene expression were examined by real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) in peripheral leukocytes of all the subjects...
June 25, 2017: Shanghai Archives of Psychiatry
https://www.readbyqxmd.com/read/28902619/a-case-control-association-study-of-12-candidate-genes-and-attempted-suicide-in-french-adolescents
#6
Bojan Mirkovic, David Cohen, Claudine Laurent, Malaika Lasfar, Christophe Marguet, Prsicille Gerardin
Background Suicide is the second leading cause of death for 10-19-year-olds. Evidence has shown that attempted suicide is a complex interplay of genes and environmental factors. In the adult population, possible associations between genetic polymorphisms and suicidal behaviors have been investigated for several genes, most often with inconsistent findings and poor replicability of significant associations. This study aimed to identify gene variants conferring risk for adolescent suicide attempt. Methods We selected the genes and variants after an analysis of the literature and a selection of the most significant associations identified...
September 13, 2017: International Journal of Adolescent Medicine and Health
https://www.readbyqxmd.com/read/28892067/association-of-the-serotonin-transporter-linked-polymorphic-region-genotype-with-lower-bone-mineral-density
#7
M I Lapid, S Kung, M A Frye, J M Biernacka, J R Geske, M T Drake, M D Jankowski, B L Clarke
The serotonin transporter-linked polymorphic region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) S allele is linked to pathogenesis of depression and slower response to selective serotonin reuptake inhibitors (SSRIs); depression and SSRIs are independently associated with bone loss. We aimed to determine whether 5-HTTLPR was associated with bone loss. This cross-sectional study included psychiatric patients with both 5-HTTLPR analysis and bone mineral density (BMD) assessment (hip and spine Z-scores if age <50 years and T-scores if ⩾50 years)...
August 22, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28888667/preimmunization-with-a-heat-killed-preparation-of-mycobacterium-vaccae-enhances-fear-extinction-in-the-fear-potentiated-startle-paradigm
#8
James H Fox, James E Hassell, Philip H Siebler, Mathew R Arnold, Andrew K Lamb, David G Smith, Heidi E W Day, Tessa M Smith, Emma M Simmerman, Alexander A Outzen, Kaley S Holmes, Christopher J Brazell, Christopher A Lowry
The hygiene hypothesis or "Old Friends" hypothesis proposes that inflammatory diseases are increasing in modern urban societies, due in part to reduced exposure to microorganisms that drive immunoregulatory circuits, and a failure to terminate inappropriate inflammatory responses. Inappropriate inflammation is also emerging as a risk factor for trauma-related, anxiety, and affective disorders, including posttraumatic stress disorder (PTSD), which is characterized as persistent re-experiencing of the trauma after a traumatic experience...
September 6, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28884473/pharmacotherapy-for-smoking-cessation-effects-by-subgroup-defined-by-genetically-informed-biomarkers
#9
REVIEW
Ewoud Schuit, Orestis A Panagiotou, Marcus R Munafò, Derrick A Bennett, Andrew W Bergen, Sean P David
BACKGROUND: Smoking cessation therapies are not effective for all smokers, and researchers are interested in identifying those subgroups of individuals (e.g. based on genotype) who respond best to specific treatments. OBJECTIVES: To assess whether quit rates vary by genetically informed biomarkers within pharmacotherapy treatment arms and as compared with placebo. To assess the effects of pharmacotherapies for smoking cessation in subgroups of smokers defined by genotype for identified genome-wide significant polymorphisms...
September 8, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28842491/conformational-state-interactions-provide-clues-to-the-pharmacochaperone-potential-of-serotonin-transporter-partial-substrates
#10
Shreyas Bhat, Peter S Hasenhuetl, Ameya Kasture, Ali El-Kasaby, Michael H Baumann, Bruce E Blough, Sonja Sucic, Walter Sandtner, Michael Freissmuth
Point mutations in SLC6 transporters cause misfolding, which can be remedied by pharmacochaperones. The serotonin transporter (SERT/SLC6A4) has a rich pharmacology including inhibitors, releasers (amphetamines, which promote the exchange mode), and more recently, discovered partial substrates. We hypothesized that partial substrates trapped the transporter in one or several states of the transport cycle. This conformational trapping may also be conducive to folding. We selected naphthylpropane-2-amines of the phenethylamine library (PAL) including the partial substrate PAL1045 and its congeners PAL287 and PAL1046...
October 6, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28821725/interplay-between-maternal-slc6a4-mutation-and-prenatal-stress-a-possible-mechanism-for-autistic-behavior-development
#11
Calvin P Sjaarda, Patrick Hecht, Amy J M McNaughton, Audrina Zhou, Melissa L Hudson, Matt J Will, Garth Smith, Muhammad Ayub, Ping Liang, Nansheng Chen, David Beversdorf, Xudong Liu
The low activity allele of the maternal polymorphism, 5HTTLPR, in the serotonin transporter, SLC6A4, coupled with prenatal stress is reported to increase the risk for children to develop autism spectrum disorder (ASD). Similarly, maternal Slc6a4 knock-out and prenatal stress in rodents results in offspring demonstrating ASD-like characteristics. The present study uses an integrative genomics approach to explore mechanistic changes in early brain development in mouse embryos exposed to this maternal gene-environment phenomenon...
August 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28774705/serotonin-transporter-gene-promoter-methylation-in-peripheral-cells-in-healthy-adults-neural-correlates-and-tissue-specificity
#12
Elmira Ismaylova, Jessica Di Sante, Moshe Szyf, Zsofia Nemoda, Wei-Jo Yu, Florence B Pomares, Gustavo Turecki, Gabriella Gobbi, Frank Vitaro, Richard E Tremblay, Linda Booij
Early adversity can influence gene expression via epigenetic mechanisms, including DNA methylation. Peripheral tissues are essential in psychiatric epigenetics, as methylation generally cannot be assessed in the living human brain. Several magnetic resonance imaging (MRI) studies show associations of peripheral serotonin transporter gene (SLC6A4) methylation with function and/or structure of frontal-limbic circuits and brain's resting-state. Commonly used samples are derived from blood, saliva or buccal cells...
July 31, 2017: European Neuropsychopharmacology: the Journal of the European College of Neuropsychopharmacology
https://www.readbyqxmd.com/read/28766852/serotonin-transporter-promoter-polymorphism-modulates-the-ability-to-control-food-intake-effect-on-total-weight-loss
#13
Gemma Bonnet, Purificación Gómez-Abellán, Beatriz Vera, Juan Francisco Sánchez-Romera, Antonio M Hernández-Martínez, Silvia Sookoian, Carlos Jose Pirola, Marta Garaulet
SCOPE: The biggest challenge for losing weight is the ability to control the amount of food eaten; the tendency to overeat is called disinhibition. Our aims were to determine whether a) the SLC6A4-promoter variant (5-HTTLPR) relates to disinhibition; b) this association could affect total weight-loss during a behavioral/dietary treatment for obesity. METHODS AND RESULTS: 2961 subjects attended voluntarily five weight-loss clinics; a subsample (n = 624) was recruited for SLC6A4 genotyping...
August 2, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28748210/dataset-on-genetic-and-physiological-adults-responses-to-social-distress
#14
Andrea Bonassi, Tommaso Ghilardi, Anna Truzzi, Ilaria Cataldo, Atiqah Azhari, Peipei Setoh, Kazuyuki Shinohara, Gianluca Esposito
Both expectations towards interactions with conspecifics, and genetic predispositions, affect adults׳ social behaviors. However, the underlying mechanisms remain largely unknown. Here, we report data to investigate the interaction between genetic factors, (oxytocin receptor (OXTR) and serotonin transporter (5-HTTLPR) polymorphisms), and adult interactional patterns in shaping physiological responses to social distress. During the presentation of distress vocalizations (cries of human female, infants and bonobos) we assessed participants׳ (N = 42 males) heart rate (HR) and peripheral nose temperature, which index state of arousal and readiness to action...
August 2017: Data in Brief
https://www.readbyqxmd.com/read/28719342/a-pilot-study-for-determination-of-anxiety-related-slc6a4-promoter-s-and-l-alleles-in-healthy-turkish-athletes
#15
A Corak, S Kapici, C Sercan, O Akkoç, K Ulucan
We aimed to analyze the allelic distribution of solute carrier family-6 member-4 promoter region in Turkish athletes. Recent studies showed the association of lesser expressing "S" allele with anxiety. Genotype percentages for LL, LS and SS genotypes were found as 46, 35 and 19, respectively. 38% of the males had LL, %38 had LS and 24% had SS genotypes. Percentages of LL, LS and SS genotypes were 54, 31 and 15 in females, respectively. 15 (58%) male and 18 (69%) females had L, 11 (42%) male and 8 (31%) females had S alleles...
May 20, 2017: Cellular and Molecular Biology
https://www.readbyqxmd.com/read/28716530/genetic-association-analysis-of-serotonin-and-signal-transduction-pathways-in-suicide-attempters-from-an-italian-sample-of-psychiatric-patients
#16
Maurizio Pompili, Giovanna Gentile, Catia Scassellati, Cristian Bonvicini, Marco Innamorati, Denise Erbuto, Franco Montebovi, Giuseppe Ducci, Alberto Forte, Eleonora De Pisa, Stefano Ferracuti, Gianluca Serafini, Vincenzo De Luca, Mario Amore, Maurizio Simmaco, Paolo Girardi
Genetic factors have been reported to contribute to the liability of suicide. We aimed to investigate functional polymorphisms in eight genes (serotonin transporter, SLC6A4; receptors, 5HTR1A, 1B, 5HTR2A; Tryptophan Hydroxylase, TPH1, TPH2; Monoamine Oxidase, MAOA and G Protein Subunit Beta 3, GNB3) to investigate their predictive value for suicide. The possible confounding effects of gender and phenotypic patients dissection were also valued. A sample of 111 consecutive psychiatric inpatients was recruited and assessed using specific psychometric instruments...
July 14, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28691545/association-of-the-functional-serotonin-transporter-haplotype-with-familial-form-of-obsessive-compulsive-disorder-in-iranian-patients
#17
Fatemeh Sadat Rashidi, Ehsan Ahmadipour, Sepideh Shiravand, Abolhassan Ahmadiani, Sareh Asadi, Jamal Shams
OBJECTIVE: Several polymorphisms have been reported in the 5-HTTLPR of the serotonin transporter gene (SLC6A4). Family-based evidences for the association of 5-HTTLPR polymorphisms with OCD were previously reported but results were controversial. The present study investigated the possible correlation of SLC6A4 polymorphisms (5-HTTLPR, rs25532, rs25531) in Iranian OCD patients considering gender, age of onset, family history of psychiatric disorders, obsessive and compulsive subtypes and severities...
July 10, 2017: International Journal of Psychiatry in Clinical Practice
https://www.readbyqxmd.com/read/28678593/neighborhood-characteristics-influence-dna-methylation-of-genes-involved-in-stress-response-and-inflammation-the-multi-ethnic-study-of-atherosclerosis
#18
Jennifer A Smith, Wei Zhao, Xu Wang, Scott M Ratliff, Bhramar Mukherjee, Sharon L R Kardia, Yongmei Liu, Ava V Diez Roux, Belinda L Needham
Living in a disadvantaged neighborhood is associated with poor health outcomes even after accounting for individual-level socioeconomic factors. The chronic stress of unfavorable neighborhood conditions may lead to dysregulation of the stress reactivity and inflammatory pathways, potentially mediated through epigenetic mechanisms such as DNA methylation. We used multi-level models to examine the relationship between two neighborhood conditions and methylation levels of 18 genes related to stress reactivity and inflammation in purified monocytes from 1,226 participants of the Multi-Ethnic Study of Atherosclerosis (MESA), a population-based sample of US adults...
July 5, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28675387/serotonin-transporter-gene-promoter-methylation-status-correlates-with-in-vivo-prefrontal-5-htt-availability-and-reward-function-in-human-obesity
#19
M Drabe, M Rullmann, J Luthardt, Y Boettcher, R Regenthal, T Ploetz, G A Becker, M Patt, C Schinke, F T Bergh, F Zientek, A Hilbert, A Bresch, W Fenske, M K Hankir, O Sabri, S Hesse
A polymorphism in the promoter region of the human serotonin transporter (5-HTT)-coding SLC6A4 gene (5-HTTLPR) has been implicated in moderating susceptibility to stress-related psychopathology and to possess regulatory functions on human in vivo 5-HTT availability. However, data on a direct relation between 5-HTTLPR and in vivo 5-HTT availability have been inconsistent. Additional factors such as epigenetic modifications of 5-HTTLPR might contribute to this association. This is of particular interest in the context of obesity, as an association with 5-HTTLPR hypermethylation has previously been reported...
July 4, 2017: Translational Psychiatry
https://www.readbyqxmd.com/read/28670115/the-influence-of-the-serotonergic-system-on-the-personality-and-quality-of-life-of-postmenopausal-women
#20
Daria Schneider-Matyka, Anna Jurczak, Małgorzata Szkup, Agnieszka Samochowiec, Anna Grzywacz, Sylwia Wieder-Huszla, Elżbieta Grochans
The aim of this study was to establish the relationship between personality traits of postmenopausal women and the presence of the 44-bp VNTR polymorphism in the serotonin transporter (5-HTT) (SLC6A4) promoter region and the 30-bp VNTR polymorphism in the MAO-A promoter region. The study's aim was also to determine the influence of personality traits on the quality of postmenopausal women's lives. The study involved 214 postmenopausal women from northwest Poland, with an average age of 56.8±4.08 years. It was performed using the Temperament and Character Inventory-Revised and the Short Form Health Survey...
2017: Clinical Interventions in Aging
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