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Bojan Mirkovic, Claudine Laurent, Marc-Antoine Podlipski, Thierry Frebourg, David Cohen, Priscille Gerardin
Suicidal behaviors (SBs), which range from suicidal ideation to suicide attempts and completed suicide, represent a fatal dimension of mental ill-health. The involvement of genetic risk factors in SB is supported by family, twin, and adoption studies. The aim of this paper is to review recent genetic association studies in SBs including (i) case-control studies, (ii) family-based association studies, and (iii) genome-wide association studies (GWAS). Various studies on genetic associations have tended to suggest that a number of genes [e...
2016: Frontiers in Psychiatry
Raheel Mushtaq, Shah Faisal Ahmad Tarfarosh, Mohammad Maqbool Dar, Arshad Hussain, Sheikh Shoib, Tabindah Shah, Sahil Shah, Mushbiq Manzoor
BACKGROUND: The progress that man has made in all domains of life, during all these years of reign over the earth, is utterly remarkable. However, it always came at a price. Each epoch of progress has seen human beings inflicted with trauma and cynical consequences. During the last two decades, Kashmiri (Indian) people have experienced continuous violence, a reign of terror, and political turmoil. Each of these disastrous events has contributed to the increase in psychiatric disorders in this part of the world, especially major depressive disorders...
2016: Curēus
Paul Faulkner, Federico Mancinelli, Patricia L Lockwood, Mar Matarin, Raymond J Dolan, Nick W Wood, Peter Dayan, Jonathan P Roiser
BACKGROUND: The effects of acute tryptophan depletion on human decision-making suggest that serotonin modulates the processing of rewards and punishments. However, few studies have assessed which of the many types of serotonin receptors are responsible. METHODS: Using a within-subject, double-blind, sham-controlled design in 26 subjects, we examined whether individual differences in serotonin system gene transcription, measured in peripheral blood, predicted the effect of acute tryptophan depletion on decision-making...
October 3, 2016: International Journal of Neuropsychopharmacology
Samantha R Weaver, Justin C Bohrer, Allan S Prichard, Paola K Perez, Liana J Streckenbach, Jake M Olson, Mark E Cook, Laura L Hernandez
Obesity is an inflammatory state associated with delayed lactogenesis stage II and altered mammary gland morphology. Serotonin mediates inflammation and mammary gland involution. The objective of this study was to determine if a genetic deficiency of tryptophan hydroxylase 1, the rate-limiting enzyme in peripheral serotonin synthesis, would result in an improved ability to lactate in dams fed a high fat diet. Twenty-six female mice were fed a high (HFD) or low fat (LFD) diet throughout pregnancy and lactation...
2016: PloS One
J Pawlak, M Dmitrzak-Węglarz, M Maciukiewicz, P Kapelski, P Czerski, A Leszczyńska-Rodziewicz, D Zaremba, J Hauser
: Introduction The influence of personality traits on suicidal behaviour risk has been well documented. Personality traits and suicidal behaviour are partially genetically determined and personality has been described as an endophenotype of suicidal behaviour. The aim of this study was to investigate a possible association between personality traits with suicidal behaviour and selected serotonergic gene polymorphisms. METHODS: In the study we included 156 patients meeting DSM-IV criteria for bipolar disorder (BP) and 93 healthy controls...
August 30, 2016: Acta Neuropsychiatrica
Onur Beden, Ender Senol, Sevcan Atay, Handan Ak, Ayse Ender Altintoprak, Guclu Selahattin Kiyan, Buket Petin, Utku Yaman, Hikmet Hakan Aydin
BACKGROUND: Serotonergic dysfunction is implicated in depression, psychiatric disorders and suicidal behaviors. The first and rate-limiting step in the synthesis of serotonin is catalyzed by tryptophan hydroxylase (TPH) which is encoded by TPH1 and THP2 genes. Genetic association studies have revealed contradictory results about the effect of the TPH1 A218C (rs1800532) polymorphism on suicidal behavior in different populations. MATERIAL AND METHOD: In this study, we investigated A218C polymorphism in 109 suicide attempters and 98 healthy controls...
July 2016: Legal Medicine
Joanna Pawlak, Monika Dmitrzak-Weglarz, Monika Wilkosc, Aleksandra Szczepankiewicz, Anna Leszczynska-Rodziewicz, Dorota Zaremba, Pawel Kapelski, Aleksandra Rajewska-Rager, Joanna Hauser
INTRODUCTION: Studies have not given yet a clear answer what is the genetic background of suicidal predisposition. The associations between polymorphisms of the TPH1 and 5-HTTLPR genes and violent suicidal behavior was revealed with the least inconsistencies. METHOD: We selected 10 "strong candidate genes" and 35 SNPs, SLC6A4 and ACP1 for replication study. We searched associations between precisely described suicidal phenotype in 825 affective patients and polymorphisms of selected neurobiological pathways genes as well as their interactions that constitute suicidal risk...
July 19, 2016: Journal of Affective Disorders
Richard W D Welford, Magali Vercauteren, Annette Trébaul, Christophe Cattaneo, Doriane Eckert, Marco Garzotti, Patrick Sieber, Jérôme Segrestaa, Rolf Studer, Peter M A Groenen, Oliver Nayler
The biogenic amine serotonin (5-HT) is a multi-faceted hormone that is synthesized from dietary tryptophan with the rate limiting step being catalyzed by the enzyme tryptophan hydroxylase (TPH). The therapeutic potential of peripheral 5-HT synthesis inhibitors has been demonstrated in a number of clinical and pre-clinical studies in diseases including carcinoid syndrome, lung fibrosis, ulcerative colitis and obesity. Due to the long half-life of 5-HT in blood and lung, changes in steady-state levels are slow to manifest themselves...
2016: Scientific Reports
Vasil Yablanski, Svetla Nikolova, Evgeni Vlaev, Alexey Savov, Ivo Kremensky
The concept of disease-modifier genes as an element of genetic heterogeneity has been widely accepted and reported. The aim of the current study is to investigate the association between the promoter polymorphism TPH1 (rs10488682) and progression of idiopathic scoliosis (IS) in Eastern European population sample. A total of 105 patients and 210 healthy gender-matched controls were enrolled in this study. The TPH1 promoter polymorphism was genotyped by amplification followed by restriction. The statistical analysis was performed by Fisher's Exact Test...
2016: Journal of Biomarkers
Hsiao-Huei Wu, Sera Choi, Pat Levitt
INTRODUCTION: Serotonin (5-HT) is an important neuromodulator, but recently has been shown to be involved in neurodevelopment. Although previous studies have demonstrated that the placenta is a major source of forebrain 5-HT during early forebrain development, the processes of how 5-HT production, metabolism, and transport from placenta to fetus are regulated are unknown. As an initial step in determining the mechanisms involved, we investigated the expression patterns of genes critical for 5-HT system function in mouse extraembryonic tissues...
June 2016: Placenta
Amene Saghazadeh, Shadi A Esfahani, Nima Rezaei
INTRODUCTION: Heterogeneity of therapeutic response to brain stimulation techniques has inspired scientists to uncover the secrets to success or failure of these projects. Genetic polymorphisms are one of the major causes of this heterogeneity. AREAS COVERED: More than twenty genetic variants within more than ten genes (e.g. BDNF, COMT, DRD2, TRPV1, 5-HT1A, 5-HHT, P2RX7, VEGF, TPH1, TPH2, ACE, APOE, GNB3, NET, NMDA receptors, and RGS4) have been investigated, among which the BDNF gene and its polymorphism, Val66Met, is the best documented variant...
September 2016: Expert Review of Neurotherapeutics
Ronadip R Banerjee, Holly A Cyphert, Emily M Walker, Harini Chakravarthy, Heshan Peiris, Xueying Gu, Yinghua Liu, Elizabeth Conrad, Lisa Goodrich, Roland W Stein, Seung K Kim
β-Cell proliferation and expansion during pregnancy are crucial for maintaining euglycemia in response to increased metabolic demands placed on the mother. Prolactin and placental lactogen signal through the prolactin receptor (PRLR) and contribute to adaptive β-cell responses in pregnancy; however, the in vivo requirement for PRLR signaling specifically in maternal β-cell adaptations remains unknown. We generated a floxed allele of Prlr, allowing conditional loss of PRLR in β-cells. In this study, we show that loss of PRLR signaling in β-cells results in gestational diabetes mellitus (GDM), reduced β-cell proliferation, and failure to expand β-cell mass during pregnancy...
August 2016: Diabetes
C Bonvicini, S V Faraone, C Scassellati
The adult form of attention-deficit/hyperactivity disorder has a prevalence of up to 5% and is the most severe long-term outcome of this common disorder. Family studies in clinical samples as well as twin studies suggest a familial liability and consequently different genes were investigated in association studies. Pharmacotherapy with methylphenidate (MPH) seems to be the first-line treatment of choice in adults with attention-deficit hyperactive disorder (ADHD) and some studies were conducted on the genes influencing the response to this drug...
July 2016: Molecular Psychiatry
Won Tae Kim, Seok Joong Yun, Chunri Yan, Pildu Jeong, Ye Hwan Kim, Il Seok Lee, Ho Won Kang, Sunghyouk Park, Sung Kwon Moon, Yung Hyun Choi, Young Deuk Choi, Isaac Yi Kim, Jayoung Kim, Wun Jae Kim
PURPOSE: Our previous high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry study identified bladder cancer (BCA)-specific urine metabolites, including carnitine, acylcarnitines, and melatonin. The objective of the current study was to determine which metabolic pathways are perturbed in BCA, based on our previously identified urinary metabolome. MATERIALS AND METHODS: A total of 135 primary BCA samples and 26 control tissue samples from healthy volunteers were analyzed...
July 2016: Yonsei Medical Journal
Zeeshan Ahmad Khan, Thangal Yumnamcha, Chongtham Rajiv, Haobijam Sanjita Devi, Gopinath Mondal, Sh Dharmajyoti Devi, Rupjyoti Bharali, Asamanja Chattoraj
The present study on zebrafish (Danio rerio) is the first attempt to demonstrate the circadian mRNA expression of melatonin biosynthesizing enzyme genes (Tph1a, Aanat1, Aanat2 and Hiomt) and clock associated genes (Bmal1a, Clock1a, Per1b, Per2 and Cry2a) in the ovary with a comparison to whole brain in normal (LD=12h L:12h D) and altered photic conditions (continuous dark, DD; continuous light, LL). Moreover, the present study also confirmed the ability of zebrafish ovary to biosynthesize melatonin both in vivo and in vitro with a significant difference at day and night...
July 1, 2016: General and Comparative Endocrinology
Daniel R Goldberg, Stéphane De Lombaert, Robert Aiello, Patricia Bourassa, Nicole Barucci, Qing Zhang, Vishwas Paralkar, Adam J Stein, Jim Valentine, William Zavadoski
An increasing number of diseases have been linked to a dysfunctional peripheral serotonin system. Given that tryptophan hydroxylase 1 (TPH1) is the rate limiting enzyme in the biosynthesis off serotonin, it represents an attractive target to regulate peripheral serotonin. Following up to our first disclosure, we report a new chemotype of TPH1 inhibitors where-by the more common central planar heterocycle has been replaced with an open-chain, acyl guanidine surrogate. Through our work, we found that compounds of this nature provide highly potent TPH1 inhibitors with favorable physicochemical properties that were effective in reducing murine intestinal 5-HT in vivo...
June 15, 2016: Bioorganic & Medicinal Chemistry Letters
Hideo Nakagawa, Takashi Ueda, Saya Ito, Takumi Shiraishi, Hidefumi Taniguchi, Naruhiro Kayukawa, Hiroyuki Nakanishi, So Ushijima, Motohiro Kanazawa, Terukazu Nakamura, Yoshio Naya, Fumiya Hongo, Kazumi Kamoi, Koji Okihara, Osamu Ukimura
Silencing of androgen receptor (AR)-meditated androgen signaling is thought to be associated with the development of testicular germ cell tumors (TGCTs). However, the role of the androgen/AR signal in TGCT development has not been investigated. In this study, we show that the androgen/AR signal suppressed the cell growth of seminomas (SEs), a type of TGCT, in vitro and in vivo. Growth of SE cells was suppressed by DHT treatment and reduction of androgen levels by surgical castration promoted cancer cell growth in an in vivo xenograft model...
June 7, 2016: Oncotarget
Takeshi Tsuruta, Shinichi Saito, Yosuke Osaki, Akihiro Hamada, Ayako Aoki-Yoshida, Kei Sonoyama
Intestinal organoids were recently established as an ex vivo model of the intestinal epithelium. The present study investigated the serotonin (5-hydroxytryptamine, 5-HT) system using organoids. Organoids from murine small intestinal and colonic crypts were successfully cultured. Reverse transcription-polymerase chain reaction (RT-PCR) analysis showed that small intestinal and colonic organoids express mRNAs encoding tryptophan hydroxylase-1 (TPH1) (the rate-limiting enzyme of 5-HT synthesis), serotonin reuptake transporter (SERT), 5-HT receptor (HTR)2A, HTR2B, and HTR4...
May 20, 2016: Biochemical and Biophysical Research Communications
Carlos Acosta-Andrade, Ana Lambertos, José L Urdiales, Francisca Sánchez-Jiménez, Rafael Peñafiel, Ignacio Fajardo
Antizymes and antizyme inhibitors are key regulatory proteins of polyamine levels by affecting ornithine decarboxylase and polyamine uptake. Our previous studies indicated a metabolic interplay among polyamines, histamine and serotonin in mast cells, and demonstrated that polyamines are present in mast cell secretory granules, being important for histamine storage and serotonin levels. Recently, the novel antizyme inhibitor-2 (AZIN2) was proposed as a local regulator of polyamine biosynthesis in association with mast cell serotonin-containing granules...
October 2016: Amino Acids
C S Reigstad, D R Linden, J H Szurszewski, J L Sonnenburg, G Farrugia, P C Kashyap
The production and handling of serotonin (5-HT) is an important determinant of colonic motility and has been reported to be altered in gastrointestinal (GI) disorders such as irritable bowel syndrome (IBS). Recent studies suggest that the intestinal microbiota and sex of the host can influence expression of genes involved in 5-HT biosynthesis and signaling. While expression of genes in serotonergic pathways has been shown to be variable, it remains unclear whether genes within this pathway are coregulated. As a first step in that direction, we investigated potential correlations in relative mRNA expression of serotonergic genes, in the proximal colon isolated from male and female mice in different states of microbial association: germ-free (GF), humanized (ex-germ-free colonized with human gut microbiota, HM), and conventionally raised (CR) mice...
September 2016: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
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