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SLC6A4 S/S

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https://www.readbyqxmd.com/read/28576508/a-review-of-the-role-of-serotonin-system-genes-in-obsessive-compulsive-disorder
#1
REVIEW
Vanessa Sinopoli, Christie L Burton, Sefi Kronenberg, Paul D Arnold
SINOPOLI, V., C.L. Burton, S. Kronenberg and P.D. Arnold. A review of the role of serotonin system genes in obsessive-compulsive disorder. NEUROSCI BIOBEHAV REV X(X) XXX-XXX, 2017.- Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder that causes the patient to experience intrusive thoughts and/or to carry out repetitive, ritualized behaviors that are time consuming and impairing. OCD is familial and heritable. The genetic factors responsible for pathogenesis, however, remain largely unknown despite the numerous candidate gene studies conducted...
May 30, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28316763/serotonin-transporter-gene-slc6a4-polymorphism-and-mucosal-serotonin-levels-in-southeastern-iranian-patients-with-irritable-bowel-syndrome
#2
Mojgan Mohammadi, Hossein Tahmasebi Abdar, Hamid Reza Mollaei, Hossein Hajghani, Mohammad Reza Baneshi, Mohammad Mahdi Hayatbakhsh
BACKGROUND Irritable bowel syndrome (IBS) is a digestive system disorder with an unknown etiology. Serotonin has a key role in the secretion and motility of the intestine. Polymorphism in serotonin re-uptake transporter (SERT or SLC6A4) gene may have a functional role in the gut of patients with IBS. The aims of the present study were to investigate the association between SLC6A4 gene polymorphism and IBS and to detect the correlation between rectal serotonin levels and IBS sub-types. METHODS SLC6A4 gene polymorphism in 131 patients with IBS and 211 healthy controls were analysed using the quantitative polymerase chain reaction high-resolution melting (qPCR-HRM) curve technique...
January 2017: Middle East Journal of Digestive Diseases
https://www.readbyqxmd.com/read/28262188/effects-of-the-serotonin-transporter-gene-sensitivity-of-response-to-alcohol-and-parental-monitoring-on-risk-for-problem-alcohol-use
#3
Lora M Cope, Emily C Munier, Elisa M Trucco, Jillian E Hardee, Margit Burmeister, Robert A Zucker, Mary M Heitzeg
The serotonin transporter-linked polymorphic region (5-HTTLPR) of the serotonin transporter gene (SLC6A4) has been previously associated with alcohol-related risk. Most findings point to short (S) allele carriers being at increased risk for negative alcohol outcomes relative to long allele homozygotes, although some work indicates a more complex relationship. The current prospective study aimed to clarify how and under what circumstances variations in 5-HTTLPR transmit risk for various alcohol-related outcomes...
March 2017: Alcohol
https://www.readbyqxmd.com/read/28137459/systematic-review-and-meta-analysis-of-genetic-studies-of-late-life-depression
#4
REVIEW
Ruby S M Tsang, Karen A Mather, Perminder S Sachdev, Simone Reppermund
Late-life depression (LLD) is thought to be multifactorial in etiology, including a significant genetic component. While a number of candidate gene studies have been carried out, results remain inconclusive. We undertook a systematic review of all genetic association studies of depression or depressive symptoms in late life published before February 2016, and performed meta-analyses on polymorphisms investigated in three or more independent studies. A total of 46 candidate gene studies examining 56 polymorphisms in 23 genes as well as a genome-wide association study (GWAS) were included...
January 27, 2017: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/28068779/norepinephrine-transporter-gene-variants-and-remission-from-depression-with-venlafaxine-treatment-in-older-adults
#5
MULTICENTER STUDY
Victoria S Marshe, Malgorzata Maciukiewicz, Soham Rej, Arun K Tiwari, Etienne Sibille, Daniel M Blumberger, Jordan F Karp, Eric J Lenze, Charles F Reynolds, James L Kennedy, Benoit H Mulsant, Daniel J Müller
OBJECTIVE: The primary objective of this study was to investigate five putatively functional variants of the norepinephrine transporter (SLC6A2, NET) and serotonin transporter (SLC6A4, SERT) genes and remission in depressed older adults treated with venlafaxine. A secondary objective was to analyze 17 other variants in serotonergic system genes (HTR1A, HTR2A, HTR1B, HTR2C, TPH1, TPH2) potentially involved in the mechanism of action of venlafaxine. METHOD: The sample included 350 adults age 60 or older with DSM-IV-defined major depressive disorder and a score of at least 15 on the Montgomery-Åsberg Depression Rating Scale (MADRS)...
May 1, 2017: American Journal of Psychiatry
https://www.readbyqxmd.com/read/27989490/paraphilic-sexual-offenders-do-not-differ-from-control-subjects-with-respect-to-dopamine-and-serotonin-related-genetic-polymorphisms
#6
Andrzej Jakubczyk, Aleksandra Krasowska, Marcin Bugaj, Maciej Kopera, Anna Klimkiewicz, Agata Łoczewska, Aneta Michalska, Aleksandra Majewska, Natalia Szejko, Anna Podgórska, Małgorzata Sołowiej, Leszek Markuszewski, Sławomir Jakima, Rafał Płoski, Kirk Brower, Marcin Wojnar
INTRODUCTION: Rape and pedophilic child molestation are the most commonly convicted sexual offenses in Poland. Recent studies have suggested a possible genetic contribution toward pathologic sexual interests and behaviors. AIM: To analyze and compare functional polymorphisms of genes associated with the activity of the serotonin and dopamine systems in a group of paraphilic sexual offenders and control subjects. METHODS: The study sample (n = 97) consisted of two groups: paraphilic sexual offenders (65 pedophilic child molesters and 32 rapists) and controls (n = 76)...
January 2017: Journal of Sexual Medicine
https://www.readbyqxmd.com/read/27743374/associations-between-genetic-risk-functional-brain-network-organization-and-neuroticism
#7
Michelle N Servaas, Linda Geerligs, Jojanneke A Bastiaansen, Remco J Renken, Jan-Bernard C Marsman, Ilja M Nolte, Johan Ormel, André Aleman, Harriëtte Riese
Neuroticism and genetic variation in the serotonin-transporter (SLC6A4) and catechol-O-methyltransferase (COMT) gene are risk factors for psychopathology. Alterations in the functional integration and segregation of neural circuits have recently been found in individuals scoring higher on neuroticism. The aim of the current study was to investigate how genetic risk factors impact functional network organization and whether genetic risk factors moderate the association between neuroticism and functional network organization...
October 14, 2016: Brain Imaging and Behavior
https://www.readbyqxmd.com/read/27509352/impulsive-choices-in-mice-lacking-imprinted-nesp55
#8
C L Dent, T Humby, K Lewis, A Plagge, R Fischer-Colbrie, J F Wilkins, L S Wilkinson, A R Isles
Genomic imprinting is the process whereby germline epigenetic events lead to parent-of-origin specific monallelic expression of a number of key mammalian genes. The imprinted gene Nesp is expressed from the maternal allele only and encodes for Nesp55 protein. In the brain, Nesp55 is found predominately in discrete areas of the hypothalamus and midbrain. Previously, we have shown that loss of Nesp55 gives rise to alterations in novelty-related behaviour. Here, we extend these findings and demonstrate, using the Nesp(m/+) mouse model, that loss of Nesp55 leads to impulsive choices as measured by a delayed-reinforcement task, whereby Nesp(m/+) mice were less willing to wait for a delayed, larger reward, preferring instead to choose an immediate, smaller reward...
November 2016: Genes, Brain, and Behavior
https://www.readbyqxmd.com/read/27505229/association-between-reduced-white-matter-integrity-in-the-corpus-callosum-and-serotonin-transporter-gene-dna-methylation-in-medication-naive-patients-with-major-depressive-disorder
#9
E Won, S Choi, J Kang, A Kim, K-M Han, H S Chang, W S Tae, K R Son, S-H Joe, M-S Lee, B-J Ham
Previous evidence suggests that the serotonin transporter gene (SLC6A4) is associated with the structure of brain regions that are critically involved in dysfunctional limbic-cortical network activity associated with major depressive disorder (MDD). Diffusion tensor imaging (DTI) and tract-based spatial statistics were used to investigate changes in white matter integrity in patients with MDD compared with healthy controls. A possible association between structural alterations in white matter tracts and DNA methylation of the SLC6A4 promoter region was also assessed...
2016: Translational Psychiatry
https://www.readbyqxmd.com/read/27238716/differential-patterning-of-genes-involved-in-serotonin-metabolism-and-transport-in-extra-embryonic-tissues-of-the-mouse
#10
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
https://www.readbyqxmd.com/read/27218411/dna-methylation-at-stress-related-genes-is-associated-with-exposure-to-early-life-institutionalization
#11
Amy L Non, Brittany M Hollister, Kathryn L Humphreys, Ainash Childebayeva, Kyle Esteves, Charles H Zeanah, Nathan A Fox, Charles A Nelson, Stacy S Drury
OBJECTIVES: Differences in DNA methylation have been associated with early life adversity, suggesting that alterations in methylation function as one pathway through which adverse early environments are biologically embedded. This study examined associations between exposure to institutional care, quantified as the proportion of time in institutional care at specified follow-up assessment ages, and DNA methylation status in two stress-related genes: FKBP5 and SLC6A4. MATERIALS AND METHODS: We analyzed data from the Bucharest Early Intervention Project, which is a prospective study in which children reared in institutional settings were randomly assigned (mean age 22 months) to either newly created foster care or care as usual (to remain in their current placement) and prospectively followed...
September 2016: American Journal of Physical Anthropology
https://www.readbyqxmd.com/read/27072889/correlated-gene-expression-encoding-serotonin-5-ht-receptor-4-and-5-ht-transporter-in-proximal-colonic-segments-of-mice-across-different-colonization-states-and-sexes
#12
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
https://www.readbyqxmd.com/read/27047556/genetic-polymorphism-in-the-promoter-region-of-serotonin-transporter-implications-for-ethanol-abuse-in-children-and-adolescents
#13
Carlos Eduardo Coral de Oliveira, Julie Massayo Maeda Oda, Carolina Batista Ariza, Roberta Losi Guembarovski, Bruna Karina Banin Hirata, Felipe Campos de Almeida, Nayara Delgado André, Maria Helena Pelegrinelli Fungaro, Maria Angelica Ehara Watanabe
OBJECTIVES: To provide a review of published literature regarding genetic polymorphism of serotonin transporter gene, named as 5-HTTLPR, and its potential role as a susceptibility marker for ethanol abuse in childhood and adolescence. METHODS: A literature review of several databases was conducted with the following keywords: 5-HTTLPR, children or adolescents or teenagers, susceptibility, alcohol or ethanol, abuse or misuse. RESULTS: Alcohol interacts with serotonergic synaptic transmission in several ways, and the reduced availability of serotonin transporters might foster brain dysfunction, driving to alcohol abuse...
2016: Journal of the Canadian Academy of Child and Adolescent Psychiatry
https://www.readbyqxmd.com/read/27023264/a-prospective-study-of-serotonin-and-norepinephrine-transporter-genes-and-the-response-to-desvenlafaxine-over-8-weeks-in-major-depressive-disorder
#14
C H Ng, C Bousman, D J Smith, N Dowling, K Byron, J King, J Sarris
No studies to date have evaluated SLC6A2 and SLC6A4 genetic polymorphisms influencing antidepressant response to desvenlafaxine. We conducted an 8-week, open-label, prospective pilot study in 35 patients with major depressive disorder to assess the effects of genetic variations in SLC6A2 and SLC6A4 on both efficacy and side effect profile of desvenlafaxine. Results revealed that homozygotes for the SLC6A4 HTTLPR S allele showed a 33% HDRS reduction compared to a 58% reduction for L allele carriers (p=0.037)...
September 2016: Pharmacopsychiatry
https://www.readbyqxmd.com/read/26782054/sexual-divergence-in-microtubule-function-the-novel-intranasal-microtubule-targeting-skip-normalizes-axonal-transport-and-enhances-memory
#15
N Amram, G Hacohen-Kleiman, S Sragovich, A Malishkevich, J Katz, O Touloumi, R Lagoudaki, N C Grigoriadis, E Giladi, A Yeheskel, M Pasmanik-Chor, Y Jouroukhin, I Gozes
Activity-dependent neuroprotective protein (ADNP), essential for brain formation, is a frequent autism spectrum disorder (ASD)-mutated gene. ADNP associates with microtubule end-binding proteins (EBs) through its SxIP motif, to regulate dendritic spine formation and brain plasticity. Here, we reveal SKIP, a novel four-amino-acid peptide representing an EB-binding site, as a replacement therapy in an outbred Adnp-deficient mouse model. We discovered, for the first time, axonal transport deficits in Adnp(+/-) mice (measured by manganese-enhanced magnetic resonance imaging), with significant male-female differences...
October 2016: Molecular Psychiatry
https://www.readbyqxmd.com/read/26679194/serotonin-transporter-genetic-variation-is-differentially-associated-with-reflexive-and-reflective-optimal-learning
#16
W Todd Maddox, Marissa A Gorlick, Seth Koslov, John E McGeary, Valerie S Knopik, Christopher G Beevers
Learning to respond optimally under a broad array of environmental conditions is a critical brain function that requires engaging the cognitive systems that are optimal for solving the task at hand. Serotonin is implicated in learning and decision-making, but the specific functions of serotonin in system-level cognitive control remain unclear. Across 3 studies, we examined the influence of a polymorphism within the promoter region of the serotonin transporter gene (5-HTTLPR polymorphism in SLC6A4) on participants' ability to engage the task appropriate cognitive system when the reflexive (Experiments 1 and 2) or the reflective (Experiment 3) system was optimal...
February 1, 2017: Cerebral Cortex
https://www.readbyqxmd.com/read/26635248/serotonin-transporter-variants-play-a-role-in-anxiety-sensitivity-in-south-african-adolescents
#17
Sian M J Hemmings, Lindi I Martin, Lize van der Merwe, Rohan Benecke, Katharina Domschke, Soraya Seedat
OBJECTIVES: Anxiety sensitivity (AS) has predictive potential for the development of anxiety disorders. We investigated the role that gene-environment (G × E) interactions, focussing on childhood trauma (CT) and selected SLC6A4 variants, play in modulating levels of AS in a South African adolescent population. METHODS: All adolescents (n = 951) completed measures for AS and CT. Six SLC6A4 polymorphisms were genotyped. G × E influences on AS levels were assessed using multiple linear regression models...
2016: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/26560754/5-httlpr-expression-outside-the-skin-an-experimental-test-of-the-emotional-reactivity-hypothesis-in-children
#18
Joyce Weeland, Meike Slagt, Eddie Brummelman, Walter Matthys, Bram Orobio de Castro, Geertjan Overbeek
BACKGROUND: There is increasing evidence that variation in the promoter region of the serotonin transporter gene SLC6A4 (i.e., the 5-HTTLPR polymorphism) moderates the impact of environmental stressors on child psychopathology. Emotional reactivity -the intensity of an individual's response to other's emotions- has been put forward as a possible mechanism underlying these gene-by-environment interactions (i.e., G×E). Compared to children homozygous for the L-allele (LL-genotypes), children carrying an S-allele (SS/SL-genotypes), specifically when they have been frequently exposed to negative emotions in the family environment, might be more emotionally reactive and therefore more susceptible to affective environmental stressors...
2015: PloS One
https://www.readbyqxmd.com/read/26542422/interaction-between-slc6a4-promoter-variants-and-childhood-trauma-on-the-age-at-onset-of-bipolar-disorders
#19
B Etain, M Lajnef, A Henrion, A A Dargél, L Stertz, F Kapczinski, F Mathieu, C Henry, S Gard, J P Kahn, M Leboyer, S Jamain, F Bellivier
Age at onset (AAO) of bipolar disorders (BD) could be influenced both by a repeat length polymorphism (5HTTLPR) in the promoter region of the serotonin transporter gene (SLC6A4) and exposure to childhood trauma. We assessed 308 euthymic patients with BD for the AAO of their first mood episode and childhood trauma. Patients were genotyped for the 5HTTLPR (long/short variant) and the rs25531. Genotypes were classified on functional significance (LL, LS, SS). A sample of 126 Brazilian euthymic patients with BD was used for replication...
November 6, 2015: Scientific Reports
https://www.readbyqxmd.com/read/26529424/a-requirement-of-serotonergic-p38%C3%AE-mitogen-activated-protein-kinase-for-peripheral-immune-system-activation-of-cns-serotonin-uptake-and-serotonin-linked-behaviors
#20
N L Baganz, K M Lindler, C B Zhu, J T Smith, M J Robson, H Iwamoto, E S Deneris, W A Hewlett, R D Blakely
Alterations in central serotonin (5-hydroxytryptamine, 5-HT) neurotransmission and peripheral immune activation have been linked to multiple neuropsychiatric disorders, including depression, schizophrenia and autism. The antidepressant-sensitive 5-HT transporter (SERT, SLC6A4), a critical determinant of synaptic 5-HT inactivation, can be regulated by pro-inflammatory cytokine signaling. Systemic innate immune system activation via intraperitoneal lipopolysaccharide (LPS) injection rapidly elevates brain SERT activity and 5-HT clearance...
November 3, 2015: Translational Psychiatry
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