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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
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 behavior. 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...
August 10, 2016: Genes, Brain, and Behavior
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
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
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
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
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
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
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
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...
December 17, 2015: Cerebral Cortex
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
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
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
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
Benedicte Meyer, Chinh Bkrong Thuy Nguyen, Aurora Moen, Even Fagermoen, Dag Sulheim, Hilde Nilsen, Vegard Bruun Wyller, Johannes Gjerstad
Earlier studies have shown that genetic variability in the SLC6A4 gene encoding the serotonin transporter (5-HTT) may be important for the re-uptake of serotonin (5-HT) in the central nervous system. In the present study we investigated how the 5-HTT genotype i.e. the short (S) versus long (L) 5-HTTLPR allele and the SNP rs25531 A > G affect the physical and psychosocial functioning in patients with chronic fatigue syndrome (CFS). All 120 patients were recruited from The Department of Paediatrics at Oslo University Hospital, Norway, a national referral center for young CFS patients (12-18 years)...
2015: PloS One
Robert S Ross, Paolo Medrano, Kaitlin Boyle, Andrew Smolen, Tim Curran, Erika Nyhus
Recognition memory is defined as the ability to recognize a previously encountered stimulus and has been associated with spatially and temporally distinct event-related potentials (ERPs). Allelic variations of the serotonin transporter gene (SLC6A4) have recently been shown to impact memory performance. Common variants of the serotonin transporter-linked polymorphic region (5HTTLPR) of the SLC6A4 gene result in long (l) and short (s) allelic variants with carriers of the s allele having lowered transcriptional efficiency...
November 2015: Neuropsychologia
Siyang Luo, Dian Yu, Shihui Han
Romantic relationship satisfaction (RRS) is important for mental/physical health but varies greatly across individuals. To date, we have known little about the biological (genetic and neural) correlates of RRS. We tested the hypothesis that the serotonin transporter promoter polymorphism (5-HTTLPR), the promoter region of the gene SLC6A4 that codes for the serotonin transporter protein, is associated with individuals' RRS. Moreover, we investigated neural activity that mediates 5-HTTLPR association with RRS by scanning short-short (s/s) and long-long (l/l) homozygotes of 5-HTTLPR, using functional MRI, during a Cyberball game that resulted in social exclusion...
February 2016: Social Cognitive and Affective Neuroscience
Anja Plemenitas, Matej Kastelic, Stefan o Porcelli, Alessandro Serretti, Vita Dolžan, Blanka Kores Plesnicar
BACKGROUND: Genes involved in the serotonin pathway may determine the susceptibility to alcohol dependence and its severity. The present study explored whether specific polymorphisms in the serotonin pathway could be associated with alcohol dependence or alcohol-related psychopathological symptoms. METHODS: The cohort comprised 101 currently and 100 formerly alcohol-dependent males, as well as 97 male healthy blood donors. The following questionnaires were employed: the Alcohol Use Disorders Identification Test, the Zung Depression and Anxiety Scale, the Brief Social Phobia Scale, the Yale-Brown Obsessive Compulsive Scale and Obsessive Compulsive Drinking Scale, and the Buss-Durkee Hostility Inventory...
2015: Neuropsychobiology
Miles D Thompson, George A Kenna
SLC6A4, the gene encoding the serotonin transporter protein (5-HTT), has been extensively examined as a risk factor for alcohol dependence (AD). More recently, variability in the transporter gene was identified to be a potential moderator of treatment response to serotonergic medications such as ondansetron and sertraline. There is an insertion-deletion polymorphism in the promoter region (5-HTTLPR) of the SLC6A4, with the most common alleles being a 14-repeat short (S) allele and a 16-repeat long (L) allele...
March 2016: Alcohol and Alcoholism: International Journal of the Medical Council on Alcoholism
Janna N Vrijsen, Indira Tendolkar, Alejandro Arias-Vásquez, Barbara Franke, Aart H Schene, Guillén Fernández, Iris van Oostrom
The tendency to recall more negative and less positive information has been frequently related to the genetic susceptibility to depression. This memory bias may be associated with depression candidate genes especially in individuals who experienced stressful childhood events. The serotonin transporter gene, SLC6A4/5-HTT, regulates the reuptake of serotonin. The 5-HTTLPR polymorphism in the gene's promoter region has a short (S) and a long (L) allele, of which L contains a further SNP (rs25531), resulting in a triallelic polymorphism: La, Lg, and S...
November 1, 2015: Journal of Affective Disorders
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