Journal ArticleDOI
Allelic Variation of Human Serotonin Transporter Gene Expression
Armin Heils,A. Teufel,Susanne Petri,Gerald Stöber,Peter Riederer,D. Bengel,Klaus-Peter Lesch +6 more
TLDR
Mood, emotion, cognition, and motor functions as well as circadian and neuroendocrine rhythms, including food intake, sleep, and reproductive activity, are modulated by the midbrain raphe serotonin (5‐HT) system and allele‐dependent differential 5‐HTT promoter activity may play a role in the expression and modulation of complex traits and behavior.Abstract:
Mood, emotion, cognition, and motor functions as well as circadian and neuroendocrine rhythms, including food intake, sleep, and reproductive activity, are modulated by the midbrain raphe serotonin (5-HT) system. By directing the magnitude and duration of postsynaptic responses, carrier-facilitated 5-HT transport into and release from the presynaptic neuron are essential for the fine tuning of serotonergic neurotransmission. Interest in the mechanism of environmental factor-, disease-, and therapy-induced modification of 5-HT transporter (5-HTT) function and its impact on early brain development, event-related synaptic plasticity, and neurodegeneration is widespread and intensifying. We have recently characterized the human and murine 5-HTT genes and performed functional analyses of their 5'-flanking regulatory regions. A tandemly repeated sequence associated with the transcriptional apparatus of the human 5-HTT gene displays a complex secondary structure, represses promoter activity in nonserotonergic neuronal cells, and contains positive regulatory components. We now report a novel polymorphism of this repetitive element and provide evidence for allele-dependent differential 5-HTT promoter activity. Allelic variation in 5-HTT-related functions may play a role in the expression and modulation of complex traits and behavior.read more
Citations
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Journal ArticleDOI
Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region
Klaus-Peter Lesch,D. Bengel,Armin Heils,Sue Z. Sabol,Benjamin D. Greenberg,Susanne Petri,Jonathan Benjamin,Clemens R. Müller,Dean H. Hamer,Dennis L. Murphy +9 more
TL;DR: The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5HTT expression and 5HT uptake in lymphoblasts as discussed by the authors, which is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs.
Journal ArticleDOI
Major depressive disorder.
Robert H. Belmaker,Galila Agam +1 more
TL;DR: This review presents the major current approaches to understanding the biologic mechanisms of major depression and defines depression as a heterogeneous disorder with a highly variable course, an inconsistent response to treatment, and no established mechanism.
Journal ArticleDOI
Serotonin transporter promoter gain-of-function genotypes are linked to obsessive-compulsive disorder.
Xian-Zhang Hu,Robert H. Lipsky,Guanshan Zhu,Longina A. Akhtar,Julie Taubman,Benjamin D. Greenberg,Ke Xu,Paul D. Arnold,Margaret A. Richter,James L. Kennedy,Dennis L. Murphy,David Goldman +11 more
TL;DR: The HTTLPR L(A)L( a) genotype exerts a moderate effect on risk of OCD, which crystallizes the evidence that the HTT gene has a role in OCD.
Journal ArticleDOI
Candidate gene studies of ADHD: a meta-analytic review.
TL;DR: A comprehensive meta-analytic review of the literature to determine which candidate genes show consistent evidence of association with childhood ADHD across studies found significant associations for several candidate genes including DAT1, DRD4,DRD5, 5HTT, HTR1B, and SNAP25.
Journal ArticleDOI
Current research trends in early life stress and depression: review of human studies on sensitive periods, gene-environment interactions, and epigenetics.
TL;DR: The evidence for the existence of sensitive periods for the adverse effects of early life stress in humans is reviewed and the potential importance of identifying sensitive time periods of opportunity for early interventions that might prevent or reverse the detrimental outcomes ofEarly life stress and its transmission across generations is discussed.
References
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Journal ArticleDOI
Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking.
Richard P. Ebstein,Olga Novick,Roberto Umansky,Beatrice Priel,Yamima Osher,Darren Blaine,Estelle R. Bennett,Lubov Nemanov,Miri Katz,Robert H. Belmaker +9 more
TL;DR: This work provides the first replicated association between a specific genetic locus involved in neuro-transmission and a normal personality trait, the 7 repeat allele in the locus for the D4 dopamine receptor gene (D4DR).
Journal ArticleDOI
Population and familial association between the D4 dopamine receptor gene and measures of Novelty Seeking
Jonathan Benjamin,Lin Li,Chavis Patterson,Benjamin D. Greenberg,Dennis L. Murphy,Dean H. Hamer +5 more
TL;DR: The relationship between DADR exon III sequence variants and personality test scores in a population of 315 mostly male siblings, other family members and individuals from the United States was investigated and the association between long alleles ofExon III and personality traits related to Novelty Seeking was confirmed.
Journal ArticleDOI
Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter.
TL;DR: Findings support the hypothesis that alterations in 5-HT neurons play a role in the pathophysiology of depression.
Journal ArticleDOI
Cloning and expression of a functional serotonin transporter from rat brain.
Randy D. Blakely,Haley E. Berson,Robert T. Fremeau,Marc G. Caron,Margaret M. Peek,Heather K. Prince,Christopher C. Bradley +6 more
TL;DR: A large family of related gene products expressed in rodent brain is identified from two highly conserved regions of the transporters for noradrenaline and γ-aminobutyric acid, and one of these products hybridizes to a single 3.7-kilobase RNA restricted to rat midbrain and brainstem, where it is highly enriched within the serotonergic raphe complex.
Journal ArticleDOI
Susceptibility to human type 1 diabetes at IDDM2 is determined by tandem repeat variation at the insulin gene minisatellite locus
Simon T. Bennett,Anneke Lucassen,S C Gough,Elizabeth E. Powell,Dag E. Undlien,L E Pritchard,Marilyn E. Merriman,Y Kawaguchi,M J Dronsfield,M J Dronsfield,Flemming Pociot +10 more
TL;DR: Although it is shown that the insulin gene is expressed biallelically in the adult pancreas, it is presented preliminary evidence that the level of transcription in vivo is correlated with allelic variation within the VNTR.