Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region

  title={Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region},
  author={Klaus-Peter Lesch and Dietmar Bengel and Armin Heils and Sue Z. Sabol and Benjamin D. Greenberg and Susanne Petri and Jonathan Benjamin and Clemens R. Müller and Dean Hamer and Dennis L. Murphy},
  pages={1527 - 1531}
Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression… 

Anxiety traits associated with a polymorphism in the serotonin transporter gene regulatory region in the Japanese

It is suggested that populations with the s/s genotype of 5-HTTLPR have stronger anxiety-related personality traits than those with the l allele.

The human serotonin transporter gene polymorphism-basic research and clinical implications

This work isolated and cloned the 5′-regulatory region of the serotonin transporter gene, which is inducible by cAMP-and PKC-dependend signal transduction pathways, and revealed a genetic polymorphism with allelic variation in transcriptional activity and protein expression.

Mouse model of the human serotonin transporter-linked polymorphic region

To investigate the impact of the polymorphism on gene expression, serotonin homeostasis, and behavioural traits, a mouse model of the human 5-HTT- LPR is developed to develop a set of mouse lines with single copy human transgenes carrying the short and long 5- HTT-LPR variants.

Polymorphism of the Serotonin Transporter

Clinical effects of the polymorphisms may be associated with effects on platelets, neural 5-HTT levels, and indices of serotonergic function, and potential confounding factors include age, gender, and population stratification.

Serotonin transporter polymorphism and response to SSRIs in major depression and relevance to anxiety disorders and substance abuse.

The 5-HTT gene polymorphisms were found to be associated with a better and faster response to SSRIs with or without pindolol augmentation in depressed patients, and further studies are needed to clarify the relationship between the 5- HTT genotype, the susceptibility to mental disorders, the response to serotonergic agents and the side effect profile.

Genetic variation in the serotonin transporter promoter region affects serotonin uptake in human blood platelets.

5-HT uptake findings support a functional difference in the two 5-HTTLPR variants, reinforcing their attractiveness as candidate genes in neuropsychiatric research.

No Association of a Functional Polymorphism in the Serotonin Transporter Gene Promoter and Anxiety-Related Personality Traits

No significant association was observed between the 5-HTTLPR genotype and STAI scores of any of the 5 major axes, including neuroticism, in all subjects, and a lack of significant genotype differences in these tests could be due to considerable individual variability in these measures.

A novel allele in the promoter region of the human serotonin transporter gene

A novel allele (termed LJ) is reported in the 5-HTTLPR site that is longer than the L allele by 43 bp, has 18 repeat units and contains two copies of the insertion/deletion sequence arranged in tandem.

Genetic polymorphisms of serotonin and dopamine transporters in mental disorders.

  • S. Ueno
  • Biology, Psychology
    The journal of medical investigation : JMI
  • 2003
Transporter-assisted uptake of serotonin (5-HT) and dopamine (DA) and their relations to psychiatric disorders are described.



Allelic Variation of Human Serotonin Transporter Gene Expression

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.

Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter.

Findings support the hypothesis that alterations in 5-HT neurons play a role in the pathophysiology of depression.

The serotonin transporter is a potential susceptibility factor for bipolar affective disorder.

It is hypothesize that either the VNTR affects regulation of expression of hSERT at the transcriptional level or it is in linkage disequilibrium with another functional polymorphism in the gene, and this results in an increased risk for the development of bipolar affective disorder.

Population and familial association between the D4 dopamine receptor gene and measures of Novelty Seeking

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.

Antidepressant- and cocaine-sensitive human serotonin transporter: molecular cloning, expression, and chromosomal localization.

A Na(+)- and Cl(-)-coupled serotonin (5-hydroxytryptamine, 5HT) transporter is expressed on human neuronal, platelet, placental, and pulmonary membranes and sequence analysis reveals a 630-amino acid open reading frame bearing 92% identity to the cloned rat brain 5HT transporter.

Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking

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).

Biological dissection of anxiety disorders: the clinical role of selective serotonin reuptake inhibitors with particular reference to fluvoxamine

Serotonergic systems are implicated in the pathophysiology of global anxiety irrespective of the nosological background, and SSRIs, exemplified by fluvoxamine, appear to be effective in panic disorder, OCD and probably also social phobia.