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

Lesch, Klaus‐Peter; Bengel, Dietmar; Heils, Armin; Sabol, Sue Z.; Greenberg, Benjamin D.; Petri, Susanne; Benjamin, Jonathan; Müller, C. R.; Hamer, Dean H.; Murphy, Dennis L.

doi:10.1126/science.274.5292.1527

Cited by 4,710 publications

(4,042 citation statements)

References 48 publications

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“…150 An association of neuroticism with 5-HTTLPR short allele has been reported and withstood the test of meta-analyses. 72,[147][148][149] However, the small effect size of this association, dependence on measure of neuroticism used and the uncertainty of recessivity or dominance of the s allele effect suggest that the present concept of 'neuroticism' does not fit the putative trait associated with the 5-HTTLPR ss genotype. Facets of neuroticism may be explored as well as other psychological traits related to the reactivity to events, including ruminative response style, 161 instability of self-esteem, 162 or experiential avoidance.…”

Section: Genetic Control Of the Environmentmentioning

confidence: 82%

“…72 However, an additive co-dominant effect was demonstrated in larger samples considering s/l 70 or S, L A /L G alleles. 106 In contrast, human functional neuroimaging studies suggest functionally dominant s allele.…”

Section: Allelic Variants Of 5-httlpr: L a And L G Or Rs25531mentioning

confidence: 93%

“…68,[70][71][72][73] However, the translation of in vitro findings into in vivo functioning does not appear straightforward. Human neuroimaging studies of 5-HTT availability [74][75][76][77][78][79] and post-mortem studies of 5-HTT bindings and rRNA expression [80][81][82] have not detected any consistent effect of 5-HTTLPR.…”

Section: The Functionality Of 5-httlprmentioning

confidence: 99%

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The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

2007

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Section: Genetic Control Of the Environmentmentioning

confidence: 82%

Section: Allelic Variants Of 5-httlpr: L a And L G Or Rs25531mentioning

confidence: 93%

Section: The Functionality Of 5-httlprmentioning

confidence: 99%

See 1 more Smart Citation

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

2007

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“…Interestingly, high concentrations of imipramine (100 μM), which have been used to inhibit serotonin uptake in lymphoblasts, 23 reduced IDT307 uptake in human lymphocytes by approximately 40% ( Figure 6A). However, at this concentration, imipramine is likely to interact nonselectively with unknown transporters, in addition to SERT (K i (SERT) = 140 ± 40 nM 50 ).…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Serotonin Uptake Is Largely Mediated by Platelets versus Lymphocytes in Peripheral Blood Cells

Beikmann

Tomlinson²,

Rosenthal³

et al. 2012

ACS Chem. Neurosci.

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ABSTRACT:The serotonin transporter (SERT), a primary target for many antidepressants, is expressed in the brain and also in peripheral blood cells. Although platelet SERT function is well accepted, lymphocyte SERT function has not been definitively characterized. Due to their small size, platelets often are found in peripheral blood mononuclear cell preparations aimed at isolating lymphocytes, monocytes, and macrophages. The presence of different cells makes it difficult to assign SERT expression and function to specific cell types. Here, we use flow cytometry and IDT307, a monoamine transporter substrate that fluoresces after uptake into cells, to investigate SERT function in lymphocyte and platelet populations independently, as well as simultaneously without prior isolation. We find that murine lymphocytes exhibit temperature-dependent IDT307 transport but uptake is independent of SERT. Lack of measurable SERT function in lymphocytes was corroborated by chronoamperometry using serotonin as a substrate. When we examined rhesus and human mixed blood cell populations, we found that platelets, and not lymphocytes, were primary contributors to SERT function. Overall, these findings indicate that lymphocyte SERT function is minimal. Moreover, flow cytometry, in conjunction with the fluorescent transporter substrate IDT307, can be widely applied to investigate SERT in platelets from populations of clinical significance.

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“…It consists of a 44-bp insertion or deletion involving repeat elements 6 to 8 (from bp À1212 to bp À1255). 59 In a previous work, 60 we found SERTPR variants associated with lithium outcome (P ¼ 0.005) in a sample of 201 patients consecutively admitted to the Lithium Clinic for Mood Disorders of S Raffaele Hospital in Milan. Subjects with the s/ s variant showed a worse response compared to both l/s and l/l variants.…”

Section: Introductionmentioning

confidence: 75%

Further evidence for a possible association between serotonin transporter gene and lithium prophylaxis in mood disorders

et al. 2004

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We previously reported an association between the functional polymorphism in the upstream regulatory region of the serotonin transporter gene (SERTPR) and the prophylactic efficacy of lithium in a sample of 201 Italian subjects affected by Mood disorders. The aim of the present study was to replicate analyses on an independent sample. In total, 83 subjects affected by Bipolar disorder were recruited in the Mood Disorders Clinic of the Eginition Hospital of the Athens University, Medical School Department of Psychiatry. All patients were administered with lithium as prophylactic therapy and they were prospectively observed for at least 3 years. Subjects were typed for their SERTPR variant using polymerase chain reaction techniques. SERTPR variants were associated with lithium outcome among those subjects who had few manic episodes before lithium treatment and, as a trend, among subjects who received a high daily dose of lithium (X1200 mg/die). In both cases, subjects with the l/l variant showed a higher probability to develop an illness episode within 3 years of prophylactic treatment with lithium. The present study confirmed our previous observation of a better response of SERTPR*l/s carriers, but could not confirm a poor efficacy in subjects with the SERTPR*s/s genotype. Notwithstanding the conflicting results, SERTPR variants are a possible liability factor for lithium long-term efficacy in mood disorders. Further studies on independent and large samples are required to determine the reliability and direction of the possible association between SERTPR variants and lithium outcome. INTRODUCTIONLithium is an effective prophylactic agent in mood disorders but not all patients equally respond to lithium therapy. Clinical predictors account for less than half of the variance, 1-8 and there are evidences suggesting that genetic factors play a substantial role in lithium prophylaxis effectiveness. [9][10][11][12][13][14][15][16][17][18][19][20] A large number of studies reported an association between prophylactic lithium response and a family history of bipolar disorder, 10,[12][13][14]17 although not unequivocally confirmed. [21][22][23][24][25] Recently, Grof et al 26 reported that lithium response in a sample of relatives of responder probands was 67% compared to 30% in the comparison group.

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

Cited by 4,710 publications

References 48 publications

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

The moderation by the serotonin transporter gene of environmental adversity in the aetiology of mental illness: review and methodological analysis

Serotonin Uptake Is Largely Mediated by Platelets versus Lymphocytes in Peripheral Blood Cells

Further evidence for a possible association between serotonin transporter gene and lithium prophylaxis in mood disorders

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