The serotonin transporter polymorphism, 5HTTLPR, is associated with a faster response time to sertraline in an elderly population with major depressive disorder

Durham, L. Kathryn; Webb, Suzin M.; Milos, Patrice M.; Clary, Cathryn M.; Seymour, Albert B.

doi:10.1007/s00213-003-1562-3

Cited by 132 publications

(79 citation statements)

References 18 publications

(21 reference statements)

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“…162 The short/long genotype was recently found to be associated with an odds ratio (OR) of 2.37 concerning adverse effects during treatment with SSRIs (dermatologic reactions, weight change and fatigue above all), and the homozygous short genotype showed an OR of 1.77. 163 These findings are generally well replicated in studies involving white popu lations, 120,[164][165][166][167][168][169][170][171][172][173][174][175] although opposite or inconsistent findings have also been reported. [176][177][178][179][180] On the other hand, studies involving Asian populations usually report conflicting results: some studies reported that the short 5-HTTLPR allele was associated with better outcomes, [181][182][183][184] some found no effect of 5-HTTLPR genotype on treatment efficacy 121,185,186 and some reported that the long 5-HTTLPR allele was associated with better outcomes.…”

Section: Comtmentioning

confidence: 73%

Pharmacogenetics of antidepressant response

Porcelli

Drago

Fabbri

et al. 2011

J Psychiatry Neurosci

156

103

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87Personalized medicine -the adaptation of therapies based on an individual's genetic and molecular profile -is one of the most promising aspects of modern medicine. The identification of the relation between genotype and drug response, including both the therapeutic effect and side effect profile, is expected to deeply affect medical practice. In this paper, we review the current knowledge about the genes related to antidepressant treatment response and provide methodologic proposals for future studies. We have mainly focused on genes associated with pharmacodynamics, for which a list of promising genes has been identified despite some inconsistency across studies. We have also synthesized the main results for pharmacokinetic genes, although so far they seem less relevant than those for pharmaco dynamic genes. We discuss possible reasons for these inconsistent findings and propose new study designs.

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Section: Comtmentioning

confidence: 73%

Pharmacogenetics of antidepressant response

Porcelli

Drago

Fabbri

et al. 2011

J Psychiatry Neurosci

156

103

View full text Add to dashboard Cite

show abstract

“…The l-allele of the 5-HTTLPR polymorphism is associated with better SSRI antidepressive effects than the s-allele 49,52,53 and with faster response to several SSRI's. 54,55 Combined treatment with a 5-HT 1A blocker to prevent negative feedback at the somatodendritic level compensated for the worse antidepressant effect of SSRIs in s/s and s/l genotypes, 56 suggesting higher 5-HT 1A negative feedback in s-allele genotypes.…”

Section: -Ht Transportermentioning

confidence: 99%

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

et al. 2006

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In recent years, the term serotonergic vulnerability (SV) has been used in scientific literature, but so far it has not been explicitly defined. This review article attempts to elucidate the SV concept. SV can be defined as increased sensitivity to natural or experimental alterations of the serotonergic (5-HTergic) system. Several factors that may disrupt the 5-HTergic system and hence contribute to SV are discussed, including genetic factors, female gender, personality characteristics, several types of stress and drug use. It is explained that SV can be demonstrated by means of manipulations of the 5-HTergic system, such as 5-HT challenges or acute tryptophan depletion (ATD). Results of 5-HT challenge studies and ATD studies are discussed in terms of their implications for the concept of SV. A model is proposed in which a combination of various factors that may compromise 5-HT functioning in one person can result in depression or other 5-HT-related pathology. By manipulating 5-HT levels, in particular with ATD, vulnerable subjects may be identified before pathology initiates, providing the opportunity to take preventive action. Although it is not likely that this model applies to all cases of depression, or is able to identify all vulnerable subjects, the strength of the model is that it may enable identification of vulnerable subjects before the 5-HT related pathology occurs. Molecular Psychiatry ( Keywords: serotonin; mood disorders; stress; genetics; sex; tryptophan Involvement of serotonin in depressionMood disorders are one of the most prevalent forms of mental illness. 1 According to the DSM-IV, the lifetime risk for major depressive disorder is between 10 and 25% for women and between 5 and 12% for men. 2 Depression has been studied intensively during the last few decades, but the psychological and neurobiological determinants of depression have not yet been precisely defined. Although several factors are known to contribute to the etiology of depression, it is not clear how these factors cause depression, and why some subjects become depressed while others remain unaffected. In terms of biological factors in the etiology of depression, there are several hypotheses. These include neurotransmitter dysfunctions (serotonin, 5-HT; dopamine, DA; norepinephrine, NE); dysregulations in hypothalamic-pituitary-adrenal (HPA) axis activity; and immune system imbalance. The aim of this article is not to discuss all of these hypotheses in detail, but to evaluate the role that serotonin may play within these hypothesized mechanisms.It is widely accepted that diminished serotonergic (5-HTergic) function is involved in the onset and course of depression. 3,4 The 5-HTergic system is a large and complex system. Although nearly all cell bodies of 5-HTergic neurons are located in the raphe nuclei in the brain stem, the axons of these neurons innervate almost the entire brain. The actions of 5-HT are mediated by 16 types and subtypes of receptors. 5 As the 5-HTergic system is assumed to be a modulatory system, the exact func...

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“…84,85 We may not rule out the possibility that gene variants may be indirectly associated with rapid onset through a mechanism of action independent from drugs, for example, predisposing to shorter episodes. This would then imply that gene variants are also associated with placebo response.…”

Section: Assessment Issuesmentioning

confidence: 99%

Pharmacogenetic studies in depression: a proposal for methodologic guidelines

2007

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Pharmacogenetic studies in mood disorders are rapidly proliferating after the initial reports linking gene variants to treatment outcomes. However, a considerable range of methodologies has been used, making it difficult to compare results across studies and limiting the representativeness of findings. Specification of sampling source (inpatients vs outpatients, primary vs tertiary settings), standardization of diagnostic systems and treatments, adequate monitoring of compliance through plasma levels, sufficient length of observation (at least 6 weeks for acute antidepressant treatments, though 3-6 months are preferable), the use of a range of response criteria and the inclusion of possible environmental confounding variables (life events, social support, temperament) are all potentially important issues when planning pharmacogenetic studies. We reviewed the state-of-the-art methodology and suggested possible guideline for future studies.

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The serotonin transporter polymorphism, 5HTTLPR, is associated with a faster response time to sertraline in an elderly population with major depressive disorder

Abstract: These results suggest that genetic variation in the serotonin transporter gene effects the response time to sertraline and provides complementing evidence to previous reports that this polymorphism affects response time to other SSRIs.

Cited by 132 publications

References 18 publications

Pharmacogenetics of antidepressant response

Pharmacogenetics of antidepressant response

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

Pharmacogenetic studies in depression: a proposal for methodologic guidelines

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