Serotonin-2A-receptor and -transporter polymorphisms: lack of association in patients with major depression

Minov, Christo; Baghai, Thomas C.; Schüle, Cornelius; Zwanzger, Peter; Schwarz, Markus J.; Zill, Peter; Rupprecht, Rainer; Bondy, Brigitta

doi:10.1016/s0304-3940(01)01704-9

Cited by 164 publications

(47 citation statements)

References 19 publications

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“…Our results confirm previous reports that genotype frequencies of 102T/C 5-HT 2A receptor gene polymorphism in mood disorders do not differ from healthy volunteers (Arranz et al, 1997;Bondy et al, 2000;Crawford et al, 2000;Mahieu et al, 1997;Minov et al, 2001;Tsai et al, 1999;Ono et al, 2001;Correa et al, 2002;Geijer et al, 2000). Nevertheless, we found an excess of the TC genotype in suicide attempters compared with nonattempters.…”

Section: Discussionsupporting

confidence: 91%

“…A more recent meta-analysis demonstrated a stronger association with schizophrenia in Caucasians compared with other ethnic groups (Abdolmaleky et al, 2004). No association of genotype or allele frequencies is found with suicide or mood disorders (Arranz et al, 1997;Bondy et al, 2000;Crawford et al, 2000;Mahieu et al, 1997;Minov et al, 2001;Tsai et al, 1999;Ono et al, 2001;Correa et al, 2002;Geijer et al, 2000). Turecki et al (2003) found that higher 5-HT 2A binding in the brain is associated with the T102C polymorphism in the 5-HT 2A gene independently of suicide, although others disagree (Hrdina and Du, 2001).…”

Section: Introductionmentioning

confidence: 99%

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Association of Serotonin 5-HT2A Receptor Binding and the T102C Polymorphism in Depressed and Healthy Caucasian Subjects

Khait

Huang

Zalsman

et al. 2004

Neuropsychopharmacol

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Serotonin 5-HT 2A receptor (5-HT 2A ) binding is reported to be altered in individuals with suicidal behavior, mood disorders, and aggressive-impulsive traits. Genetic association with major depression, suicidal behavior, and aggressive-impulsive traits has not been established. This study examines the possible association of the 5-HT 2A gene C102T polymorphism with the receptor binding kinetics, and clinical overt phenotypes. The study population included 63 healthy volunteers and 152 subjects with mood disorders, 56 of whom had a history of suicide attempts. All were Caucasian. Platelet 5-HT 2A binding kinetics (B max and K D ) were assayed and adjusted for seasonal variation. All subjects were genotyped for the T102C polymorphism. Clinical phenotype was determined by structured clinical interview. The TT genotype was associated with higher B max in all subjects (F ¼ 3.53, df ¼ 2,211; p ¼ 0.03), controlling for diagnosis. Bonferroni-adjusted post hoc testing showed higher binding in the TT compared with TC genotype in the control group (F ¼ 7.56, df ¼ 2,60, p ¼ 0.001), but not in the mood-disordered subjects. No difference was found in genotype and allele distribution between the mood-disordered subjects, with and without suicide attempt history, and controls. B max was not related to a diagnosis of mood disorders.The TT genotype appears associated with higher platelet 5-HT 2A B max in the healthy population, but this genotypic effect appears absent in mood disorders and unrelated to psychopathology.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Association of Serotonin 5-HT2A Receptor Binding and the T102C Polymorphism in Depressed and Healthy Caucasian Subjects

Khait

Huang

Zalsman

et al. 2004

Neuropsychopharmacol

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“…Studies by Kraft et al 28 and Minov et al 30 were excluded because they included patients treated by a mixture of antidepressants. The paper by Lee et al 29 was not included because it did not use HAM-D or MADRS but Clinical Global Impressions of Improvement (CGI) score.…”

Section: Resultsmentioning

confidence: 99%

Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients

et al. 2006

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The serotonin transporter gene promoter polymorphism (5-HTTLPR) has been repeatedly associated with antidepressant response in mood disorder patients, but findings are not consistent across studies. A meta-analysis was performed on 15 studies including data of 1435 subjects. We tested three phenotypes: remission rate, response rate and response rate within 4 weeks using the cochrane review manager. We observed a significant association of the s/s variant of 5-HTTLPR with remission rate (P < 0.0001) and both s/s and s/l variants with response rate (P = 0.0002). Response rate within 4 weeks was associated in both models (P = 0.003-P < 0.00001). This effect is quite robust to ethnic differences although a significant heterogeneity is present in Asian samples.

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“…39 Regarding an association between 5-HTTLPR genotype and depression, results have been mixed. Some studies reported no association, 39,43,44 others found an association between the s-allele and depression, 26,[45][46][47][48] while others conclude that the l-allele is associated with depression. 49 However, most evidence seems to suggest an association between the s-allele of 5-HTTLPR and depression.…”

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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Serotonin-2A-receptor and -transporter polymorphisms: lack of association in patients with major depression

Cited by 164 publications

References 19 publications

Association of Serotonin 5-HT2A Receptor Binding and the T102C Polymorphism in Depressed and Healthy Caucasian Subjects

Association of Serotonin 5-HT2A Receptor Binding and the T102C Polymorphism in Depressed and Healthy Caucasian Subjects

Meta-analysis of serotonin transporter gene promoter polymorphism (5-HTTLPR) association with selective serotonin reuptake inhibitor efficacy in depressed patients

Serotonergic vulnerability and depression: assumptions, experimental evidence and implications

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