Brief research communication: serotonin transporter (5-HTT) gene polymorphisms are not associated with susceptibility to mood disorders

Hoehe, Margret R.; Wendel, Birgit; Grunewald, Ingrid; Chiaroni, P.; Lévy, Nicolas; Morris-Rosendahl, Deborah J.; Macher, Jean-Paul; Sander, Thomas; Crocq, Marc‐Antoine

doi:10.1002/(sici)1096-8628(19980207)81:1<1::aid-ajmg1>3.0.co;2-2

Cited by 115 publications

(66 citation statements)

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“…In total, 17 population-based studies 9,14,33,34,38,46,50,51,56,60,61,66,[68][69][70] and six family-based studies 12,32,42,53,63,74 were about 5-HTTLPR. A total of 16 population-based studies 27,33,35,38,41,47,[49][50][51]54,56,58,60,61,70,75 and four family-based studies 12,52,57,63 were about the intron 2 VNTR. Among the population-based studies, some used matched controls according to the ethnicity 41,47,50,60,66,69 and others explicitly verified the ethnic homogeneity of the sample through the ancestry history.…”

Section: Resultsmentioning

confidence: 99%

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Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: a systematic review and meta-analysis

et al. 2005

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The serotonin transporter (5-HTT) is a candidate gene for bipolar disorder (BPD). It has been investigated for association with the illness in a series of studies, but overall results have been inconsistent and its role in the disorder remains controversial. Systematic reviews using metaanalytical techniques are a useful method for objectively and reproducibly assessing individual studies and generating combined results. We performed two meta-analyses of published studies-both population-based and family-based studies-investigating the association between BPD and the 5-HTT gene-linked polymorphic region (5-HTTLPR) and the intron 2 variable numbers of tandem repeats (VNTR) polymorphisms. The literature was searched using Medline and Embase to identify studies for inclusion. We statistically joined population-based and family-based studies into a single meta-analysis. For both polymorphisms, our review revealed significant pooled odds ratios (ORs): 1.12 (95% CI 1.03-1.21) for the 5-HTTLPR and 1.12 (95% CI 1.02-1.22) for the intron 2 VNTR. Meta-regression showed that neither the study type (population-based vs family-based; P ¼ 0.41 for the 5-HTTLPR and P ¼ 0.91 for the intron 2 VNTR) nor the sample ethnicity (Caucasian vs non-Caucasian; P ¼ 0.35 for the 5-HTTLPR and P ¼ 0.66 for the intron 2 VNTR) significantly contributed to the heterogeneity of the meta-analyses. The observed ORs could be regarded simply as a very small but detectable effect of the 5-HTT, which has an additive effect when combined with other susceptibility loci. Alternative hypotheses on this finding were also discussed: a stronger effect of the haplotypes involving the two polymorphisms or other SNP markers; a more direct effect of these polymorphisms on specific phenotypes of BPD; and the presence of gene-environment interaction as a mediator of the genetic effects of 5-HTT. Keywords: bipolar disorder; serotonin transporter; polymorphisms; genetics; association study; meta-analysis Bipolar disorder (BPD), also known as manic-depressive illness, is a frequent and severe psychiatric disorder with the lifetime prevalence between 1 and 2% in the general population, being equally distributed across sexes. 1 The etiology is unknown although the presence of a complex dysfunction at multiple levels such as neurotransmitter system, prefrontallimbic-subcortical circuit and neuroendocrinological system has been suggested. 2 Family studies have indicated a marked increase in lifetime risk of the illness in first-degree relatives of the proband, varying between five and 10 times that of the general population. 3 Twin studies have shown an increased risk in monozygotic co-twins compared with dizygotic co-twins of a proband with BPD. The risk in monozygotic co-twins has been estimated at 45-75 times that of the general population. 3,4 Adoption studies have also shown that the risk of BPD is greater in biological relatives than in adoptive relatives of the probands. 5 Most of the segregation studies have shown that the inheritance of BPD cannot be explained b...

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Section: Resultsmentioning

confidence: 99%

“…51 The remaining studies mentioned that the sample was ethnically homogeneous. 9,14,34,35,49,54,58,61,68,70,75 5-HTTLPR meta-analysis In total, 17 population-based studies comprised 1712 cases (ie 3424 alleles) and 2583 controls, whereas six family-based studies comprised 587 trios. Summaries are shown in the Tables 1 and 2.…”

Section: Resultsmentioning

confidence: 99%

Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: a systematic review and meta-analysis

et al. 2005

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“…Association studies of DRD2 gene polymorphisms and alcoholism or ADHD have suggested that this mechanism might play a role in psychiatric conditions (Comings and MacMurray 2000). However, only one out of eleven other studies investigating the association between 5-HTTLPR and major depression also found that heterozygous subjects are more at risk than the homozygotes, indicating that it is highly unlikely that negative heterosis is present (Bellivier et al 1998;Collier et al 1996;Frisch et al 1999;Furlong et al 1998;Hauser et al 2003;Hoehe et al 1998;Kunugi et al 1997;Mendlewicz et al 2004;Rees et al 1997;Serretti et al 2002;Willis-Owen et al 2005).…”

Section: Discussionmentioning

confidence: 99%

Family Based Association Analyses between the Serotonin Transporter Gene Polymorphism (5-HTTLPR) and Neuroticism, Anxiety and Depression

et al. 2007

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We studied the association between the short/long promotor-based length polymorphism of the serotonin transporter gene (5-HTTLPR) and neuroticism, anxiety and depression. Subjects included twins, their siblings and parents from the Netherlands Twin Register (559 parents and 1,245 offspring). Subjects had participated between one and five times in a survey study measuring neuroticism, anxiety and depression. Offspring of these families were also approached to participate in a psychiatric interview diagnosing DSM-IV major depression. Within-family and total association between 5-HTTLPR and these traits were tested. Only three of the 36 tests showed a significant effect of 5-HTTLPR (P < 0.05). These effects were in opposite directions, i.e. both negative and positive regression coefficients were found for the s allele. No additive effect of the s allele was found for DSM-IV depression. Our results strongly suggest that there is no straightforward association between 5-HTTLPR and neuroticism, anxiety and depression.

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“…Anguelova, et al, also found a strong association between the 5HTT gene in/del polymorphism and the risk of suicide (22), and other authors demonstrated the association between this polymorphism and bipolar affective disorder (20,23). However, in Western European descendants, Hoehe, et al, found no significant differences in the genotypic or allele frequencies of the 5-HTT polymorphism in 36 patients with major depression, 79 with bipolar I disorder, and 294 controls (24). In Germany, Minov, et al, found a greater proportion of SS homozygotes in 173 cases of major depression (23.1%) compared with 121 controls (14.0%), although the difference was not statistically significant (25).…”

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Serotonin transporter gene (5-HTT) polymorphism and major depressive disorder in patients in Bogotá, Colombia

2016

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Introduction:The 5-HTT short allele has been controversially associated with an increased risk of major depressive disorder. Objective: To determine the association of 5-HTT short allele with major depression in Bogotá, Colombia. Materials and methods: We carried out a study of cases (n=68) matched 1:1 with controls by gender and age (±5 years). Major depression was diagnosed using the Mini-International Neuropsychiatric Interview, and 5-HTT polymorphism using PCR. Results: Females were predominant (82.4%). The S (short) allele predominated in cases compared with controls (S: 72.1% vs. 63.2; L (long): 27.9% vs. 36.8%), and the SL genotype was more frequent in cases (SL: 45.6% vs. 36.8%; LL: 27.9% vs. 36.8%; SS: 26.5% vs. 26.5%), although not significantly. There were significant differences in those under age 37, with a predominance of the S allele in cases (p=0.038; OR=2.75; 95% CI: 0.88-8.64). Multivariate analysis, adjusted for comorbid anxiety disorders, showed a significant association of major depression with the SL genotype (p=0.049; OR=3.20; 95% CI: 1.00-10.23); the S allele was close to statistical significance (p=0.063; OR=2.94; 95% CI: 0.94-9.13), and it was statistically significant in cases under 37 years of age (p=0.026; OR=10.79; 95% CI: 1.32-80.36). Conclusions: The SL genotype was associated with major depressive disorder in patients of all ages. The S allele was significantly associated with major depressive disorder in patients under age 37, adjusted for comorbid anxiety disorders.

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Brief research communication: serotonin transporter (5-HTT) gene polymorphisms are not associated with susceptibility to mood disorders

Cited by 115 publications

References 11 publications

Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: a systematic review and meta-analysis

Population-based and family-based studies on the serotonin transporter gene polymorphisms and bipolar disorder: a systematic review and meta-analysis

Family Based Association Analyses between the Serotonin Transporter Gene Polymorphism (5-HTTLPR) and Neuroticism, Anxiety and Depression

Serotonin transporter gene (5-HTT) polymorphism and major depressive disorder in patients in Bogotá, Colombia

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