No Association between the Serotonin Transporter-Linked Promoter Region Polymorphism and Either Schizophrenia or Density of the Serotonin Transporter in Human Hippocampus

Naylor, Lee; Dean, Brian; Pereira, Avril; Mackinnon, Andrew; Kouzmenko, Alexander; Copolov, David L.

doi:10.1007/bf03401928

Cited by 48 publications

(24 citation statements)

References 16 publications

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“…21 These results, along with some of the findings from previous human studies, [22][23][24] demonstrate a relationship between the 5-HTTLPR and 5-HT functioning in both human and nonhuman primates (but also see Naylor et al 25 and Jonsson et al 26 ). Although the 5-HTTLPR alleles are differentially active in vitro, relatively few studies have examined direct measures of CNS serotonin function in either humans or other animals.…”

Section: Molecular Psychiatrysupporting

confidence: 51%

Early experience and serotonin transporter gene variation interact to influence primate CNS function

et al. 2002

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Nonhuman primates offer unique opportunities to study the effects of genes, environments, and their interaction, on physiology and complex behavior. We examined genotype and early environment contributions to CNS function in a large sample of rhesus monkeys. In humans, length variation of the serotonin (5-HT) transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) that results in allelic variation in 5-HTT expression is associated with decreased serotonergic function and 5-HT-mediated psychopathology. We report that an analogous variation of the gene's regulatory region in monkeys interacts with early experience to affect central 5-HT functioning. Monkeys with deleterious early rearing experiences were differentiated by genotype in cerebrospinal fluid concentrations of the 5-HT metabolite, 5-hydroxyindoleacetic acid, while monkeys reared normally were not. These findings demonstrate an environment-dependent effect of the rh5-HTTLPR genotype on CNS 5-HT function and suggest nonhuman primates may provide an important avenue for investigating gene/environment interactions using candidate genes for physiological and behavioral traits.

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Section: Molecular Psychiatrysupporting

confidence: 51%

Early experience and serotonin transporter gene variation interact to influence primate CNS function

et al. 2002

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“…39,41,42,58 Clinical association studies have further examined the relationship between SERTLPR alleles and psychiatric disorders and anxiety-related personality traits, [59][60][61][62][63][64][65][66] suicide, 67,68 alcoholism, 69,70 response to antidepressants [71][72][73] and brain function as revealed by MRI scans. [74][75][76][77] Although many studies have reported correlations between SERTLPR alleles and SERT expression levels or clinical phenotype, almost an equal number of studies have not.…”

Section: Discussionmentioning

confidence: 99%

Allelic expression of serotonin transporter (SERT) mRNA in human pons: lack of correlation with the polymorphism SERTLPR

Papp

Pinsonneault

et al. 2006

Mol Psychiatry

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An insertion/deletion polymorphism in the SERT linked promoter region (SERTLPR), previously reported to regulate mRNA expression in vitro, has been associated with mental disorders and response to psychotropic drugs. Contradictory evidence, however, has raised questions about the role of SERTLPR in regulating mRNA expression in vivo. We have used analysis of allelic expression imbalance (AEI) of SERT mRNA to assess quantitatively the contribution of SERTLPR to mRNA expression in human post-mortem pons tissue sections containing serotonergic neurons of the dorsal and median raphe nuclei. Any difference in the expression of one allele over the other indicates the presence of cis-acting elements that differentially affect transcription and/or mRNA processing and turnover. Using a marker SNP in the 3 0 untranslated region of SERT mRNA, statistically significant differences in allelic mRNA levels were detected in nine out of 29 samples heterozygous for the marker SNP. While the allelic expression differences were relatively small (15-25%), they could nevertheless be physiologically relevant. Although previous results had suggested that the long form of SERTLPR yields higher mRNA levels than the short form, we did not observe a correlation between SERTLPR and allelic expression ratios. Also in contrast to previous results, we found no correlation between SERTLPR and allelic expression ratios or SERT mRNA levels in Blymphocytes. This study demonstrates that regulation of SERT mRNA is independent of SERTLPR, but could be associated with polymorphisms in partial linkage disequilibrium with SERTLPR.

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“…Serotonin is reabsorbed after being transported to the neurons and the 5-HTT regulates the degree and duration of serotonin response during this process [3]. Some studies reported alteration of 5-HTT-related findings in patients with schizophrenia: significant increase in the maximum number of 5-HTT sites in schizophrenic patients compared with controls [4], brain region-specific decrease in the density of 5-HTT in schizophrenics [5], significant decrease in the affinity of 3 H-paroxetine binding to the hippocampus [6,7], and decreased number of serotonin uptake sites in the limbic system of schizophrenics [8]; however, a negative finding was also detected [9].…”

Section: Introductionmentioning

confidence: 99%

Polymorphism of the Serotonin Transporter Gene and Symptomatic Dimensions of Schizophrenia in the Korean Population

et al. 2003

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This study was aimed to test the association between schizophrenia and a functional serotonin polymorphism (5-HTTLPR) in the upstream regulatory region. Genomic DNA analysis with polymerase chain reaction was used for 5-HTTLPR genotyping. One hundred and eleven patients with schizophrenia and 208 healthy individuals participated in this study. There were significant differences in the negative score and general psychopathology score of the positive and negative syndrome scale according to 5-HTTLPR genotypes and alleles, although no significant differences in allele or genotype frequencies between the two groups were found. These results suggest that 5-HTTLPR may contribute to the susceptibility to the symptomatology of schizophrenia but not to the development of the disorder itself, at least in the Korean population.

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No Association between the Serotonin Transporter-Linked Promoter Region Polymorphism and Either Schizophrenia or Density of the Serotonin Transporter in Human Hippocampus

Cited by 48 publications

References 16 publications

Early experience and serotonin transporter gene variation interact to influence primate CNS function

Early experience and serotonin transporter gene variation interact to influence primate CNS function

Allelic expression of serotonin transporter (SERT) mRNA in human pons: lack of correlation with the polymorphism SERTLPR

Polymorphism of the Serotonin Transporter Gene and Symptomatic Dimensions of Schizophrenia in the Korean Population

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