Dataset Information

Failure to Replicate the Association Between Fractional Anisotropy and the Serotonin Transporter Gene (5-HTTLPR, rs25531).

ABSTRACT: Recent work underlines the importance of alterations in white matter (e.g., measured by fractional anisotropy (FA)) as a neural vulnerability marker for psychiatric disorders. In this context, the uncinate fasciculus (UF), which connects the limbic system with prefrontal areas, has repeatedly been linked to psychiatric disorders, fear processing, and anxiety-related traits. Individual differences in FA may partly be genetically determined. Variation in the promoter region of the serotonin transporter gene (serotonin transporter-linked polymorphic region [5-HTTLPR]) is a particularly promising candidate in this context, which has been linked to psychiatric disorders as well as to limbic and prefrontal reactivity. However, findings on the association between the 5-HTTLPR and FA within the UF-tract have been heterogeneous. The present study investigated this relationship and extended previous work by considering different genetic classification approaches as well as sex effects in a human sample (n = 114). All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. As a main result, we did not find any significant relationship between the 5-HTTLPR and FA in the UF-tract although power analyses showed an adequate power. In addition, genotype effects were neither found when different classification approaches were used nor when analyses were carried out in males or females only. The present findings suggest that the association of the 5-HTTLPR and FA seems to be a more labile phenomenon than previously assumed. Possible explanations and limitations are discussed.

SUBMITTER: Klucken T

PROVIDER: S-EPMC5937012 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Failure to Replicate the Association Between Fractional Anisotropy and the Serotonin Transporter Gene (5-HTTLPR, rs25531).

Klucken Tim T Tapia León Isabell I Blecker Carlo C Kruse Onno O Stalder Tobias T Stark Rudolf R

Frontiers in behavioral neuroscience 20180430

Recent work underlines the importance of alterations in white matter (e.g., measured by fractional anisotropy (FA)) as a neural vulnerability marker for psychiatric disorders. In this context, the uncinate fasciculus (UF), which connects the limbic system with prefrontal areas, has repeatedly been linked to psychiatric disorders, fear processing, and anxiety-related traits. Individual differences in FA may partly be genetically determined. Variation in the promoter region of the serotonin transp ...[more]

PMID: 29760654

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Project description:BACKGROUND: There is evidence from animal studies that serotonin (5-HT) can influence the antinociceptive effects of opioids at the spinal cord level. Therefore, there could be an influence of genetic polymorphisms in the serotonin system on individual variability in response to opioid treatment of pain. The serotonin transporter (5-HTT) is a key regulator of serotonin metabolism and availability and its gene harbors several known polymorphisms that are known to affect 5-HTT expression (e.g. 5-HTTLPR, rs25531). The aim of this study was to investigate if the triallelic 5-HTTLPR influences pain sensitivity or the analgesic effect of opioids in humans. 43 healthy volunteers (12 men, 31 women, mean age 26 years) underwent heat pain stimulations before and after intravenous injection of Remifentanil; a rapid and potent opioid drug acting on micro-type receptors. Subjects rated their perceived pain on a visual analogue scale (VAS). All participants were genotyped for the 5-HTTLPR and the rs25531 polymorphism. We recruited by advertising, with no history of drug abuse, chronic pain or psychiatric disorders. RESULTS: At baseline, there was no difference in pain ratings for the different triallelic 5-HTTLPR genotype groups. However, the opiod drug had a differential analgesic effect depending on the triallelic 5-HTTLPR genotype. Remifentanil had a significantly better analgesic effect in individuals with a genotype coding for low 5-HTT expression (SA/SA and SA/LG) as compared to those with high expression(LA/LA), p < 0.02. The analgesic effect for the three different genotype groups was linear to degree of 5-HTT expression. CONCLUSION: This is the first report showing an influence of the triallelic 5-HTTLPR on pain sensitivity or the analgesic effect of opioids in humans. Previously the 5-HTTLPR s-allele has been associated with higher risk of developing chronic pain conditions but in this study we show that the genotype coding for low 5-HTT expression is associated with a better analgesic effect of an opioid. The s-allele has been associated with downregulation of 5-HT1 receptors and we suggest that individuals with a desensitization of 5-HT1 receptors have an increased analgesic response to opioids during acute pain stimuli, but may still be at increased risk of developing chronic pain conditions.

Project description:BackgroundThe serotonin transporter polymorphism 5-HTTLPR is an extensively investigated genetic marker of autistic traits or autism spectrum disorder, and recently has also been studied in the realm of internet use disorder (IUD), yet the findings remain controversial. Therefore, the present study aimed to explore associations between 5-HTTLPR (also including SNP rs25531) and autistic traits/IUD tendencies and to assess whether the relationship between autistic traits and IUD tendencies varies by this genetic marker in participants from China and Germany.MethodsA total of 540 Chinese and 563 German subjects were genotyped for 5-HTTLPR/rs25531 and completed the Adult Autism Spectrum Quotient questionnaire and the short version of the Internet Addiction Test.ResultsCarriers of the low expressing S'S' genotype (S, LG ) showed significantly higher levels of autistic traits than the high expressing allele (e.g. LA ) carriers in both samples. There was no significant effect of 5-HTTLPR/rs25531 on IUD either in the Chinese or Germany samples, whereas positive correlations between autistic traits and IUD varied by 5-HTTLPR/rs25531 genotypes and also differed between Chinese and German samples. In the Chinese sample, positive correlations were mainly driven by S'S' and S'L' carriers, while they were mainly determined by S'L' and L'L' carriers in the German sample. Further analyses revealed that the associations between autistic traits and IUD tended in parts to be more strongly pronounced in the complete German sample compared to the complete Chinese sample, and also varied depending on 5-HTTLPR/rs25531 genotypes (in S'S' carriers: China > Germany; in S'L' and L'L' carriers: China < Germany; both in terms of more positive associations).ConclusionsOur findings suggest carriers of low expressing alleles (S, LG ) are more likely to show higher autistic traits in both Chinese and German samples. Furthermore, the present work shows that both 5-HTTLPR/rs25531 and cultural differences might be of relevance to understand associations between autistic traits and IUD tendencies, but this needs to be further backed up.

Dataset Information

Failure to Replicate the Association Between Fractional Anisotropy and the Serotonin Transporter Gene (5-HTTLPR, rs25531).

Publications

Failure to Replicate the Association Between Fractional Anisotropy and the Serotonin Transporter Gene (5-HTTLPR, rs25531).

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