The influence of psychiatric screening in healthy populations selection: a new study and meta-analysis of functional 5-HTTLPR and rs25531 polymorphisms and anxiety-related personality traits

Background: A genetic liability for anxiety-related personality traits in healthy subjects has been associated withthe functional serotonin transporter promoter polymorphism (5-HTTLPR), although the data are somewhatconflicting. Moreover, only one study has investigated the functional significance of the 5-HTTLPR/rs25531haplotypes in relation to anxiety traits in healthy subjects. We tested whether the 5-HTTLPR polymorphism and the5-HTTLPR/rs25531 haplotypes are linked to Harm Avoidance (HA) using an association study (STUDY I) and a metaanalyticapproach (STUDY II).Methods: STUDY I: A total of 287 unrelated Italian volunteers were screened for DSM-IV Axis I disorders andgenotyped for the 5-HTTLPR and rs25531 (A/G) polymorphisms. Different functional haplotype combinations werealso analyzed. STUDY II: A total of 44 studies were chosen for a meta-analysis of the putative association between5-HTTLPR and anxiety-related personality traits.Results: STUDY I: In the whole sample of 287 volunteers, we found that the SS genotype and S’S’ haplotypes wereassociated with higher scores on HA. However, because the screening assessed by Mini-International NeuropsychiatricInterview (M.I.N.I.) showed the presence of 55 volunteers affected by depression or anxiety disorders, we analyzed thetwo groups ("disordered” and “healthy”) separately. The data obtained did indeed confirm that in the “healthy” group,the significant effects of the SS genotype and S’S’ haplotypes were lost, but they remained in the “disordered” group.STUDY II: The results of the 5-HTTLPR meta-analysis with anxiety-related traits in the whole sample confirmed theassociation of the SS genotype with higher anxiety-related traits scores in Caucasoids; however, when we analyzed onlythose studies that used structured psychiatric screening, no association was found.Conclusions: This study demonstrates the relevance to perform analyses on personality traits only in DSM-IV axis Idisorder-free subjects. Furthermore, we did not find an association between functional serotonin transporter genepolymorphisms and anxiety traits in healthy subjects screened through a structured psychiatric interview.