Neuroticism is not associated with the serotonin transporter (5-HTTLPR) polymorphism

Abstract

A deletion/insertion polymorphism in the transcriptional control region of the serotonin transporter gene (5-HTTLPR) was reported to be associated with dimensional measures of neuroticism, 1 although subsequent replication attempts have failed.2-5 These replication attempts, however, have been dissimilar to the initial study in sample size, distribution of allelic frequency and/or assessment of neuroticism. The current study was conducted in a further attempt to replicate the initial finding using: (a) a sample that was more comparable to each of the individual samples in the initial report; and (b) identical psychometric methodology to assess neuroticism. Two hundred and twenty-five Caucasian adults were genotyped for the 5-HTTLPR polymorphism and completed the NEO Personality Inventory. 6 Results did not replicate the association between the 5-HTTLPR polymorphism and neuroticism; individuals with the short form of this variant did not report higher NEO Neuroticism. Indeed, men with the short form reported lower Anxiety, a finding that is directionally opposite to the initial results. These findings, combined with other failures to replicate, indicate that the reproducibility of the association between the 5-HTTLPR polymorphism and neuroticism must be regarded as questionable. The contradictory findings suggest the need for a replication attempt in a large, normative sample that is stratified by ethnicity and sex.

Further evidence for a possible association between serotonin transporter gene and lithium prophylaxis in mood disorders

“…SERPR long and short allele frequencies were, respectively, 0.51 and 0.49, similar to those of previously published samples in Caucasians 45,59,69,70 and similar to those observed in our Italian sample (0.57 and 0.43, respectively). 60 Italian and Greek samples were not different in terms of SERTPR genotypes frequencies (w 2 ¼ 4.3; df ¼ 2; P ¼ 0.1).…”

Interacting effects of the serotonin transporter gene and neuroticism in smoking practices and nicotine dependence

“…4 However, the association with personality has not been supported in subsequent studies. 9,10 Although we did not find evidence for a main effect of 5-HTTLPR on smoking status in a previous analysis, 11 Hu and colleagues 12 have provided evidence that the 5-HTTLPR modifies the association of neuroticism with smoking status. In the present report, we sought to replicate and extend the findings by Hu et al 12 examining the interacting effects of the 5-HTTLPR and neuroticism on smoking practices and nicotine dependence in an independent sample of smokers.…”

Association and linkage of anxiety-related traits with a functional polymorphism of the serotonin transporter gene regulatory region in Israeli sibling pairs

“…11 In possible support of this idea, a United States study 12 found a significant interaction between 5-HTTLPR genotype and race for NEO-PI-R neuroticism, which suggests that the relationship between the allele and anxiety-related traits may be obscured by the effects of differing phenotypes and differing gene frequencies in different populations (population stratification). Several other studies [13][14][15] found no association of the 5-HTTLPR with various personality measures. Unfortunately, none of the negative studies included family material, which is essential to distinguish genuine genetic transmission, or its lack, from artifacts of population stratification.…”