The serotonin transporter gene and peer-rated neuroticism

Abstract

Polymorphisms in the serotonin transporter gene (5HTT) have been reported to be associated with neuroticism (emotionality) and with depression. A recent report of an association between 5HTT and neuroticism involved unselected samples and self-report questionnaires. We attempted to extend these findings using a selected extremes design and peer ratings. From a sample of 2085 individuals, each assessed on neuroticism by two independent peers, we selected 52 individuals from the top 5% and 54 individuals from the bottom 5%. No association was found for either a functional 44 bp insertion/deletion polymorphism in 5HTT regulatory sequence (5HTTLPR) or for a non-functional variable number tandem repeat 5HTT polymorphism.

An association study of a functional polymorphism of the serotonin transporter gene with personality and psychiatric symptoms

“…These findings are inconsistent with those reported by Lesch et al, 1 but consistent with subsequent negative studies. [2][3][4] Given that our sample size is larger than that of Lesch et al and of the negative studies, lack of statistical power is not a likely explanation. The present sample size has nearly 80% power to detect associations accounting for 1% of the variance.…”

“…Several studies have failed to find associations of the 5-HTTLPR with neuroticism and harm avoidance. [2][3][4] Association studies with psychiatric disorders have also generally been negative, including studies on panic disorder, 5-7 unipolar and bipolar affective disorder 8 and anorexia. 9 However, a study of unipolar and bipolar affective disorder in three centres did find an association with the short allele in the combined data from the centres, even though the associations were not statistically significant in the individual centres.…”

Evidence for linkage disequilibrium between serotonin transporter protein gene (SLC6A4) and obsessive compulsive disorder

“…This hypothesis was, however, based on the report of an association between the 's' allele and neuroticism; results inconsistent with such a relationship have been reported more recently. 24 There are other reports consistent with effects of this polymorphism on phenotype, such as the report by Collier et al showing an association of the 's' allele with affective disorders in a large sample 25 and the study by Cook et al 3 discussed above. In retrospect, since the finding of an association with anxiety-related phenotypes has not yet been confirmed, while other behavioral effects for this polymorphism have been observed, it is clear that a hypothesis relating to direction of effect for OCD was premature.…”

Serotonin transporter candidate gene studies in affective disorders and personality: promises and potential pitfalls

“…9 This association was found both across and within families in a mostly male general population sample of over 500 individuals. Two subsequent studies, using smaller samples (of 106 and 120 individuals, respectively) and populationbased designs, found no significant association between 5-HTTLPR genotype and neuroticism 28 or the related trait of harm avoidance. 29 However, the sample size in both studies was likely insufficient to detect association.…”