A polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) has been associated with anxiety-related personality traits in adults. Initial studies showed that the short allele was associated with higher neuroticism, anxiety and harm avoidance. However, most attempts to replicate these findings have been negative. Because the association of candidate polymorphisms with behavioral traits may vary with stage of development, we investigated the association using participants in a longitudinal study of childhood temperament. DNA was available for 660 children who had been assessed for temperament from 4-8 months to 15-16 years, and for behaviour problems from 3-4 years to 15-16 years. No significant associations were found at most ages. However, at ages 13-14 years and 15-16 years, the long/long genotype was associated with higher anxiety. These findings do not support an association of the short allele with anxiety-related traits in early life. Molecular Psychiatry (2000) 5, 542-547. Temperament is an individual difference characteristic of the child that reflects the preponderant style of behaviour, and includes the dimensions of activity, sociability, and the characteristic emotional responses. 1 Temperamental traits are often considered to be genetic or constitutional in origin and to show relative stability over time. Evidence for genetic influences on temperament comes from twin and adoption studies which indicate that the heritability of temperamental traits is generally in the range 0.4-0.6. 2,3 There is also evidence of some stability over the first 8 years of life, with correlations in the range 0.7-0.8 after correction for error of measurement. 4 Although there has been considerable research in recent years searching for genetic polymorphisms associated with adult personality, there has been very little on childhood temperament which forms the roots of personality. To date, only one study has examined allelic associations with childhood temperament. This study began by examining temperament in 81 twoweek-old neonates using a neonatal assessment scale. 5 Two candidate polymorphisms were assessed, involving the dopamine D4 receptor gene (D4DR) and the promoter region of the serotonin transporter gene (5-HTTLPR). Long D4DR alleles were found to be associated with several behavioral clusters (orientation, motor organization, range of state and regulation of state), but 5-HTTLPR alleles were not. There was also a significant interaction between the two polymorphisms on orientation scores. The same infants were assessed later, at 2 months of age, using an infant behavior questionnaire. 6 Long D4DR alleles were associated with lower scores on Negative Emotionality and Distress to Limitations, while short 5-HRTLPR alleles were associated with higher scores on these variables. Again there was an interaction effect, such that Negative Emotionality and Distress to Limitations were greatest in infants with the short/short genotype of both genes.In this paper we report further data on allelic ...