No association between the serotonin transporter gene regulatory region polymorphism and the Tridimensional Personality Questionnaire (TPQ) temperament of harm avoidance

Ebstein, Richard P.; Gritsenko, Inga; Nemanov, Lubov; Frisch, Amos; Osher, Yamima; Belmaker, Robert H.

doi:10.1038/sj.mp.4000275

Cited by 156 publications

(122 citation statements)

References 7 publications

(14 reference statements)

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“…Although we fail to observe a direct association between 5-HTTPLR and TPQ HA in the total cohort of 455 (F = 1.69, P = 0.19, n = 455), in a previous cohort, 18 and in a combined analysis (n = 836, t = 0.58, PϾ0.1; mean HA score for 5-HTTLPR L/L = 13.34 ± 0.41 L/S and S/S = 13.08 ± 0.22), the current results (in those subjects with the met/met genotype), and our previous studies in neonates, 7,8 nevertheless provide indirect evidence for an association between 5-HTTLPR and HA. We also note that in a subset of 148 subjects recruited from the Beersheva region (by JB and YO) a significant association between HA and 5-HTTLPR is observed in the absence of any additional genetic information.…”

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Association between tridimensional personality questionnaire (TPQ) traits and three functional polymorphisms: dopamine receptor D4 (DRD4), serotonin transporter promoter region (5-HTTLPR) and catechol O-methyltransferase (COMT)

et al. 2000

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Keywords: personality; polymorphism; tridimensional personality questionnaire; catechol O-methyltransferase; dopamine D4 receptor; serotonin transporter promoter Dopamine D4 receptor (DRD4), serotonin transporter promoter regulatory region (5-HTTLPR) and catechol Omethyltransferase (COMT) polymorphisms were examined for association with TPQ personality factors in 455 subjects. Significant interactions were observed by multivariate analysis, (COMT × 5-HTTLPR: Hotelling's Trace = 2.3, P = 0.02) and by subsequent univariate 3-way ANOVA when Novelty Seeking (NS) was the dependent variable: 5-HTTLPR × D4DR (F = 6.18, P = 0.03) and COMT × 5-HTTLPR (F = 4.42, P = 0.03). In the absence of the short 5-HTTLPR allele and in the presence of the high enzyme activity COMT val/val genotype, NS scores are higher in the presence of the DRD4 seven-repeat allele. The effect of these three polymorphisms on NS was also examined using a within-families design. Siblings who shared identical genotype groups for all three polymorphisms (COMT, DRD4 and 5-HTTLPR) had significantly correlated NS scores (intraclass coefficient = 0.39, F = 2.26, P = 0.008, n = 49) whereas sibs with dissimilar genotypes in at least one polymorphism showed no significant correlation for NS scores (intraclass coefficient = 0.177, F = 1.43, P = 0.09, n = 110). Similar interactions were also observed between these three polymorphisms and Novelty Seeking when the 150 independently recruited and non-related subjects were analyzed. The current results are consistent with two earlier reports in which we demonstrated an interaction between the 5-HTTLPR and DRD4 polymorphisms in 2-week-old neonates, in the same children assessed again at 2 months of age and in adults. Molecular Psychiatry Twin studies demonstrate that personality traits measured by several self-report questionnaires including the TPQ 1 and NEO-PI-R 2 are partially inherited and between 30-60% of the observed variance can be accounted for by genes. Only recently, however, have common genetic polymorphisms especially DRD4 and 5-HTTLPR, been provisionally assigned to particular temperament factors. [3][4][5] It seems reasonable that as additional genetic information is inventoried for various cohorts, associations between DRD4, 5-HTTLPR and other candidate genes and complex phenotypes will be further clarified. We, 6-8 and others, 9-11 have begun to examine multiple interactions between common genetic polymorphisms and complex behavioral traits. The catechol O-methyltransferase (COMT) gene contains a common, functional polymorphism in which a val-to-met amino acid substitution markedly reduces enzyme activity to about 20% of wild-type (val) levels. 12 Recent studies have suggested a role for COMT in behaviors often associated with impulsivity and disinhibition, 13-15 although to our knowledge, this gene has yet to be examined for a role in normal human personality.In the current study we initially examined using multivariate ANOVA four TPQ personality factor scores for 455 subjects grouped by three polymo...

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“…DNA was extracted and genotypes determined as previously described: DRD4, 4 5-HTTLPR 18 and COMT. 22 …”

Section: Genotypingmentioning

confidence: 99%

Association between tridimensional personality questionnaire (TPQ) traits and three functional polymorphisms: dopamine receptor D4 (DRD4), serotonin transporter promoter region (5-HTTLPR) and catechol O-methyltransferase (COMT)

et al. 2000

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“…26 Recently, this observation has been replicated in independent samples in the United States, 28,29 Japan, 30,31 and Israel, 32 although not in other populations. 33,34 The present work investigated the interrelationships between the serotonin transporter gene, neuroticism, and cigarette smoking behavior in a series of sib-pairs that included never, current and former smokers. This design allowed us to examine current smoking status, initiation and cessation by both population association and within-family methods.…”

Section: Introductionmentioning

confidence: 99%

Interaction between the serotonin transporter gene and neuroticism in cigarette smoking behavior

et al. 2000

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Cigarette smoking behavior is influenced by both personality traits and inherited factors. Previous research showed that neuroticism-a broad personality domain that includes anxiety, depression, impulsiveness and vulnerability-increases the risk of being a smoker, primarily because of difficulty in quitting. Neuroticism has also been associated with the 5-HTTLPR, a functional polymorphism in the promoter for the serotonin transporter gene. We used population and family-based methods to analyze the joint effects of the 5-HTTLPR and neuroticism on smoking behavior in a population of 759 never, current, and former smokers, all members of sib-pairs. Our main finding is that smoking behavior is influenced by an interaction between neuroticism and 5-HTTLPR genotype. Specifically, neuroticism was positively correlated with current smoking and negatively associated with smoking cessation in individuals and siblings with poorly transcribed 5-HTTLPR-S genotypes, but not in those with the more highly expressed 5-HTTLPR-L genotype. Individuals with both a 5-HTTLPR-S genotype and a high level of neuroticism had the greatest difficulty in quitting smoking. These data, if replicated, suggest that smoking behavior is more strongly influenced by the combination of the serotonin transporter gene and neuroticism than by either factor alone, and that personality scores and 5-HTTLPR genotype may predict the clinical efficacy of certain smoking cessation drugs. Molecular Psychiatry (2000) 5, 181-188.

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“…Thus, the original finding of higher neuroticism and harm avoidance in adult individuals with the short variant of the 5HTTLPR has been replicated and extended to younger individuals 3 and to other anxietyrelated dimensions of personality, [4][5][6] but has also failed replication. [7][8][9][10][11][12][13] Similarly, studies examining possible association between allelic variation in the promoter region of the serotonin transporter gene and risk for unipolar and bipolar depression have produced inconsistent findings (reviewed in Furlong et al 14 ). Among the potential sources for differences among these findings is the possibility that environmental variables may play an important role in the functional expression of the genotype.…”

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Early experience and serotonin transporter gene variation interact to influence primate CNS function

et al. 2002

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Nonhuman primates offer unique opportunities to study the effects of genes, environments, and their interaction, on physiology and complex behavior. We examined genotype and early environment contributions to CNS function in a large sample of rhesus monkeys. In humans, length variation of the serotonin (5-HT) transporter (5-HTT) gene-linked polymorphic region (5-HTTLPR) that results in allelic variation in 5-HTT expression is associated with decreased serotonergic function and 5-HT-mediated psychopathology. We report that an analogous variation of the gene's regulatory region in monkeys interacts with early experience to affect central 5-HT functioning. Monkeys with deleterious early rearing experiences were differentiated by genotype in cerebrospinal fluid concentrations of the 5-HT metabolite, 5-hydroxyindoleacetic acid, while monkeys reared normally were not. These findings demonstrate an environment-dependent effect of the rh5-HTTLPR genotype on CNS 5-HT function and suggest nonhuman primates may provide an important avenue for investigating gene/environment interactions using candidate genes for physiological and behavioral traits.

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No association between the serotonin transporter gene regulatory region polymorphism and the Tridimensional Personality Questionnaire (TPQ) temperament of harm avoidance

Cited by 156 publications

References 7 publications

Association between tridimensional personality questionnaire (TPQ) traits and three functional polymorphisms: dopamine receptor D4 (DRD4), serotonin transporter promoter region (5-HTTLPR) and catechol O-methyltransferase (COMT)

Association between tridimensional personality questionnaire (TPQ) traits and three functional polymorphisms: dopamine receptor D4 (DRD4), serotonin transporter promoter region (5-HTTLPR) and catechol O-methyltransferase (COMT)

Interaction between the serotonin transporter gene and neuroticism in cigarette smoking behavior

Early experience and serotonin transporter gene variation interact to influence primate CNS function

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