Novelty Seeking Personality Trait

Description

Human personality traits that can be reliably measured by rating scales show a considerable heritable component. One such instrument is the tridimensional personality questionnaire (TPQ), which was designed by Cloninger et al. (1993) to measure 4 distinct domains of temperament--novelty seeking, harm avoidance, reward dependence, and persistence--that are hypothesized to be based on distinct neurochemical and genetic substrates.

Risk-taking is a characteristic of behaviors that occur under conditions of uncertainty and involves a tradeoff between beneficial versus detrimental outcomes, perceived or real. Risk-taking may or may not involve conscious evaluation of the probability and magnitude of possible outcomes (Anokhin et al., 2009).

See also harm avoidance (607834) and pathologic gambling (606349), which may be related.

Clinical Features

Roe et al. (2009) noted that there are 2 main bodies of literature that measure risk attitudes: that of behavioral neuroscientists and geneticists who measure harm avoidance and novelty seeking, and that of economists who measure decisions among competing financial gambles or investment opportunities. In a study of 67 individuals, Roe et al. (2009) did not find a strong correlation between risk attitudes using measurements from the psychologic and economics literature, suggesting that different genetic factors may underlie human response to risk faced in different behavioral domains.

Risk-Taking Behavior

Wang et al. (2009) presented evidence that propensity for risk-taking is influenced by variation in life history traits. A total of 448 mostly college-aged students, including 316 females and 132 males, provided information on risk-taking behavior, which was analyzed according to several life-history traits, including sex, age, parental status, reproductive goal setting, number of sibs, birth order, and subjective life expectancy. The domains examined included within- and between-group competition, mating and resource allocation, reproduction, and environmental challenge. Higher risk-taking was associated with male sex for all domains. Other associations with increased risk-taking propensity that varied by domain included younger age, lack of parental status, lower reproductive goals, being the last-born, and lower subjective life expectancy. The findings suggested that tendency for risk-taking is not necessarily a stable personality trait, but varies by life history traits and specific domains.

Inheritance

Developmental research has showed that the propensity for risk-taking is higher during adolescence compared to childhood and adulthood, and it has been suggested that this is due to the relative immaturity of neural connections involved in behavioral regulation and/or inhibition and decision making. Risk-taking in adolescence is associated with substance abuse, gambling, theft, aggression, and unprotected sex, and assessment of risk-taking can be used as an endophenotype for psychopathology in adolescence (review by Anokhin et al., 2009). Anokhin et al. (2009) evaluated 745 adolescent twin pairs, including 169 monozygotic (MZ) pairs and 203 dizygotic (DZ) pairs, using the Balloon Analogue Risk Task (BART) an experimental measure involving financial reward for risk taking. Risk-taking increased between 12 and 14 years of age overall, but also showed significant longitudinal stability for individuals. European Americans showed greater propensity for risk-taking compared to other ethnic groups, particularly African Americans. Genetic modeling showed that at age 12, heritability for risk-taking was modest but significant for both sexes (28% for males and 17% for females). However, at age 14, heritability increased to 55% in males and became nonsignificant in females. The findings indicated that there are age and sex differences in the heritability of risk-taking behavior, particularly during the years studied.

In a study of 920 Swedish twin pairs, including 141 DZ twins and 319 MZ twins, most (80%) of whom were female, Cesarini et al. (2009) estimated that approximately 20% of individual variation in economic preferences for financial giving and risk-taking can be explained by genetic differences. The findings were consistent with larger studies of behavior genetics, which have concluded that there is a genetic influence on behaviors.

Pathogenesis

Cloninger et al. (1993) proposed that individual variations in the novelty seeking trait are mediated by genetic variability in dopamine transmission. Individuals who score higher than average on the TPQ novelty seeking scale are characterized as impulsive, exploratory, fickle, excitable, quick-tempered, and extravagant, whereas those who score lower than average tend to be reflective, rigid, loyal, stoic, slow-tempered, and frugal.

In a study of 20 abstinent alcohol-dependent men, a significant correlation was found between apomorphine-induced growth hormone release and the 'novelty seeking' score of the individual (Wiesbeck et al., 1995). This supported Cloninger's hypothesis by giving neuroendocrine evidence that this personality dimension is related to dopaminergic activity, albeit in the tuberoinfundibular dopaminergic system which is not directly associated with human personality traits.

Molecular Genetics

Cloninger et al. (1996) contrasted the difference between a trait such as novelty seeking and developmentally complex disorders like schizophrenia (see 181500) which have been found to be very elusive in the delineation of genetic factors. They suggested that it may be more fruitful to map genes contributing to temperament, which have a relatively simple genetic architecture and can be quantified easily and reliably by questionnaire. Later, susceptibility to complex disorders like schizophrenia and alcoholism (see 103780) can be evaluated in terms of risk from heritable personality traits and possible disease-specific factors. In this way, success in mapping genes for a normal personality trait may signal a fruitful way to map genes for psychopathology as well.

Savitz and Ramesar (2004) reviewed the evidence that alleles of the SERT (182138) and DRD4 (126452) genes impact variations in personality. They argued for the existence of a genuine effect: a gene-personality relationship rendered periodically latent through genetic epistasis, gene-environment interactions, variation in genetic background, and the presence of other variables.

DRD4 Gene

In a group of 124 unrelated Israeli subjects, Ebstein et al. (1996) showed that higher than average novelty seeking test scores were significantly associated with a particular exonic polymorphism, the 7-repeat (7R) allele at the locus for the dopamine receptor D4 gene (DRD4; 126452). The association of high novelty seeking and the 7R allele was independent of ethnicity, sex, or age of the subjects. These results were corroborated by Benjamin et al. (1996) who investigated the relationship between DRD4 exon 3 sequence variants and personality test scores in a population of 315 mostly male sibs, other family members and individuals in the United States. The association between long alleles of exon 3 and personality traits related to novelty seeking was confirmed. Moreover, family studies showed that this association is the result of genetic transmission rather than a population stratification. Benjamin et al. (1996) pointed out that the possibility of a causal relationship between DRD4 and novelty seeking is supported by studies showing that the number of exon 3 repeats can affect the binding of ligands to the receptor; that DRD4 is expressed in limbic areas involved in cognition and emotion; that dopamine mediates exploratory behavior in experimental animals; that the rewarding effects of amphetamines and cocaine are related to dopamine release; and that novelty seeking is low in dopamine-deficient patients with Parkinson disease.

Pogue-Geile et al. (1998) administered personality questionnaires measuring novelty-seeking and positive emotional experience to 306 male and female young adult twins (92 monozygotic pairs; 61 dizygotic pairs) from the general population, 281 of whom were genotyped for DRD4 exon 1 and 3 polymorphisms. They found no significant association between novelty-seeking or positive emotional experience and the DRD4 polymorphisms. The statistical power of their study reduced confidence in the generality of the positive findings in earlier studies.

Kluger et al. (2002) conducted a metaanalysis of 20 studies, with a total of 3,907 individuals, involving the association between DRD4 polymorphisms and novelty seeking. Thirteen reports suggested that the presence of longer alleles is associated with higher novelty seeking scores and 7 reports suggested the opposite. Kluger et al. (2002) concluded that, on average, there was no association between DRD4 polymorphism and novelty seeking (average d = 0.06, 95% CI +/- 0.09). They found that there was true heterogeneity among the studies (i.e., unknown moderators exist), but that the strength of the association between DRD4 polymorphisms and novelty seeking in the presence of any moderator was likely to be weak. Kluger et al. (2002) also reported that a search for moderators had not yielded any reliable explanation for the variability among studies.

Dreber et al. (2009) noted that risk preferences may be influenced by dopaminergic pathways in the brain, which play a role in regulating the anticipation of rewards as well as the motivation for obtaining rewards. In a study of financial risk taking of 94 young men assessed through a game with real monetary payoffs, Dreber et al. (2009) found an association between the 7R allele polymorphism in the DRD4 gene and increased risk-taking. The DRD4 7R allele was estimated to account for about 20% of the heritable variation in financial risk-taking. In vitro studies have suggested that the receptor encoded by the DRD4 7R allele is associated with decreased ligand binding and requires higher levels of dopamine to produce a response of similar magnitude compared to smaller-sized repeats (Asghari et al., 1995). The findings were consistent with evolutionary selection for this allele for behaviors associated with migration and male competition, which entail an element of risk. In the study of Dreber et al. (2009), no association was found between risk taking and the A1 allele of the DRD2 gene (126450).

In a study of 65 individuals who performed a financial investment task, Kuhnen and Chiao (2009) found that carriers of the DRD4 7R allele polymorphism took 25% more risk in a financial investment risk game compared to individuals lacking the allele. The authors speculated that financial risk-taking may result from evolutionarily adaptive mechanisms that encourage novelty-seeking behavior (601696).

SLC6A4 Gene

In a study of 65 individuals who performed a financial investment task, Kuhnen and Chiao (2009) found an association between risk taking and variation in the SLC6A4 gene (182138), which regulates serotonin. Homozygous carriers of the short allele of the 5-HTTLPR SLC6A4 promoter polymorphism (182138.0001) took 28% less risk compared to those carrying the long allele. The short allele results in decreased transcriptional efficiency of SLC6A4 and has been associated with increased neuroticism and harm avoidance (see 607834).