Ebstein RP, Novick O, Umansky R, Priel B, Osher Y, Blaine D et al. Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking. Nat Genet 12: 78-80
ABSTRACT Human personality traits which can be reliably measured by any of a number of rating scales, show a considerable heritable component. The tridimensional personality questionnaire (TPQ) is one such instrument and was designed by Cloninger to measure four distinct domains of temperament - Novelty Seeking, Harm Avoidance, Reward Dependence and Persistence-that are hypothesized to be based on distinct neurochemical and genetic substrates. Cloninger 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. We now show that higher than average Novelty Seeking test scores in a group of 124 unrelated Israeli subjects are significantly associated with a particular exonic polymorphism, the 7 repeat allele in the locus for the D4 dopamine receptor gene (D4DR). The association of high Novelty Seeking and the 7-repeat allele was independent of ethnicity, sex or age of the subjects. This work, together with the accompanying confirmations in this issue, provides the first replicated association between a specific genetic locus involved in neurotransmission and a normal personality trait.
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- " - ghari et al . , 1995 ) and possibly lower gene expression ( Schoots & Van Toll , 2003 ) . Behavioral research has conventionally fo - cused on the negative implications of this polymorphism . DRD4 7þ has been linked to attention - deficit disorder ( Far - aone & Mick , 2010 ; Rowe et al . , 1999 ) and novelty seeking ( Benjamin et al . , 1996 ; Ebstein et al . , 1996 ) . In addition to the genetic associations to behavior traits , DRD4 has been associated with differences in neurocognitive function as reflected by magnetic resonance imaging of re - gional brain activation patterns and connectivity patterns in the frontal cortex ( Gilsbach et al . , 2012 ) , an area critical for ex - ecutive control "
ABSTRACT: Data drawn from the in-home subsample of the PROSPER intervention dissemination trial were used to investigate the moderation of intervention effects on underage alcohol use by maternal involvement and candidate genes. The primary gene examined was dopamine receptor D4 (DRD4). Variation in this gene and maternal involvement were hypothesized to moderate the influence of intervention status on alcohol use. The PROSPER data used were drawn from 28 communities randomly assigned to intervention or comparison conditions. Participating youth were assessed in five in-home interviews from sixth to ninth grades. A main effect of sixth-grade pretest maternal involvement on ninth-grade alcohol use was found. Neither intervention status nor DRD4 variation was unconditionally linked to ninth-grade drinking. However, moderation analyses revealed a significant three-way interaction among DRD4 status, maternal involvement, and intervention condition. Follow-up analyses revealed that prevention reduced drinking risk, but only for youth with at least one DRD4 seven-repeat allele who reported average or greater pretest levels of maternal involvement. To determine if this conditional pattern was limited to the DRD4 gene, we repeated analyses using the serotonin transporter linked polymorphic region site near the serotonin transporter gene. The results for this supplemental analysis revealed a significant three-way interaction similar but not identical to that found for DRD4.Development and Psychopathology 02/2015; 27(1):51-67. DOI:10.1017/S0954579414001291 · 4.89 Impact Factor
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- "A genetic polymorphism associated with dopamine receptor D4 gene, DRD4 VNTR, is among the first candidate genes that molecular genetics research has shown to be related to approach-related traits and behaviors (Cloninger, Adolfsson, & Svrakic, 1996; Ebstein et al., 1996). We did not develop formal hypotheses on this genetic polymorphism because prior research has generated 4 Hardy–Weinberg Equilibrium tests were run for the sample broken down by age and gender. "
ABSTRACT: Trait theories of leadership have documented the role of individual characteristics in affecting leadership. Twin studies have further revealed significant genetic effects on leadership role occupancy. In the era of genomics, the current research examines how a dopamine transporter gene, DAT1, is involved in genetic influences on leadership role occupancy. Study 1 found DAT1 10-repeat allele to negatively relate to proactive personality, which in turn was positively associated with leadership role occupancy. The negative indirect effect was significant, but the overall relationship between this gene and leadership was not. In addition to replicating Study 1's findings using a nationally representative sample, Study 2 revealed another countervailing mechanism: DAT1 was positively related to (moderate) rule breaking, which was positively associated with leadership role occupancy. Consistent findings across the two studies suggest that the pathways linking specific genes to leadership are complex and a middle-ground approach is needed in such multidisciplinary investigations.The Leadership Quarterly 01/2015; DOI:10.1016/j.leaqua.2014.12.005 · 2.70 Impact Factor
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- "The 7-repeat allele is a known risk factor of ADHD (Wu et al., 2012) and children with ADHD are often characterized as being fearless and impulsive. " Long " DRD4 variants have also been associated with increased novelty seeking in healthy 3-years olds (Ebstein et al., 1996). Children with long DRD4 VNTRs who are at risk for ADHD might also exhibit a less fearful response to facing a stranger during a laboratory setting. "
ABSTRACT: Fear of strangers is a developmental milestone in childhood that encompasses behavioral inhibition and decreased novelty seeking. Children with attention deficit/hyperactivity disorder (ADHD) often exhibit fearless and impulsive behaviors, similar to those observed in children with atypically low levels of stranger fear. It is currently unknown whether these behaviors share common underlying biological mechanisms. Polymorphisms in the dopamine receptor 4 gene (DRD4) have been implicated in the risk for developing ADHD symptoms in childhood. Here we investigate whether (1) DRD4 variable number tandem repeats (VNTRs) are associated with both stranger fear and ADHD symptoms, and (2) stranger fear in preschoolers mediates the link between DRD4 VNTRs and ADHD in later childhood. Stranger fear was observed in a large sample (N=589) of 3-year-old Caucasian children and ADHD symptoms were assessed by a validated, mother-rated questionnaire at 6 years. We found evidence that longer DRD4 variants were associated with increased ADHD symptoms at 6 years, and that this relationship was partially mediated by lower levels of observed stranger fear at 3 years. Our results suggest a common underlying neurobiological mechanism in the association between low stranger fear and ADHD symptoms; variation in DRD4 may be an important contributor to this mechanism.Psychiatry Research 09/2014; 220(3). DOI:10.1016/j.psychres.2014.09.004 · 2.68 Impact Factor