Dopamine D4 receptor and serotonin transporter promoter in the determination of neonatal temperament

Abstract

Genetic effects on behavior were evaluated at a time in early development when we hypothesized that environmental influences are minimal and least likely to confound associations between temperament and genes. The behavioral effects of two common polymorphisms linked respectively in some, but not all, studies to novelty seeking (dopamine D4 receptor -D4DR) and neuroticism and harm avoidance (serotonin transporter promoter region -STPR) were examined in a group of 81 two-week-old neonates. Neonate temperament was evaluated using the Brazelton neonatal assessment scale (NBAS). Multivariate tests of significance showed a significant association of D4DR across four behavioral clusters pertinent to temperament including orientation, motor organization, range of state and regulation of state. A significant multivariate interaction was also observed between D4DR and STPR. The effect of the homozygous short STPR genotype (s/s) was to lower the orientation score for the group of neonates lacking the long form (L) of D4DR. When adult subjects were grouped by the STPR polymorphism there is no significant effect of L-D4DR in those subjects homozygous for the STPR short form (s/s) whereas in the group without the homozygous genotype the effect of L-D4DR is significant and accounts for 13% of the variance in novelty seeking scores between groups.

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)

“…The current results are consistent with an earlier study 8 in which we demonstrated an interaction between the 5-HTTLPR and DRD4 seven-repeat on Brazelton Orientation scores (perhaps a putative antecedent temperament of adult NS) in 2-week-old neonates. At 2 months of age, these children were again assessed 7 using the Infant Behavioral Questionnaire 17 and a significant interaction between the DRD4 sevenrepeat × 5-HTTLPR promoter region polymorphisms on Negative Emotionality and Distress to Limitations was observed.…”

“…[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][7][8] and others, [9][10][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.…”

Dopamine D4 Receptor Gene Novelty or Nonsense?

“…This includes 46 items scored on 4-or 9-point cases, which are reduced to seven summary core clusters, six of which were used (orientation, motor organization, range of state and state regulation, autonomic stability, and reflexes; Ebstein et al 1998). Univariate tests produced only one result that remains significant after correction for seven comparisons for the DRD4 VNTR and orientation (uncorrected p ϭ .00038).…”

“…However, such levels of significance are not appropriate for current studies. Finally, when interactions between polymorphisms of different candidate genes are investigated (e.g., Ebstein et al 1997cEbstein et al , 1998) the number of potential tests rises exponentially, and positive results should be interpreted with great caution.…”

Association between the dopamine D4 receptor (DRD4) exon III polymorphism and measures of Novelty Seeking in a German population

“…Ebstein and colleagues report a somewhat parallel relationship. 25 In adult subjects without the short form of the 5-HTTLPR, which is supposed to have an influence on anxiety-related traits, 26 they observed a more pronounced effect of long DRD4 alleles. In our cohort, HA and NS subscales are moderately negatively correlated (r −0.20 to −0.44, P Ͻ 0.05).…”