The Association of the Dopamine D4 Receptor Gene (DRD4) and the Serotonin Transporter Promoter Gene (5‐HTTLPR) with Temperament in 12‐month‐old Infants

Abstract

This study examined the association between two common polymorphisms, the dopamine D4 receptor (DRD4) gene and the serotonin transporter promoter (5-HTTLPR) gene and temperament in 61 infants aged 12 months. Twenty-two infants had a least one copy of the 6-8 repeat DRD4 alleles (L-DRD4) and 39 had two copies of the 2-5 repeat allele (S-DRD4). Twenty infants were homozygous for the short form (s/s) of 5-HTTLPR while 41 were either heterozygous for the short and the long form (l/s) or were homozygous for the long form (l/l). The infants were observed in a series of standard temperament episodes that elicited fear, anger, pleasure, interest, and activity. L-DRD4 infants showed less interest in a structured block play situation and more activity in a free play situation. They also displayed less anger in an episode of mild physical restraint. Infants with s/s 5-HTTLPR showed less fearful distress to stranger approach and less pleasure in a structured play situation than infants with l/l or l/s 5-HTTLPR. Duration of looking during block play was affected by a significant interaction between DRD4 and 5-HTTLPR. Shortest duration of looking was associated with the L-DRD4 and s/s 5-HTTLPR genotypes. The implications and limitations of these findings are discussed.

Neuroimaging studies of serotonin gene polymorphisms: Exploring the interplay of genes, brain, and behavior

“…Since this original report, others have confirmed the association between the 5-HTTLPR short allele and heightened anxiety (Du, Bakish, & Hrdina, 2000;Katsuragi et al, 1999;Mazzanti et al, 1998;Melke et al, 2001;Munafo, Clark, & Flint, 2005;Schinka, Busch, & Robichaux-Keene, 2004;Sen, Burmeister, & Ghosh, 2004) and have also demonstrated that individuals possessing the short allele more readily acquire conditioned fear responses (Garpenstrand, Annas, Ekblom, Oreland, & Fredrikson, 2001) and develop affective illness (Lesch & Mössner, 1998), in comparison with individuals homozygous for the long allele. Infants homozygous for the S allele have similar increases in anxiety-related measures (Auerbach, Faroy, Ebstein, Kahana, & Levine, 2001;Auerbach et al, 1999).…”

Biological Systems and the Development of Self-Regulation: Integrating Behavior, Genetics, and Psychophysiology

“…83,84 However, most of the evidence points to a critical role of serotonin neurotransmitter genes. In particular, a transporter gene (5-HTTLPR) and a gene involved in the production of an enzyme that constrains serotonin production (TPH) are associated with individual differences in anger, fear, anxiety, depression, and trait neuroticism.…”

Prenatal maternal depression and child serotonin transporter linked polymorphic region (5-HTTLPR) and dopamine receptor D4 (DRD4) genotype predict negative emotionality from 3 to 36 months

“…Auerbach and colleagues (1999) report lower ratings of NE, distress towards limitations and distress to novel stimuli on the Infant Behavior Questionnaire (IBQ) at 2 months in carriers of the 6-8R allele than in carriers of the 2-5R allele. At 12 months, infants with the 6-8R allele show less active resistance, and struggle less than infants with the 2-5R (Auerbach et al, 2001b). However, the reverse has also been reported, with evidence that infants with the 7R allele are higher on NE as measured by the IBQ at 4 and 9 months of age (Holmboe et al, 2011), show less novelty preference at 12 months (Auerbach et al, 2001a), and show increased latency to accept a toy from strangers at 12 months (Lakatos et al, 2003).…”

“…There is also some evidence indicating that carriers of the low expressing S allele rate higher in NE than LL carriers (Auerbach et al, 1999;Hayden et al, 2010;Hayden et al, 2007). For example, infants with the SS genotype are reported to rate higher in NE at 2 months (Auerbach, et al, 1999), higher in fearful temperament during childhood (Hayden et al, 2007), and higher in NE in the presence of low positive emotionality during childhood (Hayden et al, 2010).Functional variants in the dopamine D4 receptor (DRD4) are also associated with NE (Auerbach et al, 1999;Auerbach, Benjamin, Faroy, Geller & Ebstein, 2001a;Auerbach, Faroy, Ebstein, Kahana, & Levine, 2001b). There is a 48-base pair variable number tandem repeats in exon 3 of the DRD4 gene ranging from 2 to 11 copies.…”