Krisztina Ney

Dopamine D4 receptor (DRD4) gene polymorphism is associated with attachment disorganization in infants.

About 15% of one-year-old infants in non-clinical, low-risk and up to 80% in high-risk (eg maltreated) populations show extensive disorganized attachment behavior1, 2 in the Strange Situation Test.3 It has also been reported that disorganization of early attachment is a major risk factor for the development of childhood behavior problems.4 The collapse of organized attachment strategy has been explained primarily by inappropriate caregiving, but recently, the contribution of child factors such as neurological impairment5 and neonatal behavioral organization6 has also been suggested. Here we report an association between the DRD4 III exon 48-bp repeat polymorphism and attachment disorganization. Attachment behavior of 90 infants was tested in the Strange Situation and they were independently genotyped for the number of the 48-bp repeats by polymerase chain reaction (PCR). The 7-repeat allele was represented with a significantly higher frequency in infants classified as disorganized compared to non-disorganized infants: 12 of 17 (71%) vs 21 of 73 (29%) had at least one 7-repeat allele (χ2 = 8.66, df = 1, P < 0.005). The estimated relative risk for disorganized attachment among children carrying the 7-repeat allele was 4.15. We suggest that, in non-clinical, low-social-risk populations, having a 7-repeat allele predisposes infants to attachment disorganization.

Transmission Disequilibrium Tests Confirm the Link Between DRD4 Gene Polymorphism and Infant Attachment

Following up the results of a previous population association study (Lakatos et al. [2000: Mol Psychiatry 5:633–637; Lakatos et al. [2002: Mol Psychiatry 7:27–31]) by analyses based on parental genetic data confirmed the link between infant attachment and the dopamine D4 receptor (DRD4) gene. Extended transmission disequilibrium tests (ETDT) were performed to determine whether biased transmission of exon III 48 basepair repeat alleles occurred to infants displaying disorganized and secure attachment behavior with their mothers. The overall allele‐wise TDTs were significant for both groups (P = 0.038 and 0.020, respectively): a trend for preferential transmission of the seven‐repeat allele to disorganized infants was observed (TDT  χ 2  = 3.27, df = 1, P = 0.071), and there was a significant non‐transmission of the same allele to securely attached infants (TDT  χ 2  = 6.00, df = 1, P = 0.014). Analysis of haplotypes of the exon III repeat and the −521 C/T promoter polymorphisms in family trios showed that the transmission bias in the larger secure group was due to the low‐rate transmission of the T.7 haplotype containing both the seven‐repeat and the −521 T alleles (TDT  χ 2  = 4.46, df = 1, P = 0.035). This suggests that not carrying the T.7 haplotype of the DRD4 gene may act as a resilience factor in the optimal development of early attachment.