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

Abstract

About 15% of one-year-old infants in non-clinical, lowrisk and up to 80% in high-risk (eg maltreated) populations show extensive disorganized attachment behavior 1,2 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 impairment 5 and neonatal behavioral organization 6 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 ( 2 = 8.66, df = 1, P Ͻ 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. Molecular Psychiatry (2000) 5, 633-637.The first publications on association between DRD4 receptor III exon polymorphism and the adult personality trait, Novelty Seeking, 7,8 were soon followed by reports demonstrating associations of the same polymorphism with pathological impulsive, compulsive behavior and substance abuse in adults 9-11 and attention deficit hyperactivity disorder (ADHD) in children. 12,13 There is a growing body of evidence linking maladaptive behavioral problems in children (and extending into adulthood) with the 7-repeat allele of the DRD4 gene.Early attachment between infant and caregiver has been considered essential for survival in the human species. 14 Attachment theory provided a widely used framework for explaining influences of early social experiences on normal and problematic development of personality. 15 Ainsworth and colleagues 3 devised an experimental procedure, the Strange Situation, and described marked individual differences in infants' coping with the stress elicited by the two brief separations from the caregiver. The three basic, coherently organized patterns of infant behavior after reunion (secure, insecure-avoidant, insecure-resistant, see Methods) have been regarded as adaptations to the experienced differences in caregiving. 16 About 15% of infants in non-clinical, low-risk and up to 80% in highsocial-risk (eg maltreated) populations were difficult to fit in the three established categories. These 'atypical' infants showed incoherent, contradictory behavior in the presence of the caregiver as if their behavioral strategy collapsed under the stress of the Strange Situation. A new organizational dimension of at...

Association of D4 dopamine receptor gene and serotonin transporter promoter polymorphisms with infants' response to novelty

“…In both VNTR polymorphisms dGTP was replaced with dITP in 50% in order to avoid allelic drop-out in heterozygotes. 32 DRD4 48 bp VNTR genotype and allele frequencies in the BIPS sample population were the same as previously reported, 21 and were similar to the frequencies recently determined in a larger Hungarian population, showing a good agreement with the Hardy-Weinberg equilibrium (P40.9). 33 Frequencies of the 14-and the 16-repeat 5-HTTLPR alleles in the BIPS sample were 0.394 and 0.606, respectively.…”

“…Signed informed consent was obtained from the parents for participating in the whole study, and again from 95 parents separately for the genetic investigation (five more cheek cell samples were received after publication of our previous report). 21 The remaining families either moved away by the time of the DNA sampling or the children refused to allow the collection of cheek cells. The sex ratio and infant characteristics in the participating and the 'drop-out' families did not differ significantly.…”

“…Attachment classification: Videotapes of the Strange Situation 30 were evaluated for attachment disorganization as described earlier by Lakatos et al 21 Each infant was rated on a nine-point scale and those with a D-score X5 were classified as disorganized (D).…”

“…20 An effect of the DRD4 III exon repeat polymorphism has recently been associated with disorganized attachment: we found a higher frequency of the DRD4 7-repeat allele in one-year-old infants whose attachment to the mother was classified as disorganized/disoriented. 21 Here we report the combined effects of the D4DR and the 5-HTTLPR VNTR polymorphisms on infant temperament at 12 months of age. In a longitudinal study of infants' behavioral development, we have assessed temperament by means of maternal reports on Rothbart's Infant Behavior Questionnaire (IBQ) 22 at 9 and 12 months, and by observing infants' initial responses to novelty in the laboratory at 12 months.…”

Disorganized attachment in infancy: a review of the phenomenon and its implications for clinicians and policy-makers

“…These other pathways often feature frightening, frightened, and dissociative parental behaviors, which are more common among caregivers struggling with unresolved loss/trauma or multiple compounded socioeconomic risks. Other causal conditions include major (extended or repeated) separations under adverse conditions, and congenital factors, possibly in combination with caregiver factors (Lakatos et al, 2000; Padrón et al, 2014; Spangler et al 1996). …”