It has also been shown that disorganization of early attachment is a major risk factor for the development of childhood behavior problems. Attachment disorganization has been supposed to be specifically related to the infant-caregiver relationship. The only child factors that have previously been found to predict disorganized attachment in a non-clinical, low-risk population are poor neonatal orientation and emotional regulation. In the authorsÕ previous report the authors suggested that a certain structural variant of the dopamine D4 receptor (DRD4) gene might impose a risk on development of disorganized attachment. The dopamine D4 receptor gene has already been associated with pathological impulsive, compulsive behavior, substance abuse in adults, and with infant temperament traits of negative emotionality and maladaptive behavioral problems, especially attention deficit hyperactivity disorder (ADHD) in children.
The authors have previously reported an association between the DRD4 III exon 48 basepair repeat polymorphism and attachment disorganization. The 7 repeat allele was significantly more frequent among infants with disorganized attachment behavior compared to non-disorganized infants. The estimated relative risk for disorganized attachment was 4-fold among children carrying the 7-repeat allele. In this report Hungarian scientists show the modifying effect of a single nucleotide polymorphism (-521 C/T) in the regulatory region of the same DRD4 gene. It has been known from a previous report that the -521 T allele reduces the rate of transcription of the DRD4 gene by approximately 40% compared to the -521 C variant, suggesting the functional relevance of this polymorphism for dopaminergic neurotransmission. By genotyping infants for both the length and the regulatory polymorphisms of the DRD4 gene, the authors found that the association between disorganized attachment and the 7-repeat allele was enhanced in the presence of the -521 T allele. In the presence of both risk alleles the relative risk for disorganized attachment increased 12-fold. This result supports the authorsÕ previous postulate that DRD4 is a genetic susceptibility factor for the atypical development of attachment behavior in low-risk, non-clinical populations.
ARTICLE: "Further evidence for the role of the dopamine D4 receptor (DRD4) gene in attachment disorganization: interaction of the exon III 48 bp repeat and the Ð521 C/T promoter polymorphisms"
AUTHORS: K Lakatos , Z Nemoda , I Toth , Z Ronai , K Ney , M Sasvari-Szekely , J Gervai
Institute of Psychology, Social Development Group, Hungarian Academy of Sciences and Institute of Medical Chemistry, Molecular Biology and Pathobiochemisty, Semmelweis University, Budapest, Hungary
Citation source: Molecular Psychiatry 2001 Volume 7, number 1, pages 27-31.
For further information on this work, please contact Judit Gervai PhD, Senior Research Fellow, Head of the Social Development Group, Institute of Psychology, Hungarian Academy of Sciences, Mail: 1394 Budapest, POB 398. Hungary, Tel.: +36-1-239 3864, Fax: +36-1-239 6727; e-mail: gervju@mtapi.hu
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