The proposed research collaboration between the Hungarian scientist Dr. M. Sasvari- Szekely and U.S. investigator Dr. K. Lyons-Ruth provides an important opportunity to explore genetic and environmental risk and/or protective factors in the development of the impulsive behavioral pattern of Antisocial and Borderline Personality Disorders (APD and BPD). In the previous FIRCA grant (Genetic and Caregiving Effects on Disordered Attachment # 1 R03 TW006014-01) the potential genetic effect of the dopamine D4 receptor gene and the serotonin transporter gene polymorphisms were assessed with respect to the quality of mother-infant interaction and infant disorganized attachment behavior. In addition to attachment data, genetic influences on adolescent psychopathology were analyzed. The preliminary genetic analyses of Axis II psychopathology based upon the examination of the first 83 young adults' data. These results showed that participants homozygous for the short 5-HTTLPR allele (s/s genotype) were more likely to display BPD or APD traits in early adulthood. Male gender and quality of care in infancy were associated with a prevalence for BPD and APD traits, as well, but did not account for the association with the short allele. The present FIRCA application seeks to confirm and extend these early findings through conducting a more detailed genetic analysis of the serotonergic neurotransmitter system associated with these impulsive self- and other-damaging behaviors. In addition, an independent population would be assessed by the Hungarian research group. Genotyping the above polymorphisms and collecting similar data on the young adults' psychopathology will enable us to verify and extend our preliminary results. Both conduct problems and the impulsive self-damaging behavioral patterns associated with borderline personality disorders impose high costs on society. Aggressive behaviors in early childhood have been shown to maintain a high rate of persistence throughout the school years and adulthood, with associated morbidities in academic impairment, delinquency, and criminal activity. Combining developmental attachment and genetic assessments has the potential to uniquely further our understanding of the family factors that may enhance or moderate genetic risk for these serious self or other damaging behaviors. ? ? ?
