No abstract

Using an adoption design to collect data on biological and adoptive parents of children adopted at birth, this study explored a possible mechanism through which heritable characteristics of adopted children evoke adoptive parent responses and lead to reciprocal influences between adoptive parent and adopted child behavior. Participants were 25 male and 20 female adoptees, 12-18 years of age, having either a biological parent with substance abuse /dependency or antisocial personality or a biological parent with no such history. The study found that psychiatric disorders of biological parents were significantly related to children's antisocial/hostile behaviors and that biological parents' psychiatric disorders were associated with adoptive parents' behaviors. This genotype-environment association was largely mediated by adoptees' antisocial / hostile behaviors. Results also suggest that the adoptee's antisocial/hostile behavior and adoptive mother's parenting practices affect each other.Genetic factors are frequently hypothesized to be involved in the way children select, modify, and create the environments that they experience (Scarr & McCartney, 1983). Although emerging evidence from a behavioral genetic perspective during the past decade suggests that heritable characteristics of children influence measures of family environment (e.g., Hur &

Environmental effects and genetic-environmental interaction account for significant variability in adoptee aggressivity, conduct disorder, and adult antisocial behavior and have important implications for the prevention and intervention of conduct disorder and associated conditions such as substance abuse and aggressivity.

This study confirms the model of two independent genetic factors involved in drug abuse/dependence and previous findings that disturbed adoptive parents are associated with adoptee drug abuse/dependency.

The serotonin reuptake transporter (5HTT) is thought to be the principal regulator of serotonergic activity and epigenetic effects at this locus are thought to be important moderators of vulnerability to neuropsychiatric illness. In attempt to understand the basis of this regulation, several gene polymorphisms that affect 5HTT mRNA levels have been described. But to date, no clear mechanism linking these polymorphisms to vulnerability to epigenetic effects have been described. In this communication, we describe a CpG island in the 5 0 region of the 5HTT gene that contains an alternative exon 1 and possible promoter for 5HTT. We then confirm the existence of this transcript and ascertain the methylation status of this CpG island in 49 lymphoblast cell lines and analyze the relationship between methylation and 5HTT mRNA levels. We demonstrate that methylation at this CpG island is associated with decreased levels of 5HTT mRNA, but that this effect is evident only when 5HTTLPR genotype is taken into account. We suggest that these findings have significant implications for the understanding of the role of this locus in behavioral illness. INTRODUCTIONThe serotonin transporter (5HTT) located at 17q11 is thought to be a major regulator of serotonergic neurotransmission and thereby vulnerability to behavioral illness. In efforts to determine whether genetic variation at 5HTT contributes variation in serotonin reuptake, a large number of studies have been conducted. To a large extent, these studies have failed to demonstrate a significant role for coding variants in regulating serotonin re-uptake. In contrast, several studies have demonstrated that non-coding variants have a significant role in regulating serotonin transport by altering 5HTT mRNA levels. The best characterized of these non-coding variants, the 5HTTLPR polymorphism, has effects on 5HTT mRNA levels in lymphoblasts Bradley et al., 2005], in platelet serotonin reuptake [Greenberg et al., 1999;Nobile et al., 1999] and platelet serotonin content [Hanna et al., 1998]. Other non-coding variants including the recently reported Long G polymorphism [Hu et al., 2005] and an intron 2 polymorphism denoted as the STin2 variable number tandem repeat (VNTR) [Hranilovic et al., 2004] also may have effects on serotonin mRNA production, although these effects are less well established.Given the importance of this gene in regulating serotonergic neurotransmission, at least several hundred studies have examined the role of the genetic variation in 5HTT, in particular, the 5HTTLPR polymorphism, in mediating vulnerability to neuropsychiatric illness such as depression, schizophrenia, and autism. The results of these studies have been mixed, with many studies inferring that the 5HTTLPR polymorphism may have effect on vulnerability to a broad range of behavioral illnesses [Conroy et al., 2004;Gorwood, 2004;Lotrich and Pollock, 2004;Savitz and Ramesar, 2004]. However, with the exception of alcoholism and schizophrenia [Fan and Sklar, 2005;Lasky-Su et al., 2005], meta-analyses of...