Man Kit Lei

Social Environmental Variation, Plasticity Genes, and Aggression: Evidence for the Differential Susceptibility Hypothesis

Although G×E studies are typically based on the assumption that some individuals possess genetic variants that enhance their vulnerability to environmental adversity, the differential susceptibility perspective posits that these individuals are simply more susceptible to environmental influence than others. An important implication of this model is that those persons most vulnerable to adverse social environments are the same ones who reap the most benefit from environmental support. The present study tested several implications of this proposition. Using longitudinal data from a sample of several hundred African Americans, we found that relatively common variants of the dopamine receptor gene and the serotonin transporter gene interact with social environmental conditions to predict aggression in a manner consonant with differential susceptibility. When the social environment was adverse, individuals with these genetic variants manifested more aggression than other genotypes, whereas when the environment was supportive they demonstrated less aggression than other genotypes. Further, we found that these genetic variants interact with environmental conditions to foster various cognitive schemas and emotions in a manner consistent with differential susceptibility and that a latent construct formed by these schemas and emotions mediated the effect of gene by environment interaction on aggression.Although gene by environment studies are typically based on the assumption that some individuals possess genetic variants that enhance their vulnerability to environmental adversity, the differential susceptibility perspective posits that these individuals are simply more susceptible to environmental influence than others. An important implication of this perspective is that individuals most vulnerable to adverse social environments are the same ones who reap the most benefit from environmental support. Using longitudinal data from a sample of several hundred African Americans, we found that relatively common variants of the dopamine receptor gene and the serotonin transporter gene interact with social conditions to predict aggression in a manner consonant with the differential susceptibility perspective. When social conditions were adverse, individuals with these genetic variants manifested more aggression than other genotypes, whereas when the environment was favorable they demonstrated less aggression than other genotypes. Furthermore, we found that these genetic variants interact with environmental conditions to foster schemas and emotions consistent with the differential susceptibility perspective and that a latent construct formed by these schemas and emotions mediates the gene by environment interaction on aggression.

Changes in DNA methylation at the aryl hydrocarbon receptor repressor may be a new biomarker for smoking.

BackgroundSmoking is the largest preventable cause of morbidity and mortality in the United States. In previous work, we demonstrated that altered DNA methylation at the aryl hydrocarbon receptor repressor (AHRR) is correlated with self-reported smoking in 19-year-old African Americans with relatively low levels of smoking. However, one limitation of the prior work is that it was based on self-reported data only. Therefore, the relationship of AHRR methylation to smoking in older subjects and to indicators such as serum cotinine levels remains unknown. To address this question, we examined the relationship between genome- wide DNA methylation and smoking status as indicated by serum cotinine levels in a cohort of 22-year-old African American men.ResultsConsistent with prior findings, smoking was associated with significant DNA demethylation at two distinct loci within AHRR (cg05575921 and cg21161138) with the degree of demethylation being greater than that observed in the prior cohort of 19-year-old smoking subjects. Additionally, methylation status at the AHRR residue interrogated by cg05575921 was highly correlated with serum cotinine levels (adjusted R2 = 0.42, P < 0.0001).ConclusionsWe conclude that AHRR DNA methylation status is a sensitive marker of smoking history and could serve as a biomarker of smoking that could supplement self-report or existing biomarker measures in clinical or epidemiological analyses of the effects of smoking. In addition, if properly configured as a clinical assay, the determination of AHRR methylation could also be used as a screening tool in efforts to target antismoking interventions to nascent smokers in the early phases of smoking.

Differential Susceptibility to Parenting Among African American Youths: Testing the DRD4 Hypothesis

To test the differential susceptibility to parenting hypothesis, a 4-wave, randomized prevention design was used to examine the impact of the Strong African American Families program on past-month substance use across 29 months as a function of DRD4 genotype. Youths (N = 337; M age = 11.65 years) were assigned randomly to treatment condition. Those carrying a 7-repeat allele showed greater differential response to intervention vs. control than those with two 4-repeat alleles. Control youths but not treatment youths with a 7-repeat allele reported increases in past-month substance use across the 29-month study period, but this pattern did not emerge for those with the 4-repeat allele. Supporting the differential susceptibility to parenting hypothesis, the results suggest a greater preventive effect for youths carrying a 7-repeat allele, a role for DRD4 in the escalation of substance use during adolescence, and potential for an enhanced understanding of early-onset substance use.

Perceived Discrimination among African American Adolescents and Allostatic Load: A Longitudinal Analysis with Buffering Effects.

This study was designed to examine the prospective relations of perceived racial discrimination with allostatic load (AL), along with a possible buffer of the association. A sample of 331 African Americans in the rural South provided assessments of perceived discrimination from ages 16 to 18 years. When youth were 18 years, caregivers reported parental emotional support and youth assessed peer emotional support. AL and potential confounder variables were assessed when youth were 20. Latent growth mixture modeling identified two perceived discrimination classes: high and stable, and low and increasing. Adolescents in the high and stable class evinced heightened AL even with confounder variables controlled. The racial discrimination to AL link was not significant for young adults who received high emotional support.

SOCIAL ADVERSITY, GENETIC VARIATION, STREET CODE, AND AGGRESSION: A GENETICLLY INFORMED MODEL OF VIOLENT BEHAVIOR

Although the diathesis-stress model guides most genetically informed behavior science, the present study investigates the hypotheses derived from the differential susceptibility perspective. This model posits that those persons most vulnerable to adverse social environments are the same ones who reap the most benefit from environmental support. Using longitudinal data from a sample of several hundred African American males, we examined the manner in which variants in 3 genes—5-serotonin transporter gene (5-HTT), dopamine receptor gene (DRD4), and monoamine oxidase gene (MAOA)—modulate the effect of community and family adversity on adoption of the street code and aggression. We found strong support for the differential susceptibility perspective.

Relational schemas, hostile romantic relationships, and beliefs about marriage among young African American adults

The present study tests a developmental model designed to explain the romantic relationship difficulties and reluctance to marry often reported for African Americans. Using longitudinal data from a sample of approximately 400 African American young adults, we examine the manner in which race-related adverse experiences during late childhood and early adolescence give rise to the cynical view of romantic partners and marriage held by many young African Americans. Our results indicate that adverse circumstances disproportionately suffered by African American youth (viz., harsh parenting, family instability, discrimination, criminal victimization, and financial hardship) promote distrustful relational schemas that lead to troubled dating relationships, and that these negative relationship experiences, in turn, encourage a less positive view of marriage.

Neighborhood Poverty and Allostatic Load in African American Youth

OBJECTIVE: This study was designed to determine whether living in a neighborhood in which poverty levels increase across adolescence is associated with heightened levels of allostatic load (AL), a biological composite reflecting cardiometabolic risk. The researchers also sought to determine whether receipt of emotional support could ameliorate the effects of increases in neighborhood poverty on AL. METHODS: Neighborhood concentrations of poverty were obtained from the Census Bureau for 420 African American youth living in rural Georgia when they were 11 and 19 years of age. AL was measured at age 19 by using established protocols for children and adolescents. When youth were 18, caregivers reported parental emotional support and youth assessed receipt of peer and mentor emotional support. Covariates included family poverty status at ages 11 and 19, family financial stress, parental employment status, youth stress, and youths’ unhealthful behaviors. RESULTS: Youth who lived in neighborhoods in which poverty levels increased from ages 11 to 19 evinced the highest levels of AL even after accounting for the individual-level covariates. The association of increasing neighborhood poverty across adolescence with AL was not significant for youth who received high emotional support. CONCLUSIONS: This study is the first to show an association between AL and residence in a neighborhood that increases in poverty. It also highlights the benefits of supportive relationships in ameliorating this association.

Impact of child sex abuse on adult psychopathology: A genetically and epigenetically informed investigation

Genetic, environmental, and epigenetic influences and their transactions were examined in a sample of 155 women from the Iowa adoptee sample who had been removed from their biological parents shortly after birth and assessed when participants were an average of 41.10 years old. We observed an interactive effect of child sex abuse (CSA) and biological parent psychopathology (i.e., genetic load) on substance abuse as well as a main effect of CSA on substance abuse in adulthood. We also observed main effects of CSA and genetic load on depression and on antisocial characteristics. As predicted, CSA, but not genetic load or later substance abuse, was associated with epigenetic change. In addition, the interaction between genetic load and CSA predicted epigenetic change, indicating a potential genetic basis for a differential impact of CSA on epigenetic change. Finally, epigenetic change partially mediated the effect of CSA on antisocial characteristics. The results suggest the relevance of genetic and epigenetic processes for future theorizing regarding marital and family precursors of several forms of adult psychopathology. Implications for preventive intervention are discussed.

Parenting, Socioeconomic Status Risk, and Later Young Adult Health: Exploration of Opposing Indirect Effects via DNA Methylation.

A sample of 398 African American youth, residing in rural counties with high poverty and unemployment, were followed from ages 11 to 19. Protective parenting was associated with better health, whereas elevated socioeconomic status (SES) risk was associated with poorer health at age 19. Genome-wide epigenetic variation assessed in young adulthood (age 19), was associated with both SES risk and protective parenting. Three categories of genes were identified whose methylation was associated with parenting, SES risk, and young adult health. Methylation was a significant mediator of the impact of parenting and SES risk on young adult health. Variation in mononuclear white blood cell types was also examined and controlled, showing that it did not account for observed effects of parenting and SES risk on health.

Exposure to harsh parenting and pornography as explanations for males' sexual coercion and females' sexual victimization

Sexual violence against women is a major concern to researchers and policy makers, as well as to the general public. This study uses a sample of more than 2,000 college students to investigate the extent to which exposure to harsh parenting practices and sexually explicit materials contributes to perpetration and victimization. Findings indicate that frequent corporal punishment in the family of origin combined with consumption of pornographic materials increased the probability that males reported engaging in coercive sexual practices. For females, both frequent corporal punishment and exposure to paternal hostility combined with consumption of pornographic materials were associated with higher levels of reported sexual victimization. These results provide increased understanding of the impact of pornography use among a nonclinical sample, as well as the consequences of experiencing harsh corporal punishment in one’s family of origin, on the sexual victimization of females.