Smoking is associated with poorer health outcomes for both African and European Americans. In order to better understand whether ethnic-specific genetic variation may underlie some of these differences, we compared the smoking-associated genome-wide methylation signatures of African Americans with those of European Americans, and followed up this analysis with a focused examination of the most ethnically divergent locus, cg19859270, at the GPR15 gene. We examined the association of methylation at this locus to the rs2230344 SNP and GPR15 gene and protein expression. Consistent with prior analyses, AHRR residue cg05575921 was the most differentially methylated residue in both African Americans and European Americans. However, the second most differentially methylated locus in African Americans, cg19859270, was only modestly differentially methylated in European Americans. Interrogation of the methylation status of this CpG residue found in GPR15, a chemokine receptor involved in HIV pathogenesis, showed a significant interaction of ethnicity with smoking as well as a marginal effect of genotype at rs2230344, a neighboring non-synonymous SNP, but only among African Americans. Gene and protein expression analyses showed that demethylation at cg19859270 was associated with an increase in both mRNA and protein levels. Since GPR15 is involved in the early stages of viral replication for some HIV-1 and HIV-2 isolates, and the prevalence of HIV is increased in African Americans and smokers, these data support a possible role for GPR15 in the ethnically dependent differential prevalence of HIV.

The current investigation was designed to examine the association of parenting during late childhood and early adolescence, a time of rapid physical development, with biological propensity for inflammation. Based on life course theory, it was hypothesized that parenting during this period of rapid growth and development would be associated with biological outcomes and self-reported health assessed in young adulthood. It was expected that association of parenting with health would be mediated either by effects on methylation of a key inflammatory factor, Tumor necrosis factor (TNF), or else by association with a pro-inflammatory shift in the distribution of mononuclear blood cells. Supporting expectations, in a sample of 398 African American youth residing in rural Georgia, followed from age 11 to age 19, parenting at ages 11-13 was associated with youth reports of better health at age 19. We found that parenting was associated with changes in TNF methylation as well as with changes in cell-type composition. However, whereas methylation of TNF was a significant mediator of the association of parenting with young adult health, variation in mononuclear white blood cell types was not a significant mediator of the association of parenting with young adult health. The current research suggests the potential value of examining the health-related effects of parenting in late childhood and early adolescence. Further examination of protection against pro-inflammatory tendencies conferred by parenting appears warranted.

Parent-child relationships with high conflict and low warmth and support are associated with later adverse behavioral and physiological child outcomes. These outcomes include shorter telomere lengths, the repetitive sequences at the ends of chromosomes that have been utilized as a biomarker for chronic stress. Our research group furthered this by exploring telomere length outcomes following a family-based prevention program and identified reduced telomere shortening 5 years post intervention among those originally exposed to nonsupportive parenting and randomized to the intervention condition. However, not all individuals respond equally, and a growing literature suggests genetic sensitivity to one's environment, with variations in the oxytocin receptor gene (OXTR) potentially influencing this sensitivity.

The stressors associated with poverty increase the risks for externalizing psychopathology; however, specific patterns of neurobiology and higher self-regulation may buffer against these effects. This study leveraged a randomized control trial, aimed at increasing self-regulation at ~11 years of age. As adults, these same individuals completed functional MRI scanning (Mage  = 24.88 years; intervention n = 44; control n = 49). Functional connectivity between the hippocampus and ventromedial prefrontal cortex was examined in relation to the intervention, gains in self-regulation, and present-day externalizing symptoms. Increased connectivity between these brain areas was noted in the intervention group compared to controls. Furthermore, individual gains in self-regulation, instilled by the intervention, statistically explained this brain difference. These results begin to connect neurobiological and psychosocial markers of risk and resiliency.

Neighborhood violence increases children's risk for a variety of health problems. Yet, little is known about biological pathways involved or neural mechanisms that might render children more or less vulnerable. Here, we address these questions by considering whether neighborhood violence is associated with the expression of a proinflammatory phenotype and whether this relationship is moderated by resting-state functional connectivity (rsFC) of the central executive network (CEN).

Rurally situated African Americans suffer from stress and drug-related health disparities. Unfortunately, research on potential mechanisms that underlie this public health problem have received limited focus in the scientific literature. This study investigated the effects of perceived stress, alcohol consumption, and genotype on the hypothalamic-pituitary-adrenal (HPA) Axis.

Psychosocial stress, including stress resulting from racial discrimination (RD), has been associated with elevated depressive symptoms. However, individuals vary in their reactivity to stress, with some variability resulting from genetic differences. Specifically, genetic variation within the linked promoter region of the serotonin transporter gene (5-HTTLPR) is related to heightened reactivity to emotional environmental cues. Likewise, variations within this region may interact with stressful life events (e.g., discrimination) to influence depressive symptoms, but this has not been empirically examined in prior studies. The objective of this study was to examine whether variation in the 5-HTTLPR gene interacts with RD to predict depressive symptoms among a sample of African-American adolescent females. Participants were 304 African-American adolescent females enrolled in a sexually transmitted disease prevention trial. Participants completed a baseline survey assessing psychosocial factors including RD (low vs. high) and depressive symptomatology (low vs. high) and provided a saliva sample for genotyping the risk polymorphism 5-HTTLPR (s allele present vs. not present). In a logistic regression model adjusting for psychosocial correlates of depressive symptoms, an interaction between RD and 5-HTTLPR group was significantly associated with depressive symptomatology (AOR = 3.79, 95% CI: 1.20-11.98, p = 0.02). Follow-up tests found that high RD was significantly associated with greater odds of high depressive symptoms only for participants with the s allele. RD and 5-HTTLPR status interact to differentially impact depressive symptoms among African-American adolescent females. Efforts to decrease depression among minority youth should include interventions which address RD and strengthen factors (e.g., coping, emotion regulation, building support systems) which protect youth from the psychological costs of discrimination.

Regular smoking is associated with a wide variety of syndromes with prominent inflammatory components such as cancer, obesity and type 2 diabetes. Heavy regular smoking is also associated with changes in the DNA methylation of peripheral mononuclear cells. However, in younger smokers, inflammatory epigenetic findings are largely absent which suggests the inflammatory response(s) to smoking may be dose dependent. To help understand whether peripheral mononuclear cells have a role in mediating these responses in older smokers with higher cumulative smoke exposure, we examined genome-wide DNA methylation in a group of well characterized adult African American subjects informative for smoking, as well as serum C-reactive protein (CRP) and interleukin-6 receptor (IL6R) levels. In addition, complementary bioinformatic analyses were conducted to delineate possible pathways affected by long-term smoking.

How the brain processes cigarette cost-benefit decision making remains largely unknown. Using functional magnetic resonance imaging (fMRI), this study investigated the neural correlates of decisions for cigarettes (0-10 cigarettes) at varying levels of price during a Cigarette Purchase Task (CPT) in male regular smokers (N = 35). Differential neural activity was examined between choices classified as inelastic, elastic, and suppressed demand, operationalized as consumption unaffected by cost, partially suppressed by cost, and entirely suppressed by cost, respectively. Decisions reflecting elastic demand, putatively the most effortful decisions, elicited greater activation in regions associated with inhibition and planning (e.g., middle frontal gyrus and inferior frontal gyrus), craving and interoceptive processing (anterior insula), and conflict monitoring (e.g., anterior cingulate cortex). Exploratory examination in a harmonized dataset of both cigarette and alcohol demand (N = 59) suggested common neural activation patterns across commodities, particularly in the anterior insula, caudate, anterior cingulate, medial frontal gyrus, and dorsolateral prefrontal cortex. Collectively, these findings provide initial validation of a CPT fMRI paradigm; reveal the interplay of brain regions associated with executive functioning, incentive salience, and interoceptive processing in cigarette decision making; and add to the literature implicating the insula as a key brain region in addiction.

Responsive parenting interventions that shape parenting behaviors in the areas of sleep and soothing, appropriate and responsive feeding, and routines represent a promising approach to early obesity prevention and have demonstrated effectiveness in our previous trials. However, this approach has yet to be applied to the populations most at-risk for the development of early obesity, including African Americans. The Sleep SAAF (Strong African American Families) study is a two-arm randomized controlled clinical trial evaluating whether a responsive parenting intervention focused on promoting infant sleeping and self-soothing can prevent rapid weight gain during the first 16 weeks postpartum among first-born African American infants. The responsive parenting intervention is compared to a child safety control intervention.