Detroit Neighborhood Health Study Research Articles

Does biological age mediate the relationship between childhood adversity and depression? Insights from the Detroit Neighborhood Health Study

The link between childhood adversity and adulthood depression is well-established; however, the underlying mechanisms are still being explored. Recent research suggests biological age may mediate the relationship between childhood adversity and depression in later life. This study examines if biological age mediates the relationship between childhood adversity and depression symptoms using an expanded set of biological age measures in an urban population-based cohort. Data from waves 1–3 of the Detroit Neighborhood Health Study (DNHS) were used in this analysis. Questions about abuse during childhood were coded to form a childhood adversity score similar to the Adverse Childhood Experience measure. Multiple dimensions of biological age, defined as latent variables, were considered, including systemic biological age (GrimAge, PhenoAge), epigenetic age (Horvath, SkinBlood), and immune age (cytomegalovirus, herpes simplex virus type 1, C-reactive protein, interleukin-6). Depression symptoms, modeled as a latent variable, were captured through the Patient Health Questionnaire-9 (PHQ-9). Models were adjusted for age, gender, race, parent education, and past depressive symptoms. Total and direct effects of childhood adversity on depression symptoms and indirect effects mediated by biological age were estimated. For total and direct effects, we observed a dose-dependent relationship between cumulative childhood adversity and depression symptoms, with emotional abuse being particularly influential. However, contrary to prior studies, in this sample, we found few direct effects of childhood adversity on biological age or biological age on depression symptoms and no evidence of mediation through the measures of biological age considered in this study. Further research is needed to understand how childhood maltreatment experiences are embodied to influence health and wellness.

The effect of residential proximity to brownfields, highways, and heavy traffic on serum metal levels in the Detroit Neighborhood Health Study.

Research in environmental sciences has demonstrated that land in close proximity to brownfields and heavily trafficked highways is contaminated with toxic metals. Despite this, little is known about the influence of brownfields and highways on metal levels in residents living nearby. We used data from 774 participants in the Detroit Neighborhood Health Study to estimate the effect of residential proximity to brownfields, highways, and present-day traffic on serum levels of lead, mercury, manganese, and copper using generalized estimating equations. We found that a 1 standard deviation increase in residential brownfield density within 200m was associated with increased serum lead levels (β: 0.04, 95% CI: -0.01, 0.09). The same modeled increase in a subset of historic industrial-use brownfields was associated with elevated serum mercury (β: 0.06, 95% CI: 0.03, 0.09). Increased highway and traffic density was positively associated with serum manganese (β: 0.02, 95% CI: 0.01, 0.04). Highway and traffic density was also positively associated with serum lead (β: 0.02, 95% CI: 0.01, 0.03) after restricting the analysis to participants who did not move during the study follow-up period. These findings draw attention to the importance of remediating polluted post-industrial sites in heavily populated areas, particularly as residents continue to move into densely populated cities around the globe.

Serum lead, mercury, manganese, and copper and DNA methylation age among adults in Detroit, Michigan.

Although the effects of lead, mercury, manganese, and copper on individual disease processes are well understood, estimating the health effects of long-term exposure to these metals at the low concentrations often observed in the general population is difficult. In addition, the health effects of joint exposure to multiple metals are difficult to estimate. Biological aging refers to the integrative progression of multiple physiologic and molecular changes that make individuals more at risk of disease. Biomarkers of biological aging may be useful to estimate the population-level effects of metal exposure prior to the development of disease in the population. We used data from 290 participants in the Detroit Neighborhood Health Study to estimate the effect of serum lead, mercury, manganese, and copper on three DNA methylation-based biomarkers of biological aging (Horvath Age, PhenoAge, and GrimAge). We used mixed models and Bayesian kernel machine regression and controlled for participant sex, race, ethnicity, cigarette use, income, educational attainment, and block group poverty. We observed consistently positive estimates of the effects between lead and GrimAge acceleration and mercury and PhenoAge acceleration. In contrast, we observed consistently negative associations between manganese and PhenoAge acceleration and mercury and Horvath Age acceleration. We also observed curvilinear relationships between copper and both PhenoAge and GrimAge acceleration. Increasing total exposure to the observed mixture of metals was associated with increased PhenoAge and GrimAge acceleration and decreased Horvath Age acceleration. These findings indicate that an increase in serum lead or mercury from the 25th to 75th percentile is associated with a ∼0.25-year increase in two epigenetic markers of all-cause mortality in a population of adults in Detroit, Michigan. While few of the findings were statistically significant, their consistency and novelty warrant interest.

Heterogeneous Mediation Analysis on Epigenomic PTSD and Traumatic Stress in a Predominantly African American Cohort

DNA methylation (DNAm) has been suggested to play a critical role in post-traumatic stress disorder (PTSD), through mediating the relationship between trauma and PTSD. However, this underlying mechanism of PTSD for African Americans still remains unknown. To fill this gap, in this paper, we investigate how DNAm mediates the effects of traumatic experiences on PTSD symptoms in the Detroit Neighborhood Health Study (DNHS) (2008–2013) which involves primarily African Americans adults. To achieve this, we develop a new mediation analysis approach for high-dimensional potential DNAm mediators. A key novelty of our method is that we consider heterogeneity in mediation effects across sub-populations. Specifically, mediators in different sub-populations could have opposite effects on the outcome, and thus could be difficult to identify under a traditional homogeneous model framework. In contrast, the proposed method can estimate heterogeneous mediation effects and identifies sub-populations in which individuals share similar effects. Simulation studies demonstrate that the proposed method outperforms existing methods for both homogeneous and heterogeneous data. We also present our mediation analysis results of a dataset with 125 participants and more than 450, 000 CpG sites from the DNHS study. The proposed method finds three subgroups of subjects and identifies DNAm mediators corresponding to genes such as HSP90AA1 and NFATC1 which have been linked to PTSD symptoms in literature. Our finding could be useful in future finer-grained investigation of PTSD mechanism and in the development of new treatments for PTSD.

Neighborhood environment, social cohesion, and epigenetic aging.

Living in adverse neighborhood environments has been linked to risk of aging-related diseases and mortality; however, the biological mechanisms explaining this observation remain poorly understood. DNA methylation (DNAm), a proposed mechanism and biomarker of biological aging responsive to environmental stressors, offers promising insight into potential molecular pathways. We examined associations between three neighborhood social environment measures (poverty, quality, and social cohesion) and three epigenetic clocks (Horvath, Hannum, and PhenoAge) using data from the Detroit Neighborhood Health Study (n=158). Using linear regression models, we evaluated associations in the total sample and stratified by sex and social cohesion. Neighborhood quality was associated with accelerated DNAm aging for Horvath age acceleration (β = 1.8; 95% CI: 0.4, 3.1), Hannum age acceleration (β = 1.7; 95% CI: 0.4, 3.0), and PhenoAge acceleration (β = 2.1; 95% CI: 0.4, 3.8). In models stratified on social cohesion, associations of neighborhood poverty and quality with accelerated DNAm aging remained elevated for residents living in neighborhoods with lower social cohesion, but were null for those living in neighborhoods with higher social cohesion. Our study suggests that living in adverse neighborhood environments can speed up epigenetic aging, while positive neighborhood attributes may buffer effects.

THOSE LEFT BEHIND: Socioeconomic Predictors and Social Mediators of Psychological Distress among Working-age African Americans in a Post-industrial City.

While the socioeconomic status (SES)-psychological distress gradient is well-documented in the social science literature, less attention has been devoted to how this relationship varies within sociodemographic subgroups. I contribute to this small but growing literature by first examining the relationship between multiple dimensions of SES and two measures of psychological distress (depression and anxiety) among working-aged African Americans. I then test whether three social mediators explain the SES-psychological distress relationship, and whether gender modifies these associations and/or the social mediators that shape them. To address these aims, I analyze two waves of population-representative data from the Detroit Neighborhood Health Study (N=685). Data were collected between 2008 and 2010 in the wake of the Great Recession. I utilize structural equation modeling with latent variables to assess these relationships, and test indirect and conditional effects to detect the presence of mediation and/or moderation, respectively. Findings revealed associations between higher total household income and lower levels of depression/anxiety, as well as unemployment and increased depression/anxiety among working age African Americans. Furthermore, higher educational attainment was associated with reduced anxiety, but not depression, in this population. Gender moderated these findings such that unemployment was associated with higher levels of depression/anxiety among women but not men. I also found that trauma mediated the relationship between unemployment and depression/anxiety as well as educational attainment and anxiety. Gender, however, moderated the association between unemployment and depression/anxiety via traumatic events such that the relationship was stronger among women than men. Collectively, these findings contribute to our limited understanding of African Americans' mental health and underscore the importance of how both socioeconomic forces and life course experiences with traumatic events contribute to poor mental health among this population.

The association between residential proximity to brownfield sites and high-traffic areas and measures of immunity.

The mechanisms by which neighborhood environmental exposures influence health are poorly understood, although immune system dysregulation represents a potential biological pathway. While many neighborhood exposures have been investigated, there is little research on residential proximity to brownfield waste. Using biomarker data from 262 participants in the Detroit Neighborhood Health Study, we estimated the association between proximity to brownfields and heavy traffic and signal joint T-cell receptor excision circles (sjTRECs, a measure of naive T-cell production), C-reactive protein (CRP, a measure of systemic inflammation), and interleukin-6 (IL-6, a pro-inflammatory cytokine). We assessed residential proximity ≤200 m from brownfields and highways on all three biomarkers using multivariate regression. We demonstrated that living ≤200 m from a brownfield site was associated with a 0.30 (95% CI = 0.59, 0.02, p = 0.04) loge-unit decrease in sjTRECs per million whole blood cells, as well as non-significantly elevated levels of CRP and IL-6. Heavy traffic was not associated with any biomarker. Persons living in close proximity to brownfield sites had significantly lower naive T-cell production, suggesting accelerated immune aging. Decreased T-cell production associated with brownfield proximity may be caused by toxicant exposure in brownfield sites, or may serve as a marker of other neighborhood stressors.

Epigenetic predictors of all-cause mortality are associated with objective measures of neighborhood disadvantage in an urban population

BackgroundNeighborhood characteristics are robust predictors of overall health and mortality risk for residents. Though there has been some investigation of the role that molecular indicators may play in mediating neighborhood exposures, there has been little effort to incorporate newly developed epigenetic biomarkers into our understanding of neighborhood characteristics and health outcomes.MethodsUsing 157 participants of the Detroit Neighborhood Health Study with detailed assessments of neighborhood characteristics and genome-wide DNA methylation profiling via the Illumina 450K methylation array, we assessed the relationship between objective neighborhood characteristics and a validated DNA methylation-based epigenetic mortality risk score (eMRS). Associations were adjusted for age, race, sex, ever smoking, ever alcohol usage, education, years spent in neighborhood, and employment. A secondary model additionally adjusted for personal neighborhood perception. We summarized 19 neighborhood quality indicators assessed for participants into 9 principal components which explained over 90% of the variance in the data and served as metrics of objective neighborhood quality exposures.ResultsOf the nine principal components utilized for this study, one was strongly associated with the eMRS (β = 0.15; 95% confidence interval = 0.06–0.24; P = 0.002). This principal component (PC7) was most strongly driven by the presence of abandoned cars, poor streets, and non-art graffiti. Models including both PC7 and individual indicators of neighborhood perception indicated that only PC7 and not neighborhood perception impacted the eMRS. When stratified on neighborhood indicators of greenspace, we observed a potentially protective effect of large mature trees as this feature substantially attenuated the observed association.ConclusionObjective measures of neighborhood disadvantage are significantly associated with an epigenetic predictor of mortality risk, presenting a potential novel avenue by which neighborhood-level exposures may impact health. Associations were independent of an individual’s perception of their neighborhood and attenuated by neighborhood greenspace features. More work should be done to determine molecular risk factors associated with neighborhoods, and potentially protective neighborhood features against adverse molecular effects.

Methylomic profiles reveal sex-specific differences in leukocyte composition associated with post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is a debilitating mental disorder precipitated by trauma exposure. However, only some persons exposed to trauma develop PTSD. There are sex differences in risk; twice as many women as men develop a lifetime diagnosis of PTSD. Methylomic profiles derived from peripheral blood are well-suited for investigating PTSD because DNA methylation (DNAm) encodes individual response to trauma and may play a key role in the immune dysregulation characteristic of PTSD pathophysiology. In the current study, we leveraged recent methodological advances to investigate sex-specific differences in DNAm-based leukocyte composition that are associated with lifetime PTSD. We estimated leukocyte composition on a combined methylation array dataset (483 participants, ∼450 k CpG sites) consisting of two civilian cohorts, the Detroit Neighborhood Health Study and Grady Trauma Project. Sex-stratified Mann-Whitney U test and two-way ANCOVA revealed that lifetime PTSD was associated with significantly higher monocyte proportions in males, but not in females (Holm-adjusted p-val < 0.05). No difference in monocyte proportions was observed between current and remitted PTSD cases in males, suggesting that this sex-specific difference may reflect a long-standing trait of lifetime history of PTSD, rather than current state of PTSD. Associations with lifetime PTSD or PTSD status were not observed in any other leukocyte subtype and our finding in monocytes was confirmed using cell estimates based on a different deconvolution algorithm, suggesting that our sex-specific findings are robust across cell estimation approaches. Overall, our main finding of elevated monocyte proportions in males, but not in females with lifetime history of PTSD provides evidence for a sex-specific difference in peripheral blood leukocyte composition that is detectable in methylomic profiles and that may reflect long-standing changes associated with PTSD diagnosis.

The legacy of redlining in the effect of foreclosures on Detroit residents' self-rated health.

Historical practices, such as housing discrimination in Detroit, have been shown to have lasting impacts on communities. Perhaps the most explicit example is the practice of redlining in the 1930s, whereby lenders outlined financially undesirable neighborhoods, populated by minority families, on maps and prevented residents from moving to better resourced neighborhoods. Awareness of historical housing discrimination may improve research assessing the impacts of current neighborhood characteristics on health. Using the Detroit Neighborhood Health Study (DNHS), we assessed the association between two-year changes in home foreclosure rates following the 2007-2008 Great Recession, and residents' five-year self-rated health trajectories (2008-2013); and estimated the confounding bias introduced by ignoring historical redlining practices in the city. We used both ecological and multilevel models to make inference about person- and community-level processes. In a neighborhood-level linear regression adjusted for confounders (including percent redlined); a 10%-point slower foreclosure rate recovery was associated with an increase in prevalence of poor self-rated health of 0.31 (95% CI:-0.02 to 0.64). At the individual level, it was associated with a within-person increase in probability of poor health of 0.45 (95% CI:0.15-0.72). Removing redlining from the model biased the estimated effect upward to 0.38 (95% CI:0.07-0.69) and 0.56 (95% CI:0.21-0.84) in the neighborhood and individual-level models, respectively. Stratum-specific foreclosure recovery effects indicate stronger influence in neighborhoods with a greater proportion of residents identifying as white and a greater degree of historic redlining. These findings support earlier theory suggesting a historical influence of structural discrimination on the association between current neighborhood characteristics and health, and suggests that historical redlining specifically may increase vulnerability to contemporary neighborhood foreclosures. Community interventions should consider historical discrimination in conjunction with current place-based indicators to more equitably improve population health.

FKBP5 DNA methylation does not mediate the association between childhood maltreatment and depression symptom severity in the Detroit Neighborhood Health Study

FKBP5 DNA methylation does not mediate the association between childhood maltreatment and depression symptom severity in the Detroit Neighborhood Health Study

The Great Recession and Immune Function

The Great Recession precipitated unprecedented home foreclosures increases, but documentation of related neighborhood changes and population health is scant. Using the Detroit Neighborhood Health Study (N = 277), we examined associations between neighborhood-level recession indicators and thymic function, a life course immunological health indicator. In covariate-adjusted multilevel models, each 10 percentage point increase in abandoned home prevalence and 1 percentage point increase in 2009 home foreclosures was associated with 1.7-year and 3.3-year increases in thymic aging, respectively. Associations attenuated after adjustment for neighborhood-level social cohesion, suggesting community ties may buffer recession-related immune aging. Effects of neighborhood stressors were strongest in middle-income households, supporting theory of excess vulnerability in this group. Future research should assess whether ongoing foreclosure and blight reduction efforts improve health for residents of recession impacted neighborhoods.

FKBP5 DNA methylation does not mediate the association between childhood maltreatment and depression symptom severity in the Detroit Neighborhood Health Study

Exposure to childhood maltreatment increases the risk of developing mental illness later in life. Childhood maltreatment and depression have both been associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis—a key regulator of the body's stress response. Additionally, HPA axis dysregulation has been implicated in the etiology of a range of mental illnesses. A substantial body of work has shown history of childhood maltreatment alters DNA methylation levels within key HPA axis genes. We therefore investigated whether one of these key genes, FKBP5 mediates the relationship between childhood maltreatment and depression, and assessed FKBP5 DNA methylation and gene expression within 112 adults from the Detroit Neighborhood Health Study (DNHS). DNA methylation was assessed in 4 regions, including the upstream promoter, downstream promoter, and two glucocorticoid response elements (GREs) via pyrosequencing using whole blood derived DNA; Taqman assays measured relative RNA expression from leukocytes. Mediation analyses were conducted using sequential linear regression. Childhood maltreatment was significantly associated with depression symptom severity (FDR < 0.006), but was not a significant predictor of DNA methylation in any of the four loci examined. FKBP5 showed elevated expression levels in participants with vs. without a history of depression (p < 0.001); no significant difference in gene expression levels was observed in relation to childhood maltreatment (p > 0.05). Our results suggest DNA methylation does not mediate the childhood maltreatment-depression association in the DNHS.

Use of Archived Neonatal Bloodspots for Examining Associations between Prenatal Exposure to Potentially Traumatic or Stressful Life Events, Maternal Herpesvirus Infection and Lifetime History of Generalized Anxiety Disorder in Offspring

Background: Lifetime prevalence of anxiety disorders is over 32% among U.S. adolescents, warranting further investigation into early life risk factors for such conditions. We conducted a pilot study to examine the role that maternal herpesvirus infection may play in the pathway between maternal trauma and stress during pregnancy and offspring generalized anxiety disorder (GAD). Methods: Participants included 69 women in the Detroit Neighborhood Health Study with data on past exposure to 19 potentially traumatic (PTEs) and 9 stressful life events (SLEs). Lifetime history of GAD in the youngest biologic child between 6-17 years old born in Michigan (i.e., index child) of each woman was ascertained via the Diagnostic Interview Schedule for Children, 4th edition, parent version. We obtained written informed consent from participants for retrieval of archived neonatal bloodspot samples corresponding to their index child from the Michigan Neonatal Biobank (MNB) and testing of these samples for markers of maternal herpes simplex virus (HSV)-1 and cytomegalovirus (CMV) seropositivity. Logistic regression was used to examine the association between maternal PTEs or SLEs during pregnancy and offspring GAD. Results: A total of 18.1% and 31.9% of women experienced ≥ 1 PTE or SLE during pregnancy, respectively, and 10.8% of offspring met the criteria for lifetime history of GAD. We obtained maternal consent for retrieval of and tested bloodspot samples corresponding to the index child of 22 women (38%), of which 4.5% and 40.9% were seropositive for HSV-1 and CMV, respectively. We observed positive, although not statistically significant associations between ≥ 1 PTE or SLE during pregnancy and offspring lifetime history of GAD. While a greater proportion of offspring with lifetime history of GAD were born to women seropositive for CMV and HSV-1, compared to those without lifetime history, these differences were not statistically significant and we did not further examine the mediating role of maternal herpesvirus seropositivity in this pathway. Conclusion: Findings from this study support the feasibility of utilizing neonatal bloodspots archived in the MNB to examine the role of herpesviruses as mediators between maternal traumatic or stressful life events during pregnancy and offspring anxiety disorders in larger Michigan cohorts.

Glucocorticoid receptor DNA methylation, childhood maltreatment and major depression

IntroductionAltered DNA methylation (DNAm) levels of hypothalamic-pituitary-adrenal (HPA) axis genes has been associated with exposure to childhood maltreatment (CM) and depression; however, it is unknown whether CM and depression have joint and potentially interacting effects on the glucocorticoid receptor (NR3C1) DNAm. We investigated the impact of CM and lifetime major depressive disorder (MDD) on NR3C1 DNAm and gene expression (GE) in 147 adult participants from the Detroit Neighborhood Health Study. MethodsNR3C1 promoter region DNAm was assessed via pyrosequencing using whole blood-derived DNA. Quantitative RT-PCR assays measured GE from leukocyte-derived RNA. Linear regression models were used to examine the relationship among CM, MDD, and DNAm. ResultsBoth CM and MDD were significant predictors of NR3C1 DNAm: CM was associated with an increase in DNAm in an EGR1 transcription factor binding site (TFBS), whereas MDD was associated with a decrease in DNAm downstream of the TFBS. No significant CM-MDD interactions were observed. CM alone was associated with significantly lower NR3C1 GE. LimitationsOur report of CM is a retrospective self-report of abuse, which may introduce recall bias. DNAm was measured in whole blood and may not reflect brain-derived DNAm levels. ConclusionsCM and MDD are both associated with altered DNAm levels in the NR3C1 promoter region, however the location and direction of effects differ between the two exposures, and the functional effects, as measured by GE, appear to be limited to CM exposure alone. CM exposure may be biologically embedded in this key HPA axis gene.

Income and Markers of Immunological Cellular Aging.

Socioeconomic disadvantage may contribute to poor health through immune-related biological mechanisms. We examined the associations between socioeconomic status, as measured by annual household income, and T-cell markers of aging, including the ratios of CD4 and CD8 effector cells to naïve cells (E/N ratio) and the CD4/CD8 T-cell ratio. We hypothesized that participants with a lower income would have higher E/N ratios and lower CD4/CD8 ratios compared with participants with a higher income, and that these associations would be partially mediated by elevated cytomegalovirus (CMV) IgG antibody levels, a virus implicated in aging and clonal expansion of T cells. Data were from 79 individuals who participated in the population-based Detroit Neighborhood Health Study. We used linear regression to quantify the association between a $10,000 decrease in income and each ratio outcome. After adjustment for age, sex, race, smoking, medication use, and lifetime history of mental health conditions, lower income was associated with a 0.41 (95% confidence interval = 0.09-0.72) log-unit increase in the CD4 E/N ratio and a 0.20 (95% confidence interval = 0.02-0.39) log-unit increase in the CD8 E/N ratio. CMV immunoglobulin G antibody level partially mediated these associations. Our study suggests that low socioeconomic status is associated with immunological aging as measured by the E/N ratio and that impaired immune control of CMV may partially mediate these associations.

Population Distributions of Thymic Function in Adults: Variation by Sociodemographic Characteristics and Health Status

ABSTRACTThe thymus is critical for mounting an effective immune response and maintaining health. However, epidemiologic studies characterizing thymic function in the population setting are lacking. Using data from 263 adults in the Detroit Neighborhood Health Study, we examined thymic function as measured by the number of signal joint T-cell receptor excision circles (sjTREC) and assessed associations with established indicators of physiological health. Overall, increasing age and male gender were significantly associated with reduced thymic function. Adjusting for covariates, individuals with elevated levels of the pro-inflammatory biomarkers C-reactive protein (β: −0.50 [95% CI: −0.82, −0.18] for moderate elevation, β: −0.29 [95% CI: −0.59, 0.00] for high elevation) and interleukin-6 (β: −0.60 [95% CI: −0.92, −0.28] for moderate elevation, β: −0.43 [95% CI: −0.77, −0.08] for severe elevation) also had lower thymic function. Compared to individuals with a BMI < 25, individuals who were overweight (β: 0.36 [95% CI: 0.07, 0.64]) or obese (β: 0.27 [95% CI: −0.03, 0.56]) had higher thymic function. Differences by self-rated health were not statistically significant. Our findings underscore demographic- and health-related gradients in thymic function among adult residents of Detroit, suggesting thymic function may be an important biomarker of health status in adults at the population level.

PTSD is associated with an increase in aged T cell phenotypes in adults living in Detroit

BackgroundPsychosocial stress is thought to play a key role in the acceleration of immunological aging. This study investigated the relationship between lifetime and past-year history of post-traumatic stress disorder (PTSD) and the distribution of T cell phenotypes thought to be characteristic of immunological aging. MethodsData were from 85 individuals who participated in the community-based Detroit Neighborhood Health Study. Immune markers assessed included the CD4:CD8 ratio, the ratio of late-differentiated effector (CCR7-CD45RA+CD27-CD28-) to naïve (CCR7+CD45RA+CD27+CD28+) T cells, the percentage of KLRG1-expressing cells, and the percentage of CD57-expressing cells. ResultsIn models adjusted for age, gender, race/ethnicity, education, smoking status, and medication use, we found that past-year PTSD was associated with statistically significant differences in the CD8+ T cell population, including a higher ratio of late-differentiated effector to naïve T cells, a higher percentage of KLRG1+ cells, and a higher percentage of CD57+ cells. The percentage of CD57+ cells in the CD4 subset was also significantly higher and the CD4:CD8 ratio significantly lower among individuals who had experienced past-year PTSD. Lifetime PTSD was also associated with differences in several parameters of immune aging. ConclusionsPTSD is associated with an aged immune phenotype and should be evaluated as a potential catalyzer of accelerated immunological aging in future studies.

Do private practitioners provide quality care to adolescents with substance abuse disorders?

s / Drug and Alcohol Dependence 156 (2015) e102–e182 e151 Preliminary analyses show significant group by visit interactions for breath CO (p=0.006) and urinary cotinine (p=0.03), with lower CO and cotinine levels in the Incentive vs. Control group. Final biochemical and abstinence data will be available for presentation at the June 2015 meeting, as will additional measures of nicotine withdrawal, craving, and respiratory symptomatology. Conclusions: These results suggest that an incentive-based intervention may be feasible and effective in producing initial smoking abstinence in this hard-to-treat sample of smokers.Financial support: T32 DA007242, P20 GM103644. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.410 Trauma exacerbates the effect of genetic variants in the dopamine system on cannabis use Jacquelyn L. Meyers1, Monica Uddin2, Sandro Galea1, Allison Aiello3, Derek Wildman2, Karestan C. Koenen1 1 Epidemiology, Columbia University, New York, NY, United States 2 University of Champagne-Urbana, Urbana, IL, United States 3 University of North Carolina Chapel Hill, Chapel Hill, NC, United States Aims: Although cannabis use is heritable, few studies have examined genetic risk for cannabis use alone, and of the studies that have been published, few genetic risk variants have been identified. In addition, the evidence for gene–environment interactions (GxE) in substance use behaviors is growing, with several GxE studies indicating that the effects of specific genetic variants are exacerbated by traumatic experiences. However, there have been no published GxE studies for cannabis involvement to date. Several biological systems that potentially incur risk for cannabis involvement have been identified via neurobiological studies, including variation in the dopaminergic system. For example, Volkow and colleagues investigated the effects of chronic cannabis use on the human brain using PET imaging, and found that cannabis abusers showed markedly blunted responses when challenged with methylphenidate, a drug that elevates dopamine. Methods: In this study, we provide evidence of association between sets of genetic variants in the dopamine system (96 single nucleotide polymorphisms across DRD1–DRD4) and frequency of cannabis use (days/month, within the past 30 days) in two independent majority African-American population based samples (Detroit Neighborhood Health Study, n=788; Grady Trauma Project, n=3752; p 33% treating prescription stimulants and prescription depressants, and ∼50% treating alcohol and marijuana. Over 50% referred youth to specialty care if use includedheroinormethamphetamine. The use of standardized assessments was rare and only ∼33% reported use of motivational interventions. Cognitive behavioral therapy was the predominate treatment delivered in individual youth sessions (85%); 75% provided family sessions but 90% of cases, it is critical that PPs be included in our effort to improve adolescent treatment quality.Financial support: P50-DA027841. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.412 Trends in use of and attitudes toward marijuana among youth before and after decriminalization: The case of California 2007–2013 Richard Miech, Lloyd A. Johnston, Patrick O’Malley, Jerald Bachman, John Schulenberg, Megan Patrick University of Michigan, Ann Arbor, MI, United States Aims: This analysis examines decriminalization as a risk factor for future increases in youthmarijuana acceptance and use. Specifically, we examine marijuana-related behaviors and attitudes of 8th, 10th, and 12th graders in California as compared to other U.S. states during the years before and after California passed legislation in 2010 to decriminalize marijuana. Methods: Data come from the annual Monitoring the Future study, which since 1975 has used questionnaires administered in classrooms to survey nationally representative samples of

Trauma exacerbates the effect of genetic variants in the dopamine system on cannabis use

s / Drug and Alcohol Dependence 156 (2015) e102–e182 e151 Preliminary analyses show significant group by visit interactions for breath CO (p=0.006) and urinary cotinine (p=0.03), with lower CO and cotinine levels in the Incentive vs. Control group. Final biochemical and abstinence data will be available for presentation at the June 2015 meeting, as will additional measures of nicotine withdrawal, craving, and respiratory symptomatology. Conclusions: These results suggest that an incentive-based intervention may be feasible and effective in producing initial smoking abstinence in this hard-to-treat sample of smokers.Financial support: T32 DA007242, P20 GM103644. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.410 Trauma exacerbates the effect of genetic variants in the dopamine system on cannabis use Jacquelyn L. Meyers1, Monica Uddin2, Sandro Galea1, Allison Aiello3, Derek Wildman2, Karestan C. Koenen1 1 Epidemiology, Columbia University, New York, NY, United States 2 University of Champagne-Urbana, Urbana, IL, United States 3 University of North Carolina Chapel Hill, Chapel Hill, NC, United States Aims: Although cannabis use is heritable, few studies have examined genetic risk for cannabis use alone, and of the studies that have been published, few genetic risk variants have been identified. In addition, the evidence for gene–environment interactions (GxE) in substance use behaviors is growing, with several GxE studies indicating that the effects of specific genetic variants are exacerbated by traumatic experiences. However, there have been no published GxE studies for cannabis involvement to date. Several biological systems that potentially incur risk for cannabis involvement have been identified via neurobiological studies, including variation in the dopaminergic system. For example, Volkow and colleagues investigated the effects of chronic cannabis use on the human brain using PET imaging, and found that cannabis abusers showed markedly blunted responses when challenged with methylphenidate, a drug that elevates dopamine. Methods: In this study, we provide evidence of association between sets of genetic variants in the dopamine system (96 single nucleotide polymorphisms across DRD1–DRD4) and frequency of cannabis use (days/month, within the past 30 days) in two independent majority African-American population based samples (Detroit Neighborhood Health Study, n=788; Grady Trauma Project, n=3752; p 33% treating prescription stimulants and prescription depressants, and ∼50% treating alcohol and marijuana. Over 50% referred youth to specialty care if use includedheroinormethamphetamine. The use of standardized assessments was rare and only ∼33% reported use of motivational interventions. Cognitive behavioral therapy was the predominate treatment delivered in individual youth sessions (85%); 75% provided family sessions but 90% of cases, it is critical that PPs be included in our effort to improve adolescent treatment quality.Financial support: P50-DA027841. http://dx.doi.org/10.1016/j.drugalcdep.2015.07.412 Trends in use of and attitudes toward marijuana among youth before and after decriminalization: The case of California 2007–2013 Richard Miech, Lloyd A. Johnston, Patrick O’Malley, Jerald Bachman, John Schulenberg, Megan Patrick University of Michigan, Ann Arbor, MI, United States Aims: This analysis examines decriminalization as a risk factor for future increases in youthmarijuana acceptance and use. Specifically, we examine marijuana-related behaviors and attitudes of 8th, 10th, and 12th graders in California as compared to other U.S. states during the years before and after California passed legislation in 2010 to decriminalize marijuana. Methods: Data come from the annual Monitoring the Future study, which since 1975 has used questionnaires administered in classrooms to survey nationally representative samples of