An in-depth look into PTSD-depression comorbidity: A longitudinal study of chronically-exposed Detroit residents

Background Although PTSD-major depressive disorder (MDD) co-morbidity is well-established, the vast majority of studies have examined comorbidity at the level of PTSD total severity, rather than at the level of specific PTSD symptom clusters. This study aimed to examine the long-term associations between MDD and PTSD symptom clusters (intrusion, avoidance, hyperarousal), and the moderating role of gender in these associations. Methods 942 residents of urban Detroit neighborhoods were interviewed at 3 waves, 1 year apart. At each wave, they were assessed for PTSD, depression, trauma exposure, and stressful life events. Results At all waves, hyperarousal was the PTSD cluster most strongly correlated with MDD. For the full sample, a reciprocal relationship was found between MDD and all three PTSD clusters across time. Interestingly, the relative strength of associations between MDD and specific PTSD clusters changed over time. Women showed the same bidirectional MDD-PTSD pattern as in the entire sample, while men sometimes showed non-significant associations between early MDD and subsequent PTSD clusters. Limitations First, our analyses are based on DSM-IV criteria, as this was the existing edition at the time of this study. Second, although this is a longitudinal study, inferences regarding temporal precedence of one disorder over another must be made with caution. Conclusions Early identification of either PTSD or MDD following trauma may be crucial in order to prevent the development of the other disorder over time. The PTSD cluster of hyper-arousal may require special therapeutic attention. Also, professionals are encouraged to develop more gender-specific interventions post-trauma

Interaction between polygenic risk for cigarette use and environmental exposures in the Detroit neighborhood health study

Cigarette smoking is influenced both by genetic and environmental factors. Until this year, all large-scale gene identification studies on smoking were conducted in populations of European ancestry. Consequently, the genetic architecture of smoking is not well described in other populations. Further, despite a rich epidemiologic literature focused on the social determinants of smoking, few studies have examined the moderation of genetic influences (for example, gene-environment interactions) on smoking in African Americans. In the Detroit Neighborhood Health Study (DNHS), a sample of randomly selected majority African American residents of Detroit, we constructed a genetic risk score (GRS), in which we combined top (P-value <5 × 10-7) genetic variants from a recent meta-analysis conducted in a large sample of African Americans. Using regression (effective n=399), we first tested for association between the GRS and cigarettes per day, attempting to replicate the findings from the meta-analysis. Second, we examined interactions with three social contexts that may moderate the genetic association with smoking: traumatic events, neighborhood social cohesion and neighborhood physical disorder. Among individuals who had ever smoked cigarettes, the GRS significantly predicted the number of cigarettes smoked per day and accounted for ∼3% of the overall variance in the trait. Significant interactions were observed between the GRS and number of traumatic events experienced, as well as between the GRS and average neighborhood social cohesion; the association between genetic risk and smoking was greater among individuals who had experienced an increased number of traumatic events in their lifetimes, and diminished among individuals who lived in a neighborhood characterized by greater social cohesion. This study provides support for the utility of the GRS as an alternative approach to replication of common polygenic variation, and in gene-environment interaction, for smoking behaviors. In addition, this study indicates that environmental determinants have the potential to both exacerbate (traumatic events) and diminish (neighborhood social cohesion) genetic influences on smoking behaviors. © 2013 Macmillan Publishers Limited. All rights reserved

Gene expression and methylation signatures of MAN2C1 are associated with PTSD

As potential regulators of DNA accessibility and activity, epigenetic modifications offer a mechanism by which the environment can moderate the effects of genes. To date, however, there have been relatively few studies assessing epigenetic modifications associated with post-traumatic stress disorder (PTSD). Here we investigate PTSD-associated methylation differences in 33 genes previously shown to differ in whole blood-derived gene expression levels between those with vs. without the disorder. Drawing on DNA samples similarly obtained from whole blood in 100 individuals, 23 with and 77 without lifetime PTSD, we used methylation microarray data to assess whether these 33 candidate genes showed epigenetic signatures indicative of increased risk for, or resilience to, PTSD. Logistic regression analyses were performed to assess the main and interacting effects of candidate genes' methylation values and number of potentially traumatic events (PTEs), adjusting for age and other covariates. Results revealed that only one candidate gene-MAN2C1}-showed a significant methylation x PTE interaction, such that those with both higher MAN2C1 methylation and greater exposure to PTEs showed a marked increase in risk of lifetime PTSD (OR 4.35, 95% CI: 1.07, 17.77, p=0.04). These results indicate that MAN2C1 methylation levels modify cumulative traumatic burden on risk of PTSD, and suggest that both gene expression and epigenetic changes at specific loci are associated with this disorder

Street Audits to Measure Neighborhood Disorder: Virtual or In-Person?

Neighborhood conditions may influence a broad range of health indicators, including obesity, injury, and psychopathology. In particular, neighborhood physical disorder - a measure of urban deterioration - is thought to encourage crime and high-risk behaviors, leading to poor mental and physical health. In studies to assess neighborhood physical disorder, investigators typically rely on time-consuming and expensive in-person systematic neighborhood audits. We compared 2 audit-based measures of neighborhood physical disorder in the city of Detroit, Michigan: One used Google Street View imagery from 2009 and the other used an in-person survey conducted in 2008. Each measure used spatial interpolation to estimate disorder at unobserved locations. In total, the virtual audit required approximately 3% of the time required by the in-person audit. However, the final physical disorder measures were significantly positively correlated at census block centroids (r = 0.52), identified the same regions as highly disordered, and displayed comparable leave-one-out cross-validation accuracy. The measures resulted in very similar convergent validity characteristics (correlation coefficients within 0.03 of each other). The virtual audit-based physical disorder measure could substitute for the in-person one with little to no loss of precision. Virtual audits appear to be a viable and much less expensive alternative to in-person audits for assessing neighborhood conditions

Mooney et al. Respond to "observing Neighborhood Physical Disorder"

[No abstract available

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

Epigenetic meta-analysis across three civilian cohorts identifies NRG1 and HGS as blood-based biomarkers for post-traumatic stress disorder

Aim: Trauma exposure is a necessary, but not deterministic, contributor to post-traumatic stress disorder (PTSD). Epigenetic factors may distinguish between trauma-exposed individuals with versus without PTSD. Materials & methods: We conducted a meta-analysis of PTSD epigenome-wide association studies in trauma-exposed cohorts drawn from civilian contexts. Whole blood-derived DNA methylation levels were analyzed in 545 study participants, drawn from the three civilian cohorts participating in the PTSD working group of the Psychiatric Genomics Consortium. Results: Two CpG sites significantly associated with current PTSD in NRG1 (cg23637605) and in HGS (cg19577098). Conclusion: PTSD is associated with differential methylation, measured in blood, within HGS and NRG1 across three civilian cohorts

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 (0 = 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

Epigenome-wide association of PTSD from heterogeneous cohorts with a common multi-site analysis pipeline

Compelling evidence suggests that epigenetic mechanisms such as DNA methylation play a role in stress regulation and in the etiologic basis of stress related disorders such as Post traumatic Stress Disorder (PTSD). Here we describe the purpose and methods of an international consortium that was developed to study the role of epigenetics in PTSD. Inspired by the approach used in the Psychiatric Genomics Consortium, we brought together investigators representing seven cohorts with a collective sample size of N = 1147 that included detailed information on trauma exposure, PTSD symptoms, and genome-wide DNA methylation data. The objective of this consortium is to increase the analytical sample size by pooling data and combining expertise so that DNA methylation patterns associated with PTSD can be identified. Several quality control and analytical pipelines were evaluated for their control of genomic inflation and technical artifacts with a joint analysis procedure established to derive comparable data over the cohorts for meta-analysis. We propose methods to deal with ancestry population stratification and type I error inflation and discuss the advantages and disadvantages of applying robust error estimates. To evaluate our pipeline, we report results from an epigenome-wide association study (EWAS) of age, which is a well-characterized phenotype with known epigenetic associations. Overall, while EWAS are highly complex and subject to similar challenges as genome-wide association studies (GWAS), we demonstrate that an epigenetic meta-analysis with a relatively modest sample size can be well-powered to identify epigenetic associations. Our pipeline can be used as a framework for consortium efforts for EWAS

Evaluating a screener to quantify PTSD risk using emergency care information: a proof of concept study

Stress and Psychopatholog