Background: Exposure to traumatic events is a risk factor for negative physical and mental health outcomes. However, the underlying biological mechanisms that perpetuate these lasting effects are not known. Methods: We investigated the impact and timing of sexual trauma, a specific type of interpersonal violence, experienced during key developmental windows of childhood, adolescence, or adulthood on adult health outcomes and associated biomarkers, including circulating cell-free mitochondrial DNA levels and extracellular vesicles (EVs), in a predominantly Black cohort of women (N = 101). Results: Significant changes in both biomarkers examined, circulating cell-free mitochondrial DNA levels and EV proteome, were specific to developmental timing of sexual trauma. Specifically, we identified a large number of keratin-related proteins from EVs unique to the adolescent sexual trauma group. Remarkably, the majority of these keratin proteins belong to a 17q21 gene cluster, which suggests a potential local epigenetic regulatory mechanism altered by adolescent trauma to impact keratinocyte EV secretion or its protein cargo. These results, along with changes in fear-potentiated startle and skin conductance detected in these women, suggest that sexual violence experienced during the specific developmental window of adolescence may involve unique programming of the skin, the body's largest stress organ. Conclusions: Together, these descriptive studies provide novel insight into distinct biological processes altered by trauma experienced during specific developmental windows. Future studies will be required to mechanistically link these biological processes to health outcomes.
Growing research suggests that posttraumatic stress disorder (PTSD) may be a risk factor for poor cardiovascular health, and yet our understanding of who might be at greatest risk of adverse cardiovascular outcomes after trauma is limited. In this study, we conducted the first examination of the individual and synergistic contributions of PTSD symptoms and blood pressure genetics to continuous blood pressure levels. We harnessed the power of the Psychiatric Genomics Consortium-PTSD Physical Health Working Group and investigated these associations across 11 studies of 72,224 trauma-exposed individuals of European (n = 70,870) and African (n = 1,354) ancestry. Genetic contributions to blood pressure were modeled via polygenic scores (PGS) for systolic blood pressure (SBP) and diastolic blood pressure (DBP) that were derived from a prior trans-ethnic blood pressure genome-wide association study (GWAS). Results of trans-ethnic meta-analyses revealed significant main effects of the PGS on blood pressure levels [SBP: β = 2.83, standard error (SE) = 0.06, p < 1E-20; DBP: β = 1.32, SE = 0.04, p < 1E-20]. Significant main effects of PTSD symptoms were also detected for SBP and DBP in trans-ethnic meta-analyses, though there was significant heterogeneity in these results. When including data from the largest contributing study – United Kingdom Biobank – PTSD symptoms were negatively associated with SBP levels (β = −1.46, SE = 0.44, p = 9.8E-4) and positively associated with DBP levels (β = 0.70, SE = 0.26, p = 8.1E-3). However, when excluding the United Kingdom Biobank cohort in trans-ethnic meta-analyses, there was a nominally significant positive association between PTSD symptoms and SBP levels (β = 2.81, SE = 1.13, p = 0.01); no significant association was observed for DBP (β = 0.43, SE = 0.78, p = 0.58). Blood pressure PGS did not significantly moderate the associations between PTSD symptoms and blood pressure levels in meta-analyses. Additional research is needed to better understand the extent to which PTSD is associated with high blood pressure and how genetic as well as contextual factors may play a role in influencing cardiovascular risk.
The current study investigated the relationship between trauma exposure and psychopathology in a sample of predominately African-American women of low socioeconomic status (SES). Women (N = 7430) were recruited from medical clinics at two large public hospitals in Atlanta, GA, from 2005 to 2017. Women were assessed for sociodemographics, life-course trauma burden, posttraumatic stress disorder (PTSD), and major depressive disorder (MDD) utilizing self-report and structured clinical interview assessments. The effects of trauma exposure on current and lifetime PTSD and MDD were examined. Ninety-one percent of women reported trauma exposure, 83% reported a monthly household income of less than $2000, and 41% reported a history of arrest. Regarding psychiatric diagnoses, 30.8% met the criteria for probable MDD, and 32.3% met the criteria for probable PTSD. History of childhood abuse and total lifetime trauma significantly increased PTSD and depressive symptoms with additional incremental trauma exposure. PTSD and depressive symptom scores (95% CI) increased from 5.5 (5.0–6.1) and 8.4 (7.9–9.0) in the no trauma group to 20.8 (20.1–21.5) and 20.4 (19.7–21.2), respectively, in those exposed to four or more types of trauma. These results show high rates of adult and childhood trauma exposure, PTSD, MDD, and an additive effect of lifetime trauma exposure on the development of PTSD and MDD in a sample of low SES African-American women. These findings bring light to the high psychiatric symptom burden in this population and call for increased availability of interventions to address symptoms as well as policies aimed at reducing trauma exposure across the lifespan.
Background: Norepinephrine (NE) plays a central role in post-traumatic stress disorder (PTSD). Dopamine β-hydroxylase (DβH) converts dopamine (DA) to NE and its activity varies widely across individuals. Mustapic et al. (2007) reported a PTSD-associated deficit in serum DβH activity (sDβH) in a genotype-controlled analysis of combat veterans. We tested whether such a deficit would occur in a sample of civilians.
Methods: The severity of current adult PTSD symptoms and current DSM-IV diagnosis of PTSD were determined by the PTSD Symptom Scale (PSS). Adulthood trauma exposure was assessed using the Traumatic Experience Inventory (TEI). sDβH was assayed by HPLC with electrochemical detection and genotypes were determined using the Taqman® platform.
Results: Two hundred and twenty seven African American (AA) subjects were enrolled in this study, with a mean age (± SD) of 42.9 (±12.9) years. We found a strong association between rs1611115 genotype and sDβH (p<0.0001). After controlling for adulthood trauma exposure, there were no significant differences of sDβH between subjects who met a PTSD diagnosis and those who did not (p>0.05) in any genotype group. No significant correlations were found between sDβH and PTSD severity, but sDβH significantly associated with the status of comorbid depression based on the cutoff of HAMD (p=0.014) in subjects with PTSD.
Conclusions: We have replicated in this sample the prior finding that DBH rs1611115 genotype strongly associates with sDβH. No associations between sDβH and PTSD diagnosis or symptom severity in this civilian sample.
Reduced heart rate variability (HRV) in response to stress is a biomarker of emotion dysregulation (ED) and is related to posttraumatic stress disorder (PTSD), yet less is known about its role with dissociation in trauma-exposed adults. The goals of the current study were to examine unique patterns of associations between ED, dissociation, and PTSD with HRV at 15, 30, and 45 min (T1, T2, T3) following an acute psychosocial stressor task in a sample of 49 trauma-exposed, urban-dwelling Black women. Associations with baseline psychophysiology measures were also examined. ED and dissociation were assessed using self-report; PTSD was determined using a semi-structured interview. Heart rate (HR) and HRV, indexed with low frequency/high frequency (LF/HF) ratio and respiratory sinus arrhythmia (RSA), were measured with electrocardiogram recordings. ED and dissociation were positively correlated with LF/HF ratio at T3 (p < .05). There were no significant differences between individuals with PTSD versus those without PTSD in HR or HRV following acute stressor; PTSD diagnosis was related to higher HR at baseline. Latent growth modeling revealed that ED was associated with higher LF/HF ratio directly following acute stressor, while dissociation was associated with increase in LF/HF ratio over time. These findings demonstrate that ED is related to higher sympathetic reactivity for a prolonged period of time following stress exposure, while dissociation shows a delayed association with LF/HF ratio, suggesting a distinct impaired parasympathetic activation pattern exists for dissociation.
Schizophrenia (SCZ) is an etiologically heterogeneous disease with genetic and environmental risk factors (e.g., Toxoplasma gondii infection) differing among affected individuals. Distinguishing such risk factors may point to differences in pathophysiological pathways and facilitate the discovery of individualized treatments. Toxoplasma gondii (TOXO) has been implicated in increasing the risk of schizophrenia. To determine whether TOXO-positive individuals with SCZ have a different polygenic risk burden than uninfected people, we applied the SCZ polygenic risk score (SCZ-PRS) derived from the Psychiatric GWAS Consortium separately to the TOXO-positive and TOXO-negative subjects with the diagnosis of SCZ as the outcome variable. The SCZ-PRS does not include variants in the major histocompatibility complex. Of 790 subjects assessed for TOXO, the 662 TOXO-negative subjects (50.8% with SCZ) reached a Bonferroni corrected significant association (p = 0.00017, R2 = 0.023). In contrast, the 128 TOXO-positive individuals (53.1% with SCZ) showed no significant association (p = 0.354) for SCZ-PRS and had a much lower R2 (R2 = 0.007). To account for Type-2 error in the TOXO-positive dataset, we performed a random sampling of the TOXO-negative subpopulation (n = 130, repeated 100 times) to simulate equivalent power between groups: the p-value was <0.05 for SCZ-PRS 55% of the time but was rarely (6% of the time) comparable to the high p-value of the seropositive group at p > 0.354. We found intriguing evidence that the SCZ-PRS predicts SCZ in TOXO-negative subjects, as expected, but not in the TOXO-positive individuals. This result highlights the importance of considering environmental risk factors to distinguish a subgroup with independent or different genetic components involved in the development of SCZ.
Introduction: There has long been an interest in the effects of diet on mental health, and the interaction of the two with stress; however, the nature of these relationships is not well understood. Although associations between diet, obesity and the related metabolic syndrome (MetS), stress, and mental disorders exist, causal pathways have not been established. Methods: We reviewed the literature on the relationship between diet, stress, obesity and psychiatric disorders related to stress. Results: Diet and obesity can affect mood through direct effects, or stress-related mental disorders could lead to changes in diet habits that affect weight. Alternatively, common factors such as stress or predisposition could lead to both obesity and stress-related mental disorders, such as depression and posttraumatic stress disorder (PTSD). Specific aspects of diet can lead to acute changes in mood as well as stimulate inflammation, which has led to efforts to assess polyunsaturated fats (PUFA) as a treatment for depression. Bidirectional relationships between these different factors are also likely. Finally, there has been increased attention recently on the relationship between the gut and the brain, with the realization that the gut microbiome has an influence on brain function and probably also mood and behavior, introducing another way diet can influence mental health and disorders. Brain areas and neurotransmitters and neuropeptides that are involved in both mood and appetite likely play a role in mediating this relationship. Conclusions: Understanding the relationship between diet, stress and mood and behavior could have important implications for the treatment of both stress-related mental disorders and obesity.
Posttraumatic stress disorder (PTSD) is characterized by intrusive thoughts, avoidance, negative alterations in cognitions and mood, and arousal symptoms that adversely affect mental and physical health. Recent evidence links changes in DNA methylation of CpG cites to PTSD. Since clusters of proximal CpGs share similar methylation signatures, identification of PTSD-associated differentially methylated regions (DMRs) may elucidate the pathways defining differential risk and resilience of PTSD. Here we aimed to identify epigenetic differences associated with PTSD. DNA methylation data profiled from blood samples using the MethylationEPIC BeadChip were used to perform a DMR analysis in 187 PTSD cases and 367 trauma-exposed controls from the Grady Trauma Project (GTP). DMRs were assessed with R package bumphunter. We identified two regions that associate with PTSD after multiple test correction. These regions were in the gene body of HLA-DPB1 and in the promoter of SPATC1L. The DMR in HLA-DPB1 was associated with PTSD in an independent cohort. Both DMRs included CpGs whose methylation associated with nearby sequence variation (meQTL) and that associated with expression of their respective genes (eQTM). This study supports an emerging literature linking PTSD risk to genetic and epigenetic variation in the HLA region.
Context
The serotonin transporter (SLC6A4) has been associated with several stress-related syndromes including posttraumatic stress disorder (PTSD). The ability to detect meaningful associations is largely dependent on reliable measures of preexisting trauma.
Objective
To study the association of genetic variants within SLC6A4 with acute and posttraumatic stress symptoms in a civilian cohort with known levels of preexisting trauma and PTSD symptoms collected prior to a shared index traumatic event.
Design
Ongoing longitudinal study.
Setting
On February 14, 2008, a lone gunman shot multiple people on the campus of Northern Illinois University in DeKalb, Illinois, killing 5 and wounding 21. As part of an ongoing longitudinal study on that campus, a cohort of female undergraduate students, interviewed prior to the shooting, completed follow-up trauma-related measures including PTSD symptom severity (follow-up survey was launched 17 days postshooting; n=691). To obtain DNA, salivary samples were collected from a subset of the original study population based on willingness to participate (n=276).
Participants
Two hundred four undergraduate women.
Main Outcome Measures
SLC6A4 polymorphisms STin2, 5-HTTLPR, and rs25531 were genotyped in 235 individuals.
Results
We found that although the STin2 variant and 5-HTTLPR alone did not associate with increased PTSD symptoms, rs25531 and the 5-HTTLPRmultimarker genotype (combined 5-HTTLPR and rs25531) were associated with significantly increased acute stress disorder symptoms at 2 to 4 weeks postshooting (n = 161; P<.05). This association remained significant when controlling for race and for level of shooting exposure (n = 123; P<.007). The association was most robust with the 5-HTTLPR multimarker genotype and avoidance symptoms (P=.003).
Conclusion
These data suggest that differential function of the serotonin transporter may mediate differential response to a severe trauma. When examined in a relatively homogenous sample with shared trauma and known prior levels of child and adult trauma, the 5-HTTLPR multimarker genotype may serve as a useful predictor of risk for PTSD-related symptoms in the weeks and months following the trauma.
Background: Higher subjective social status (SSS) or a person’s perception of their social standing is related to better health outcomes, but few studies examined SSS in relation to obesity. Emotional eating and food addiction have been linked to obesity. Some studies indicated that manipulating SSS may lead to altered food intake, but the relationship between SSS and dysregulated eating, such as emotional eating and food addiction (FA), has not been examined. The goal of this study was to examine the associations between SSS in the community and the larger society, dysregulated eating (emotional eating and FA), and body mass index (BMI) in a majority racial minority sample. Methods: The participants (N = 89; 93% Black, 86% women, and 56% with obesity; 72% income lower than USD 2000), recruited from a publicly funded hospital in Atlanta, GA, completed the MacArthur Scale, Dutch Eating Behaviors Questionnaire, Yale Food Addiction Scale, Beck Depression Inventory, PTSD Symptom Checklist, and demographics questionnaire. Results: Twenty-two percent of the sample met the criteria for FA; those with FA had significantly higher BMI than those without (p = 0.018). In the hierarchical linear regression, the SSS community (but not in society) predicted higher severity of emotional eating (β = 0.26, p = 0.029) and FA (β = 0.30, p = 0.029), and higher BMI (β = 0.28, p = 0.046), independent from depression and PTSD symptoms. Conclusions: The findings indicate that, among Black individuals with predominantly low income in the U.S., perceived role in their community is associated with eating patterns and body mass. Given the small sample size, the results should be interpreted with caution.