Table 1 Detailed entries for example studies of biological mechanisms potentially linking trauma and/or PTSD with cardiovascular disease risk.
From: Psychological and biological mechanisms linking trauma with cardiovascular disease risk
Study | Sample | Design | Measure(s) of trauma and/or PTSD | Measure(s) of biological mechanism | Key comparison | Summary of key findings | Notable points |
|---|---|---|---|---|---|---|---|
Immune dysregulation and elevated inflammation | |||||||
Tawakol et al. [76] | 13 adults with a history of PTSD | Cross-sectional | Participants had a history of PTSD based on the SCID-IV and CAPS; perceived stress assessed with the PSS-10 | Imaging-based marker of arterial inflammation capturing cellular glycolysis (18F-FDG-PET); CRP levels | Association between perceived stress and arterial and peripheral inflammation among individuals with a history of PTSD | • Perceived stress was positively correlated with amygdalar activity, arterial inflammation, and CRP levels • Amygdalar activity mediated the majority of the association between perceived stress and arterial inflammation | • This study utilized a unique, imaging-based measure of arterial inflammation • Example of integrating multiple measures of inflammation |
Carvalho et al. [90] | Genetic data from the PGC-PTSD Working Group (23,185 PTSD cases and 151,309 trauma-exposed controls) and the CHARGE Inflammation Working Group (148,164 individuals) | Cross-sectional | Genetically determined PTSD based on genome-wide summary statistics from the PGC-PTSD | Genetically determined CRP based on genome-wide summary statistics from the CHARGE Inflammation Working Group | Bidirectional associations between genetically predicted CRP and PTSD | • In Mendelian randomization analyses, genetically predicted PTSD and CRP showed significant bidirectional positive associations with one another | • This study utilized Mendelian randomization methods, which can help to illuminate causal relations using genetic data |
Oxidative stress | |||||||
Atli et al. [110] | 102 adults | Cross-sectional | PTSD diagnosis determined using the SCID-IV; PTSD symptom severity assessed with the PCL-C | Serum markers of antioxidant enzyme activity (PON1) and lipid peroxidation (MDA) | Compared PON1 activity and MDA levels across 3 groups (earthquake survivors with PTSD, earthquake survivors without PTSD, and healthy controls without a history of trauma) | • The PTSD group showed significantly elevated MDA levels and decreased PON1 activity compared to healthy controls • PTSD symptom severity was positively correlated with MDA levels • No significant differences between earthquake survivors with and without PTSD | • This study assessed oxidative stress with markers that reflect potential damage to due to oxidants and antioxidant enzyme activity • Comparing trauma-exposed individuals with and without PTSD to a no trauma control group provided an opportunity to assess differences due to trauma vs. trauma-related psychopathology |
Boeck et al. [107] | 30 adult postpartum women with and without a history of childhood maltreatment | Cross-sectional | Childhood maltreatment assessed with the CTQ | Serum metabolite markers of oxidative stress (arginine:citrulline ratio) and antioxidant capacity (L-carnitine and acetylcarnitine) | Association between childhood maltreatment and arginine:citrulline ratio, free L-carnitine, and acetylcarnitine | • Greater severity of childhood maltreatment was associated with higher levels of oxidative stress (greater arginine:citrulline ratio and lower L-carnitine and acetylcarnitine levels) | • Example of assessing serum metabolite markers reflecting greater oxidative stress and reduced antioxidant activity |
Mitochondrial dysfunction | |||||||
Brunst et al. [148] | 147 adult prenatal/ postpartum women enrolled in the PRISM Study | Longitudinal (PTSD symptoms assessed prenatally, mtDNAcn assessed postpartum) | Prenatal PTSD symptoms assessed with the PCL-C | Placental mtDNAcn | Association between prenatal PTSD symptoms and placental mtDNAcn | • Greater prenatal PTSD symptom severity was associated with lower placental mtDNAcn • Non-White individuals had higher PTSD symptom levels and lower mtDNAcn than White individuals; some differences in the PTSD-mtDNAcn relation emerged by race/ethnicity | • Longitudinal design in a prospective pregnancy cohort is a strength • Considered potential racial/ethnic differences in the relations between maternal psychological experiences and a biological marker relevant to maternal-fetal health |
Gumpp et al. [137] | 102 mother- newborn dyads | Cross-sectional | Childhood maltreatment assessed with the CTQ | Measures of mitochondrial respiration (e.g., routine respiration, ATP-turnover- related respiration) and intracellular mitochondrial density (citrate synthase activity) in UBMCs of newborns and in PBMCs of mothers | Compared measures of mitochondrial respiration and density in mothers with and without childhood maltreatment and in their newborns | • Childhood maltreatment was significantly positively associated with some measures of mitochondrial respiration and with citrate synthase activity in mothers • Maternal history of childhood maltreatment had a small but nonsignificant positive effect on citrate synthase activity in newborns | • Considered multiple measures of mitochondrial function and content • Measured mitochondrial dysfunction in mothers and newborns, though evidence for maternal childhood maltreatment alterations in mitochondrial measures was lacking |
Renin-angiotensin system dysregulation | |||||||
Terock et al. [161] | 3,092 adults enrolled in the SHIP | Cross-sectional | PTSD diagnosis based on the SCID-IV | Plasma concentrations of renin and aldosterone | Compared renin and aldosterone levels, and aldosterone:renin ratio, across 3 groups (individuals with PTSD, trauma-exposed individuals without PTSD, and individuals without a history of trauma) | • Relative to those with no trauma history, trauma-exposed individuals with and without PTSD showed elevated renin levels, with effects most pronounced for individuals with PTSD • Greater trauma load was positively associated with renin level and negatively associated with aldosterone:renin ratio • PTSD continued to significantly predict renin when adjusting for trauma load | • Comparing trauma-exposed individuals with and without PTSD to a no trauma control group provided an opportunity to assess differences due to trauma vs. trauma-related psychopathology |
Seligowski et al. [164] | 840 trauma-exposed adults (Primary sample); 116,389 adults in the Partners Healthcare Biobank (Replication sample) | Cross-sectional | PTSD symptoms assessed by the M-PSS (Primary sample); PTSD diagnosis based on diagnostic codes in the electronic health record (Replication sample) | Treatment with ACE-Is or ARBs (RAS blocker) | Association between ACE-I/ARB status and PTSD, plus differences by sex and race | • In the Primary sample, among individuals treated with ACE-Is/ARBs, women had higher PTSD symptom levels than men • In the Replication sample, ACE-I/ARB treatment was significantly associated with a lower rate of PTSD diagnosis • The relation between ACE-I/ARB treatment and PTSD diagnosis was significant among White but not Black individuals in the Replication sample | • Targeted medication use provides a unique measure of RAS functioning • Large sample for replication derived from a biorepository database • Considered sex and race as potential moderating factors |
Accelerated biological aging | |||||||
Copeland et al. [220] | 381 individuals in the Great Smoky Mountains Study followed from childhood to young adulthood | Longitudinal (Early life adversity assessed in childhood; DNAm measured in childhood and adulthood) | Dimensions of early life adversity (i.e., threat, material deprivation, loss, and unpredictability) assessed with the CAPA | DNAm from bloodspots; DNAm age estimated using elastic nets to predict chronological age; change over time=difference score between childhood and adulthood DNAm age estimates | Associations between early life adversity (dimensions and cumulative measure) with DNAm age, cross-sectionally in childhood and in terms of change over time | • No significant early life adversity- DNAm age associations in childhood in cross-sectional analyses • Greater cumulative early life adversity was significantly associated with increased DNAm aging from childhood to adulthood • No unique effects emerged for adversity dimensions when testing all dimensions simultaneously | • DNAm age was assessed longitudinally in childhood and adulthood • Example of studying longitudinal within-in person changes in DNAm age rather than examining between-group differences at a given time point |
Mehta et al. [226] | 40 adult paramedicine students | Longitudinal (PTSD and DNAm measured before and after trauma exposure) | PTSD symptom severity assessed with the PCL-5 | DNAm from saliva; DNAm age calculated using Horvath, GrimAge, and Skin & Blood Age clocks; Horvath age was residualized on chronological age and GrimAge and Skin & Blood Age were chronological age-adjusted | Associations between PTSD symptom severity and DNAm age, cross-sectionally and longitudinally | • Significant positive associations cross-sectionally and longitudinally were observed for PTSD symptom severity and epigenetic age acceleration for the Horvath and GrimAge clocks • No significant associations observed between PTSD symptoms and Skin & Blood age acceleration | • Longitudinal design in which DNAm was measured before and after trauma exposure is a strength |
