The impact of PTSD on associations between sex hormones and cardiovascular disease symptoms.

Background: Women have twice the lifetime prevalence of posttraumatic stress disorder (PTSD) relative to men, and PTSD is a known risk factor for cardiovascular disease (CVD). Two sex hormones - estradiol and progesterone - have been found to impact both PTSD and CVD symptomatology, but the way in which sex hormones influence cardiovascular physiology among individuals with PTSD is not well understood.Objective: This study sought to clarify the association between sex hormones, PTSD, and CVD among trauma-exposed women.Method: Sixty-six trauma-exposed women (M age = 31.45, SD = 8.92) completed a clinical interview for PTSD and self-reported CVD symptoms; estradiol and progesterone were assayed from blood samples. The association between each sex hormone and CVD symptoms was analyzed, controlling for age, systolic blood pressure (BP), and diastolic BP.Results: Neither estradiol nor the PTSD-by-estradiol interaction was significantly associated with CVD symptoms. Higher progesterone and, relatedly, progesterone-to-estradiol ratio (PE ratio) were each significantly associated with greater CVD symptom severity, but only for individuals with lower relative PTSD severity.Conclusions: The findings indicate that PTSD moderates the relationship between progesterone and CVD symptoms, and further research is warranted to reconcile findings in existing literature regarding the direction of and mechanisms behind this relationship.

Posttraumatic stress disorder (PTSD) is a risk factor for cardiovascular disease (CVD) and sex hormones have been implicated in their link.The current study examined associations between sex hormones, PTSD, and CVD symptoms among 66 trauma-exposed women.Estradiol was not significantly associated with CVD symptoms, but higher progesterone was significantly associated with greater CVD symptom severity, but only for individuals with lower relative PTSD severity.

PTSD and depression severity are associated with cardiovascular disease symptoms in trauma-exposed women.

Background: Posttraumatic stress disorder (PTSD) and depression are associated with increased risk for cardiovascular disease (CVD), which is the leading cause of death and disability worldwide. Epidemiological studies have revealed these illnesses to be highly comorbid, particularly among women. In the current study, we explored associations between indices of cardiovascular health, PTSD, and depression among a sample of trauma-exposed individuals assigned female at birth.Methods: Participants were N = 49 individuals without CVD who reported lifetime Criterion A trauma exposure. Blood pressure (BP), heart rate (HR), and high-frequency heart rate variability (HF-HRV) were collected during a 5-minute resting period. Symptoms of CVD (e.g. extremity pain and swelling, shortness of breath), PTSD, and depression were assessed, along with an exploratory measure of anhedonia.Results: Trauma exposure was positively correlated with systolic BP (r = .32, p = .029) and diastolic BP (r = .30, p = .040). The number of reported CVD symptoms was positively correlated with symptoms of PTSD (r = .41, p = .004), depression (r = .40, p = .005) and anhedonia (r = .38, p = .007). CVD symptoms were also significantly associated with PTSD (ß = .41, t = 2.43, p = .023), depression (ß = .40, t = 2.76, p = .009), and anhedonia (ß = .38, t = 2.51, p = .017) after controlling for age and trauma exposure. These associations were not moderated by HF-HRV in our sample.Conclusions: Our results support the association between PTSD and depressive symptoms and worse cardiovascular functioning among an often-overlooked population that is particularly vulnerable to these illnesses. Future studies should investigate residual impacts of PTSD and depression treatment on CVD risk among trauma-exposed individuals, particularly women.

Trauma exposure and PTSD are associated with depression and cardiovascular disease (CVD) risk.We explored cardiovascular health, PTSD, and depression among 49 trauma-exposed individuals assigned female at birth.Trauma exposure positively correlated with blood pressure.CVD symptoms were positively correlated with PTSD, depression, and anhedonia.Associations were not moderated by heart rate variability.

Persistent Dissociation and Its Neural Correlates in Predicting Outcomes After Trauma Exposure.

OBJECTIVE: Dissociation, a disruption or discontinuity in psychological functioning, is often linked with worse psychiatric symptoms; however, the prognostic value of dissociation after trauma is inconsistent. Determining whether trauma-related dissociation is uniquely predictive of later outcomes would enable early identification of at-risk trauma populations. The authors conducted the largest prospective longitudinal biomarker study of persistent dissociation to date to determine its predictive capacity for adverse psychiatric outcomes following acute trauma. METHODS: All data were part of the Freeze 2 data release from the Advancing Understanding of Recovery After Trauma (AURORA) study. Study participants provided self-report data about persistent derealization (N=1,464), a severe type of dissociation, and completed a functional MRI emotion reactivity task and resting-state scan 2 weeks posttrauma (N=145). Three-month follow-up reports were collected of posttraumatic stress, depression, pain, anxiety symptoms, and functional impairment. RESULTS: Derealization was associated with increased ventromedial prefrontal cortex (vmPFC) activation in the emotion reactivity task and decreased resting-state vmPFC connectivity with the cerebellum and orbitofrontal cortex. In separate analyses, brain-based and self-report measures of persistent derealization at 2 weeks predicted worse 3-month posttraumatic stress symptoms, distinct from the effects of childhood maltreatment history and current posttraumatic stress symptoms. CONCLUSIONS: The findings suggest that persistent derealization is both an early psychological and biological marker of worse later psychiatric outcomes. The neural correlates of trauma-related dissociation may serve as potential targets for treatment engagement to prevent posttraumatic stress disorder. These results underscore dissociation assessment as crucial following trauma exposure to identify at-risk individuals, and they highlight an unmet clinical need for tailored early interventions.

Heart rate variability and HbA1c predict plasma interleukin-6 response to psychosocial stress challenge in trauma-exposed women with type 2 diabetes.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a major public health problem in the United States. Although cardiovascular autonomic functioning, blood glucose control, and inflammation are known to play a role in T2DM, the interaction between these variables remains largely unexplored, particularly in the context of stress. To address this gap, we examined the relationship between these variables in a sample that is uniquely vulnerable to the health consequences of T2DM. METHODS: Participants were 37 trauma-exposed Black women with a diagnosis of T2DM. High frequency heart rate variability (HF-HRV), blood glucose control (HbA1c), and a stressor-evoked biomarker of inflammation (interleukin 6; IL-6) were obtained as part of a larger study of the genetic risk factors for and consequences of trauma exposure. RESULTS: The interaction of HbA1c and HF-HRV was significantly associated with IL-6 response calculated as area under the curve with respect to ground. Post-hoc simple slopes analyses revealed HbA1c, rather than HF-HRV, as the moderator in this association such that higher HF-HRV conferred higher circulating levels of IL-6 only in the presence of lower HbA1c, (ߠ​= â€‹0.60, t â€‹= â€‹3.51, p â€‹= â€‹.001). CONCLUSIONS: Cardiovascular autonomic functioning and blood glucose control were significantly associated with stressor-evoked IL-6 responses when controlling for BMI and age. Moreover, the association between cardiovascular autonomic functioning and inflammation varied at different levels of HbA1c. This highlights the possibility that individuals with trauma exposure and T2DM may benefit from stratification by HbA1c levels for research analysis and treatment decision making.

Prognostic neuroimaging biomarkers of trauma-related psychopathology: resting-state fMRI shortly after trauma predicts future PTSD and depression symptoms in the AURORA study.

Neurobiological markers of future susceptibility to posttraumatic stress disorder (PTSD) may facilitate identification of vulnerable individuals in the early aftermath of trauma. Variability in resting-state networks (RSNs), patterns of intrinsic functional connectivity across the brain, has previously been linked to PTSD, and may thus be informative of PTSD susceptibility. The present data are part of an initial analysis from the AURORA study, a longitudinal, multisite study of adverse neuropsychiatric sequalae. Magnetic resonance imaging (MRI) data from 109 recently (i.e., ~2 weeks) traumatized individuals were collected and PTSD and depression symptoms were assessed at 3 months post trauma. We assessed commonly reported RSNs including the default mode network (DMN), central executive network (CEN), and salience network (SN). We also identified a proposed arousal network (AN) composed of a priori brain regions important for PTSD: the amygdala, hippocampus, mamillary bodies, midbrain, and pons. Primary analyses assessed whether variability in functional connectivity at the 2-week imaging timepoint predicted 3-month PTSD symptom severity. Left dorsolateral prefrontal cortex (DLPFC) to AN connectivity at 2 weeks post trauma was negatively related to 3-month PTSD symptoms. Further, right inferior temporal gyrus (ITG) to DMN connectivity was positively related to 3-month PTSD symptoms. Both DLPFC-AN and ITG-DMN connectivity also predicted depression symptoms at 3 months. Our results suggest that, following trauma exposure, acutely assessed variability in RSN connectivity was associated with PTSD symptom severity approximately two and a half months later. However, these patterns may reflect general susceptibility to posttraumatic dysfunction as the imaging patterns were not linked to specific disorder symptoms, at least in the subacute/early chronic phase. The present data suggest that assessment of RSNs in the early aftermath of trauma may be informative of susceptibility to posttraumatic dysfunction, with future work needed to understand neural markers of long-term (e.g., 12 months post trauma) dysfunction. Furthermore, these findings are consistent with neural models suggesting that decreased top-down cortico-limbic regulation and increased network-mediated fear generalization may contribute to ongoing dysfunction in the aftermath of trauma.

Posttraumatic cognitions predict distorted body perceptions in women with dissociative identity disorder.

BACKGROUND: Dissociative identity disorder (DID) is a psychobiological syndrome associated with a history of exposure to childhood abuse and neglect. The consequences of these traumatic events often include a profound impact on the way individuals inhabit and experience their bodies. Despite this, there is a paucity of empirical research on the subject. The aim of this study was to systematically document the occurrence of distorted body perceptions in DID and examine childhood maltreatment, posttraumatic stress disorder (PTSD) symptom severity, and posttraumatic cognitions as predictors of distorted body perceptions in DID. METHODS: Participants were adult women with histories of childhood abuse and neglect and a current DID diagnosis receiving treatment at a psychiatric care facility. Data were obtained through a battery of self-report measures, including the Body Uneasiness Test, Childhood Trauma Questionnaire, PTSD Checklist for DMS-5, and Posttraumatic Cognitions Inventory. RESULTS: A series of unpaired t-tests documented elevated levels of weight phobia, body image concerns, body avoidance, compulsive self-monitoring, and depersonalization in DID compared to published non-clinical data on the Body Uneasiness Test. A series of multiple regression models including measures of childhood trauma, PTSD symptoms, and posttraumatic cognitions demonstrated that over and above childhood trauma and PTSD symptom severity, posttraumatic cognitions significantly predicted distorted body perceptions. CONCLUSIONS: In a treatment-seeking sample of women with DID, distorted body perceptions were elevated. Furthermore, posttraumatic cognitive distortions significantly predicted distorted body perceptions when controlling for childhood maltreatment and PTSD symptom severity. This suggests that distorted cognitions are a key target for therapeutic intervention.

The renin-angiotensin system in PTSD: a replication and extension.

Prior observational studies have suggested that medications targeting the renin-angiotensin system, such as angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs), may be associated with decreased PTSD symptoms. Given known sex differences in PTSD prevalence and cardiovascular disease, here we tested whether the effects of ACE-I/ARB status on PTSD differ by sex. We also expanded these observations with replication analyses in a large biorepository database. Participants in the initial sample included 840 trauma-exposed individuals recruited as part of the Grady Trauma Project. The Modified PTSD Symptom Scale (M-PSS) was administered and ACE-I/ARB status was determined by self-report. Replication analyses were conducted using a large biorepository database (Partners Healthcare Biobank, N = 116,389) with diagnoses and medication status based on available electronic health records. Among individuals treated with ACE-Is/ARBs in the initial sample, women had significantly higher M-PSS total and Re-experiencing severity compared to men (p's < 0.05). Analyses with the large biorepository sample robustly replicated the overall effects of ACE-I/ARB medication associated with lower rate of PTSD diagnosis (p < 0.001). We also demonstrated that this effect may be specific to the renin-angiotensin system as it did not replicate for beta-blockers, calcium channel blockers, or diuretics. When we examined more specific drug classes, results indicated that the ACE-I/ARB effect on PTSD may be driven more by ARBs (e.g., Losartan) than by ACE-Is. Post-hoc analyses indicated that racial differences may exist in these effects. Overall, our results replicate and extend prior observations that the renin-angiotensin system is associated with PTSD. Medications targeting this system may be worthy of further investigation for PTSD treatment. Our findings suggest that sex and race effects should be considered in future treatment research.

Examining the cardiovascular response to fear extinction in a trauma-exposed sample.

BACKGROUND: Trauma and symptoms of posttraumatic stress disorder (PTSD) have repeatedly been linked to impaired cardiovascular functioning. Poor fear extinction is a well-established biomarker of PTSD that may provide insight into mechanisms underlying cardiovascular risk. The current study probed the cardiovascular response to extinction in a sample of trauma-exposed individuals. METHODS: Participants were 51 trauma-exposed women who underwent a fear conditioning paradigm. Heart rate (HR) during extinction was examined in response to a conditioned stimulus that was previously paired with an aversive unconditioned stimulus (CS+) and one that was never paired (CS-). Heart rate variability (HRV) was calculated at baseline and during the extinction session. RESULTS: Consistent with fear bradycardia, initial HR deceleration (.5-2s) after CS + onset occurred during early extinction and appeared to extinguish over time. Higher baseline HRV was significantly associated with greater fear bradycardia during early extinction. CONCLUSIONS: This is the first study to demonstrate a pattern of fear bradycardia in early extinction, which was associated with higher HRV levels and decreased over the course of the extinction phase. These results suggest that increased fear bradycardia may be indicative of greater vagal control (i.e., HRV), both of which are psychophysiological biomarkers that may influence cardiovascular and autonomic disease risk in trauma-exposed individuals.

Nervous and Endocrine System Dysfunction in Posttraumatic Stress Disorder: An Overview and Consideration of Sex as a Biological Variable.

Decades of research into the biological mechanisms of posttraumatic stress disorder (PTSD) suggests that chronic activation of the stress response leads to long-lasting changes in the structure and function of the nervous and endocrine systems. While the prevalence of PTSD is twice as high in females as males, little is known about how sex differences in neuroendocrine systems may contribute to PTSD. In response to the paucity of research on sex-related mechanisms, the National Institutes of Health created a policy that asks researchers to consider sex as a biological variable. This review provides an overview of the current understanding of nervous and endocrine dysfunction in PTSD (e.g., neural circuitry, autonomic arousal, hormonal response), highlighting areas where the influence of sex has been characterized and where further research is needed. We also provide recommendations for using the sex-as-a-biological-variable policy to address specific gaps in PTSD neuroscience research.