Post-traumatic stress symptoms as a predictor of treatment outcomes in a partial hospital program.

Introduction: Post-traumatic stress symptoms (PTSS) have been shown to negatively impact treatment outcomes in outpatient settings, but few have investigated in acute settings, such as partial hospital programs (PHP). The present study examined how PTSS may influence treatment outcomes- depression, anxiety, overall functioning- among patients attending a PHP. Methods: 1298 (Female n = 728) adults underwent standard transdiagnostic treatment at a PHP in which patients attend the day-long program for approximately 2 weeks for stabilization primarily focused on mood and anxiety symptoms. We utilized previously validated questionnaires to measure PTSD severity (PCL-5), anxiety (GAD-7), depression (PHQ-9), and overall functioning (WSAS). Linear regression analyses were conducted to determine the degree of improved symptoms and functioning across three trauma groups: patients with no trauma history, patients with trauma exposure, and patients who had severe PTSS. Results: Patients in the PTSS group were more likely to endorse higher depression and anxiety symptoms, as well as functional impairment at admission. Severe PTSS, not trauma exposure, predicted less improvement of depression, anxiety, and overall functioning at discharge. Limitations: Due to the nature of the private hospital, results may not generalize to a wider clinical population. Further, we were unable to test any potential mechanisms because the current naturalistic treatment study relied on a deidentified clinical database that was not designed with these research questions. Conclusions: Severe PTSS above and beyond anxiety and depression symptoms potentially serve as predictors of treatment outcomes in acute psychiatric settings such as PHPs, further emphasizing the need for enhanced trauma-informed care.

PTSD-related differences in resting-state functional connectivity and associations with sex hormones.

Background: Posttraumatic stress disorder (PTSD) is a debilitating condition that disproportionately impacts individuals who are female. Prior research indicates that males with PTSD exhibit hypoconnectivity of frontal brain regions measured with resting electroencephalography (EEG). The present study examined functional connectivity among females with PTSD and trauma-exposed controls, as well as the impact of sex hormones. Methods: Participants included 61 females (Mage = 31.41, SD = 8.64) who endorsed Criterion A trauma exposure. Resting state EEG data were recorded for five minutes in the eyes open position. Using a Linear Mixed Effects model, paired region-of-interest power envelope connectivity of the theta band (4-7 Hz) served as the response variables. Results: Compared to controls, the PTSD group displayed hyperconnectivity between visual brain regions and the rest of the cerebral cortex (pFDR < 0.05). Additionally, participants with PTSD demonstrated enhanced connectivity between the default mode network and frontoparietal control network compared to controls (pFDR < 0.05), as well as increased connectivity between the ventral attention network and the rest of the cerebral cortex (pFDR < 0.05). Estradiol was associated with higher connectivity, while progesterone was associated with lower connectivity, but these did not survive correction. Conclusions: Results are consistent with prior research indicating that PTSD is associated with altered connectivity in visual brain regions, which may reflect disrupted visual processing related to reexperiencing symptoms (e.g., intrusive memories). Our findings provide additional support for the relevance of the theta frequency range in PTSD given its role in fear learning and regulation processes.

Anxiety and Depression Associated With Increased Cardiovascular Disease Risk Through Accelerated Development of Risk Factors.

Background: Prior studies have incompletely assessed whether the development of cardiometabolic risk factors (CVDRF) (hypertension, hyperlipidemia, and diabetes mellitus) mediates the association between anxiety and depression (anxiety/depression) and cardiovascular disease (CVD). Objectives: The authors aimed to evaluate the following: 1) the association between anxiety/depression and incident CVDRFs and whether this association mediates the increased CVD risk; and 2) whether neuro-immune mechanisms and age and sex effects may be involved. Methods: Using a retrospective cohort design, Mass General Brigham Biobank subjects were followed for 10 years. Presence and timing of anxiety/depression, CVDRFs, and CVD were determined using ICD codes. Stress-related neural activity, chronic inflammation, and autonomic function were measured by the assessment of amygdalar-to-cortical activity ratio, high-sensitivity CRP, and heart rate variability. Multivariable regression and mediation analyses were employed. Results: Among 71,214 subjects (median age 49.6 years; 55.3% female), 27,048 (38.0%) developed CVDRFs during follow-up. Pre-existing anxiety/depression associated with increased risk of incident CVDRF (OR: 1.71 [95% CI: 1.59-1.83], P < 0.001) and with a shorter time to their development (ß = -0.486 [95% CI: -0.62 to -0.35], P < 0.001). The development of CVDRFs mediated the association between anxiety/depression and CVD events (log-odds: 0.044 [95% CI: 0.034-0.055], P < 0.05). Neuro-immune pathways contributed to the development of CVDRFs (P < 0.05 each) and significant age and sex effects were noted: younger women experienced the greatest acceleration in the development of CVDRFs after anxiety/depression. Conclusions: Anxiety/depression accelerate the development of CVDRFs. This association appears to be most notable among younger women and may be mediated by stress-related neuro-immune pathways. Evaluations of tailored preventive measures for individuals with anxiety/depression are needed to reduce CVD risk.

Posttraumatic stress disorder increases thrombosis risk: Evidence from a biobank data set.

Depression and anxiety are linked to deep venous thrombosis (DVT) and posttraumatic disorder (PTSD) increases risk of venous thromboembolism in women. However, the mechanisms underlying this relationship remain unknown. We hypothesized that PTSD would associate with increased DVT risk, that neuroimmune mechanisms would mediate the PTSD-DVT link, and that these associations would be stronger in women. This cohort study included N = 106 427 participants from a large biobank. PTSD and DVT were defined using ICD-10 codes. A subset (N = 1520) underwent imaging, from which we assessed stress-associated neural activity (SNA). High-sensitivity C-reactive protein (hs-CRP) levels and heart rate variability (HRV) were used as indicators of systemic inflammation and autonomic activity, respectively. Linear, logistic, and Cox regressions and mediation analyses were used to test our hypotheses. Of 106 427 participants, 4192 (3.9%) developed DVT. PTSD associated with increased DVT risk (HR [95% CI]: 1.66 [1.34, 2.07], p < .001), and this finding remained significant after adjustment for age, sex, and traditional DVT risk factors. When analyzed separately by sex, PTSD was significantly associated with DVT risk in women but not men. Further, heightened SNA and lower HRV mediated the effect of PTSD on DVT risk. Results suggest that individuals with PTSD are at increased risk for DVT, and that risk is higher in women. This relationship was partially driven by alterations in stress-associated neural activity and autonomic function, suggesting potential targets for preventive therapies. Future studies are needed to investigate whether intervening on PTSD-DVT mechanisms has downstream beneficial effects on DVT, especially among women.

Probing the neurocardiac circuit in trauma and posttraumatic stress.

The neurocardiac circuit is integral to physiological regulation of threat and trauma-related responses. However, few direct investigations of brain-behavior associations with replicable physiological markers of PTSD have been conducted. The current study probed the neurocardiac circuit by examining associations among its core regions in the brain (e.g., insula, hypothalamus) and the periphery (heart rate [HR], high frequency heart rate variability [HF-HRV], and blood pressure [BP]). We sought to characterize these associations and to determine whether there were differences by PTSD status. Participants were N = 315 (64.1 % female) trauma-exposed adults enrolled from emergency departments as part of the prospective AURORA study. Participants completed a deep phenotyping session (e.g., fear conditioning, magnetic resonance imaging) two weeks after emergency department admission. Voxelwise analyses revealed several significant interactions between PTSD severity 8-weeks posttrauma and psychophysiological recordings on hypothalamic connectivity to the prefrontal cortex (PFC), insula, superior temporal sulcus, and temporoparietaloccipital junction. Among those with PTSD, diastolic BP was directly correlated with right insula-hypothalamic connectivity, whereas the reverse was found for those without PTSD. PTSD status moderated the association between systolic BP, HR, and HF-HRV and hypothalamic connectivity in the same direction. While preliminary, our findings may suggest that individuals with higher PTSD severity exhibit compensatory neural mechanisms to down-regulate autonomic imbalance. Additional study is warranted to determine how underlying mechanisms (e.g., inflammation) may disrupt the neurocardiac circuit and increase cardiometabolic disease risk in PTSD.

Cortico-limbic interactions and carotid atherosclerotic burden during chronic stress exposure.

BACKGROUND AND AIMS: Chronic stress associates with cardiovascular disease, but mechanisms remain incompletely defined. Advanced imaging was used to identify stress-related neural imaging phenotypes associated with atherosclerosis. METHODS: Twenty-seven individuals with post-traumatic stress disorder (PTSD), 45 trauma-exposed controls without PTSD, and 22 healthy controls underwent 18F-fluorodeoxyglucose positron emission tomography/magnetic resonance imaging (18F-FDG PET/MRI). Atherosclerotic inflammation and burden were assessed using 18F-FDG PET (as maximal target-to-background ratio, TBR max) and MRI, respectively. Inflammation was assessed using high-sensitivity C-reactive protein (hsCRP) and leucopoietic imaging (18F-FDG PET uptake in spleen and bone marrow). Stress-associated neural network activity (SNA) was assessed on 18F-FDG PET as amygdala relative to ventromedial prefrontal cortex (vmPFC) activity. MRI diffusion tensor imaging assessed the axonal integrity (AI) of the uncinate fasciculus (major white matter tract connecting vmPFC and amygdala). RESULTS: Median age was 37 years old and 54% of participants were female. There were no significant differences in atherosclerotic inflammation between participants with PTSD and controls; adjusted mean difference in TBR max (95% confidence interval) of the aorta 0.020 (-0.098, 0.138), and of the carotids 0.014 (-0.091, 0.119). Participants with PTSD had higher hsCRP, spleen activity, and aorta atherosclerotic burden (normalized wall index). Participants with PTSD also had higher SNA and lower AI. Across the cohort, carotid atherosclerotic burden (standard deviation of wall thickness) associated positively with SNA and negatively with AI independent of Framingham risk score. CONCLUSIONS: In this study of limited size, participants with PTSD did not have higher atherosclerotic inflammation than controls. Notably, impaired cortico-limbic interactions (higher amygdala relative to vmPFC activity or disruption of their intercommunication) associated with carotid atherosclerotic burden. Larger studies are needed to refine these findings.

Sex-dependent differences in vulnerability to early risk factors for posttraumatic stress disorder: results from the AURORA study.

BACKGROUND: Knowledge of sex differences in risk factors for posttraumatic stress disorder (PTSD) can contribute to the development of refined preventive interventions. Therefore, the aim of this study was to examine if women and men differ in their vulnerability to risk factors for PTSD. METHODS: As part of the longitudinal AURORA study, 2924 patients seeking emergency department (ED) treatment in the acute aftermath of trauma provided self-report assessments of pre- peri- and post-traumatic risk factors, as well as 3-month PTSD severity. We systematically examined sex-dependent effects of 16 risk factors that have previously been hypothesized to show different associations with PTSD severity in women and men. RESULTS: Women reported higher PTSD severity at 3-months post-trauma. Z-score comparisons indicated that for five of the 16 examined risk factors the association with 3-month PTSD severity was stronger in men than in women. In multivariable models, interaction effects with sex were observed for pre-traumatic anxiety symptoms, and acute dissociative symptoms; both showed stronger associations with PTSD in men than in women. Subgroup analyses suggested trauma type-conditional effects. CONCLUSIONS: Our findings indicate mechanisms to which men might be particularly vulnerable, demonstrating that known PTSD risk factors might behave differently in women and men. Analyses did not identify any risk factors to which women were more vulnerable than men, pointing toward further mechanisms to explain women's higher PTSD risk. Our study illustrates the need for a more systematic examination of sex differences in contributors to PTSD severity after trauma, which may inform refined preventive interventions.

Effect of Stress-Related Neural Pathways on the Cardiovascular Benefit of Physical Activity.

BACKGROUND: The mechanisms underlying the psychological and cardiovascular disease (CVD) benefits of physical activity (PA) are not fully understood. OBJECTIVES: This study tested whether PA: 1) attenuates stress-related neural activity, which is known to potentiate CVD and for its role in anxiety/depression; 2) decreases CVD in part through this neural effect; and 3) has a greater impact on CVD risk among individuals with depression. METHODS: Participants from the Mass General Brigham Biobank who completed a PA survey were studied. A subset underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomographic imaging. Stress-related neural activity was measured as the ratio of resting amygdalar-to-cortical activity (AmygAC). CVD events were ascertained from electronic health records. RESULTS: A total of 50,359 adults were included (median age 60 years [Q1-Q3: 45-70 years]; 40.1% male). Greater PA was associated with both lower AmygAC (standardized ß: -0.245; 95% CI: -0.444 to -0.046; P = 0.016) and CVD events (HR: 0.802; 95% CI: 0.719-0.896; P < 0.001) in multivariable models. AmygAC reductions partially mediated PA's CVD benefit (OR: 0.96; 95% CI: 0.92-0.99; P < 0.05). Moreover, PA's benefit on incident CVD events was greater among those with (vs without) preexisting depression (HR: 0.860; 95% CI: 0.810-0.915; vs HR: 0.929; 95% CI: 0.910-0.949; P interaction = 0.011). Additionally, PA above guideline recommendations further reduced CVD events, but only among those with preexisting depression (P interaction = 0.023). CONCLUSIONS: PA appears to reduce CVD risk in part by acting through the brain's stress-related activity; this may explain the novel observation that PA reduces CVD risk to a greater extent among individuals with depression.

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 increases risk for major adverse cardiovascular events through neural and cardio-inflammatory pathways.

While posttraumatic stress disorder (PTSD) is known to associate with an elevated risk for major adverse cardiovascular events (MACE), few studies have examined mechanisms underlying this link. Recent studies have demonstrated that neuro-immune mechanisms, (manifested by heightened stress-associated neural activity (SNA), autonomic nervous system activity, and inflammation), link common stress syndromes to MACE. However, it is unknown if neuro-immune mechanisms similarly link PTSD to MACE. The current study aimed to test the hypothesis that upregulated neuro-immune mechanisms increase MACE risk among individuals with PTSD. This study included N = 118,827 participants from a large hospital-based biobank. Demographic, diagnostic, and medical history data collected from the biobank. SNA (n = 1,520), heart rate variability (HRV; [n = 11,463]), and high sensitivity C-reactive protein (hs-CRP; [n = 15,164]) were obtained for a subset of participants. PTSD predicted MACE after adjusting for traditional MACE risk factors (hazard ratio (HR) [95 % confidence interval (CI)] = 1.317 [1.098, 1.580], ß = 0.276, p = 0.003). The PTSD-to-MACE association was mediated by SNA (CI = 0.005, 0.133, p < 0.05), HRV (CI = 0.024, 0.056, p < 0.05), and hs-CRP (CI = 0.010, 0.040, p < 0.05). This study provides evidence that neuro-immune pathways may play important roles in the mechanisms linking PTSD to MACE. Future studies are needed to determine if these markers are relevant targets for PTSD treatment and if improvements in SNA, HRV, and hs-CRP associate with reduced MACE risk in this patient population.

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.

Structural inequities contribute to racial/ethnic differences in neurophysiological tone, but not threat reactivity, after trauma exposure.

Considerable racial/ethnic disparities persist in exposure to life stressors and socioeconomic resources that can directly affect threat neurocircuitry, particularly the amygdala, that partially mediates susceptibility to adverse posttraumatic outcomes. Limited work to date, however, has investigated potential racial/ethnic variability in amygdala reactivity or connectivity that may in turn be related to outcomes such as post-traumatic stress disorder (PTSD). Participants from the AURORA study (n = 283), a multisite longitudinal study of trauma outcomes, completed functional magnetic resonance imaging and psychophysiology within approximately two-weeks of trauma exposure. Seed-based amygdala connectivity and amygdala reactivity during passive viewing of fearful and neutral faces were assessed during fMRI. Physiological activity was assessed during Pavlovian threat conditioning. Participants also reported the severity of posttraumatic symptoms 3 and 6 months after trauma. Black individuals showed lower baseline skin conductance levels and startle compared to White individuals, but no differences were observed in physiological reactions to threat. Further, Hispanic and Black participants showed greater amygdala connectivity to regions including the dorsolateral prefrontal cortex (PFC), dorsal anterior cingulate cortex, insula, and cerebellum compared to White participants. No differences were observed in amygdala reactivity to threat. Amygdala connectivity was associated with 3-month PTSD symptoms, but the associations differed by racial/ethnic group and were partly driven by group differences in structural inequities. The present findings suggest variability in tonic neurophysiological arousal in the early aftermath of trauma between racial/ethnic groups, driven by structural inequality, impacts neural processes that mediate susceptibility to later PTSD symptoms.

Vagal control moderates the association between endothelial function and PTSD symptoms in women with T2DM.

Background: Individuals with posttraumatic stress disorder (PTSD) are more likely to present with metabolic diseases such as type-2 diabetes mellitus (T2DM), and cardiovascular dysfunction has been implicated in this link. These diseases disproportionately affect women and individuals exposed to chronic environmental stressors (e.g., community violence, poverty). We examined associations among PTSD, cardiovascular indices, and metabolic function in highly trauma-exposed Black women with T2DM. Methods: Participants (N = 80) were recruited for a follow-up study of stress and T2DM as part of the Grady Trauma Project. PTSD symptoms were assessed with the Clinician Administered PTSD Scale (CAPS-IV). Cardiovascular indices included heart rate (HR), blood pressure (BP), respiratory sinus arrhythmia (RSA), and endothelial function (assessed via flow-mediated dilation; FMD). An oral glucose tolerance test was used as an indicator of metabolic function. Results: Of the cardiovascular indices, only FMD was significantly associated with PTSD symptoms (CAPS Avoidance symptoms; ß = -0.37, p = .042), and glucose tolerance (ß = -0.44, p = .019), controlling for age and body mass index. The association between FMD and PTSD Avoidance was moderated by RSA such that the effect of FMD was only significant at low levels of RSA (simple slopes ß = -0.87, p = .004). Conclusions: Our results indicate that endothelial function is significantly related to PTSD and glucose tolerance, over and above other cardiovascular measures (HR, BP, RSA). Further, our results suggest that low RSA may be a risk factor for the link between poor endothelial function and PTSD in women with T2DM.

Leveraging Large-Scale Genetics of PTSD and Cardiovascular Disease to Demonstrate Robust Shared Risk and Improve Risk Prediction Accuracy.

OBJECTIVE: Individuals with posttraumatic stress disorder (PTSD) are significantly more likely to be diagnosed with cardiovascular disease (CVD) (e.g., myocardial infarction, stroke). The evidence for this link is so compelling that the National Institutes of Health convened a working group to determine gaps in the literature, including the need for large-scale genomic studies to identify shared genetic risk. The aim of the present study was to address some of these gaps by utilizing PTSD and CVD genome-wide association study (GWAS) summary statistics in a large biobank sample to determine the shared genetic risk of PTSD and CVD. METHODS: A large health care biobank data set was used (N=36,412), combined with GWAS summary statistics from publicly available large-scale PTSD and CVD studies. Disease phenotypes (e.g., PTSD) were collected from electronic health records. De-identified genetic data from the biobank were genotyped using Illumina SNP array. Summary statistics data sets were processed with the following quality-control criteria: 1) SNP heritability h2 >0.05, 2) compute z-statistics (z=beta/SE or z=log(OR)/SE), 3) filter nonvariable SNPs (0

Hippocampal Threat Reactivity Interacts with Physiological Arousal to Predict PTSD Symptoms.

Hippocampal impairments are reliably associated with post-traumatic stress disorder (PTSD); however, little research has characterized how increased threat-sensitivity may interact with arousal responses to alter hippocampal reactivity, and further how these interactions relate to the sequelae of trauma-related symptoms. In a sample of individuals recently exposed to trauma (N=116, 76 Female), we found that PTSD symptoms at 2-weeks were associated with decreased hippocampal responses to threat as assessed with functional magnetic resonance imaging (fMRI). Further, the relationship between hippocampal threat sensitivity and PTSD symptomology only emerged in individuals who showed transient, high threat-related arousal, as assayed by an independently collected measure of Fear Potentiated Startle. Collectively, our finding suggests that development of PTSD is associated with threat-related decreases in hippocampal function, due to increases in fear-potentiated arousal.Significance StatementAlterations in hippocampal function linked to threat-related arousal are reliably associated with post-traumatic stress disorder (PTSD); however, how these alterations relate to the sequelae of trauma-related symptoms is unknown. Prior models based on non-trauma samples suggest that arousal may impact hippocampal neurophysiology leading to maladaptive behavior. Here we show that decreased hippocampal threat sensitivity interacts with fear-potentiated startle to predict PTSD symptoms. Specifically, individuals with high fear-potentiated startle and low, transient hippocampal threat sensitivity showed the greatest PTSD symptomology. These findings bridge literatures of threat-related arousal and hippocampal function to better understand PTSD risk.

Heart Rate Variability Features as Predictors of Intermittent Theta-Burst Stimulation Response in Posttraumatic Stress Disorder.

BACKGROUND: Posttraumatic stress disorder (PTSD) is associated with autonomic dysfunction as indicated by deficits in the sympathetic and parasympathetic nervous systems. These abnormalities are expressed as elevated heart rate and reduced heart rate variability (HRV), respectively. Intermittent theta-burst stimulation (iTBS), a form of transcranial magnetic stimulation, has demonstrated effectiveness in PTSD. Nevertheless, it remains unclear whether HRV may be an iTBS biomarker for PTSD and whether iTBS impacts autonomic activity. MATERIALS AND METHODS: Fifty veterans with PTSD participated in a randomized controlled trial, receiving ten daily sessions of sham-controlled iTBS (right dorsolateral prefrontal cortex, 1800 pulses/day, 80% active motor threshold, 9.5 min). With a usable dataset (N = 47), HRV parameters were assessed as predictors of clinical response immediately after stimulation. iTBS effects on autonomic response (mean RR interval, root mean square of successive differences [RMSSD], total power [TP], and low-frequency/high-frequency [LF/HF] ratio) were evaluated using an ultra-short approach. RESULTS: TP and RMSSD were significant predictors of acute clinical response to iTBS. Individuals with higher TP had better response to iTBS with improved symptoms on the Clinician-Administered PTSD Scale (rs = -0.58, p = 0.004), and higher functionality on the Social and Occupational Function Scale (rs = 0.43, p = 0.04). Similarly, higher RMSSD was associated with superior outcomes (rs = -0.44, p = 0.04). No other significant changes in HRV metrics were observed (p ≥ 0.05). CONCLUSIONS: Our findings indicate that autonomic activity is a potential low-cost and technically simple predictive biomarker of iTBS response in PTSD. Less autonomic dysfunction was associated with superior clinical improvements with iTBS. Future studies might consider HRV acquisition during iTBS, as well as prospective testing of these findings in patients with elevated hyperarousal.

Involvement of the brain-heart axis in the link between PTSD and cardiovascular disease.

Posttraumatic stress disorder (PTSD) has long been associated with a heightened risk of cardiovascular disease (CVD). A number of mechanisms have been implicated to underlie this brain-heart axis relationship, such as altered functioning of the autonomic nervous system and increased systemic inflammation. While neural alterations have repeatedly been observed in PTSD, they are rarely considered in the PTSD-CVD link. The brain-heart axis is a pathway connecting frontal and limbic brain regions to the brainstem and periphery via the autonomic nervous system and it may be a promising model for understanding CVD risk in PTSD given its overlap with PTSD neural deficits. We first provide a summary of the primary mechanisms implicated in the association between PTSD and CVD. We then review the brain-heart axis and its relevance to PTSD, as well as findings from PTSD trials demonstrating that a number of PTSD treatments have effects on areas of the brain-heart axis. Finally, we discuss sex considerations in the PTSD-CVD link. A critical next step in this study is to determine if PTSD treatments that affect the brain-heart axis (e.g., brain stimulation that improves autonomic function) also reduce the risk of CVD.

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.