Accelerated development of cardiovascular risk factors mediates risk for major adverse cardiovascular events in posttraumatic stress disorder.

Background: Individuals with posttraumatic stress disorder (PTSD) have high rates of cardiovascular disease (CVD) and increased cardiometabolic CVD risk factors (CVDRFs, e.g., hypertension, hyperlipidemia, or diabetes mellitus).

Anxiety and depression are associated with heightened risk of incident deep vein thrombosis: Mediation through stress-related neural mechanisms.

Controversy exists as to whether anxiety and depression increase deep vein thrombosis (DVT) risk, and the mechanisms mediating potential links remain unknown. We aimed to evaluate the association between anxiety and depression and DVT risk and determine whether upregulated stress-related neural activity (SNA), which promotes chronic inflammation, contributes to this link. Our retrospective study included adults (N = 118 871) enrolled in Mass General Brigham Biobank.

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).

A late-life neurogenetic signature of exposure to combat stress - A monozygotic discordant twin study.

Animal models suggest that experiencing high-stress levels induces changes in amygdalar circuitry and gene expression. In humans, combat exposure has been shown to alter amygdalar responsivity and connectivity, but abnormalities have been indicated to normalize at least partially upon the termination of stress exposure. In contrast, other evidence suggests that combat exposure continues to exert influence on exposed individuals well beyond deployment and homecoming, as indicated by longitudinal psychosocial evidence from veterans, and observation of greater health decline in veterans late in life.

Pre-treatment amygdala activation and habituation predict symptom change in post-traumatic stress disorder.

Trauma-focused psychotherapy approaches are the first-line treatment option for post-traumatic stress disorder (PTSD); however, up to a third of patients remain symptomatic even after completion of the treatment. Predicting which patients will respond to a given treatment option would support personalized treatments and improve the efficiency of healthcare systems. Although previous neuroimaging studies have examined possible pre-treatment predictors of response to treatment, the findings have been somewhat inconsistent, and no other study has examined habituation to stimuli as a predictor.

Reduced Stress-Related Neural Network Activity Mediates the Effect of Alcohol on Cardiovascular Risk.

Background: Chronic stress associates with major adverse cardiovascular events (MACE) via increased stress-related neural network activity (SNA). Light/moderate alcohol consumption (AC) has been linked to lower MACE risk, but the mechanisms are unclear.

Objectives: The purpose of this study was to evaluate whether the association between AC and MACE is mediated by decreased SNA.

Exaggerated amygdala activation to ambiguous facial expressions is a familial vulnerability factor for posttraumatic stress disorder.

Objective: Previous research has reported hyperresponsivity in the amygdala and hyporesponsivity in ventral portions of the medial prefrontal cortex to threat-related stimuli in posttraumatic stress disorder (PTSD). Whether such findings generalize to more ambiguous stimuli and whether such brain activation abnormalities reflect familial vulnerabilities, trauma-exposure, or acquired characteristics of PTSD remain unclear. In this study, we measured brain responses to emotionally ambiguous stimuli (i.

Exaggerated amygdala response to threat and association with immune hyperactivity in depression.

Background: Depression is characterized by altered neurobiological responses to threat and inflammation may be involved in the development and maintenance of symptoms. However, the mechanistic pathways underlying the relationship between the neural underpinnings of threat, inflammation and depressive symptoms remain unknown.

Methods: Twenty participants with major depressive disorder (MDD) and 17 healthy controls (HCs) completed this study.

Neuroimaging correlates and predictors of response to repeated-dose intravenous ketamine in PTSD: preliminary evidence.

Promising initial data indicate that the glutamate N-methyl-D-aspartate (NMDA) receptor antagonist ketamine may be beneficial in post-traumatic stress disorder (PTSD). Here, we explore the neural correlates of ketamine-related changes in PTSD symptoms, using a rich battery of functional imaging data (two emotion-processing tasks and one task-free scan), collected from a subset of participants of a randomized clinical trial of repeated-dose intravenous ketamine vs midazolam (total N = 21). In a pre-registered analysis, we tested whether changes in an a priori set of imaging measures from a target neural circuit were predictive of improvement in PTSD symptoms, using leave-one-out cross-validated elastic-net regression models (regions of interest in the target circuit consisted of the dorsal and rostral anterior cingulate cortex, ventromedial prefrontal cortex, anterior hippocampus, anterior insula, and amygdala).

A neurobiological link between transportation noise exposure and metabolic disease in humans.

Background: Chronic transportation noise exposure associates with cardiovascular events through a link involving heightened stress-associated neurobiological activity (as amygdalar metabolic activity, AmygA) on F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG-PET/CT). Increased AmygA also associates with greater visceral adipose tissue (VAT) and type 2 diabetes mellitus (DM). While relationships between noise exposure and VAT and DM have been reported, the underlying mechanisms remain incompletely understood.

Stress-associated neurobiological activity associates with the risk for and timing of subsequent Takotsubo syndrome.

Aims: Activity in the amygdala, a brain centre involved in the perception of and response to stressors, associates with: (i) heightened sympathetic nervous system and inflammatory output and (ii) risk of cardiovascular disease. We hypothesized that the amygdalar activity (AmygA) ratio is heightened among individuals who develop Takotsubo syndrome (TTS), a heart failure syndrome often triggered by acute stress. We tested the hypotheses that (i) heightened AmygA precedes development of TTS and (ii) those with the highest AmygA develop the syndrome earliest.

Disentangling the Links Between Psychosocial Stress and Cardiovascular Disease.

Stress is a pervasive component of the human experience. While often considered an adversity to be ignored, chronic stress has important pathological consequences, including cardiovascular disease (CVD). Stress also increases the prevalence and severity of several CVD risk factors, including hypertension, diabetes mellitus, and obesity.

Greater Neurobiological Resilience to Chronic Socioeconomic or Environmental Stressors Associates With Lower Risk for Cardiovascular Disease Events.

Background: Chronic exposure to socioeconomic or environmental stressors associates with greater stress-related neurobiological activity (ie, higher amygdalar activity [AmygA]) and higher risk of major adverse cardiovascular events (MACE). However, among individuals exposed to such stressors, it is unknown whether neurobiological resilience (NBResilience, defined as lower AmygA despite stress exposure) lowers MACE risk. We tested the hypotheses that NBResilience protects against MACE, and that it does so through decreased bone marrow activity and arterial inflammation.

Targeting the anterior cingulate with bipolar and high-definition transcranial direct current stimulation.

Research on the feasibility of using transcranial direct current stimulation to modulate the function of the anterior cingulate cortex is limited in part due to its anatomical depth. However, high-definition transcranial direct current stimulation may be better able to reach the anterior cingulate cortex and modulate its function and behavioral outputs. The purpose of this study was to assess the feasibility of using high-definition transcranial direct current stimulation, as compared to traditional bipolar transcranial direct current stimulation, to modulate behavioral measures of anterior cingulate cortex function.

A neurobiological mechanism linking transportation noise to cardiovascular disease in humans.

Aims: Chronic noise exposure associates with increased cardiovascular disease (CVD) risk; however, the role of confounders and the underlying mechanism remain incompletely defined. The amygdala, a limbic centre involved in stress perception, participates in the response to noise. Higher amygdalar metabolic activity (AmygA) associates with increased CVD risk through a mechanism involving heightened arterial inflammation (ArtI).

Cingulate subregions in posttraumatic stress disorder, chronic stress, and treatment.

Decades of research have revealed that the cingulate cortex is important in posttraumatic stress disorder (PTSD). Initially inspired by basic rodent research examining the mechanisms of fear learning, researchers have attempted to determine the respective roles of the anterior cingulate cortex (ACC), anterior midcingulate cortex (aMCC), and posterior cingulate cortex (PCC) in PTSD. Various neuroimaging techniques have shown the ACC is both functionally hypoactive and structurally diminished in PTSD, while the aMCC is functionally hyperactive and structurally diminished.

Stress-Associated Neurobiological Pathway Linking Socioeconomic Disparities to Cardiovascular Disease.

Background: Lower socioeconomic status (SES) associates with a higher risk of major adverse cardiac events (MACE) via mechanisms that are not well understood.

Objectives: Because psychosocial stress is more prevalent among those with low SES, this study tested the hypothesis that stress-associated neurobiological pathways involving up-regulated inflammation in part mediate the link between lower SES and MACE.

Methods: A total of 509 individuals, median age 55 years (interquartile range: 45 to 66 years), underwent clinically indicated whole-body F-fluorodeoxyglucose positron emission tomography/computed tomography imaging and met pre-defined inclusion criteria, including absence of known cardiovascular disease or active cancer.

Amygdalar Metabolic Activity Independently Associates With Progression of Visceral Adiposity.

Context: Epidemiologic data link psychological stress to adiposity. The underlying mechanisms remain uncertain.

Objectives: To test whether (i) higher activity of the amygdala, a neural center involved in the response to stress, associates with greater visceral adipose tissue (VAT) volumes and (ii) this association is mediated by increased bone marrow activity.

Amygdalar activity predicts future incident diabetes independently of adiposity.

While it is established that psychosocial stress increases the risk of developing diabetes mellitus (DM), two key knowledge gaps remain: 1) the neurobiological mechanisms that are involved in mediating that risk, and 2) the role, if any, that adiposity plays in that mechanism. We tested the hypotheses that: 1) metabolic activity in the amygdala (AmygA), a key center involved in the neurobiological response to stress, associates with subsequent DM risk, and 2) this association is independent of adiposity. AmygA and adipose tissue volumes were measured, and serial blood assessments for DM were obtained in 232 subjects who underwent combined F-fluorodeoxyglucose positron emission tomography/computed tomography (F-FDG-PET/CT) imaging.