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Neurobiologically Resilient Individuals Have Reduced Risk of Cardiovascular Disease

Key findings

  • This retrospective study investigated the effect of "neurobiological resilience"—lower amygdalar metabolic activity—on the risk of cardiovascular disease among individuals chronically exposed to socioeconomic and/or environmental stressors
  • Exposure to conditions of low income, high crime or high ambient noise was associated with greater amygdalar activity
  • Stress-exposed individuals with lower amygdalar activity—higher neurobiological resilience—had a significantly lower risk of major adverse cardiovascular events
  • This study supports efforts to develop interventions that would improve neurobiological resilience, especially among individuals who are exposed to chronic external stressors or have an increased risk of developing cardiovascular disease

Psychosocial stress has long been known to be associated with increased risk of cardiovascular disease. Individuals vary in their perception of stress, and assessments of psychological "resilience" capture the ratio of the stressor's emotional costs, modulated by the interpretation of the threat associated with that stressor, to a host of mind body protective factors and maladaptive behaviors.

Several studies have suggested that psychological resilience is associated with lower cardiovascular (CVD) risk. Now, Massachusetts General Hospital researchers offer a novel definition of resilience—neurobiological resilience—characterized by lower metabolic activity in the amygdala, the brain's stress-responding region.

In Circulation: Cardiovascular Imaging, Tawseef Dar, MD, former research fellow, and Ahmed Tawakol, MD, co-director of the Cardiac MR PET CT Program in the Cardiology Division, and Gregory Fricchione, MD, associate chief of the Department of Psychiatry at Mass General, show that neurobiological resilience affects the risk of CVD.

Study Methods

18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) can quantify metabolic activity in the bone marrow (a measure of leukopoiesis) and the arterial wall (a measure of atherosclerotic inflammation) as well as the amygdala. The researchers analyzed data on 256 adults who underwent 18F-FDG-PET/CT between 2005 and 2008 and were free of CVD.

Using zip codes and home addresses, it was determined that 166 of the patients were "stress-exposed," meaning they resided in low-income and/or high-crime neighborhoods and/or were chronically exposed to noise >45 dBA.

Amygdalar Activity and Stressors

Amygdalar activity (AmygA) was quantified as the ratio of metabolic activity of the amygdala to the metabolic activity of regulatory regions in the cerebral cortex. AmygA increased significantly in proportion to the number of measured stressors. Neurobiological resilience was defined as having lower AmygA (<1 standard deviation above the mean) despite chronic exposure to at least one of the three chronic stressors that were assessed.

AmygA Predicts CVD Among Those Exposed to Stressors

The primary endpoint was major adverse cardiovascular events (MACE), defined as CVD death, myocardial infarction, unstable angina, cerebrovascular accident, heart failure or need for revascularization for coronary or peripheral artery disease. 7% of stress-exposed individuals developed MACE over a median follow-up of 3.75 years.

In the stress-exposed group, the researchers found:

  • AmygA as a continuous variable was associated with MACE risk even after adjustment for age, sex and CVD risk factors (HR, 1.93; 95% CI, 1.37–2.71; P < 0.001)
  • AmygA remained associated with MACE regardless of the number or type of stressors
  • When AmygA was dichotomized, lower AmygA (i.e., higher neurobiological resilience) was linked to significantly lower MACE risk (>50% relative risk reduction)

Potential Mechanisms

In the stress-exposed group, higher AmygA was associated with significantly higher leukopoiesis and arterial inflammation regardless of the number or type of stressors. The link between lower neurobiological resilience and higher MACE risk was significantly mediated by higher arterial inflammation.

Laying the Groundwork for Novel Interventions

Neurobiological resilience appears to be able to provide a protective effect against MACE. It may represent improvement in emotion regulation, i.e., enhancement of medial prefrontal cortical (mPFC) inhibition of amygdalar overactivation. Psychological resilience strengthens this mPFC modulation of amygdalar tone. Therefore, this study supports efforts to develop mind body interventions that would improve neurobiological resilience, especially among individuals who are exposed to chronic external stressors or have an increased risk of CVD.

7%
of patients exposed to chronic socioeconomic and/or environmental stressors had cardiovascular events

2x
greater risk of cardiovascular events in stress-exposed patients with lower neurobiological resilience

>50%
relative reduction in risk of cardiovascular events among stress-exposed patients with higher neurobiological resilience

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