ABSTRACT
Chronic stress can be challenging, lead to maladaptive coping strategies, and cause negative mental and physical health outcomes. Early-life adversity exposes developing young to physical or psychological experiences that risks surpassing their capacity to effectively cope, thereby impacting their lifetime physical and mental wellbeing. Sensitivity to stressful events, like social isolation, has the potential to magnify stress-coping. Chronic stress through social defeat is an established paradigm that models adverse early-life experiences and can trigger enduring alterations in behavioral and neural phenotypes. To assess the degree to which stress resilience and sensitivity stemming from early-life chronic stress impact sociability, we exposed male prairie voles to chronic social defeat stress (CSDS) during adolescence. We simultaneously exposed subjects to either social isolation (CSDS+Isol) or group housing (CSDS+Soc) during this crucial time of development. On PND41, all subjects underwent a social approach test to examine the immediate impact of isolation, CSDS, or their combined effects on sociability. Unlike the CSDS+Isol group which primarily displayed social avoidance, the CSDS+Soc group was split by individuals exhibiting susceptible or resilient stress phenotypes. Notably, the Control+Soc and CSDS+Soc animals and their cage-mates significantly gained body weight between PND31 and PND40, whereas the Control+Isol and CSDS+Isol animals did not. These results suggest that the effects of early-life stress may be mitigated by having access to social support. Vasopressin, oxytocin, and opioids and their receptors (avpr1a, oxtr, oprk1, oprm1, and oprd1) are known to modulate social and stress-coping behaviors in the lateral septum (LS). Therefore, we did an mRNA expression analysis with RT-qPCR of the avpr1a, oxtr, oprk1, oprm1, and oprd1 genes to show that isolation and CSDS, or their collective influence, can potentially differentially bias sensitivity of the LS to early-life stressors. Collectively, our study supports the impact and dimensionality of early-life adversity because the type (isolation vs. CSDS), duration (acute vs. chronic), and combination (isolation + CSDS) of stressors can dynamically alter behavioral and neural outcomes.
ABSTRACT
B-type natriuretic peptide (BNP) has prognostic implications in patients with acute and chronic cardiac symptoms. Its prognostic role in asymptomatic patients with evidence of subclinical disease remains unclear. The population of this study included 2,458 asymptomatic adults (47% women) with an average Framingham risk score of 8.8 +/- 7% who underwent computed tomographic evaluation of coronary artery calcium (CAC). BNP levels were measured using the Triage CardioProfilER panel method. Cox proportional-hazards models were used to estimate time to a cardiovascular (CV) event (n = 84; 16 deaths, 12 myocardial infarctions, 8 cerebrovascular accidents or transient ischemic attacks, and 48 diagnoses of incident symptomatic coronary disease). Relative risk was calculated. The median follow-up time was 3.9 years (25th and 75th percentiles 2.9 and 4.0). The relative hazard for a CV event ranged from 2.2 to 7.5 for BNP values of 40 to 99.9 and > or =100 pg/ml (p <0.0001) compared to BNP <40 pg/ml. Similarly, CAC score was also highly predictive of CV events, with elevated hazard ratios of 2.8- to 48.7-fold for scores of 11 to 100 to > or =1,000 (p <0.0001) compared to no CAC. In a stepwise model, BNP was the second greatest estimator of CV outcomes (p = 0.016) after CAC (p <0.0001), even in models that included blood pressure and age. Hypertension, age > or =65 years, and CAC contained 28.4%, 40.7%, and 56.8%, respectively, of BNP risk. The combination of BNP > or =100 pg/ml and CAC score > or =400 identified 52.4% and 35.7% of CV events in patients with hypertension and in elderly patients beyond the Framingham risk score. In conclusion, BNP and CAC are independently predictive of CV events.
