A randomized controlled trial for symptoms of anxiety and depression: Effects of a 1-day acceptance and commitment training workshop.

BACKGROUND: Cognitive-behavioral therapies often are recommended for anxiety disorders. However, treatment adherence and compliance are major barriers for these treatments, which are often delivered in 10 to 12 sessions over several months. This randomized controlled trial (trial registration NCT02915874 at www.clinicaltrials.gov) examined the effectiveness and feasibility of a 1-day cognitive-behavioral intervention for mixed anxiety. METHODS: A total of 72 adults with moderate-to-high anxiety were randomized into a 1-day acceptance and commitment therapy (ACT) work-shop (n = 44) or treatment as usual (n = 28). Follow-up assessments were conducted 6 and 12 weeks after the workshop. Clinical outcomes were anxiety (primary) and depressive (secondary) symptoms, as measured by the Beck Anxiety Inventory and Beck Depression Inventory-II, respectively. Proposed mediators of ACT-psychological flexibility and commit-ted action-also were examined. RESULTS: Participants assigned to the ACT workshop showed significant improvements in anxiety (beta = -1.13; P = .02) and depression (beta = -1.09; P = .02) after 12 weeks. Consistent with the theoretical model, these clinical improvements were mediated by psychological flexibility and committed action. Notable limitations included the sample size, inability to blind to treatment condition, and a racially and ethnically homogeneous sample. CONCLUSIONS: Our 1-day ACT workshop was effective for anxiety with co-occurring depressive symptoms. One-day interventions are a promising alternative to weekly treatments.

One-day acceptance and commitment therapy (ACT) workshop improves anxiety but not vascular function or inflammation in adults with moderate to high anxiety levels in a randomized controlled trial.

OBJECTIVE: Acceptance and Commitment Therapy (ACT) is a behavioral intervention demonstrating sustained improvements in anxiety in individuals with chronic anxiety and psychological distress. Because anxiety disorders are associated with the development of cardiovascular disease (CVD), we hypothesized that a novel 1-day ACT workshop would both lower anxiety and improve vascular function in persons with moderate/high anxiety. METHODS: In a randomized controlled study, 72 adults (age 33.9 ± 8.6 (SD) years) with baseline moderate/high anxiety completed a one-day ACT intervention (n = 44, age 33.9 ± 8.7 years) or control (n = 28, age 37.1 ± 10.1 years). Pre-specified secondary outcomes were measured over 12 weeks: aortic stiffness (carotid-femoral pulse wave velocity [cfPWV]), forearm vascular endothelial function (post-ischemic peak forearm blood flow [FBF] via plethysmography), and brachial artery flow-mediated dilation (FMD). Carotid artery stiffness (ß-stiffness index), and inflammatory markers (C-reactive protein and tumor necrosis factor-alpha) were also explored. RESULTS: Although the intervention had a significant and sustained effect on the primary outcome of anxiety as measured by the Beck Anxiety Inventory, the 1-day ACT workshop was not associated with improvement in vascular or inflammatory endpoints. The intervention was unexpectedly associated with increases in ß-stiffness index that were also associated with changing trait anxiety. CONCLUSION: Anxiety improvements did not translate into improvements in any of the vascular function outcomes. This may reflect a less-than-robust effect of the intervention on anxiety, failure in design to select those with vascular dysfunction, or not intervening on a relevant causal pathway. (Trial registration NCT02915874 at www.clinicaltrials.gov).

Bipolar disorder and related mood states are not associated with endothelial function of small arteries in adults without heart disease.

BACKGROUND: Individuals with bipolar disorder are at increased risk for adverse cardiovascular disease (CVD) events. This study aimed to assess endothelial function and wave reflection, a risk factor for CVD, as measured by finger plethysmography in bipolar disorder to investigate whether CVD risk was higher in bipolar disorder and altered during acute mood episodes. We hypothesized that EndoPAT would detect a lower reactive hyperemia index (RHI) and higher augmentation index (AIX) in individuals with bipolar disorder compared with controls. Second, we predicted lower RHI and higher AIX during acute mood episodes. METHODS: Reactive hyperemia index and augmentation index, measures of microvascular endothelial function and arterial pressure wave reflection respectively, were assessed using the EndoPAT 2000 device in a sample of 56 participants with a DSM-IV diagnosis of bipolar I disorder with 82 measures spanning different mood states (mania, depression, euthymia) and cross-sectionally in 26 healthy controls. RESULTS: RHI and AIX were not different between adults with and without bipolar disorder (mean age 40.3 vs. 41.2years; RHI: 2.04±0.67 vs. 2.05±0.51; AIX@75 (AIX adjusted for heart rate of 75): 1.4±19.7 vs. 0.8±22.4). When modeled in linear mixed models with a random intercept (to account for repeated observations of persons with bipolar disorder) and adjusting for age and sex, there were no significant differences between those with bipolar disorder and controls (p=0.89 for RHI; p=0.85 for AIX@75). CONCLUSIONS: Microvascular endothelial function and wave reflection estimated by finger plethysmography were unable to detect differences between adults with and without bipolar disorder or changes with mood states. Future research is necessary to identify more proximal and sensitive, yet relevant, biomarkers of abnormal mood-related influences on CVD risk or must target higher risk samples.

High trans but not saturated fat beverage causes an acute reduction in postprandial vascular endothelial function but not arterial stiffness in humans.

A diet high in trans-fatty acids (TFAs) is associated with a higher risk of cardiovascular disease (CVD) than a diet high in saturated fatty acids (SFAs), but the mechanisms remain unclear. We hypothesized that a beverage high in TFAs would cause a larger reduction in postprandial endothelial function and an increase in arterial stiffness, in part from greater reductions in insulin sensitivity, compared with a beverage high in SFAs. Eleven healthy adults (aged 47±5 years) ingested a warm test beverage (520 kcal, 56 g total fat, 5 g carbohydrate, 1 g protein) high in either TFAs or SFAs in a randomized cross-over study. Ingestion of the beverage high in TFAs (p<0.01) but not high in SFAs (p=0.49) decreased endothelial function (brachial artery flow-mediated dilation, mmΔ) at 3-4 hours (p<0.01 for time; p=0.034 for interaction), but did not alter aortic stiffness or carotid ß-stiffness. The homeostasis model of insulin resistance (interaction p=0.062) tended to decrease after SFAs but not TFAs. A beverage high in TFAs but not SFAs results in a postprandial reduction in endothelial function and a trend for decreased insulin sensitivity, potentially explaining the higher risk of CVD with a diet high in TFAs.

Regulation of lung neutrophil recruitment by VE-cadherin.

Lung inflammatory disease is characterized by increased polymorphonuclear leukocyte (PMN) infiltration and vascular permeability. PMN infiltration into tissue involves signaling between endothelial cells and migrating PMNs, which leads to alterations in the organization of adherens junctions (AJs). We addressed the possible role of the protein constituents of AJs, endothelium-specific vascular-endothelial (VE)-cadherin, in the migration of PMNs. Studies were made using VE-cadherin mutant constructs lacking the extracellular domain (DeltaEXD) or, additionally, lacking the COOH-terminus beta-catenin-binding domain (DeltaEXDDeltabeta). Either construct was transduced in pulmonary microvessel endothelia of mice using cationic liposome-encapuslated cDNA constructs injected intravenously. Optimal expression of constructs was seen by Western blot analysis within 24 h. Vessel wall liquid permeability measured as the lung microvessel capillary filtration coefficient increased threefold in DeltaEXD-transduced lungs, indicating patency of interendothelial junctions, whereas the control DeltaEXDDeltabeta construct was ineffective. To study lung tissue PMN recruitment, we challenged mice intraperitoneally with LPS (3 mg/kg) for 6 h and measured PMN numbers by bronchoalveolar lavage and their accumulation morphometrically in lung tissue. DeltaEXD expression markedly reduced the PMN sequestration and migration seen in nontransfected (control wild type) or DeltaEXDDeltabeta-transfected (negative control) mice challenged with LPS. In addition, DeltaEXD transfection suppressed LPS-induced activation of NF-kappaB and consequent ICAM-1 expression. These results suggest that disassembly of VE-cadherin junctions serves as a negative signal for limiting transendothelial PMN migration secondary to decreased ICAM-1 expression in the mouse model of LPS-induced sepsis.

De novo ICAM-1 synthesis in the mouse lung: model of assessment of protein expression in lungs.

Because most studies addressing the regulatory mechanisms of intercellular adhesion molecule (ICAM)-1 expression have used cultured endothelial cells, we set out to develop an isolated mouse lung preparation to study gene and protein expression in its proper cellular context in the organ. Lungs from CD1 mice were isolated and perfused (2 ml/min, 37 degrees C) with a recirculating volume of RPMI 1640 solution supplemented with 3 g/100 ml albumin. Lungs maintained their isogravimetric state for 4 h. Tumor necrosis factor (TNF-alpha; 2,000 U/ml) was added to the perfusate for 0.5, 1, 2, or 3.5 h to induce ICAM-1 expression or lungs received no treatment (control). After quick-freezing the lungs using liquid nitrogen at different time points, the prepared tissue homogenates were analyzed for ICAM-1 protein expression by Western blotting and NF-kappaB activation by electrophoretic mobility shift assay. TNF-alpha caused a progressive increase in NF-kappaB activity after 0.5 h and ICAM-1 protein expression two- to threefold of basal after 2 h. Untreated lungs expressed a low and constant level of ICAM-1 between 0 and 3.5 h. TNF-alpha failed to induce NF-kappaB activation and ICAM-1 expression in lungs of NADPH oxidase-deficient mice lacking p47(phox). We disaggregated mouse lungs using collagenase and stained the cells for ICAM-1 and VE-cadherin (used as an endothelial marker) to assess the in situ endothelial-specific expression of ICAM-1. We observed that TNF-alpha challenge resulted in increased ICAM-1 expression in endothelial cells freshly isolated from lungs. These data show the role of NADPH oxidase-derived oxidant signaling in the mechanism of NF-kappaB activation and ICAM-1 expression in mouse lung endothelial cells. Moreover, the general method presented herein has potential value in assessing mechanisms of gene and protein expression in the isolated-perfused mouse lung model.