ABSTRACT
Alcohol use disorder (AUD) is a highly prevalent, yet heterogenous condition linked to anxiety, reward sensitivity, and cognitive biases. Understanding cognitive mechanisms of specific AUD symptoms is crucial for developing tailored, effective interventions. This pilot study sought to assess whether two potential cognitive correlates of AUD-intolerance of uncertainty and delay discounting-differentially influence the relationship between AUD, anxiety sensitivity, and drinking motives. Individuals with mild-to-moderate AUD (n = 31) and healthy control participants (n = 31) completed a single-session lab study in which they performed a decision making under uncertainty task as a behavioral measure of uncertainty tolerance, completed a delay discounting task as a measure of reward sensitivity, and responded to surveys related to anxiety sensitivity, state and trait anxiety, intolerance of uncertainty, and drinking motives. Hierarchical regression results demonstrated a significant interaction between AUD status (AUD vs. control) on both self-reported (ß = 0.687, p = .020) and behavioral (ß = 0.777, p = .012) intolerance of uncertainty. Greater anxiety sensitivity was associated with heightened intolerance of uncertainty in those with AUD but not controls. Correlations showed that the coping drinking motive was significantly positively associated with anxiety sensitivity (r = 0.462, p = .010), self-reported (r = 0.535, p = .002), and behavioral intolerance of uncertainty (r = 0.396, p < .027) in participants with AUD but not controls. No significant associations between anxiety sensitivity, drinking motives, and delay discounting were observed in either the AUD or the control group. Intolerance of uncertainty may therefore represent a cognitive bias in which individuals with AUD and anxiety sensitivity drink to cope with environmental and internal uncertainty. (PsycInfo Database Record (c) 2024 APA, all rights reserved).
ABSTRACT
AIMS: Arrhythmogenic cardiomyopathy (ACM) is a myocardial disease caused mainly by mutations in genes encoding desmosome proteins ACM patients present with ventricular arrhythmias, cardiac dysfunction, sudden cardiac death, and a subset with fibro-fatty infiltration of the right ventricle predominantly. Endurance exercise is thought to exacerbate cardiac dysfunction and arrhythmias in ACM. The objective was to determine the effects of treadmill exercise on cardiac phenotype, including myocyte gene expression in myocyte-specific desmoplakin (Dsp) haplo-insufficient (Myh6-Cre:DspW/F) mice. METHODS AND RESULTS: Three months old sex-matched wild-type (WT) and Myh6-Cre:DspW/F mice with normal cardiac function, as assessed by echocardiography, were randomized to regular activity or 60 min of daily treadmill exercise (5.5 kJ work per run). Cardiac myocyte gene expression, cardiac function, arrhythmias, and myocardial histology, including apoptosis, were analysed prior to and after 3 months of routine activity or treadmill exercise. Fifty-seven and 781 genes were differentially expressed in 3- and 6-month-old Myh6-Cre:DspW/F cardiac myocytes, compared to the corresponding WT myocytes, respectively. Genes encoding secreted proteins (secretome), including inhibitors of the canonical WNT pathway, were among the most up-regulated genes. The differentially expressed genes (DEGs) predicted activation of epithelial-mesenchymal transition (EMT) and inflammation, and suppression of oxidative phosphorylation pathways in the Myh6-Cre:DspW/F myocytes. Treadmill exercise restored transcript levels of two-third (492/781) of the DEGs and the corresponding dysregulated transcriptional and biological pathways, including EMT, inflammation, and secreted inhibitors of the canonical WNT. The changes were associated with reduced myocardial apoptosis and eccentric cardiac hypertrophy without changes in cardiac function. CONCLUSION: Treadmill exercise restored transcript levels of the majority of dysregulated genes in cardiac myocytes, reduced myocardial apoptosis, and induced eccentric cardiac hypertrophy without affecting cardiac dysfunction in a mouse model of ACM. The findings suggest that treadmill exercise has potential beneficial effects in a subset of cardiac phenotypes in ACM.