Background COVID-19 and home isolation has impacted quality of life, but the perceived impact on anxiety and sleep remains equivocal. The purpose of this study was to assess the impact of COVID-19 and stay-at-home orders on self-report anxiety and sleep quality, with a focus on sex differences. We hypothesized that the COVID-19 pandemic would be associated with increased anxiety and decreased sleep quality, with stronger associations in women. Methods One hundred three participants (61 female, 38 ± 1 years) reported perceived changes in anxiety and sleep quality due to stay-at-home orders during the COVID-19 pandemic and were administered the Spielberger State-Trait Anxiety Inventory (STAI), Pittsburgh Sleep Quality Index (PSQI), and Insomnia Severity Index (ISI). Chi-square and T test analyses were utilized to assess sex differences in reported anxiety and sleep. Analysis of covariance was used to compare the associations between reported impact of COVID-19 and anxiety/sleep parameters. Results Women (80.3%) reported higher prevalence of increased general anxiety due to COVID-19 when compared to men (50%; p = 0.001) and elevated STAI state anxiety compared to men (43 ± 1 vs. 38 ± 1 a.u., p = 0.007). Despite these differences in anxiety, the perceived impact of COVID-19 on PSQI was not different between sexes. However, when stratified by perceived changes in anxiety due to COVID-19, participants with higher anxiety responses to COVID-19 had higher ISI compared to those with no perceived changes in anxiety (9 ± 1 vs. 5 ± 1 a.u., p = 0.003). Additionally, participants who reported reduced sleep quality due to COVID-19 reported higher state anxiety (45 ± 1 a.u.) compared to those that perceived no change (36 ± 2 a.u., p = 0.002) or increased (36 ± 2 a.u., p < 0.001) sleep quality. Conclusion COVID-19 and state-ordered home isolation was associated with higher anxiety and reduced sleep quality, with a stronger association in women with respect to anxiety.

Binge alcohol consumption elicits acute and robust increases of muscle sympathetic nerve activity (MSNA), yet the impact of evening binge drinking on morning-after MSNA is unknown. The present study examined the effects of evening binge alcohol consumption on polysomnographic sleep and morning-after MSNA. We hypothesized that evening binge drinking (i.e. 4-5 drink equivalent in <2hrs) would reduce sleep quality and increase morning-after blood pressure (BP) and MSNA. Following a familiarization night within the sleep laboratory, twenty-two participants (12 men, 10 women; 25±1 years) were examined after simulated binge drinking or fluid control (randomized, crossover design). Morning MSNA was successfully recorded across both conditions in 16 participants (8 men, 8 women) during a 10-minute baseline and three Valsalva's maneuvers (VM). Binge drinking reduced rapid eye movement (REM) sleep (15±1 vs. 20±1%; p=0.003), increased stage II sleep (54±1 vs. 51±1%; p=0.002), increased total urine output (2.9±0.2 vs. 2.1±0.1 liters; p<0.001), but did not alter morning-after urine specific gravity. Binge drinking increased morning-after heart rate (65 (54-72) vs. 58 (51-67) beats/min; p=0.013), but not resting BP or MSNA. Binge drinking elicited greater sympathoexcitation during VM (38±3 vs. 43±3 bursts/min, p=0.036). Binge drinking augmented heart rate (p=0.002), systolic BP (p=0.022) and diastolic (p=0.037) BP reactivity to VM phase IV, and blunted cardiovagal baroreflex sensitivity during VM phases II (p=0.028) and IV (p=0.043). In conclusion, evening binge alcohol consumption disrupted REM sleep and morning-after autonomic function. These findings provide new mechanistic insight into the potential role of binge drinking on cardiovascular risk.

Hyperactivity of the orexin system within the paraventricular nucleus (PVN) has been shown to contribute to increased sympathetic nerve activity (SNA) and blood pressure (BP) in rodent animals. However, the underlying molecular mechanisms remain unclear. Here, we test the hypothesis that orexin system activation stimulates calcium/calmodulin-dependent kinase II (CaMKII) expression and activation, and stimulation of CaMKII expressing PVN neurons increases SNA and BP. Real-time PCR and/or western blot were carried out to test the effect of orexin-A administration on CaMKII expression in the PVN of normal Sprague Dawley (SD) rats and orexin receptor 1 (OX1R) expressing PC12 cells. Immunostaining was performed to assess OX1R cellular localization in the PVN of SD rats as well as orexin-A treatment on CaMKII activation in cultured hypothalamic neurons. In vivo sympathetic nerve recordings were employed to test the impact of optogenetic stimulation of CaMKII-expressing PVN neurons on the renal SNA (RSNA) and BP. The results showed that intracerebroventricular injection of orexin-A into the SD rat increases mRNA expression of CaMKII subunits in the PVN. In addition, Orexin-A treatment increases CaMKII expression and its phosphorylation in OX1R-expressing PC12 cells. Furthermore, Orexin-A treatment increases CaMKII activation in cultured hypothalamic neurons from neonatal SD rats. Finally, optogenetic excitation of PVN CaMKII-expressing neurons results in robust increases in RSNA and BP in SD rats. Our results suggest that increased orexin system activity activates CaMKII expression in cardiovascular relevant regions, and this may be relevant to the downstream cardiovascular effects of CaMKII.