A Comparative Analysis of a Perceptual Hearing Loss Assessment Dataset and the International Classification of Functioning, Disability, and Health Core Sets for Hearing Loss.

The body's response to an acute stressful situation enables individuals to respond adequately to the perceived threat and helps restore homeostasis (). Stressors trigger a chain of behavioral and physiological responses. The physiological responses are mainly characterized by the activation of the two main stress systems – the hypothalamic-pituitary-adrenal (HPA) axis and the sympathetic nervous system (). In parallel, the immune system is activated, leading to the release of proinflammatory cytokines, such as interleukin-6 (IL-6) (). In healthy conditions, this inflammatory response is predominantly suppressed by cortisol, released through HPA axis activity (). Importantly, immune activation occurs not only in response to physical stressors or injury, but also in response to psychological stressors, such as experimentally induced psychosocial stress (), with IL-6 levels typically peaking around 90 min after stressor onset (). Chronic activation of physiological stress systems results in alterations of HPA axis and autonomic activity (), as well as a disruption of immune functioning. One factor that causes sustained activation of stress systems is chronic alcohol consumption. Not only has it been shown that chronic alcohol use leads to elevated basal stress system activity, but also blunted responses of the HPA axis to acute stressors (; , ; ). Similarly, previous analyses from our own group showed dampened physiological stress responses in patients with AUD during early abstinence, despite elevated self-reported affective stress experience (). In line with chronically elevated stress systems’ activity, higher levels of the inflammatory markers IL-6 (; ) and C-reactive protein (CRP) (; ) have been found in patients with AUD in comparison to healthy controls. However, it is yet unclear how chronic alcohol consumption perturbs the inflammatory responses to acute stressful situations, such as the release of IL-6. Given reduced glucocorticoid-mediated suppression, it can be hypothesized that IL-6 might increase more strongly in response to acute stress in these individuals. To our knowledge, only two studies have examined IL-6 responses to acute stress in AUD, both using a personalized stress imagery script and a relaxing, non-physiologically arousing script as a control condition. Fox and colleagues measured cytokine concentrations beginning approximately 1 h after insertion of a catheter until 30 min () or 60 min () after the script imagery. The studies reported a reduced IL-6 response of patients with AUD during early abstinence compared to a control group 15 to 30 min after the imagery, but no significant differences afterwards. These results contradict a meta-analysis that showed that the effects of stress on IL-6 levels are not significant within the first 30 min and increase until approximately 90 min after the exposure to the stressor (). In addition, the findings in both studies were not specific to the stress script imagery, but also occurred for the control condition. Whether or not these deviations from the expected IL-6 response reflect true underlying differences in AUD that can also be found in stress paradigms involving social-evaluative elements — which elicit stronger stress responses than imagery paradigms () — or arise from sampling error remains to be clarified. Importantly, systemic inflammation has also been connected to depressive symptoms: Several studies have found associations between depressive symptoms and circulating IL-6 levels in healthy subjects and patients diagnosed with depression (; ), with the connection being driven in particular by somatic symptoms (). In the context of AUD, however, the relationship appears to be more complex. reported that the amount of alcohol intake moderated the relationship between depression severity and IL-6 levels in patients with AUD during early to prolonged abstinence. In particular, they found higher IL-6 levels in AUD patients with major depression compared to non-depressed patients only among individuals consuming lower amounts of alcohol, whereas this difference was absent in patients with higher alcohol use. This could possibly reflect a ceiling effect in heavy drinkers, where alcohol-related systemic inflammation masks depression-related IL-6 elevations, although the exact mechanisms remain unclear.