Salivary Aldosterone, Central and Peripheral Mineralocorticoid Receptor Function and Their Impact on the Course of Depression

Background: Aldosterone and mineralocorticoid receptor (MR) function appear to play a role in depression. Central and peripheral biomarker parameters of MR function at baseline, their early (change within two weeks) and late (change within six weeks) plasticity were examined with regard to their relationship to clinical treatment outcome after six weeks in patients with acute major depression. Methods: Twenty-four patients with major depression were examined three times during six weeks. Aldosterone and cortisol salvia samples were taken at 7:00 am before patients got out of bed. Easy to use e-devices were used to measure markers of central MR function, i.e. slow wave sleep (SWS) and heart rate variability (HRV). A newly developed scale determined salt taste intensity (STI) and salt pleasantness (SP) of a 0.9% salt solution. In addition, systolic blood pressure (SBP) and plasma electrolytes (Mg2+, Na+, K+) were determined as markers of peripheral MR activity. The relationship between the levels of these biomarkers at baseline, their early and late plasticity and the relative change in clinical outcome parameters (Hamilton Depression Rating Scale with 6 and 21 items, QIDS-SR-16 and BDI) after six weeks of treatment was investigated. Results: By trend a higher baseline aldosterone to cortisol ratio (aldo/cort) (p < 0.1) and lower baseline SBP (p < 0.05) predicted poor outcome, independent of gender. Only in male patients lower baseline SP, lower SWS and higher HRV predicted beneficial outcome (p < 0.05). Likewise, in male patients low baseline Na+ appeared to be by trend predictive for a poor outcome (p = 0.050). Independent of gender an early cortisol reduction (p < 0.05) did predict clinical improvement, whereas by trend an early SWS increase was associated with better outcome (p < 0.1). Only in female patients an early Na+/K+ ratio increase appeared to be related to a better outcome (p < 0.05). By trend only in male patients a late HRV reduction was associated with beneficial outcome (p < 0.1). Conclusion: Correlates of higher baseline central MR activation were associated with poorer clinical improvement, particularly in men. This contrasted with a lower sensitivity of peripheral MR function at baseline in more refractory patients. As one potential mechanism to consider, Na+ loss on the basis of dysfunctional peripheral MR function and additional environmental factors may trigger increased aldosterone secretion and consequently lead to a less favorable outcome. Results for the parameter plasticity were heterogeneous. In the course of depression markers of increasing central as well as peripheral MR activation were found to be related to a favorable outcome. These makers were: decreasing cortisol (independent of aldosterone), increasing SWS, decreasing HRV and increasing Na+ plasma concentrations. Of note gender differences may exist in terms of MR function. This study showcases the usefulness of biological markers, which can be obtained at bedside, to achieve individualized medicine in therapy refractory depression