Mineralocorticoid Receptor Dysfunction in Major Depressive Disorder: Its Effect on Gait, Potential Relationship to Normal Pressure Hydrocephalus and the Influence of the Inhibition of 11ß-Hydroxysteroid-Dehydrogenase with an Extract from Glycyrrhiza Glabra

Background: Mineralocorticoid receptor (MR) dysfunction plays an important role in the pathophysiology of a subtype of major depressive disorder (MDD). Desensitised peripheral MR appears to lead to an increase in aldosterone levels and consequently to central MR overactivity. Since this subtype is particularly associated with a therapy-refractory course, a detection by means of specific biomarkers and a targeted therapy would be of special value. Some related biomarkers have already been identified. In the context of this study, the gait pattern as a potential biomarker will be addressed in particular. Furthermore, the influence of the additional administration of Glycyrrhiza glabra extract (GG), which is involved in blood pressure and neuroendocrine regulation by affecting MR activity, on the clinical course and change of biomarkers will be investigated. Methods: Twenty-four inpatients were included in the study. The examinations took place at baseline, after two weeks and after six weeks. Depression severity was assessed by questionnaires (Hamilton Depression Rating Scale, Beck Depression Inventory, Global Assessment of Functioning, Quick Inventory of Depressive Symptomatology). Aldosterone and cortisol levels were determined via saliva samples, electrolytes via blood samples. Gait analysis was performed using the GaitAnalysisPro® application. In addition, a questionnaire was assessed (iNPHGS), which also included gait disturbances as a symptom. Furthermore, heart rate variability and blood pressure were determined. Twelve subjects received antidepressant therapy according to German guidelines (treatment as usual, TAU group). The other twelve subjects additionally received glycyrrhiza glabra extract (GG) twice a day (GG group) which is a moderator of MR activity and may therefore affect the selected biomarkers. Results: Gait disturbances, as measured by higher scores in the iNPHGS, were associated with more severe depression at baseline (p < 0.05). Furthermore, a more symmetrical gait was demonstrated in subjects with more severe depression (p < 0.1). In the TAU group, the decrease in depressive symptoms correlated with the decrease in gait symmetry by late follow-up (p < 0.1) and a clinical improvement was associated with a decrease in aldosterone levels (p < 0.05). A small vertical center of mass displacement (COMD), which can be regarded as a sign of more stable gait, was positively predictive (p < 0.1) of improvement in depressive symptoms by early follow-up in the GG group. In the TAU group, there was a correlation between clinical outcome and a decrease in vertical COMD at late follow-up (p < 0.05). Faster clinical improvement was observed under adjunct GG administration (p < 0.01). In accordance with this, there was a significant difference in the changes of iNPHGS between the two groups until early follow-up (p < 0.01) and in the alteration of the sodium (Na⁺) to potassium (K⁺) ratio until late follow-up (p < 0.05). Although not significant, there was a decrease in systolic and diastolic blood pressure in the TAU group, whereas the parameters increased in the GG group at early follow-up. Conclusion: In the gait analysis, vertical COMD, bilateral symmetry and iNPHGS proved to be particularly promising parameters for assessing MDD associated with MR dysfunction. Furthermore, a faster clinical improvement was observed under adjunct GG administration. In the context of GG administration, iNPHGS and blood pressure were found to be potential markers for early, and the Na⁺/K⁺ ratio for late clinical improvement. It would be conceivable to use these parameters to monitor the therapy.