Introduction:
Increased aldosterone levels cause central mineralocorticoid receptor (MR) overactivity
and is associated with therapy refractoriness in patients with major depression. Heart-rate-variability,
changes in slow-wave sleep and an increased salt appetite have recently been demonstrated
to be predictive biomarkers for such a condition. Those patients also show increased
volume of the cerebral ventricular system, potentially related to MR activation of
cerebrospinal fluid secretion. This resembles mild forms of idiopathic normal pressure
hydrocephalus (iNPH). Therefore, the present study was conducted to investigate possible
relationships between the MR overactivity and gait disturbances, which are typical
symptoms of iNPH.
Methods:
Ten inpatients with major depression were observed for six weeks. They were examined
at the baseline and, after two weeks and 6 weeks of entering the observational study.
MR-related biomarkers and clinical outcome were determined (saliva aldosterone and
cortisol, HAMD-21, GAF). Furthermore, the gait of the patients was analyzed by measuring
gait speed, cadence, step length, its coefficient of variation, with the smartphone
app GaitAnalysisPro Application, which analyzes gait after mounting the device to
the subject. To explore the symptoms of normal pressure hydrocephalus the idiopathic
normal pressure hydrocephalus grading scale (iNPHGS) was used. A correlative analysis
of the pooled dataset, combining data from all visits, was performed.
Results:
High aldosterone levels correlated to a lower gait speed (p = 0.031; Pearson Corellations
Coefficient R =-0.45). Also, a low cortisol-aldosterone-ratio correlated with low
gait speed (p = 0.036; R = 0.44) and a shorter step length (p = 0.022; R = 0.485).
A low coefficient of variation of gait cycle correlated with higher scores in iNPHGS
(p = 0.026; R =-0.453). Higher scores in iNPHGS also correlated by trend with higher
scores in HAMD-21 (p = 0.062; R = 0.372) and significantly with lower scores in GAF
(p = 0.021) as well as with lower HRV (p = 0.050; R =-0.396). No relationship to sleep
parameters were detected.
Conclusion:
Low gait speed, a low coefficient of variation and a low step length seem to be marker
for increased aldosterone levels, which previously have been linked to therapy refractoriness
of depression as well as increased cerebral ventricular volume. If confirmed, gait
disturbances in MDE may reflect iNPH like symptoms and point to therapy refractoriness.
