In the Western world approximately 10% of the population experience severe depression at least once in
their lifetime and many more experience a mild form of depression. Depression has been associated with
malfunctions in the hypothalamus–pituitary–adrenal (HPA) axis. We suggest a novel mechanistic nonlinear
model capable of showing both circadian as well as ultradian oscillations of the hormone concentrations
related to the HPA-axis. The fast ultradian rhythm is assumed to originate from the hippocampus
whereas the slower circadian rhythm is assumed to be caused by the circadian clock. The model is able to
describe the oscillatory patterns in hormone concentration data from 29 patients and healthy controls.
Using non-linear mixed effects modeling with statistical hypothesis testing, three of the model parameters
are identified to be related to depression. These parameters represent underlying physiological
mechanisms controlling the average levels as well as the ultradian frequencies and amplitudes of the hormones
ACTH and cortisol. The results are promising since they point toward an exact etiology for depression.
As a consequence new biomarkers and pharmaceutical targets may be identified.