Johnny Ottesen

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  Patient specific modelling of the endocrine HPA-axis and its relation to depression: Ultradian and circadian oscillations
  Johnny Ottesen

  Depression is a widely spread disease: 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. We establish a statistical significant correlation between depression and a recently defined index characterising the hypothalamus-pituitary-adrenal (HPA) axis. The relation supports the common belief that depression is caused by malfunctions in the HPA-axis. We suggest a novel 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 generated in the hippocampus whereas the slower circadian rhythm is caused by the circadian clock. We show that these patterns fit data from 29 subjects. We demonstrate that patient-specific modelling is capable of making more precise diagnostics and offers a tool for individual treatment plans and more effective design of pharmaceutical molecules as a consequence. Three parameters related to depression are identified by non-linear mixed effects modelling and statistical hypothesis testing. These parameters represent underlying physiological mechanisms controlling the average levels as well as the ultradian frequency and amplitudes of the hormones ACTH and cortisol. The results are promising since they offer an exact aetiology for depression going from molecular level to systems physiology.