Patient specific modeling of the HPA axis related to clinical diagnosis of depression.
A novel model of the hypothalamic-pituitary-adrenal axis is presented. The axis is an endocrine system responsible for coping with stress and it is likely to be involved in depression. The dynamics of the system is studied and existence, uniqueness and positivity of the solution and the existence of an attracting trapping region are proved. The model is calibrated and compared to data for healthy and depressed subjects. A sensitivity analysis resulting in a set of identifiable physiological parameters is provided. A subset is selected for parameter estimation and a reduced version of the model is stated and an approximated version is discussed. The model is physiologically based, thus parameters are representative for gland functions or elimination processes. Hence the model may be used for pointing out pathologies by parameter estimation and hypothesis testing whereby it may be used as an objective and refined method for diagnosing depression and suggesting individual treatment protocols. Finally, the method may inspire pharmaceutical companies to develop target specific psychopharmaca for more effective and individual treatment.
Department of Applied Mathematics and Computer Science, Technical University of Denmark, 2800 Kgs. Lyngby, Denmark.
Elisabeth O
EO
Bangsgaard
Department of Science and Environment, Roskilde University, Building 27.1, 4000 Roskilde, Denmark. Electronic address: johnny@ruc.dk.
Johnny T
JT
Ottesen
D003866:Depressive Disorder / Q000378:metabolism*; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D066230:Patient-Specific Modeling; D010913:Pituitary-Adrenal System / Q000378:metabolism*
Bio-marker; Clinical impact; Depression; HPA axis; Mathematical modeling; Non-linear ODE model; Parameter estimation; Patient specific