Patient-specific modeling of the neuroendocrine HPA-axis and its relation to depression: Ultradian and circadian oscillations

Johanne Gudmand-Høyer, Stine Timmermann Ottesen, Johnny T. Ottesen

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.
OriginalsprogEngelsk
TidsskriftMathematical Biosciences
Vol/bind257
Sider (fra-til)23-32
Antal sider12
ISSN0025-5564
DOI
StatusUdgivet - 3 sep. 2014

Citer dette

@article{dba1b77121a44b00b5508bc4973b26c6,
title = "Patient-specific modeling of the neuroendocrine HPA-axis and its relation to depression: Ultradian and circadian oscillations",
abstract = "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 non-linear 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",
author = "Johanne Gudmand-H{\o}yer and Ottesen, {Stine Timmermann} and Ottesen, {Johnny T.}",
year = "2014",
month = "9",
day = "3",
doi = "10.1016/j.mbs.2014.07.013",
language = "English",
volume = "257",
pages = "23--32",
journal = "Mathematical Biosciences",
issn = "0025-5564",
publisher = "Elsevier Inc.",

}

Patient-specific modeling of the neuroendocrine HPA-axis and its relation to depression: Ultradian and circadian oscillations. / Gudmand-Høyer, Johanne; Ottesen, Stine Timmermann; Ottesen, Johnny T.

I: Mathematical Biosciences, Bind 257, 03.09.2014, s. 23-32.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Patient-specific modeling of the neuroendocrine HPA-axis and its relation to depression: Ultradian and circadian oscillations

AU - Gudmand-Høyer, Johanne

AU - Ottesen, Stine Timmermann

AU - Ottesen, Johnny T.

PY - 2014/9/3

Y1 - 2014/9/3

N2 - 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 non-linear 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

AB - 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 non-linear 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

U2 - 10.1016/j.mbs.2014.07.013

DO - 10.1016/j.mbs.2014.07.013

M3 - Journal article

VL - 257

SP - 23

EP - 32

JO - Mathematical Biosciences

JF - Mathematical Biosciences

SN - 0025-5564

ER -