Testosterone levels in healthy men correlate negatively with serotonin 4 receptor binding

TY - JOUR

T1 - Testosterone levels in healthy men correlate negatively with serotonin 4 receptor binding

AU - Perfalk, Erik

AU - Cunha-Bang, Sofi da

AU - Holst, Klaus K.

AU - Keller, Sune

AU - Svarer, Claus

AU - Knudsen, Gitte M.

AU - Frokjaer, Vibe G.

PY - 2017/7

Y1 - 2017/7

N2 - The serotonergic system integrates sex steroid information and plays a central role in mood and stress regulation, cognition, appetite and sleep. This interplay may be critical for likelihood of developing depressive episodes, at least in a subgroup of sensitive individuals. The serotonin 4 receptor (5-HT4R) indexes central serotonergic tonus, which may be related to endogenous sex-steroid levels in the mentally healthy state even though this remains elusive. Here we evaluate if peripheral levels of estradiol and testosterone are associated with 5-HT4R binding as imaged by [11C]SB207145 positron emission tomography in a group of 41 healthy men. We estimated global 5-HT4R binding using a latent variable model framework, which models shared correlation between 5-HT4R across multiple brain regions (hippocampus, amygdala, posterior and anterior cingulate, thalamus, pallidostriatum and neocortex). We tested whether testosterone and estradiol predict global 5-HT4R, adjusting for age. We found that testosterone, but not estradiol, correlated negatively with global 5-HT4R levels (p = 0.02) suggesting that men with high levels of testosterone have higher cerebral serotonergic tonus. Our findings corroborate the link between sex hormone levels and serotonin signalling. Future longitudinal studies in clinical relevant populations are needed to elucidate the potential importance of testosterone in the pathophysiology of e.g. major depression and its treatment.

AB - The serotonergic system integrates sex steroid information and plays a central role in mood and stress regulation, cognition, appetite and sleep. This interplay may be critical for likelihood of developing depressive episodes, at least in a subgroup of sensitive individuals. The serotonin 4 receptor (5-HT4R) indexes central serotonergic tonus, which may be related to endogenous sex-steroid levels in the mentally healthy state even though this remains elusive. Here we evaluate if peripheral levels of estradiol and testosterone are associated with 5-HT4R binding as imaged by [11C]SB207145 positron emission tomography in a group of 41 healthy men. We estimated global 5-HT4R binding using a latent variable model framework, which models shared correlation between 5-HT4R across multiple brain regions (hippocampus, amygdala, posterior and anterior cingulate, thalamus, pallidostriatum and neocortex). We tested whether testosterone and estradiol predict global 5-HT4R, adjusting for age. We found that testosterone, but not estradiol, correlated negatively with global 5-HT4R levels (p = 0.02) suggesting that men with high levels of testosterone have higher cerebral serotonergic tonus. Our findings corroborate the link between sex hormone levels and serotonin signalling. Future longitudinal studies in clinical relevant populations are needed to elucidate the potential importance of testosterone in the pathophysiology of e.g. major depression and its treatment.

KW - 5-HT4

KW - Brain imaging

KW - Estradiol

KW - Positron emission tomography

KW - Sex hormones

U2 - 10.1016/j.psyneuen.2017.03.018

DO - 10.1016/j.psyneuen.2017.03.018

M3 - Journal article

C2 - 28426945

AN - SCOPUS:85017560850

SN - 0306-4530

VL - 81

SP - 22

EP - 28

JO - Psychoneuroendocrinology

JF - Psychoneuroendocrinology

ER -