Central serotonin transporter levels are associated with stress hormone response and anxiety.
BACKGROUND
Negative mood states are characterized by both stress hormone dysregulation and serotonergic dysfunction, reflected by altered thalamic serotonin transporter (5-HTT) levels. However, so far, no study examined the individual association between cortisol response and cerebral in vivo 5-HTT levels in patients suffering from negative mood states.


OBJECTIVE
The objective of this cross-sectional study was to assess the interrelation of cortisol response, thalamic 5-HTT levels, and anxiety in healthy subjects and two previously published samples of patients with unipolar major depression (UMD) and obsessive-compulsive disorder (OCD), controlling for age, gender, 5-HTT genotype, smoking, and seasonality.


METHODS
Regional 5-HTT levels and cortisol response to dexamethasone-corticotropin (Dex-CRH) challenge were assessed in consecutive samples of medication-free patients suffering from UMD (N = 10) and OCD (N = 10), and 20 healthy volunteers. The intervention used was combined Dex-CRH test and [(11)C]DASB positron emission tomography. The main outcome measures were: 5-HTT binding potential (BP(ND)) in a predefined thalamic ROI, cortisol response defined as the maximum cortisol increase in the combined Dex-CRH-test, and state of anxiety from the state-trait-anxiety inventory.


RESULTS
Reduced thalamic 5-HTT BP(ND) was associated with increased cortisol response (r = -0.35, p < 0.05; in patients: r = -0.53, p < 0.01) and with increased state anxiety (r = -0.46, p < 0.01), surviving correction for age, gender, 5-HTT genotype, smoking, and seasonality (p < 0.05). The 5-HTT genotype, on the contrary, was not significantly associated with cortisol response (p = 0.19) or negative mood (p = 0.23).


CONCLUSIONS
The association between stress hormone response, thalamic 5-HTT levels, and anxiety in patients suffering from negative mood states suggests an interaction between two major mechanisms implicated in negative mood states in humans.
Reimold
Matthias
M
Department of Nuclear Medicine, University of Tübingen, Tübingen, Germany.
Knobel
Astrid
A
Rapp
Michael A
MA
Batra
Anil
A
Wiedemann
Klaus
K
Ströhle
Andreas
A
Zimmer
Anke
A
Schönknecht
Peter
P
Smolka
Michael N
MN
Weinberger
Daniel R
DR
Goldman
David
D
Machulla
Hans-Jürgen
HJ
Bares
Roland
R
Heinz
Andreas
A
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology; D000328:Adult; D001008:Anxiety Disorders / Q000503:physiopathology*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000503:physiopathology*; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009771:Obsessive-Compulsive Disorder / Q000503:physiopathology*; D049268:Positron-Emission Tomography / Q000379:methods; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D013788:Thalamus / Q000378:metabolism
D050486:Serotonin Plasma Membrane Transport Proteins; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone