title: Central serotonin transporter levels are associated with stress hormone response and anxiety.
abstract: 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.
authors.affiliation: Department of Nuclear Medicine, University of Tübingen, Tübingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Reimold
authors.forename: Astrid
authors.initials: A
authors.lastname: Knobel
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rapp
authors.forename: Anil
authors.initials: A
authors.lastname: Batra
authors.forename: Klaus
authors.initials: K
authors.lastname: Wiedemann
authors.forename: Andreas
authors.initials: A
authors.lastname: Ströhle
authors.forename: Anke
authors.initials: A
authors.lastname: Zimmer
authors.forename: Peter
authors.initials: P
authors.lastname: Schönknecht
authors.forename: Michael N
authors.initials: MN
authors.lastname: Smolka
authors.forename: Daniel R
authors.initials: DR
authors.lastname: Weinberger
authors.forename: David
authors.initials: D
authors.lastname: Goldman
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Machulla
authors.forename: Roland
authors.initials: R
authors.lastname: Bares
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
mesh_terms: 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
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D003907:Dexamethasone; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone