Prefrontal serotonin transporter availability is positively associated with the cortisol awakening response.
Stress sensitivity and serotonergic neurotransmission interact, e.g. individuals carrying the low-expressing variants (S and LG) of the 5-HTTLPR promoter polymorphism of the serotonin transporter (SERT) gene are at higher risk for developing mood disorders when exposed to severe stress and display higher cortisol responses when exposed to psychosocial stressors relative to high expressing 5-HTTLPR variants. However, it is not clear how the relation between SERT and cortisol output is reflected in the adult brain. We investigated the relation between cortisol response to awakening (CAR) and SERT binding in brain regions considered relevant to modify the cortisol awakening response.


METHODS
thirty-two healthy volunteers underwent in vivo SERT imaging with [(11)C]DASB-Positron Emission Tomography (PET), genotyping, and performed home-sampling of saliva to assess CAR.


RESULTS
CAR, defined as the area under curve with respect to increase from baseline, was positively coupled to prefrontal SERT binding (p=0.02), independent of adjustment for 5-HTTLPR genotype. Although S- and LG-allele carriers tended to show a larger CAR (p=0.07) than LA homozygous, 5-HTTLPR genotype did not modify the coupling between CAR and prefrontal SERT binding as tested by an interaction analysis (genotype×CAR).


CONCLUSIONS
prefrontal SERT binding is positively associated with cortisol response to awakening. We speculate that in mentally healthy individuals prefrontal serotonergic neurotransmission may exert an inhibitory control on the cortisol awakening response.
Center for Integrated Molecular Brain Imaging, DK-2100 Copenhagen, Denmark; Neurobiology Research Unit, DK-2100 Copenhagen, Denmark. vibe@nru.dk
Vibe Gedsoe
VG
Frokjaer
David
D
Erritzoe
Klaus Kähler
KK
Holst
Peter Steen
PS
Jensen
Peter Mondrup
PM
Rasmussen
Patrick Macdonald
PM
Fisher
William
W
Baaré
Kathrine Skak
KS
Madsen
Jacob
J
Madsen
Claus
C
Svarer
Gitte Moos
GM
Knudsen
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D017397:Prefrontal Cortex / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D012463:Saliva / Q000737:chemistry / Q000378:metabolism; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D012894:Sleep Stages / Q000502:physiology; D014851:Wakefulness / Q000502:physiology*; D055815:Young Adult
D050486:Serotonin Plasma Membrane Transport Proteins; D006854:Hydrocortisone