Hypothalamic serotonin-1A receptor binding measured by PET predicts the plasma level of dehydroepiandrosterone sulfate in healthy women

Serotonin modulates the activity of the hypothalamic-pituitary-adrenal (HPA) axis particularly via the serotonin-1A receptor (5-HT(1A)). Therefore, the rationale of this positron emission tomography (PET) study was to investigate the influence of the 5-HT(1A) receptor distribution in the human brain on plasma levels of dehydroepiandrosterone sulfate (DHEAS) and cortisol in vivo. Eighteen healthy female were measured with PET and the selective 5-HT(1A) receptor radioligand [carbonyl-(11)C]WAY-100635. Nine a priori defined brain regions (hypothalamus, orbitofrontal cortex, amygdala, hippocampus, anterior and posterior cingulate cortices, dorsal raphe nucleus, retrosplenial cortex, and insula) and the cerebellum (reference region) were delineated on coregistered MR images. DHEAS and cortisol plasma levels were collected by blood sampling in the morning of the PET day. Linear regression analysis of DHEAS plasma level as dependent variable and hypothalamic 5-HT(1A) receptor binding potential (BP) as independent variable showed a highly significant association (r=.691, p=.002). The hypothalamic 5-HT(1A) BP predicted 47.7% of the variability in DHEAS plasma levels. Regressions were borderline significant (p.01, Bonferroni corrected threshold.0056) between 5-HT(1A) BP in the anterior cingulate and orbitofrontal cortices and free cortisol levels. No significant associations between DHEAS or cortisol and the 5-HT(1A) receptor BP in other investigated brain regions were found. In conclusion, the serotonergic system may influence the DHEAS plasma level by modulating CRH and ACTH release via hypothalamic 5-HT(1A) receptors as reported for cortisol before. As disturbances of the HPA axis as well as changes of the 5-HT(1A) receptor distribution have been reported in affective disorders, future studies should focus on these interactions.