Cortisol Stress Response and in Vivo PET Imaging of Human Brain Serotonin 1A Receptor Binding.

BACKGROUND: Abnormalities in the hypothalamic-pituitary-adrenal axis, serotonergic system, and stress response have been linked to the pathogenesis of major depressive disorder. State-dependent hyper-reactivity of the hypothalamic-pituitary-adrenal axis is seen in major depressive disorder, and higher binding to the serotonin 1A receptor is observed as a trait in both currently depressed and remitted untreated major depressive disorder. Here, we sought to examine whether a relationship exists between cortisol secretion in response to a stressor and serotonin 1A receptor binding throughout the brain, both in healthy controls and participants with major depressive disorder. METHODS: Research participants included 42 medication-free, depressed subjects and 31 healthy volunteers. Participants were exposed to either an acute, physical stressor (radial artery catheter insertion) or a psychological stressor (Trier Social Stress Test). Levels of serotonin 1A receptor binding on positron emission tomography with [11C]WAY-100635 were also obtained from all participants. The relationship between [11C]WAY-100635 binding and cortisol was examined using mixed linear effects models with group (major depressive disorder vs control), cortisol, brain region, and their interactions as fixed effects and subject as a random effect. RESULTS: We found a positive correlation between post-stress cortisol measures and serotonin 1A receptor ligand binding levels across multiple cortical and subcortical regions, independent of diagnosis and with both types of stress. The relationship between [11C]WAY-100635 binding and cortisol was homogenous across all a priori brain regions. In contrast, resting cortisol levels were negatively correlated with serotonin 1A receptor ligand binding levels independently of diagnosis, except in the RN. There was no significant difference in cortisol between major depressive disorder participants and healthy volunteers with either stressor. Similarly, there was no correlation between cortisol and depression severity in either stressor group. CONCLUSIONS: This study suggests that there may be a common underlying mechanism that links abnormalities in the serotonin system and hypothalamic-pituitary-adrenal axis hyper-reactivity to stress. Future studies need to determine how hypothalamic-pituitary-adrenal axis dysfunction affects mood to increase the risk of suicide in major depression.

Cortical Pain Response of Newborn Infants to Venepuncture: A Randomized Controlled Trial Comparing Analgesic Effects of Sucrose Versus Breastfeeding.

OBJECTIVE: Sucrose administration and breastfeeding decrease behavioral expressions of pain in neonates. However, recent studies indicated that there is a persistent cortical response with sucrose. This study compared the efficacy of sucrose administration versus breastfeeding to decrease cortical responses to pain during venepuncture. PATIENTS AND METHODS: A randomized, prospective, controlled trial was conducted in a tertiary level maternity ward. Healthy, 3-day-old term neonates, undergoing venepuncture for neonatal screening, were randomly assigned to receive sucrose solution or be breastfed before venepuncture. Variations in the total hemoglobin concentration [HbT] in the contralateral somatosensory cortex were assessed with near infrared spectroscopy. The Neonatal Facial Coding System (NFCS) was used to assess reactions. RESULTS: There were 114 term neonates included, with 102 included for the primary outcome (breastfed group: 48; sucrose group: 54). Similar maximum increases in [HbT] were observed in both groups (mean±SD: sucrose group: 31.2±58.1 µmol/L; breastfed group: 38.9±61.4 µmol/L; P=0.70). Breastfed neonates presented more behavioral expressions that indicated pain compared with sucrose-administered neonates (46.8% vs. 26.8% of NFCS ≥1, P=0.04). The maximum increase in [HbT] was persistent, although newborn infants who did not express behavioral signs of pain had lower concentrations than neonates who did (mean±SD: 21.2±29.1 vs. 60.0±89.8 µmol/L, P<0.01). DISCUSSION: There was no difference in the cortical responses to pain during venepuncture in newborn infants who were administered sucrose versus those who were breastfed.