期刊
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
卷 13, 期 9, 页码 1129-1143出版社
OXFORD UNIV PRESS
DOI: 10.1017/S1461145710000581
关键词
Cortisol; PET; SAD; serotonin; 5-HT1A
资金
- Austrian Science Fund [FWF P16549]
- Austrian National Bank [OENB P11468]
- Medical Science Fund of the City of Vienna [BMF P2515]
- Eli Lilly
- Lundbeck
- Bristol-Myers Squibb
- Servier
- Sepracor
- GlaxoSmithKline
- Organon
- AstraZeneca
- Pfizer
Dysregulation of the hypothalamic-pituitary-adrenocortical axis with deficient glucocorticoid feedback and alterations in the serotonergic system have been identified as biological correlates of mood disorders. Close examination of the interaction between these systems may offer insights into the pathophysiology of anxiety disorders and depression to understand how stress and these disorders are related. In this study, we investigated the relationship between plasma levels of cortisol and the dominant inhibitory serotonergic receptor, serotonin-1A (5-HT1A). Using positron emission tomography (PET) and the radioligand [carbonyl-C-11] WAY-100635, we quantified the 5-HT1A receptor binding. Data from 12 male patients with social phobia and 18 matched control subjects were analysed. Seven brain regions were investigated: the anterior and posterior cingulate cortices, hippocampus, amygdala, medial orbitofrontal and retrosplenial cortices, and dorsal raphe nucleus. Partial correlation analysis, controlled for age and radiochemical variables, was performed to demonstrate the association between cortisol plasma levels and 5-HT1A receptor binding. Cortisol plasma levels were significantly lower in patients with social phobia compared to healthy controls. Moreover, we found strong negative correlations between cortisol plasma levels and 5-HT1A binding in the amygdala (r=-0.93, p=0.0004), hippocampus (r=-0.80, p=0.009), and retrosplenial cortex (r=-0.48, p=0.04) in patients with social phobia. Within the former two regions, these associations were significantly higher in patients than in healthy controls. This PET study confirms a negative association between plasma cortisol levels and the 5-HT1A receptor distribution consistent with studies in rodents and non-human primates. Dysregulation of the cortisol level might increase the vulnerability for mood disorders by altering limbic 5-HT1A receptors.
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