endothelin-1 and Mood-Disorders

Recent evidence supports a pathological link between heart disease and depressive symptoms, suggesting that depression is both etiologic and prognostic to heart disease. Thus, biological molecules which are at the interface between heart and mind are plausible candidate genes for depressive disorders. To investigate this line of enquiry we have investigated two genes, Endothelin 1 (EDN1) and Angiotensin-converting enzyme (ACE) in a family-based sample with childhood-onset mood disorders (COMDs). EDN1 is highly expressed in endothelium where it acts as a potent vasoconstrictor, and is also expressed in the brain where it exhibits neurotransmitter characteristics. ACE acts as a potent vasopressor, and interacts with the hypothalamic-pituitary-adrenocortical (HPA) system, which is often dysregulated in mood disorders. Furthermore, ACE has recently been found to be associated with major depression. Polymorphisms were selected to best capture the genetic variation at the two loci, and to replicate previous associations. The markers were genotyped across EDN1 and ACE in a sample comprised of 382 Hungarian nuclear families ascertained through affected probands diagnosed with a mood disorders before the age of 15. We found no evidence of association between either of these genes and COMD. Consequently, we were unable to support our hypothesis that these two genes, which are involved in both vascular and brain functions are contributing to the susceptibility to mood disorders of children/adolescents.

Topics: Age of Onset; Child; Endothelin-1; Humans; Mood Disorders; Peptidyl-Dipeptidase A; Polymorphism, Single Nucleotide

Psychosocial factors have been reported to be independently associated with coronary heart disease (CHD). Though corticotropin-releasing hormone (CRH) is the major hormone activated during adaptive responses to stressful stimuli, the undergoing pathophysiological mechanism related to stress-induced endothelial dysfunction is still poorly understood. This study sought to investigate the effects of extrahypothalamic CRH on monocyte/endothelium adhesion. Second we elucidate the influence of CRH on monocytic endothelin-1 (ET-1) and nitric oxide (NO) release and the receptors involved. Cell adhesion was determined using an adhesion assay, MAC-1 expression by flow cytometry. ET-1/NO release were quantified via ELISA or fluorometrically, monocytic CRH-receptors were confirmed by mRNA. Corticotropin-releasing hormone induced a significant time- and concentration-dependent increase of cell adhesion as well as monocytic MAC-1 expression; endothelial ICAM-1 and VCAM-1 expression was not altered. In addition, corticotropin-releasing hormone significantly increased monocytic ET-1 release whereas nitric oxide release was decreased. The effect was abolished by the selective CRH-receptor antagonist astressin. Our findings support the importance of peripherally circulating corticotropin-releasing hormones, by influencing specific homeostatic properties of monocytes. Our data may provide a novel concept of how specific CRH-receptor antagonists may prevent CRH (stress)-related endothelial dysfunction up to cardiovascular complications.

Topics: CD11b Antigen; Cell Adhesion; Cell Line; Corticotropin-Releasing Hormone; Dose-Response Relationship, Drug; Endothelial Cells; Endothelin-1; Humans; Intercellular Adhesion Molecule-1; Monocytes; Mood Disorders; Nitric Oxide; Receptors, Corticotropin-Releasing Hormone; Vascular Cell Adhesion Molecule-1