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Angiotensin-converting enzyme gene variants are associated with both cortisol secretion and late-life depression
Angiotensin-converting enzyme (ACE) is assumed to influence the activity of the hypothalamic–pituitary–adrenocortical (HPA) axis, which shows hyperactivity in depressed patients. ACE could thus be a promising candidate gene for late-life depression but this has not been examined previously. Depressi...
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Published in: | Translational psychiatry 2013-11, Vol.3 (11), p.e322-e322 |
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Main Authors: | , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | Angiotensin-converting enzyme (ACE) is assumed to influence the activity of the hypothalamic–pituitary–adrenocortical (HPA) axis, which shows hyperactivity in depressed patients.
ACE
could thus be a promising candidate gene for late-life depression but this has not been examined previously. Depression was assessed in 1005 persons aged at least 65 years, at baseline and over the 10-year follow-up. A clinical level of depression (DEP) was defined as having a score of ⩾16 on the Centre for Epidemiology Studies-Depression scale or a diagnosis of current major depression based on the Mini International Neuropsychiatric Interview and according to DSM-IV criteria. Seven single-nucleotide polymorphisms (SNPs) in the
ACE
gene were genotyped and diurnal cortisol secretion, as an index of HPA axis activity, was measured. Multivariable analyses were adjusted for socio-demographic and vascular factors, cognitive impairment, and apolipoprotein E. Strong significant associations were found between all seven SNPs and DEP and, in particular, first-onset DEP in persons without a past history of depression (
P
-values ranging from 0.005 to 0.0004). These associations remained significant after correction for multiple testing. The genotypes that were associated with an increased risk of DEP were also significantly associated with an increase in cortisol secretion under stress conditions. Variants of the
ACE
gene influence cortisol secretion and appear as susceptibility factors for late-life depression in the elderly population. Whether this could represent a common pathophysiological mechanism linking HPA axis and late-life depression remains to be explored. |
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ISSN: | 2158-3188 2158-3188 |
DOI: | 10.1038/tp.2013.95 |