Hypothalamic-pituitary-adrenocortical axis dysregulation in patients with major depression is influenced by the insertion/deletion polymorphism in the angiotensin I-converting enzyme gene

Baghai, Thomas C.; Schüle, Cornelius; Zwanzger, Peter; Minov, Christo; Zill, Peter; Ella, Robin; Eser, Daniela; Oezer, Sebnem; Bondy, Brigitta; Rupprecht, Rainer

doi:10.1016/s0304-3940(02)00527-x

Cited by 91 publications

(44 citation statements)

References 18 publications

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“…ACE gene variations play a significant role in the HPA axis hyperactivity in depression. It has shown that variations in the ACE gene have an important impact on the HPA axis hyperactivity found in depression 16 . Captopril, an ACE inhibitor, is proved to have an antidepressant effect 17 .…”

Section: Discussionmentioning

confidence: 99%

Relationship between major depressive disorder and ACE gene I/D polymorphism in a Turkish population

Inanir¹,

Yığıt²,

Celikel³

et al. 2016

Arch. Clin. Psychiatry (São Paulo)

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Background: Major depressive disorder (MDD) is a complex disease and a significant health problem that is prevalent across the world. Angiotensin-converting enzyme (ACE) has an important role in renin-angiotensin system (RAS) and converts inactive angiotensin I to a potent vasopressor and aldosterone-stimulating peptide angiotensin II. Levels of ACE in plasma vary according to the insertion/deletion (I/D) polymorphism of ACE gene. Objective: The aim of the current study was to examine the influence ACE gene I/D variations on the risk of MDD. Methods: In the present case-control study, we analyzed ACE I/D polymorphism in 346 MDD patients and 210 healthy subjects using polymerase chain reaction technique. Results: Comparing the two groups, no significant difference was observed with regard to either genotype distributions or allele frequencies of the I/D polymorphism of ACE gene. Discussion: Our findings suggest that the ACE I/D polymorphism is not associated with MDD in Turkish case-control study. Further studies are still needed.

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Section: Discussionmentioning

confidence: 99%

Relationship between major depressive disorder and ACE gene I/D polymorphism in a Turkish population

Inanir¹,

Yığıt²,

Celikel³

et al. 2016

Arch. Clin. Psychiatry (São Paulo)

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“…Patients homozygous for the T-allele had higher stimulated cortisol concentrations than patients with the two other genotypes. Thus, during depression there appears to be an interrelationship not only between the functional ACE I/D-polymorphism and the HPA-axis overdrive 7 but also between SNP rs4291 variants and the HPAaxis. As several animal studies have demonstrated a strong interrelationship between intracerebral AT-II and the secretion of pituitary hormones, such an interrelation may also influence the susceptibility to develop a depressive disorder.…”

Section: Discussionmentioning

confidence: 99%

“…7 A standard PCR was performed in a 25 ml PCR buffer (1.5 mM MgCl) containing 50 ng genomic DNA, 200 mM of each dNTP, 100 mM 7-deaza-guanosine 5 0 -triphosphate lithium salt (GTP), 1.25 U Ampli-Taq Gold DNA polymerase (Perkin-Elmer), 5% dimethylsulfoxide (DMSO) and 0.4 mM of the forward and reverse primers. This setting, which means that 7-deaza (GTP) and DSMO are included, was chosen to avoid mistyping of heterozygotes.…”

Section: Ace I/d-polymorphism Genotypingmentioning

confidence: 99%

“…6 The renin-angiotensin-system (RAS) 3 plays a modulatory role during stress-induced HPA-axis activation. In fact, the ACE I/D-polymorphism has been shown to exert a marked influence on HPA-axis hyperactivity in depressed patients 7 and seems to be related to both, the onset of action of antidepressant pharmacotherapies 8 and the stability of therapeutic response after partial sleep deprivation. 9 In contrast to biochemical and neuroendocrinological data that implicate ACE as a candidate gene for affective disorders, genetic association studies of the ACE I/D-polymorphism with major depression revealed divergent results.…”

Section: Introductionmentioning

confidence: 99%

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Polymorphisms in the angiotensin-converting enzyme gene are associated with unipolar depression, ACE activity and hypercortisolism

et al. 2006

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Angiotensin-converting enzyme (ACE) is assumed to influence the activity of the hypothalamic-pituitary-adrenocortical (HPA) system, which shows hyperactivity in the majority of patients with major depression. The ACE gene, known to be associated with cardiovascular disorders, which in turn are accompanied with an increased susceptibility for depression, is therefore a promising candidate gene for affective disorders. We investigated the genetic association between 35 single-nucleotide polymorphisms (SNPs) and an insertion/deletion (I/D)-polymorphism in the ACE gene and the susceptibility for unipolar major depression together with the genetic association with ACE serum activity and functional parameters of the HPA system. Two independent case/control samples with a total of 843 unrelated unipolar depressed patients and 1479 healthy controls were investigated. A case/control sample was screened to detect genetic associations with unipolar major depression. In addition, a replication sample was used to confirm the detected associations and to further investigate functional consequences of the genetic variants associated with depression. In the screening sample, two SNPs within the ACE gene were significantly associated with unipolar major depression. The association with unipolar major depression of one SNP (rs4291) located in the promoter region of the ACE gene was confirmed in our replication sample. The T-allele of this SNP was associated with depression and depressed T-allele carriers showed higher ACE serum activity and HPA-axis hyperactivity. Variants of the ACE gene such as SNP rs4291 are suggested susceptibility factors for unipolar major depression. We could show that SNP rs4291 influences ACE activity and HPA-axis hyperactivity and might therefore represent a common pathophysiologic link for unipolar depression and cardiovascular disease.

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“…One possible interpretation of these data is that there might be biologically distinct subtypes of patients with depression who could be distinguished according to their HPA-axis status during a depressive episode, especially if treatment modalities are taken into account. In fact, an insertion/deletion polymorphism in the angiotensin converting enzyme gene has been associated with a genotype-dependent difference in the magnitude of the Dex-CRH test (Baghai et al, 2002). One might therefore envisage to use this test as an endophenotype to distinguish pathogenetically different and genetically more homogeneous groups of depressed patients for genetic case/control association studies (Almasy and Blangero, 2001).…”

Section: Discussionmentioning

confidence: 99%

Pharmacological and Nonpharmacological Factors Influencing Hypothalamic–Pituitary–Adrenocortical Axis Reactivity in Acutely Depressed Psychiatric In-patients, Measured by the Dex-CRH Test

Künzel

Binder

Nickel

et al. 2003

Neuropsychopharmacol

135

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The most consistent biological findings in patients with depression are abnormalities in the hypothalamic-pituitary-adrenal (HPA)-axis, which can be measured using the combined dexamethasone-suppression/CRH-stimulation (Dex-CRH) test. The reactivity of the HPAaxis in this test, however, ranges over several orders of magnitude in depressed patients with comparable severity of symptoms. In this present study, we investigate which factors influence the magnitude of the response in the Dex-CRH test in 235 acutely depressed inpatients. We first examined the effects of common confounders shown to influence the HPA-axis, such as caffeine and nicotine consumption, acute stressors during the test, weight, gender, and age. Of all these variables, only female sex and nicotine consumption were positively correlated with the cortisol or ACTH response, respectively. As for the effects of psychopharmacological treatment, only the intake of carbamazepine and the fact of having relapsed under an established pharmacotherapy significantly increased the response in the Dex-CRH test, whereas the presence or absence of antidepressant treatment, the type of antidepressant treatment, or the number of ineffective antidepressant treatment trials during the index episode up to admission did not have any effect. We also found a positive correlation of the number of previous episodes, the overall HAM-D score and the severity of somatic/vegetative symptoms with the results in the Dex-CRH test. These results underline that in depressed patients this test is not majorly influenced by disease-unrelated factors. In addition, current antidepressant treatment does not appear to affect test outcome in the absence of clinical response. The influence of the number of previous episodes and relapse under pharmacotherapy suggests that HPA-axis reactivity may be altered by repetitive states of hypercortisolemia or continuous antidepressant treatment. Finally, more severe vegetative symptoms are associated with an enhanced HPA-axis activity.

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Hypothalamic-pituitary-adrenocortical axis dysregulation in patients with major depression is influenced by the insertion/deletion polymorphism in the angiotensin I-converting enzyme gene

Cited by 91 publications

References 18 publications

Relationship between major depressive disorder and ACE gene I/D polymorphism in a Turkish population

Relationship between major depressive disorder and ACE gene I/D polymorphism in a Turkish population

Polymorphisms in the angiotensin-converting enzyme gene are associated with unipolar depression, ACE activity and hypercortisolism

Pharmacological and Nonpharmacological Factors Influencing Hypothalamic–Pituitary–Adrenocortical Axis Reactivity in Acutely Depressed Psychiatric In-patients, Measured by the Dex-CRH Test

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