Polymorphisms of the Glucocorticoid Receptor Gene and Major Depression

Rossum, Elisabeth F.C. van; Binder, Elisabeth B.; Majer, Matthias; Koper, Jan W.; Ising, Marcus; Modell, S.; Salyakina, Daria; Lamberts, Steven W. J.; Holsboer, Florian

doi:10.1016/j.biopsych.2006.02.007

Cited by 292 publications

(234 citation statements)

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“…The lack of a significant difference in depressive symptoms between the ER22/23EK carriers and noncarriers in our study may result from the low number of participants carrying the variant allele. Despite that, the trend observed in our study, is in accordance with two recent studies, showing an enrichment of the 22/23EK-allele in patients with major depression (van Rossum et al, 2006;van West et al, 2006). It could be that in our study the lack of a distinct influence of the GR gene SNPs on cognitive functioning and mood is a result of the nonstressful testing conditions.…”

Section: Discussionsupporting

confidence: 91%

“…In the MR gene, the 215G/C and I180V single-nucleotide polymorphisms (SNPs) have been shown to change cortisol signaling in vitro (Arai et al, 2003), whereas in the GR gene the ER22/23EK, N363S, and BclI SNPs have been shown to change HPA-axis reactivity after a dexamethasone suppression test or a psychosocial stressor (Huizenga et al, 1998;van Rossum et al, 2002van Rossum et al, , 2003. In addition, the ER22/23EK variant has been associated with major depression in two studies (van Rossum et al, 2006;van West et al, 2006). To date, there are no publications that examine the role of these MR and GR variants in cognitive functioning and as yet no study has assessed the effects of variants in the MR gene on mood.…”

Section: Introductionmentioning

confidence: 99%

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Mental Performance in Old Age Dependent on Cortisol and Genetic Variance in the Mineralocorticoid and Glucocorticoid Receptors

Kuningas

Rijk

Westendorp

et al. 2006

Neuropsychopharmacol

120

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Depression and cognitive decline have been associated with changes in circulating cortisol concentrations. Cortisol exerts its functions through mineralocorticoid (MR) and glucocorticoid (GR) receptors. However, data on the influence of variations in the MR and GR genes on depressive symptoms and cognitive functioning in older adults are scarce. Therefore, we explored the impact of MR-215G/C, MR-I180V, GR-ER22/23EK, GR-N363S, and GR-BclI polymorphisms on these end points in the population-based Leiden 85-plus Study. This prospective study includes 563 participants aged 85 years and older, with a mean follow-up of 4.2 years. In this study, high morning cortisol levels (per 1 SD cortisol) associated with impairments in global cognitive functioning (p ¼ 0.002) at baseline (age 85). These impairments were mainly attributable to lower attention (p ¼ 0.057) and slower processing speed (p ¼ 0.014). Similar effects were also observed during follow-up (age 85-90), where participants with higher cortisol levels (per 1 SD cortisol) had impaired global cognitive functioning (p ¼ 0.003), as well as impairments in attention (p ¼ 0.034) and processing speed (p ¼ 0.013). Changes in depressive symptoms were observed for the MR-I180V single-nucleotide polymorphism (SNP), where during follow-up the prevalence of depressive symptoms was higher in the 180V-allele carriers (p ¼ 0.049) compared to noncarriers. Dependent on these polymorphisms, no differences in overall and in specific domains of cognitive functioning were observed. In conclusion, the MR-I180V SNP has a specific effect on depressive symptoms, independent from cognitive functioning, and other polymorphisms in the MR and GR genes. In contrast, these genetic variants in the MR and GR genes do not influence cognitive functioning in old age.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Mental Performance in Old Age Dependent on Cortisol and Genetic Variance in the Mineralocorticoid and Glucocorticoid Receptors

Kuningas

Rijk

Westendorp

et al. 2006

Neuropsychopharmacol

120

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Section: Introductionmentioning

confidence: 99%

“…Animal studies have shown that the activity of the HPA axis changes in response to extreme and/or chronic stress and that these changes may be part of the causal mechanisms by which environmental stress contributes to the development of depression, the persistence of symptoms, and the recurrence of depressive disorders [21,22] . However, the latter hypothesis is based on pre-existing differences in HPA axis functioning in certain individuals that result in increased susceptibility to stress-inducing "depressionergic effects" [23,24] .Irrespective of whether these hypotheses are convincing, they both highlight the importance of the putative role of adrenocortical deregulation in depression.Limbic structures and the HPA axis are co-regulated in order to diminish the stress response, and the prefrontal cortices play a critical role in control over the HPA axis. In vivo studies have demonstrated that frontolimbic dysregulation of HPA-axis dysfunction is related to difficulties in emotion regulation, a characteristic of depression [25] .…”

mentioning

confidence: 99%

Hypothalamic-pituitary-adrenal axis function during perinatal depression

et al. 2015

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Abnormal function of the hypothalamic-pituitary-adrenal (HPA) axis is an important pathological finding in pregnant women exhibiting major depressive disorder. They show high levels of cortisol proinflammatory cytokines, hypothalamic-pituitary peptide hormones and catecholamines, along with low dehydroepiandrosterone levels in plasma. During pregnancy, the TH2 balance together with the immune system and placental factors play crucial roles in the development of the fetal allograft to full term. These factors, when altered, may generate a persistent dysfunction of the HPA axis that may lead to an overt transfer of cortisol and toxicity to the fetus at the expense of reduced activity of placental 11β-hydroxysteroid dehydrogenase type 2. Epigenetic modifications also may contribute to the dysregulation of the HPA axis. Affective disorders in pregnant women should be taken seriously, and therapies focused on preventing the deleterious effects of stressors should be implemented to promote the welfare of both mother and baby.Keywords: brain; depression; neuroendocrine; pregnancy; stress; glucocorticoids Extensive studies have demonstrated that early life stressors produce changes in behavior and enhance the sensitivity of the stress response systems [1][2][3][4] . Although the genetic background has been implicated in the development of mood-related disorders, and genetic research has identified some chromosomal regions and genes that are involved in susceptibility to mood disorders, the etiology of anxiety and depressive disorders is still not clear in humans, particularly in women with major depressive disorder (MDD) [1] .The pathogenesis of perinatal depression is an emerging field. Although considerable progress has been made in this area in the last few years, there still remain unanswered questions and gaps in our knowledge of the underlying pathogenesis, the long-term impact of perinatal depression on the developing fetus, and the best methods for counseling pregnant women concerning the risks of untreated MDD versus the risks of psychopharmacologic treatment during pregnancy and lactation [5] . Meta-analysis studies have reported that the mean prevalence rate of prenatal depression is ~12% (this varies greatly according to location, mode of assessment, and socioeconomic conditions), and show that a large percentage of pregnant women displaying major depression remain depressed in the postpartum period and/or continuously [6,7] . Anxiety, depressive disorder, and stress during pregnancy are risk Phillipe Leff Gelman, et al. HPA axis in perinatal depression 339 factors for negative outcomes in newborns, like preterm birth or low birth weight; also, insecure attachment and impaired child development could be a consequence of mental disorders during pregnancy [6,[8][9][10] . The mechanisms by which maternal depression impacts fetal and neonatal development are currently under investigation; there is some evidence that depressive symptoms impact the infant's hypothalamic-pituitary-adrenal (HPA) axis, enhancing the ...

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“…Upon binding to GCs, the GR translocates into the nucleus and transcriptionally regulates various genes through its binding to GC response elements (GRE) in the promoter regions of target genes. Several functional polymorphisms of the GR gene (NR3C1, nuclear receptor subfamily 3, group C, member 1, glucocorticoid receptor) have been described; the N363S polymorphism in codon 363 and the BclI restriction site in intron 2 have been associated with hypersensitivity to GCs [16,17], whereas the ER22/23EK polymorphism, also located in exon 2, seems implicated in GC resistance [18].…”

Section: Introductionmentioning

confidence: 99%

Glutathione-S-transferase-P1 I105V polymorphism and response to antenatal betamethasone in the prevention of respiratory distress syndrome

Oretti

Marino

Mosca³

et al. 2009

Eur J Clin Pharmacol

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PHARMACOGENETICSGlutathione-S-transferase-P1 I105V polymorphism and response to antenatal betamethasone in the prevention of respiratory distress syndrome Abstract Purpose The aim of this pilot study was to assess the association between polymorphisms in genes that encode for proteins involved in the pharmacokinetics/pharmacodynamics of glucocorticoids and the occurrence of respiratory distress syndrome (RDS) in preterm infants born to mothers treated with a complete course of betamethasone. Methods Sixty-two preterm infants were enrolled. The C1236T, G2677T, and C3435T polymorphisms in the ABCB1 gene, BclI, N363S and ER22/23EK in the NR3C1 gene, I105V in the GST-P1 gene and GST-M1 and GST-T1 deletions were analyzed, and their association with the occurrence of RDS was assessed. Results In univariate analysis, the heterozygous and homozygous presence of the I105V variant in the GST-P1 gene seemed to confer protection against the occurrence of RDS (P=0.032), while no association for all other polymorphisms was observed. In multivariate analysis, selection from the reference model of independent variables based on AIC (Akaike information criteria) maintained three variables in the model: gestation, C3435T, and GST-P1 genotype.

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Polymorphisms of the Glucocorticoid Receptor Gene and Major Depression

Cited by 292 publications

References 52 publications

Mental Performance in Old Age Dependent on Cortisol and Genetic Variance in the Mineralocorticoid and Glucocorticoid Receptors

Mental Performance in Old Age Dependent on Cortisol and Genetic Variance in the Mineralocorticoid and Glucocorticoid Receptors

Hypothalamic-pituitary-adrenal axis function during perinatal depression

Glutathione-S-transferase-P1 I105V polymorphism and response to antenatal betamethasone in the prevention of respiratory distress syndrome

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