Evidence for the involvement of the glucocorticoid receptor gene in bipolar disorder in an isolated northern Swedish population

Ceulemans, Shana; Zutter, Sonia De; Heyrman, Lien; Norrbäck, Karl-Fredrik; Nordin, Annelie; Nilsson, L-G; Adolfsson, Rolf; Del-Favero, Jurgen; Claes, Stephan

doi:10.1111/j.1399-5618.2011.00960.x

Cited by 18 publications

(14 citation statements)

References 44 publications

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“…68 On the other hand, we did find an association with polymorphism of the glucocorticoid receptor (NR3C1) gene located on chromosome 5q31−32, 69 implicated in the pathogenesis of bipolar disorder. 70 Positive results have been obtained concerning associations of three genes located on chromosome 22q11−13 with lithium response. A significant association between lithium response and genetic variations in the breakpoint cluster region (BCR) gene located on chromosome 22q11 71 and with the X-box binding protein 1 (XBP1) gene located on chromosome 22q12 72 was found.…”

Section: ■ Clinical Factors Associated With Lithium Efficacymentioning

confidence: 99%

Response to Lithium in Bipolar Disorder: Clinical and Genetic Findings

Rybakowski

2014

ACS Chem. Neurosci.

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The use of lithium is a cornerstone for preventing recurrences in bipolar disorder (BD). The response of patients with bipolar disorder to lithium has different levels of magnitude. About one-third of lithium-treated patients are excellent lithium responders (ELR), showing total prevention of the episodes. A number of clinical characteristics were delineated in patients with favorable response to lithium as regards to clinical course, family history of mood disorders, and psychiatric comorbidity. We have also demonstrated that temperamental features of hypomania (a hyperthymic temperament) and a lack of cognitive disorganization predict the best results of lithium prophylaxis. A degree of prevention against manic and depressive episodes has been regarded as an endophenotype for pharmacogenetic studies. The majority of data have been gathered from so-called "candidate" gene studies. The candidates were selected on the basis of neurobiology of bipolar disorder and mechanisms of lithium action including, among others, neurotransmission, intracellular signaling, neuroprotection or circadian rhythms. We demonstrated that response to lithium has been connected with the genotype of BDNF gene and serum BDNF levels and have shown that ELR have normal cognitive functions and serum BDNF levels, even after long-term duration of the illness. A number of genome-wide association studies (GWAS) of BD have been also performed in recent years, some of which also focused on lithium response. The Consortium on Lithium Genetics (ConLiGen) has established the large sample for performing the genome-wide association study (GWAS) of lithium response in BD, and the first results have already been published.

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Section: ■ Clinical Factors Associated With Lithium Efficacymentioning

confidence: 99%

Response to Lithium in Bipolar Disorder: Clinical and Genetic Findings

Rybakowski

2014

ACS Chem. Neurosci.

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“…In addition, exposure to CM has been shown to dysregulate the hypothalamic-pituitary-adrenal (HPA) axis, a master regulator of the body’s stress response (reviewed in (Van Voorhees and Scarpa, 2004)). Substantial work has demonstrated that dysregulation of the HPA axis increases the likelihood of developing mood and anxiety disorders (Appel et al, 2011; Ceulemans et al, 2011; Espejo et al, 2007; Guerry and Hastings, 2011; Nemeroff, 2004). Moreover, it has been well-documented that exposures during early life, including CM, impact DNA methylation (5mC) levels within genes of the HPA axis (Martin-Blanco et al, 2014; McGowan et al, 2009; Romens et al, 2015; van der Knaap et al, 2014) making the HPA axis is a logical starting point for studies examining the epigenetic impact of CM.…”

Section: Introductionmentioning

confidence: 99%

FKBP5 DNA methylation does not mediate the association between childhood maltreatment and depression symptom severity in the Detroit Neighborhood Health Study

Bustamante

Aiello²,

Guffanti

et al. 2018

Journal of Psychiatric Research

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Exposure to childhood maltreatment increases the risk of developing mental illness later in life. Childhood maltreatment and depression have both been associated with dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis-a key regulator of the body's stress response. Additionally, HPA axis dysregulation has been implicated in the etiology of a range of mental illnesses. A substantial body of work has shown history of childhood maltreatment alters DNA methylation levels within key HPA axis genes. We therefore investigated whether one of these key genes, FKBP5 mediates the relationship between childhood maltreatment and depression, and assessed FKBP5 DNA methylation and gene expression within 112 adults from the Detroit Neighborhood Health Study (DNHS). DNA methylation was assessed in 4 regions, including the upstream promoter, downstream promoter, and two glucocorticoid response elements (GREs) via pyrosequencing using whole blood derived DNA; Taqman assays measured relative RNA expression from leukocytes. Mediation analyses were conducted using sequential linear regression. Childhood maltreatment was significantly associated with depression symptom severity (FDR < 0.006), but was not a significant predictor of DNA methylation in any of the four loci examined. FKBP5 showed elevated expression levels in participants with vs. without a history of depression (p < 0.001); no significant difference in gene expression levels was observed in relation to childhood maltreatment (p > 0.05). Our results suggest DNA methylation does not mediate the childhood maltreatment-depression association in the DNHS.

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“…Altered GR signaling has also been reported in BD [187][188][189][190], and peripheral blood biomarkers targeting GR proteins and genetic variants [188,[191][192][193][194], mRNA expression [195][196][197], or function [155] have been proposed. Other studies suggested that reduced GR function was related to the dysregulation of GR co-factors such as FKBP5/FKBP51, BAG1, PTGES3, and HSP70 [191,[198][199][200][201][202][203].…”

Section: Glucocorticoid Receptorsmentioning

confidence: 99%