Functional polymorphism of the glucocorticoid receptor gene associates with mania and hypomania in bipolar disorder
Open accessAbstract
Objectives: In affective disorders, dysregulation of the hypothalamus‐pituitary‐adrenal (HPA) axis is a frequently observed phenomenon. Subtle changes in glucocorticoid receptor (GR) functioning caused by polymorphisms of the GR gene (NR3C1) may be at the base of the altered reaction of the HPA axis to stress and subsequently related to the development and course of affective disorders. The aim of our study is to evaluate associations between GR gene polymorphisms and bipolar disorder (BD). Methods: In this study, 245 patients with BD were interviewed to confirm diagnosis and BD subtype. Data on medication use and sociodemographic details were also collected. The control group consisted of 532 healthy blood donors, from which data on sex and age were collected. To perform genotyping, blood was collected from all patients and healthy controls. Results: A trend was found for a protective effect of the exon 9β polymorphism (p = 0.14) and the TthIII I polymorphism (p < 0.05) on the manifestation of the disease. These effects were significantly influenced by male gender for both polymorphisms. Patients with BD and the A/G variant in exon 9β had significantly fewer manic and hypomanic episodes than noncarriers (p < 0.05). No further associations were found with the other investigated GR gene polymorphisms and BD. These findings were not corrected for multiple comparisons. Conclusions: We conclude that the exon 9β polymorphism and the TthIII I polymorphism of the GR gene may be associated with a protective effect on the clinical manifestation and course in patients with BD. Furthermore, no associations were found between the other studied GR gene polymorphisms and this disease.
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Two studies found significant associations between GR gene polymorphisms and bipolar disorder, while one did not.
“While two studies found significant associations between GR gene polymorphisms and BD (Spijker et al. 2009;Ceulemans et al. 2011) one did not (Szczepankiewicz et al. 2011a).”
From The HPA axis in bipolar disorder: Systematic review and meta-analysis (2016) · cites this paper as Spijker et al. 2009
Common polymorphisms of HPA-related genes were associated with different clinical features of bipolar disorder, including number of manic episodes, seasonal pattern, lithium response, suicidality, and psychotic symptoms.
“common polymorphisms of HPA-related genes were associated with different clinical features of BD, namely between the number of manic episodes (Spijker et al. 2009), seasonal pattern (Spijker et al. 2011), lithium response (Szczepankiewicz et al. 2011b), suicidality (De Luca et al. 2007) and psychotic symptoms (Leszczynska-Rodziewicz et al. 2012).”
From The HPA axis in bipolar disorder: Systematic review and meta-analysis (2016) · cites this paper as Spijker et al. 2009
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- Authors
- Spijker, A. T., Van Rossum, E. F. C., Hoencamp, E., DeRijk, R. H., Haffmans, J., Blom, M., Manenschijn, L., Koper, J. W., Lamberts, S. W., & Zitman, F. G.
- Affiliations
- Parnassia Groep (NL)
- Leiden University (NL)
- Erasmus MC (NL)
- Corresponding author
- Spijker, Anne T
- Venue
- Bipolar Disorders
- Publisher
- Wiley
- Published
- 2009-01-09
- Volume
- 11
- Issue
- 1
- Pages
- 95-101
- ISSN
- 1398-5647 (ISSN-L)
- 1399-5618
- OpenAlex
- W2072512866
- Cited by
- 36
- References
- 21
- Citations by year
- 2023: 1 · 2021: 2 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 4 · 2015: 2 · 2014: 3 · 2013: 4 · 2012: 4
- FWCI
- 2.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Bipolar Disorders (publishedVersion)
- PubMed (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (publishedVersion)
- EUR Research Repository (Erasmus University Rotterdam) (submittedVersion)
- Funders
- Universiteit Leiden
- Erasmus Medisch Centrum
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- glucocorticoid receptor, NR3C1, genetic polymorphism, bipolar disorder, mania, hypomania, hypothalamic-pituitary-adrenal axis, genetic association, sex differences
- MeSH terms
- Adult, Bipolar Disorder, Cross-Sectional Studies, Exons, Female, Genotype, Humans, Male, Middle Aged, Polymorphism, Genetic, Receptors, Glucocorticoid, Odds Ratio, Case-Control Studies, Genetic Predisposition to Disease
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