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Gender-specific association of variants in the AKR1C1 gene with dimensional anxiety in patients with panic disorder: additional evidence for the importance of neurosteroids in anxiety?
- Source :
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Depression and anxiety [Depress Anxiety] 2014 Oct; Vol. 31 (10), pp. 843-50. Date of Electronic Publication: 2014 Jan 03. - Publication Year :
- 2014
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Abstract
- Background: Neurosteroids are synthesized both in brain and peripheral steroidogenic tissue from cholesterol or steroidal precursors. Neurosteroids have been shown to be implicated in neural proliferation, differentiation, and activity. Preclinical and clinical studies also suggest a modulatory role of neurosteroids in anxiety-related phenotypes. However, little is known about the contribution of genetic variants in genes relevant for the neurosteroidogenesis to anxiety disorders.<br />Methods: We performed an association analysis of single nucleotide polymorphisms (SNPs) in five genes related to the neurosteroidal pathway with emphasis on progesterone and allopregnanolone biosynthesis (steroid-5-alpha-reductase 1A (SRD5A1), aldo-keto reductase family 1 C1-C3 (AKR1C1-AKR1C3) and translocator protein 18 kDA (TSPO) with panic disorder (PD) and dimensional anxiety in two German PD samples (cases N = 522, controls N = 1,115).<br />Results: Case-control analysis for PD and SNPs in the five selected genes was negative in the combined sample. However, we detected a significant association of anticipatory anxiety with two intronic SNPs (rs3930965, rs41314625) located in the gene AKR1C1 surviving correction for multiple testing in PD patients. Stratification analysis for gender revealed a female-specific effect of the associations of both SNPs.<br />Conclusions: These results suggest a modulatory effect of AKR1C1 activity on anxiety levels, most likely through changes in progesterone and allopregnanolone levels within and outside the brain. In summary, this is the first evidence for the gender-specific implication of the AKR1C1 gene in the expression of anticipatory anxiety in PD. Further analyses to unravel the functional role of the SNPs detected here and replication analyses are needed to validate our results.<br /> (© 2014 Wiley Periodicals, Inc.)
- Subjects :
- 3-Hydroxysteroid Dehydrogenases genetics
3-Oxo-5-alpha-Steroid 4-Dehydrogenase genetics
Adult
Aldo-Keto Reductase Family 1 Member C3
Anxiety metabolism
Anxiety psychology
Case-Control Studies
Female
Genetic Predisposition to Disease
Humans
Hydroxyprostaglandin Dehydrogenases genetics
Hydroxysteroid Dehydrogenases genetics
Male
Membrane Proteins genetics
Middle Aged
Panic Disorder metabolism
Panic Disorder psychology
Polymorphism, Single Nucleotide
Receptors, GABA genetics
Sex Factors
20-Hydroxysteroid Dehydrogenases genetics
Anxiety genetics
Panic Disorder genetics
Pregnanolone metabolism
Progesterone metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1520-6394
- Volume :
- 31
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Depression and anxiety
- Publication Type :
- Academic Journal
- Accession number :
- 24390875
- Full Text :
- https://doi.org/10.1002/da.22229