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. METHODS: 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. 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.
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Authors | Carina Quast, Andreas Reif, Tanja Brückl, Hildegard Pfister, Heike Weber, Manuel Mattheisen, Sven Cichon, Thomas Lang, Alfons Hamm, Lydia Fehm, Andreas Ströhle, Volker Arolt, Katharina Domschke, Tilo Kircher, Hans-Ulrich Wittchen, Paul Pauli, Alexander L Gerlach, Georg W Alpers, Jürgen Deckert, Rainer Rupprecht, Elisabeth B Binder, Angelika Erhardt |
Journal | Depression and anxiety
(Depress Anxiety)
Vol. 31
Issue 10
Pg. 843-50
(Oct 2014)
ISSN: 1520-6394 [Electronic] United States |
PMID | 24390875
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | © 2014 Wiley Periodicals, Inc. |
Chemical References |
- Membrane Proteins
- Receptors, GABA
- TSPO protein, human
- Progesterone
- Pregnanolone
- 3-Hydroxysteroid Dehydrogenases
- Hydroxysteroid Dehydrogenases
- 20-Hydroxysteroid Dehydrogenases
- 3 alpha-beta, 20 beta-hydroxysteroid dehydrogenase
- Hydroxyprostaglandin Dehydrogenases
- AKR1C2 protein, human
- AKR1C3 protein, human
- Aldo-Keto Reductase Family 1 Member C3
- 3-Oxo-5-alpha-Steroid 4-Dehydrogenase
- SRD5A1 protein, human
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Topics |
- 20-Hydroxysteroid Dehydrogenases
(genetics)
- 3-Hydroxysteroid Dehydrogenases
(genetics)
- 3-Oxo-5-alpha-Steroid 4-Dehydrogenase
(genetics)
- Adult
- Aldo-Keto Reductase Family 1 Member C3
- Anxiety
(genetics, metabolism, psychology)
- Case-Control Studies
- Female
- Genetic Predisposition to Disease
- Humans
- Hydroxyprostaglandin Dehydrogenases
(genetics)
- Hydroxysteroid Dehydrogenases
(genetics)
- Male
- Membrane Proteins
(genetics)
- Middle Aged
- Panic Disorder
(genetics, metabolism, psychology)
- Polymorphism, Single Nucleotide
- Pregnanolone
(metabolism)
- Progesterone
(metabolism)
- Receptors, GABA
(genetics)
- Sex Factors
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