Quast, Carina and Reif, Andreas and Brueckl, Tanja and Pfister, Hildegard and Weber, Heike and Mattheisen, Manuel and Cichon, Sven and Lang, Thomas and Hamm, Alfons and Fehm, Lydia and Stroehle, Andreas and Arolt, Volker and Domschke, Katharina and Kircher, Tilo and Wittchen, Hans-Ulrich and Pauli, Paul and Gerlach, Alexander L. and Alpers, Georg W. and Deckert, Juergen and Rupprecht, Rainer and Binder, Elisabeth B. and Erhardt, Angelika (2014) 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? DEPRESSION AND ANXIETY, 31 (10). pp. 843-850. ISSN 1091-4269, 1520-6394
Full text not available from this repository. (Request a copy)Abstract
BackgroundNeurosteroids 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. MethodsWe 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). ResultsCase-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. ConclusionsThese 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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ALPHA-HYDROXYSTEROID DEHYDROGENASE; RANDOMIZED CONTROLLED-TRIAL; KETO REDUCTASE SUPERFAMILY; PROGESTERONE-RECEPTOR GENE; TISSUE DISTRIBUTION; 3-ALPHA-HYDROXYSTEROID DEHYDROGENASES; PSYCHIATRIC-DISORDERS; NEUROACTIVE STEROIDS; EMOTIONAL MEMORY; BINDING PROTEIN; panic disorder; neurosteroids; association; SNPs; gender-specific; anxiety |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 12 Aug 2019 09:08 |
| Last Modified: | 12 Aug 2019 09:08 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9397 |
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