Quast, Carina, Reif, Andreas, Brueckl, Tanja, Pfister, Hildegard, Weber, Heike ORCID: 0000-0002-9421-1292, Mattheisen, Manuel ORCID: 0000-0002-8442-493X, Cichon, Sven, Lang, Thomas, Hamm, Alfons, Fehm, Lydia ORCID: 0000-0002-0825-8466, Stroehle, Andreas, Arolt, Volker, Domschke, Katharina, Kircher, Tilo ORCID: 0000-0002-2514-2625, Wittchen, Hans-Ulrich ORCID: 0000-0002-6311-7711, Pauli, Paul ORCID: 0000-0003-0692-6720, Gerlach, Alexander L. ORCID: 0000-0001-6794-5349, Alpers, Georg W. ORCID: 0000-0001-9896-5158, Deckert, Juergen, Rupprecht, Rainer, 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? Depress. Anxiety, 31 (10). S. 843 - 851. HOBOKEN: WILEY. ISSN 1520-6394

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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: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Quast, CarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Reif, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brueckl, TanjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pfister, HildegardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Weber, HeikeUNSPECIFIEDorcid.org/0000-0002-9421-1292UNSPECIFIED
Mattheisen, ManuelUNSPECIFIEDorcid.org/0000-0002-8442-493XUNSPECIFIED
Cichon, SvenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lang, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hamm, AlfonsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fehm, LydiaUNSPECIFIEDorcid.org/0000-0002-0825-8466UNSPECIFIED
Stroehle, AndreasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Arolt, VolkerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Domschke, KatharinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kircher, TiloUNSPECIFIEDorcid.org/0000-0002-2514-2625UNSPECIFIED
Wittchen, Hans-UlrichUNSPECIFIEDorcid.org/0000-0002-6311-7711UNSPECIFIED
Pauli, PaulUNSPECIFIEDorcid.org/0000-0003-0692-6720UNSPECIFIED
Gerlach, Alexander L.UNSPECIFIEDorcid.org/0000-0001-6794-5349UNSPECIFIED
Alpers, Georg W.UNSPECIFIEDorcid.org/0000-0001-9896-5158UNSPECIFIED
Deckert, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rupprecht, RainerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Binder, Elisabeth B.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Erhardt, AngelikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-427896
DOI: 10.1002/da.22229
Journal or Publication Title: Depress. Anxiety
Volume: 31
Number: 10
Page Range: S. 843 - 851
Date: 2014
Publisher: WILEY
Place of Publication: HOBOKEN
ISSN: 1520-6394
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
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 PROTEINMultiple languages
Psychology, Clinical; Psychiatry; PsychologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/42789

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