Universität zu Köln

Quast, Carina, Reif, Andreas ORCID: 0000-0002-0992-634X, Brueckl, Tanja, Pfister, Hildegard, Weber, Heike ORCID: 0000-0002-9421-1292, Mattheisen, Manuel ORCID: 0000-0002-8442-493X, Cichon, Sven ORCID: 0000-0002-9475-086X, 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. ORCID: 0000-0001-7088-6618 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:	Creators Email ORCID ORCID Put Code Quast, Carina UNSPECIFIED UNSPECIFIED UNSPECIFIED Reif, Andreas UNSPECIFIED orcid.org/0000-0002-0992-634X UNSPECIFIED Brueckl, Tanja UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfister, Hildegard UNSPECIFIED UNSPECIFIED UNSPECIFIED Weber, Heike UNSPECIFIED orcid.org/0000-0002-9421-1292 UNSPECIFIED Mattheisen, Manuel UNSPECIFIED orcid.org/0000-0002-8442-493X UNSPECIFIED Cichon, Sven UNSPECIFIED orcid.org/0000-0002-9475-086X UNSPECIFIED Lang, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Hamm, Alfons UNSPECIFIED UNSPECIFIED UNSPECIFIED Fehm, Lydia UNSPECIFIED orcid.org/0000-0002-0825-8466 UNSPECIFIED Stroehle, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Arolt, Volker UNSPECIFIED UNSPECIFIED UNSPECIFIED Domschke, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Kircher, Tilo UNSPECIFIED orcid.org/0000-0002-2514-2625 UNSPECIFIED Wittchen, Hans-Ulrich UNSPECIFIED orcid.org/0000-0002-6311-7711 UNSPECIFIED Pauli, Paul UNSPECIFIED orcid.org/0000-0003-0692-6720 UNSPECIFIED Gerlach, Alexander L. UNSPECIFIED orcid.org/0000-0001-6794-5349 UNSPECIFIED Alpers, Georg W. UNSPECIFIED orcid.org/0000-0001-9896-5158 UNSPECIFIED Deckert, Juergen UNSPECIFIED UNSPECIFIED UNSPECIFIED Rupprecht, Rainer UNSPECIFIED UNSPECIFIED UNSPECIFIED Binder, Elisabeth B. UNSPECIFIED orcid.org/0000-0001-7088-6618 UNSPECIFIED Erhardt, Angelika UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Faculty of Human Sciences
Divisions:	Faculty of Human Sciences > Department Psychologie
Subjects:	Medical sciences Medicine
Uncontrolled Keywords:	Keywords Language 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 Multiple languages Psychology, Clinical; Psychiatry; Psychology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/42789