Gender-specific Association of Variants in Theakr1c1gene With Dimensional Anxiety in Patients With Panic Disorder: Additional Evidence for the Importance of Neurosteroids in Anxiety?
Year: 2014
Type: article
Study design: Observational Study
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: 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). 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.
Source: Depression and Anxiety
DOI: 10.1002/da.22229
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
Institutions: Max Planck Institute of Psychiatry, University of Würzburg, University of Bonn, Aarhus University, University of Basel, Universität Greifswald, Humboldt-Universität zu Berlin, Charité – Universitätsmedizin Berlin, University of Münster, Philipps University of Marburg, Technische Universität Dresden, University of Cologne, University of Mannheim, University of Regensburg
Language: English
Subfield: Experimental and Cognitive Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: bronze
OpenAlex ID: W1959412014