TY  - JOUR
A1  - Hommers, L. G.
A1  - Richter, J.
A1  - Yang, Y.
A1  - Raab, A.
A1  - Baumann, C.
A1  - Lang, K.
A1  - Schiele, M. A.
A1  - Weber, H.
A1  - Wittmann, A.
A1  - Wolf, C.
A1  - Alpers, G. W.
A1  - Arolt, V.
A1  - Domschke, K.
A1  - Fehm, L.
A1  - Fydrich, T.
A1  - Gerlach, A.
A1  - Gloster, A. T.
A1  - Hamm, A. O.
A1  - Helbig-Lang, S.
A1  - Kircher, T.
A1  - Lang, T.
A1  - Pané-Farré, C. A.
A1  - Pauli, P.
A1  - Pfleiderer, B.
A1  - Reif, A.
A1  - Romanos, M.
A1  - Straube, B.
A1  - Ströhle, A.
A1  - Wittchen, H.-U.
A1  - Frantz, S.
A1  - Ertl, G.
A1  - Lohse, M. J.
A1  - Lueken, U.
A1  - Deckert, J.
T1  - A functional genetic variation of SLC6A2 repressor hsa-miR-579-3p upregulates sympathetic noradrenergic processes of fear and anxiety
JF  - Translational Psychiatry
N2  - Increased sympathetic noradrenergic signaling is crucially involved in fear and anxiety as defensive states. MicroRNAs regulate dynamic gene expression during synaptic plasticity and genetic variation of microRNAs modulating noradrenaline transporter gene (SLC6A2) expression may thus lead to altered central and peripheral processing of fear and anxiety. In silico prediction of microRNA regulation of SLC6A2 was confirmed by luciferase reporter assays and identified hsa-miR-579-3p as a regulating microRNA. The minor (T)-allele of rs2910931 (MAFcases = 0.431, MAFcontrols = 0.368) upstream of MIR579 was associated with panic disorder in patients (pallelic = 0.004, ncases = 506, ncontrols = 506) and with higher trait anxiety in healthy individuals (pASI = 0.029, pACQ = 0.047, n = 3112). Compared to the major (A)-allele, increased promoter activity was observed in luciferase reporter assays in vitro suggesting more effective MIR579 expression and SLC6A2 repression in vivo (p = 0.041). Healthy individuals carrying at least one (T)-allele showed a brain activation pattern suggesting increased defensive responding and sympathetic noradrenergic activation in midbrain and limbic areas during the extinction of conditioned fear. Panic disorder patients carrying two (T)-alleles showed elevated heart rates in an anxiety-provoking behavioral avoidance test (F(2, 270) = 5.47, p = 0.005). Fine-tuning of noradrenaline homeostasis by a MIR579 genetic variation modulated central and peripheral sympathetic noradrenergic activation during fear processing and anxiety. This study opens new perspectives on the role of microRNAs in the etiopathogenesis of anxiety disorders, particularly their cardiovascular symptoms and comorbidities.
KW  - clinical genetics
KW  - psychiatric disorders
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-322497
VL  - 8
ER  - 
TY  - JOUR
A1  - Rayner, Christopher
A1  - Coleman, Jonathan R. I.
A1  - Purves, Kirstin L.
A1  - Hodsoll, John
A1  - Goldsmith, Kimberley
A1  - Alpers, Georg W.
A1  - Andersson, Evelyn
A1  - Arolt, Volker
A1  - Boberg, Julia
A1  - Bögels, Susan
A1  - Creswell, Cathy
A1  - Cooper, Peter
A1  - Curtis, Charles
A1  - Deckert, Jürgen
A1  - Domschke, Katharina
A1  - El Alaoui, Samir
A1  - Fehm, Lydia
A1  - Fydrich, Thomas
A1  - Gerlach, Alexander L.
A1  - Grocholewski, Anja
A1  - Hahlweg, Kurt
A1  - Hamm, Alfons
A1  - Hedman, Erik
A1  - Heiervang, Einar R.
A1  - Hudson, Jennifer L.
A1  - Jöhren, Peter
A1  - Keers, Robert
A1  - Kircher, Tilo
A1  - Lang, Thomas
A1  - Lavebratt, Catharina
A1  - Lee, Sang-hyuck
A1  - Lester, Kathryn J.
A1  - Lindefors, Nils
A1  - Margraf, Jürgen
A1  - Nauta, Maaike
A1  - Pané-Farré, Christiane A.
A1  - Pauli, Paul
A1  - Rapee, Ronald M.
A1  - Reif, Andreas
A1  - Rief, Winfried
A1  - Roberts, Susanna
A1  - Schalling, Martin
A1  - Schneider, Silvia
A1  - Silverman, Wendy K.
A1  - Ströhle, Andreas
A1  - Teismann, Tobias
A1  - Thastum, Mikael
A1  - Wannemüller, Andre
A1  - Weber, Heike
A1  - Wittchen, Hans-Ulrich
A1  - Wolf, Christiane
A1  - Rück, Christian
A1  - Breen, Gerome
A1  - Eley, Thalia C.
T1  - A genome-wide association meta-analysis of prognostic outcomes following cognitive behavioural therapy in individuals with anxiety and depressive disorders
JF  - Translational Psychiatry
N2  - Major depressive disorder and the anxiety disorders are highly prevalent, disabling and moderately heritable. Depression and anxiety are also highly comorbid and have a strong genetic correlation (r(g) approximate to 1). Cognitive behavioural therapy is a leading evidence-based treatment but has variable outcomes. Currently, there are no strong predictors of outcome. Therapygenetics research aims to identify genetic predictors of prognosis following therapy. We performed genome-wide association meta-analyses of symptoms following cognitive behavioural therapy in adults with anxiety disorders (n = 972), adults with major depressive disorder (n = 832) and children with anxiety disorders (n = 920; meta-analysis n = 2724). We (h(SNP)(2)) and polygenic scoring was used to examine genetic associations between therapy outcomes and psychopathology, personality and estimated the variance in therapy outcomes that could be explained by common genetic variants learning. No single nucleotide polymorphisms were strongly associated with treatment outcomes. No significant estimate of h(SNP)(2) could be obtained, suggesting the heritability of therapy outcome is smaller than our analysis was powered to detect. Polygenic scoring failed to detect genetic overlap between therapy outcome and psychopathology, personality or learning. This study is the largest therapygenetics study to date. Results are consistent with previous, similarly powered genome-wide association studies of complex traits.
KW  - Human behaviour
KW  - Personalized medicine
KW  - Prognostic markers
KW  - Psychiatric disorders
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-225048
VL  - 9
IS  - 150
ER  -