Research Article DEPRESSION AND ANXIETY 0 : 1–10 (2011) SEROTONIN TRANSPORTER GENE AND CHILDHOOD TRAUMA — A G Â E EFFECT ON ANXIETY SENSITIVITY Benedikt Klauke, M.Sc., 1,2 Ju ¨ rgen Deckert, M.D., 3 Andreas Reif, M.D., 3 Paul Pauli, Ph.D., 4 Peter Zwanzger, M.D., 1 Christian Baumann, M.Sc., 3,4 Volker Arolt, M.D., 1 Angelika Glo ¨ ckner-Rist, Ph.D., 5 and Katharina Domschke, M.A. M.D. Ph.D. 1Ã Background: Genetic factors and environmental factors are assumed to inter- actively influence the pathogenesis of anxiety disorders. Thus, a gene–environment interaction (G Â E) study was conducted with respect to anxiety sensitivity (AS) as a promising intermediate phenotype of anxiety disorders. Method: Healthy subjects (N 5 363) were assessed for AS, childhood maltreatment (Childhood Trauma Questionnaire), and genotyped for functional serotonin transporter gene variants (5-HTTLPR/5-HTT rs25531). The influence of genetic and environmental variables on AS and its subdimensions was determined by a step-wise hierarchical regression and a multiple indicator multiple cause (MIMIC) model. Results: A significant G Â E effect of the more active 5-HTT genotypes and childhood maltreatment on AS was observed. Furthermore, genotype (LL)–childhood trauma interaction particularly influenced somatic AS subdimensions, whereas cognitive subdimensions were affected by childhood maltreatment only. Conclusions: Results indicate a G Â E effect of the more active 5-HTT genotypes and childhood maltreatment on AS, with particular impact on its somatic subcomponent. Depression and Anxiety 0:1–10, 2011. r 2011 Wiley-Liss, Inc. Key words: gene–environment interaction; serotonin transporter gene; 5-HTTLPR; childhood trauma; anxiety sensitivity INTRODUCTION Anxiety disorders are considered complex genetic disorders, with an interaction of biological factors and environmental influences. The contribution of genetic factors to the pathogenesis of anxiety disorders (heritability) varies from 30 to 60% [1,2] with the remaining part of the variance being attributed to most probably one unique environmental factor shared across anxiety disorders and a common shared environ- mental factor. [3] Also, dimensional anxiety traits such as anxiety sensitivity (AS) have been suggested to be interactively influenced by additive genetic as well as environmental factors such as stressful life events (LEs). [4,5] AS, a measure of cognitive vulnerability to anxiety, reflects fear of anxiety symptoms [6] and was found to be a predictor for anxiety disorders, especially panic dis- order. [7–9] The most frequently used measure of AS is the Anxiety Sensitivity Index (ASI). [6] Originally constructed as a one-dimensional scale, several studies revealed Published online in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/da.20840 Received for publication 11 February 2011; Revised 27 April 2011; Accepted 27 April 2011 The authors disclose the following financial relationships within the past 3 years: Contract grant sponsor: Deutsche Forschungs- gemeinschaft; Contract grant number: (SFB-TRR-58, projects C1, C2 and Z2). Ã Correspondence to: Katharina Domschke, Department of Psychiatry, University of Muenster, Albert-Schweitzer-Strasse 11, D-48143 Muenster, Germany. E-mail: katharina.domschke@ukmuenster.de 1 Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany 2 Department of Psychology, University of Muenster, Muenster, Germany 3 Department of Psychiatry, Psychosomatics and Psychother- apy, University of Wuerzburg, Wuerzburg, Germany 4 Department of Psychology, University of Wuerzburg, Wuerzburg, Germany 5 Department of Survey Research and Methodology, German Social Science Infrastructure Services (GESIS), Manheim, Germany r r 2011 Wiley-Liss, Inc.