TPH2 gene variants and anxiety during alcohol detoxification outcome Alessandro Serretti a, ⁎ , Ioannis Liappas b , Laura Mandelli a , Diego Albani c , Gianluigi Forloni c , Petros Malitas d , Christina Piperi e , Antonis Politis f , Elias O. Tzavellas b , Zeta Papadopoulou-Daifoti g , Aikaterini Zisaki e , Francesca Prato c , Sara Batelli c , Letizia Polito c , Diana De Ronchi a , Anastasios Kalofoutis d,e a Institute of Psychiatry, University of Bologna, Italy b Department of Psychiatry, Eginition Hospital, University of Athens Medical School, Athens, Greece c Neuroscience Department. Istituto di ricerche Farmacologiche “Mario Negri”, Milan, Italy d European Centre for the Quality of Life — E.C.Qua.L., Athens, Greece e Laboratory of Biological Chemistry, University of Athens Medical School, Athens, Greece f Division of Geriatric Psychiatry Department of Psychiatry, Eginition Hospital, University of Athens Medical School, Athens, Greece g Department of Experimental Pharmacology, University of Athens Medical School, Athens, Greece Received 2 August 2007; received in revised form 16 November 2007; accepted 5 December 2007 Abstract Clinical outcome of alcoholism may be partly under genetic control. The serotonergic system is involved in alcohol intake, and it has been widely investigated in alcohol dependence. Recently, attention has been focused on the neuronal tryptophan hydroxylase 2 gene (TPH2). TPH2 variants have been consistently associated with anxiety-related traits; since anxiety is critical for alcohol dependence treatment, in the present paper we investigated 9 SNPs within the THP2 gene in anxiety symptoms during the detoxification procedure. The sample comprised 68 alcohol-dependent patients who where evaluated with the Hamilton Rating Scale for Anxiety, before and after the detoxification procedure. Other psychopathological indicators of outcome, such as depression and anxiety sub- features were also investigated. We did not observe a role for TPH2 variants in the efficacy of treatment in relieving anxiety and other psychopathological symptoms. However, a haplotype that included the promoter rs4570625 polymorphism (associated with anxiety-related traits in previous studies) showed an association with the severity of anxiety symptoms on admission. This preliminary finding, although obtained on a small sample, may provide further support for a role of the TPH2 gene in emotional behaviors. Furthermore, the present study suggests the possible functional significance of the promoter rs4570625 polymorphism. The present preliminary results are of interest in alcoholism, given that comorbidity with anxiety represents a critical problem in treatment settings and response to detoxification. © 2007 Elsevier Ireland Ltd. All rights reserved. Keywords: Pharmacogenetic; Serotonin; Anxiety; Depression; Alcoholism Available online at www.sciencedirect.com Psychiatry Research 167 (2009) 106 – 114 www.elsevier.com/locate/psychres ⁎ Corresponding author. Institute of Psychiatry, University of Bologna, Viale Carlo Pepoli 5, 40123 Bologna, Italy. Tel.: +39 051 6584233; fax: +39 051 521030. E-mail address: alessandro.serretti@unibo.it (A. Serretti). 0165-1781/$ - see front matter © 2007 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.psychres.2007.12.006