Research Report STin2 VNTR polymorphism is associated with comorbid tobacco use and mood disorders Márcia Regina Pizzo de Castro a , Sandra Odebrecht Vargas Nunes a,b , Roberta Losi Guembarovski c , Carolina Batista Ariza c , Julie Massayo Maeda Oda c , Heber Odebrecht Vargas a,b , Luiz Gustavo Piccoli de Melo a , Maria Angelica Ehara Watanabe c , Michael Berk d,e,f , Michael Maes d,g,h,n a Center of Approach and Treatment for Smokers, University Hospital, Londrina State University, Campus Universitário, Londrina, Paraná, Brazil b Department of Clinical Medicine, Health Sciences Center, Londrina State University, University Hospital, Londrina, Paraná, Brazil c Department of Pathological Sciences, Biological Sciences Centre, Londrina State University, Paraná, Brazil d IMPACT Strategic Research Centre, School of Medicine, Deakin University, Geelong, Victoria, Australia e Orygen Youth Health Research Centre, Centre for Youth Mental Health, Department of Psychiatry and the Florey Institute for Neuroscience and Mental Health, University of Melbourne, Parkville, Australia f Barwon Health and the Geelong Clinic, Swanston Centre, Geelong, Victoria, Australia g Department of Psychiatry, Chulalongkorn University, Faculty of Medicine, Bangkok, Thailand h Health Sciences Graduate Program, Health Sciences Center, State University of Londrina, Brazil article info Article history: Received 4 June 2014 Received in revised form 11 October 2014 Accepted 11 October 2014 Available online 23 October 2014 Keywords: Mood disorders Tobacco use disorder Genetic polymorphism Serotonin transporter Oxidative stress Inflammation abstract Background: There is a significant comorbidity between mood disorders and tobacco use disorder (TUD), which may be related to both genetic and environmental factors. Gene variants of the 5-HT transporter, such as STin2 VNTR (a variable number of tandem repeats in the functional serotonin transporter intron 2) may be associated with mood disorders and TUD. Aims: This study aimed to delineate the association between the STin2 genetic polymorphism and comorbid TUD and mood disorders, including depression or bipolar disorder. Methods: We examined the STin2 VNTR polymorphism in never-smokers (n ¼113); patients with mood disorders without TUD (n ¼62); patients with TUD without mood disorders (n ¼90); and patients with both disorders (n ¼95). Results: We found a significant association between the STin2 genetic polymorphism and the above diagnostic groups whereby the STin2.12 allele shows a positive association with comorbid TUD and mood disorders (Odds ratio ¼3.07, 95% CI ¼1.41–6.68), while the STin2.10/10 homozygous genotype shows a negative association (Odds ratio ¼0.34, 95% CI ¼0.16–0.74). Adjusting for years of education, age, gender, marital status and ethnicity did not change these results, but showed that TUD was associated with lower education levels and less stable relationships, whereas mood disorders were related to female gender. A family history of TUD was significantly associated with TUD in subjects without mood disorders only. Conclusions: The STin2.12 allele is positively and the STin2.10/10 genotype is negatively associated with comorbid TUD and mood disorders, depression or bipolar depression, suggesting that biological endophenotypes, e.g. disorders in serotonin metabolism, may in part underpin this comorbidity. & 2014 Elsevier B.V. All rights reserved. 1. Background Many studies have reported on the comorbidity between mood disorders and tobacco use disorder (TUD) (Patton et al., 1998; Lasser et al., 2000; Glassman et al., 2001; Murphy et al., 2003; Klungsøyr et al., 2006; Ziedonis et al., 2008; Pasco et al., 2008; Berlin et al., 2009; Pedersen and von Soest, 2009; Boden et al., 2010; Flensborg-Madsen et al., 2011; Jamal et al., 2012; Good- win et al., 2013). Estimates of the prevalence rate of current TUD among individuals with major depressive disorder and bipolar disorder range from 40% to 60% and 50% and 65% (Anthenelli, 2014). TUD is associated with an increased risk of depres- sive disorders, including suicide (Malone et al., 2003; Breslau et al., 2005; McGee et al., 2005; Hughes, 2008; Goodwin et al., 2012). Increased depression or current TUD rates may elevate the Contents lists available at ScienceDirect journal homepage: www.elsevier.com/locate/jad Journal of Affective Disorders http://dx.doi.org/10.1016/j.jad.2014.10.023 0165-0327/& 2014 Elsevier B.V. All rights reserved. n Correspondence to: Center of Approach and Treatment for Smokers, Londrina ZIP 86055630, Paraná, Brazil. Tel.: þ55 43 33368058; fax: þ55 43 33480990. E-mail addresses: mpizzo@sercomtel.com.br (M.R. Pizzo de Castro), dr.michaelmaes@hotmail.com (M. Maes). URL: http://scholar.google.com.br/citations? user ¼1wzMZ7UAAAAJ&hl ¼pt-BR&oi ¼ao (M. Maes). Journal of Affective Disorders 172 (2015) 347–354