Prediction of remission of depression with clinical variables, neuropsychological performance, and serotonergic/dopaminergic gene polymorphisms Esteve Gudayol-Ferré 1,2,3 *, Ixchel Herrera-Guzmán 1,2,3 , Beatriz Camarena 6 , Carlos Cortés-Penagos 7 , Jorge E. Herrera-Abarca 1,3 , Patricia Martínez-Medina 4 , Juan Asbun-Bojalil 3 , Yuridia Lira-Islas 2 , Celia Reyes-Ponce 2 and Joan Guàrdia-Olmos 5 1 Facultad de Psicología, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Mich., Mexico 2 Clínica de Enfermedades Crónicas y Procedimientos Especiales CECYPE, Morelia, Mich., Mexico 3 Escuela Superior de Medicina, Sección de Estudios de Postgrado e Investigación, Instituto Politécnico Nacional, I.P.N. Mexico City, Mexico 4 Centro Michoacano de Salud Mental, Secretaría de Salud, Morelia, Mich., Mexico 5 Departament de Metodologia, Facultat de Psicologia, Universitat de Barcelona, Barcelona, Institut de Recerca en Cervell, Cognició i Conducta IR3C, Spain 6 Departamento de Genética Psiquiátrica, Instituto Nacional de Psiquiatría “Ramón de la Fuente”, Mexico City, Mexico 7 Facultad de Quimicofarmacobiología, Universidad Michoacana de San Nicolás de Hidalgo, Morelia, Mich., Mexico Objective The aim of our work is to study the possible role of clinical variables, neuropsychological performance, and the 5HTTLPR, rs25531, and val108/58Met COMT polymorphisms on the prediction of depression remission after 12 weeks’ treatment with fluoxetine. These variables have been studied as potential predictors of depression remission, but they present poor prognostic sensitivity and specificity by themselves. Methods Seventy-two depressed patients were genotyped according to the aforementioned polymorphisms and were clinically and neuropsychologically assessed before a 12-week fluxetine treatment. Results Only the La allele of rs25531 polymorphism and the GG and AA forms of the val 108/158 Met polymorphism predict major depressive disorder remission after 12 weeks’ treatment with fluoxetine. None of the clinical and neuropsychological variables studied predicted remission. Conclusions Our results suggest that clinical and neuropsychological variables can initially predict early response to fluoxetine and mask the predictive role of genetic variables; but in remission, where clinical and neuropsychological symptoms associated with depression tend to disappear thanks to the treatment administered, the polymorphisms studied are the only variables in our model capable of predicting remission. However, placebo effects that are difficult to control require cautious interpretation of the results. Copyright © 2012 John Wiley & Sons, Ltd. key words—major depressive disorder; neuropsychological assessment; 5HTTLPR; COMT; polymorphism; antidepressant response INTRODUCTION Major depressive disorder (MDD) is usually treated with antidepressant drugs, and among these drugs, the selective serotonin reuptake inhibitors (SSRI) are widely prescribed because of their effectiveness, relatively low toxicity, and tolerability (Stahl, 2002; Rush et al., 2006). Unfortunately, only between 50% and 70% of the patients respond to the initial treatment with antidepressants (Berrettini, 2002), and only about 40% remit with pharmacological treatment (Warden et al., 2007). Remission in depression has become a focus of attention in the mental health community since MDD was conceived as a chronic condition (Keller, 2004), and it is regarded as a preferred treatment goal over response (Keller, 2004). The choice of a particular antidepressant for a particular patient is made randomly (Taylor et al., 2006; Gartlehner et al., 2008), as there is little empirical evidence for choosing one treatment or another (Taylor et al., 2006). In addition, patients must remain on their antidepressant for up to 8weeks to know whether they *Correspondence to: E. Gudayol-Ferré, Facultad de Psicología Universidad Michoacana de San Nicolás de Hidalgo, Francisco Villa 450, C.P. 58120, Morelia, Mich., Mexico. Tel: +443 3149913; Fax: +443 3149909. E-mail: ferre@umich.mx Received 13 April 2012 Accepted 18 September 2012 Copyright © 2012 John Wiley & Sons, Ltd. human psychopharmacology Hum. Psychopharmacol Clin Exp 2012; 27: 577–586. Published online in Wiley Online Library (wileyonlinelibrary.com) DOI: 10.1002/hup.2267