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Irene Gonzalez,1 Rocio Polvillo,1,2 Maximiliano Ruiz-Galdon,1 Armando Reyes-Engel,1 Jose Luis Royo1 1Department of Surgery, Biochemistry and Immunology School of Medicine, University of Malaga, Malaga, Spain; 2Centro Andaluz de Biología del Desarrollo, Seville, 41013, SpainCorrespondence: Armando Reyes-Engel; Jose Luis Royo Tel +34 952131531; +34 952136655Email engel@uma.es; jlroyo@uma.esPurpose: Tryptophan is the only precursor of serotonin, the hormone which helps regulate key human functions such as appetite, memory, mood, and sexual behavior. Connections have been identified between serotonin system dysfunction and the molecular etiology and treatment of mood disorders in a wide range of studies. Proposals have been put forward to co-administer tryptophan supplementation together with serotonin reuptake inhibitors in major depression patients, and also to exploit the sub-therapeutic depressive status in healthy populations. The reported responses, however, have been very dissimilar and this uneven effect may largely be explained by interindividual genetic differences.Materials and Methods: We studied mood change in 138 healthy subjects using both Goldberg’s General Health Questionnaire and the Profile of Mood States Questionnaire to determine the effects of a daily supplementation of 1g of tryptophan or placebo. Buccal DNA samples were provided and TPH1 (rs1800532), MAOA (rs3788862 and rs979605), MAOB (rs3027452), and COMT (rs6269 and rs4680) variants were genotyped.Results: MAOB rs3027452 was equally associated with tryptophan supplementation efficacy in the depression subscales of both questionnaires (ΔT-Score.D; ΔT-Score.TMD and ΔPOMS.D p-values < 0.01).Conclusion: Here we provide evidence that tryptophan supplementation has an uneven effect on mood improvement in the general population.Keywords: tryptophan, serotonin, 5-HT, mood, pharmacogenetics, monoamine oxidase