1. Introduction Dysfunctional cognitions act as a vulnerability to depressed mood and depression (Scher, Ingram & Segal, 2005). Also, alterations in the serotonin (5- HT) system are implicated in the pathophysiology of depression (Walderhaug, et al., 2007). However, the interaction between dysfunctional cognitions and decreased serotonin neurotransmission in the development of depressed mood and depression, remains unstudied. Females have higher prevalence rates of depression, higher degrees of dysfunctional cognitions and slower rates of serotonin synthesis than men. The main objective of this study was to investigate whether there is an interaction between dysfunctional cognitions and an experimentally induced lowering of serotonin neurotransmission in the prediction of depressed mood. Also, a potential influence of sex on this interaction was investigated. Participants and Methods A between-subjects, double-blind experimental design was used. Eighty- four healthy students (mean 24.5 years) without a recent psychological disorder were randomized to sham depletion or rapid tryptophan depletion (RTD), the method used to induce decreased serotonin neurotransmission. Prior to the manipulation, dysfunctional cognitions were measured by the Automatic Thoughts Questionnaire-30 (ATQ-30). Depressed mood was assessed with the depression subscale of the Profile of Mood States (POMS) after the experimental intervention. Results An interaction between dysfunctional cognitions and decreased serotonin neurotransmission in the prediction of depressed mood was found at trend-level (p<.066). There was no significant interaction effect involving sex. However, when analysing the interaction in sub-samples of males and females, a significant effect was found for males only (p<.031). Conclusions The results indicate an interaction between dysfunctional cognitions and decreased serotonin neurotransmission in the prediction of depressed mood. As this study was intended to serve as a model for depression, the mechanisms may apply to clinical depression. References Scher, C. D., Ingram, R. E., & Segal, Z. V. (2005). Cognitive reactivity and vulnerability: Empirical evaluation of construct activation and cognitive diatheses in unipolar depression. Clinical Psychology Review, 25(4), 487-510. Walderhaug, E., Magnusson, A., Neumeister, A., Lappalainen, J., Lunde, H., Refsum, H., & Landrø, N. I. (2007). Interactive effects of sex and 5-HTTLPR on mood and impulsivity during tryptophan depletion in healthy people. Biological Psychiatry, 62, 593-599. COGNITIVE VULNERABILITY AS A PREDICTOR OF THE MOOD-LOWERING EFFECT OF RAPID TRYPTOPHAN DEPLETION (RTD) L. T. Fikke,a M. I. Fikke,a N. I. Landrø,a & E. Walderhaug,a a Department of Psychology, University of Oslo, Norway Figure 1. Interaction plot showing the rapid tryptophan depletion (RTD) by Automatic Thoughts Questionnaire (ATQ) interaction effect for depression (Poms) Correspondence: Linn T. Fikke, The Cognitive Developmental Research Unit, Institute of Psychology, University of Oslo, Postboks 1094, Blindern, 0317 Oslo, Norway. E- mail: l.t.fikke@psykologi.uio.no