Philipp T Neukam1, Nils B Kroemer1,2, Yacila I Deza Araujo1, Lydia Hellrung1,3, Shakoor Pooseh1, Marcella Rietschel4, Stephanie H Witt4, Uwe Schwarzenbolz5, Thomas Henle5, Michael N Smolka6. 1. Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany. 2. Department of Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany. 3. Department of Economics, University of Zürich, Zürich, Switzerland. 4. Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. 5. Institute of Food Chemistry, Technische Universität Dresden, Dresden, Germany. 6. Department of Psychiatry and Neuroimaging Center, Technische Universität Dresden, Dresden, Germany. michael.smolka@tu-dresden.de.
Abstract
RATIONALE: Serotonin (5-HT) plays a key role in different aspects of value-based decision-making. A recent framework proposed that tonic 5-HT (together with dopamine, DA) codes future average reward expectations, providing a baseline against which possible choice outcomes are compared to guide decision-making. OBJECTIVES: To test whether high 5-HT levels decrease loss aversion, risk-seeking for gains, and risk-seeking for losses. METHODS: In a first session, 611 participants were genotyped for 5-HTTLPR and performed a mixed gambles (MGA) task and two probability discounting tasks for gains and losses, respectively (PDG/PDL). Afterwards, a subsample of 105 participants (44 with S/S, 6 with S/L, 55 with L/L genotype) completed the pharmacological study using a crossover design with tryptophan depletion (ATD), loading (ATL), and balanced (BAL) conditions. The same decision constructs were assessed. RESULTS: We found increased risk-seeking for losses in S/S compared to L/L individuals at the first visit (p = 0.002). Neither tryptophan depletion nor loading affected decision-making, nor did we observe an interaction between intervention and 5-HTTLPR genotype. CONCLUSION: Our data do not support the idea that transient changes of tonic 5-HT affect value-based decision-making. We provide evidence for an association of 5-HTTLPR with risk-seeking for losses, independent of acute 5-HT levels. This indicates that the association of 5-HTTLPR and risk-seeking for losses is mediated via other mechanisms, possibly by differences in the structural development of neural circuits of the 5-HT system during early life phases.
RATIONALE: Serotonin (5-HT) plays a key role in different aspects of value-based decision-making. A recent framework proposed that tonic 5-HT (together with dopamine, DA) codes future average reward expectations, providing a baseline against which possible choice outcomes are compared to guide decision-making. OBJECTIVES: To test whether high 5-HT levels decrease loss aversion, risk-seeking for gains, and risk-seeking for losses. METHODS: In a first session, 611 participants were genotyped for 5-HTTLPR and performed a mixed gambles (MGA) task and two probability discounting tasks for gains and losses, respectively (PDG/PDL). Afterwards, a subsample of 105 participants (44 with S/S, 6 with S/L, 55 with L/L genotype) completed the pharmacological study using a crossover design with tryptophan depletion (ATD), loading (ATL), and balanced (BAL) conditions. The same decision constructs were assessed. RESULTS: We found increased risk-seeking for losses in S/S compared to L/L individuals at the first visit (p = 0.002). Neither tryptophan depletion nor loading affected decision-making, nor did we observe an interaction between intervention and 5-HTTLPR genotype. CONCLUSION: Our data do not support the idea that transient changes of tonic 5-HT affect value-based decision-making. We provide evidence for an association of 5-HTTLPR with risk-seeking for losses, independent of acute 5-HT levels. This indicates that the association of 5-HTTLPR and risk-seeking for losses is mediated via other mechanisms, possibly by differences in the structural development of neural circuits of the 5-HT system during early life phases.
Entities:
Keywords:
5-HTTLPR; Acute tryptophan intervention; Decision-making; Mixed gambles; Probability discounting
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