Risk-seeking for losses is associated with 5-HTTLPR, but not with transient changes in 5-HT levels

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.

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Acknowledgments

We like to thank all our student assistants and the medical staff for helping with the recruitment process and data collection throughout the study and the radiographers at the neuroimaging centre. And the last but not least, we like to thank our enduring participants who dedicated their time to this study.

Funding

This research was supported by the Deutsche Forschungsgemeinschaft (DFG) grants SFB 940/1, SFB 940/2, SM80/7-1, and SM80/7-2.

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Correspondence to Michael N. Smolka.

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Neukam, P.T., Kroemer, N.B., Deza Araujo, Y.I. et al. Risk-seeking for losses is associated with 5-HTTLPR, but not with transient changes in 5-HT levels. Psychopharmacology 235, 2151–2165 (2018). https://doi.org/10.1007/s00213-018-4913-9

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Keywords

  • Decision-making
  • Probability discounting
  • Mixed gambles
  • Acute tryptophan intervention
  • 5-HTTLPR