Connection Failure: Differences in White Matter Microstructure Are Associated with 5-HTTLPR but Not with Risk Seeking for Losses

Int J Mol Sci. 2024 Jun 18;25(12):6666. doi: 10.3390/ijms25126666.

Abstract

S/S carriers of 5-HTTLPR have been found to be more risk seeking for losses compared to L/L carriers. This finding may be the result of reduced top-down control from the frontal cortex due to altered signal pathways involving the amygdala and ventral striatum. The serotonergic system is known to be involved in neurodevelopment and neuroplasticity. Therefore, the aim of this study was to investigate whether structural differences in white matter can explain the differences in risk-seeking behaviour. Lower structural connectivity in S/S compared to L/L carriers and a negative relationship between risk seeking for losses and connectivity were assumed. Diffusion-weighted imaging was used to compute diffusion parameters for the frontostriatal and uncinate tract in 175 genotyped individuals. The results showed no significant relationship between diffusion parameters and risk seeking for losses. Furthermore, we did not find significant differences in diffusion parameters of the S/S vs. L/L group. There were only group differences in the frontostriatal tract showing stronger structural connectivity in the S/L group, which is also reflected in the whole brain approach. Therefore, the data do not support the hypothesis that the association between 5-HTTLPR and risk seeking for losses is related to differences in white matter pathways implicated in decision-making.

Keywords: 5-HTTLPR; DTI; decision-making; risky choice; structural connectivity.

MeSH terms

  • Adult
  • Diffusion Magnetic Resonance Imaging
  • Female
  • Genotype
  • Humans
  • Male
  • Risk-Taking
  • Serotonin Plasma Membrane Transport Proteins* / genetics
  • White Matter* / diagnostic imaging
  • White Matter* / pathology

Substances

  • Serotonin Plasma Membrane Transport Proteins
  • SLC6A4 protein, human