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Connection Failure: Differences in White Matter Microstructure are associated with 5-HTTLPR but not with Risk-Seeking for Losses

By Philipp T. Neukam, Dirk K. Mueller, Yacila I. Deza-Araujo, Shakoor Pooseh, Stephanie H. Witt, Marcella Rietschel, Michael N. Smolka

Posted 05 Feb 2021
bioRxiv DOI: 10.1101/2021.02.03.429606

In a previous study (Neukam, Kroemer et al. 2018), we found for the 5-HTTLPR genotype higher risk-seeking for losses in S/S vs. L/L carrier, which could not be explained by acutely changed central serotonin levels. This finding alternatively 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 that we observed in our previous study and whether 5-HTTLPR groups differ in their white matter microstructure. These differences can be detected using diffusion-weighted imaging (DWI). We assumed lower structural connectivity in S/S compared to L/L carrier, and a negative relationship between risk-seeking for losses and connectivity. We used DWI to compute diffusion parameters for the frontostriatal and uncinate tract in 175 individuals (39 S/S, 80 S/L, 56 L/L). 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 our hypothesis that the association between 5-HTTLPR and risk-seeking for losses is related to differences in white matter pathways implicated in decision-making.

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