Disruption of Accumbens and Thalamic White Matter Connectivity Revealed by Diffusion Tensor Tractography in Young Men with Genetic Risk for Obesity

Gaia Olivo, Francesco Latini, Lyle Wiemerslage, Elna-Marie Larsson, Helgi B. Schiöth

Background: Neurovascular coupling is associated with white matter (WM) structural integrity, and it is regulated by specific subtypes of dopaminergic receptors. An altered activity of such receptors, highly expressed in reward-related regions, has been reported in carriers of obesity-risk alleles of the fat mass and obesity associated (FTO) gene. Among the reward-related regions, the thalamus and the nucleus accumbens are particularly vulnerable to blood pressure dysregulation due to their peculiar anatomo-vascular characteristics, and have been consistently reported to be altered in early-stage obesity. We have thus hypothesized that a disruption in thalamus and nucleus accumbens WM microstructure, possibly on neurovascular basis, could potentially be a predisposing factor underlying the enhanced risk for obesity in the risk-allele carriers. Methods: We have tested WM integrity in 21 male participants genotyped on the FTO risk single nucleotide polymorphisms (SNP) rs9939609, through a deterministic tractography analysis. Only homozygous participants (9 AA, 12 TT) were included. 11 tracts were selected and categorized as following according to our hypothesis: "risk tracts", "obesity-associated tracts", and a control tract (forcpes major). We investigated whether an association existed between genotype, body mass index (BMI) and WM microstructural integrity in the "risk-tracts" (anterior thalamic radiation and accumbofrontal fasciculus) compared to other tracts. Moreover, we explored whether WM diffusivity could be related to specific personality traits in terms of punishment and reward sensitivity, as measure by the BIS/BAS questionnaire. Results: An effect of the genotype and an interaction effect of genotype and BMI were detected on the fractional anisotropy (FA) of the "risk tracts". Correlations between WM diffusivity parameters and measures of punishment and reward sensitivity were also detected in many WM tracts of both networks. Conclusions: A disruption of the structural connectivity from the nucleus accumbens and the thalamus might occur early in carriers of the FTO AA risk-allele, and possibly act as a predisposing factor to the development of obesity.