Dopamine and Serotonin Transporter Genes Regulation in Highly Sensitive Individuals during Stressful Conditions: A Focus on Genetics and Epigenetics

<b>Background</b>: Coping with stress is essential for mental well-being and can be critical for highly sensitive individuals, characterized by a deeper perception and processing of stimuli. So far, the molecular bases characterizing high-sensitivity traits have not been completely investigated and gene × environment interactions might play a key role in making some people more susceptible than others. <b>Methods</b>: In this study, 104 young adult university students, subjects that might face overwhelming experiences more than others, were evaluated for the genetics and epigenetics of dopamine (<i>DAT1</i>) and serotonin (<i>SERT</i>) transporter genes, in addition to the expression of miR-132, miR-491, miR-16, and miR-135. <b>Results</b>: We found an increase in DNA methylation at one specific CpG site at <i>DAT1</i> 5'UTR in highly sensitive students reporting high levels of perceived stress when compared to those less sensitive and/or less stressed. Moreover, considering <i>DAT1</i> VNTR at 3'UTR, we observed that this effect was even more pronounced in university students having the 9/9 genotype when compared to those with the 9/10 genotype. These data are corroborated by the higher levels of miR-491, targeting <i>DAT1</i>, in highly sensitive subjects with high levels of perceived stress. <i>SERT</i> gene DNA methylation at one specific CpG site was reported to instead be higher in subjects reporting lower perceived stress when compared to more stressed subjects. Consistently, miR-135 expression, regulating <i>SERT</i>, was lower in subjects with higher perceived stress. <b>Conclusions</b>: We here suggest that the correlation of <i>DAT1</i> and <i>SERT</i> genetic and epigenetic data with the analysis of stress and sensitivity might be useful to suggest possible biomarkers to monitor mental health wellness in vulnerable subjects.