The long rather than the short allele of 5-HTTLPR predisposes Han Chinese to anxiety and reduced connectivity between prefrontal cortex and amygdala

The short allele of the serotonin-transporter gene is associated with higher risk for anxiety and depression in Caucasians, but this association is still unclear in Asians. Here, we addressed this issue using behavioral and multi-modal MRI approaches in a large group of healthy Han Chinese participants （n = 233）. In contrast to findings in Caucasians, we found that long-allele （L） carriers had higher anxiety scores. In another group （n = 64） experiencing significant levels of depression or anxiety, the L-allele frequency was also significantly higher. In healthy participants, L-carriers had reduced functional and anatomical connectivity between the amygdala and prefrontal cortex （PFC）, which was correlated with anxiety or depression scores. Our findings demonstrated that in Chinese Han participants, in contrast to Caucasians, the L-allele confers vulnerability to anxiety or depression and weakens top-down emotional control between the PFC and amygdala. Therefore, ethnic background should be taken into account in gene-related studies and their potential clinical applications.

A potential ethnic difference in the association between 5-HTTLPR polymorphisms and the brain default mode network

The serotonin-transporter-linked polymorphic region(5-HTTLPR)is associated with mood disorders.This association is thought to be due to amygdala hyperresponsiveness to negative emotional stimuli as a result of reduced frontal cortical control.In Caucasians,the short form is associated with this effect,but in Han Chinese we recently found that the long form is involved.Serotonin receptors have rich expression in default mode network(DMN)regions and the recent studies have found an association between the short form of the 5-HTTLPR and DMN functional connectivity(FC)in Caucasians.The present study has investigated whether there may also be anethnic difference in this influence of 5-HTTLPR on the DMN.We recruited 233 young Han Chinese subjects and calculated the resting-state default-network FC.Our study found that the L carriers had decreased FC in the bilateral medial prefrontal cortex,right parahippocampal gyrus,left middle temporal gyrus,and increased FC in left precuneus(Pcu)compared to SS.The PCC-Pcu FC in L carriers was significantly negatively correlated with the depression scores.Our findings,therefore,suggest that there is also a difference between Caucasian and Han Chinese subjects in the association between the different forms of the5-HTTLPR and DMN functional connectivity.