Abstract
OBJECTIVE: Neuroinflammation's role is increasingly emphasized in the pathology of major depressive disorder (MDD), and its close association with the risk of suicide is being reported. The Forkhead Box O1 (FoxO1) gene is known to play a role in regulating mood and emotion and is associated with susceptibility to suicidality in relation to environmental stress. This research aims to explore the relationship between FoxO1 and the risk of suicide in individuals with MDD. METHODS: We enrolled 127 healthy controls (HC) and 231 patients diagnosed with MDD, including 119 individuals with high suicide risk (HSR). All participants underwent the Hamilton Rating Scale for Depression Assessment and magnetic resonance imaging. Cortical thickness and white matter integrity were evaluated. RESULTS: In the HSR group, cortical thinning was observed in the left triangular part of the inferior frontal gyrus and right transverse frontopolar gyrus compared to HC. Additionally, fractional anisotropy (FA) values were decreased in the left posterior thalamic radiation, sagittal stratum, and uncinate fasciculus. Although no differences were observed based on allele variations for the two FoxO1 single nucleotide polymorphisms (SNPs), those with the minor allele of FoxO1 rs34733279, especially in the HSR group, displayed increased cortical thinning and reduced FA values in the left cingulum. CONCLUSION: Our study reveals close association between the minor allele of the FoxO1 gene rs34733279 and suicide risk in the left cingulum highlights the potential key role of the FoxO1 gene rs34733279 in the context of suicidal vulnerability. Further investigations are warranted to elucidate the underlying biological mechanisms.