Regional Gene Expression Patterns are Associated with Functional Connectivity Alterations in Major Depressive Disorder with Anxiety Symptoms.

Background: Understanding gene expression and functional connectivity (FC) changes in depressed patients with anxiety can help develop personalized therapies. Herein we examine the link between transcriptome data and FC differences in patients with major depressive disorder with significant anxiety (MDD/ANX+) and patients with major depressive disorder without significant anxiety (MDD/ANX-).

Methods: We compared the FC between the MDD/ANX+ group (n = 294) and the MDD/ANX- group (n = 218) to identify FC differences at both edge-based and network levels. Using the Allen Human Brain Atlas, we performed partial least squares regression analysis to identify genes associated with the observed FC disparities, followed by a functional enrichment analysis.

Results: The results from both edge-based and network-level FC analyses consistently indicated significantly increased FC between the subcortical network (SC) and visual network, as well as between the SC and dorsal attention network, in the MDD/ANX+ group compared with the MDD/ANX- group. Additionally, transcriptome-neuroimaging correlation analysis revealed that the expression of 1066 genes was spatially correlated with the FC differences between the MDD/ANX+ and MDD/ANX- groups. These genes were enriched in translation at synapses and adenosine triphosphate (ATP) generation.

Conclusions: Our results indicate that gene expression variations in synaptic translation and ATP generation may affect FC and anxiety risk in MDD patients.