Global-brain functional connectivity related with trait anxiety and its association with neurotransmitters and gene expression profiles

Background: Numerous studies have explored the neural correlates of trait anxiety, a predisposing factor for several stress-related disorders. However, the findings from previous studies are inconsistent, which might be due to the limited regions of interest (ROI). A recent approach, named global-brain functional connectivity (GBC), has been demonstrated to address the shortcomings of ROI-based analysis. Furthermore, research on the transcriptome-connectome association has provided an approach to link the microlevel transcriptome profile with the macroscale brain network. In this paper, we aim to explore the neurobiology of trait anxiety with an imaging transcriptomic approach using GBC, biological neurotransmitters, and transcriptome profiles. Methods: Using a sample of resting-state fMRI data, we investigated trait anxiety-related alteration in GBC. We further used behavioral analysis, spatial correlation analysis, and postmortem gene expression to separately assess the cognitive functions, neurotransmitters, and transcriptional profiles related to alteration in GBC in individuals with trait anxiety. Results: GBC values in the ventromedial prefrontal cortex and the precuneus were negatively correlated with levels of trait anxiety. This alteration was correlated with behavioral terms including social cognition, emotion, and memory. A strong association was revealed between trait anxiety-related alteration in GBC and neurotransmitters, including dopaminergic, serotonergic, GABAergic, and glutamatergic systems in the ventromedial prefrontal cortex and the precuneus. The transcriptional profiles explained the functional connectivity, with correlated genes enriched in transmembrane signaling. Limitations: Several limitations should be taken into account in this research. For example, future research should consider using some different approaches based on dynamic or task-based functional connectivity analysis, include more neurotransmitter receptors, additional gene expression data from different samples or more genes related to other stress-related disorders. Meanwhile, it is of great significance to include a larger sample size of individuals with a diagnosis of major depression disorder or other disorders for analysis and comparison and apply stricter multiple-comparison correction and threshold settings in future research. Conclusions: Our research employed multimodal data to investigate GBC in the context of trait anxiety and to establish its associations with neurotransmitters and transcriptome profiles. This approach may improve understanding of the neural mechanism, together with the biological and molecular genetic foundations of GBC in trait anxiety.