Disruption of functional and structural networks in first-episode, drug-naïve adolescents with generalized anxiety disorder

Abstract

Background: Individuals with generalized anxiety disorder (GAD) tend to worry exaggeratedly and uncontrollably about various daily routines. Previous studies have demonstrated that the GAD patients exhibited widespread alternations in both functional networks (FN) and structural networks (SN). However, the simultaneous alternations of the topological organization of FN, SN, as well as their couplings in GAD still remain unknown.

Methods: Using multimodal approach, we constructed FN from resting-state functional magnetic imaging (R-fMRI) data and SN from diffusion magnetic resonance imaging (dMRI) data of 32 adolescent GAD patients and 25 healthy controls (HC). Graph theory analysis was employed to investigate the topological properties of FN, SN, and FN-SN coupling.

Results: Compared to HC, the GAD patients showed disruptions in global (i.e., decreased clustering coefficient, global, and local efficiency) and subnetwork (i.e., reduced intermodular connections, rich club, and feeder connections) levels in FN. Abnormal global level properties (i.e., increased characteristic path length and reduced global efficiency) were also observed in SN. Altered FN-SN couplings in normalized characteristic path length and feeder connections were identified in the GAD patients. The identified network measures were correlated with anxiety severity in the GAD patients.

Limitations: The sample size of the current study is small and the cross-sectional nature can not infer causal relationship.

Conclusions: Our findings identified GAD-related topological alternations in both FN and SN, together with the couplings between FN and SN, providing us with a novel perspective for understanding the pathophysiological mechanisms of GAD.

Keywords: Functional connectome; Functional-structural coupling; Generalized anxiety disorder; Graph theory; Structural connectome.