Work

Aberrant single-subject cortical morphological networks and their associations with multiple symptoms in generalized anxiety disorder

Year: 2026

Type: article

Abstract: Generalized anxiety disorder (GAD) is a prevalent disorder associated with disrupted topological organization of large-scale brain networks. However, the morphological basis for network disruption and its clinical relevance remains unexplored. We constructed single-subject cortical morphological networks for 58 drug-free GAD patients and 86 age- and sex-matched healthy controls (HCs) separately based on cortical thickness, surface area, cortical volume, mean curvature, sulcal depth and local gyrification index. Between-group differences in local morphology and network topology were analyzed using general linear models. Partial correlation analyses were conducted to examine the relationship between brain alterations and clinical characteristics in GAD patients, while controlling for age, sex, education years and intracranial volume. Compared with HCs, GAD patients showed increased thickness in the left middle temporal gyrus and decreased local gyrification index in the left superior frontal gyrus. At the network level, GAD patients exhibited increased local efficiency, normalized clustering coefficient, and small-worldness, alongside decreased characteristic path length in cortical volume-based networks. Local morphology and network topological properties were associated with clinical characteristics such as illness duration, age of onset, anxiety severity, and personality traits. Our findings revealed both region-specific cortical abnormalities and global network reorganization in GAD patients. In particular, the shift toward stronger small-world configurations suggests enhanced local integration and global communication efficiency. These results highlight that GAD is associated not only with focal cortical alterations but also with systemic structural network changes that ma y underlie excessive anxiety and personality traits associated with the disorder.

Source: Translational Psychiatry

DOI: 10.1038/s41398-026-04434-3