Regional brain functional abnormalities in adolescents with social anxiety disorder: a resting-state fMRI study

Adolescence represents a critical developmental period characterized by the emergence of social anxiety disorder (SAD) and continued maturation of neural circuits underlying social cognition. Nevertheless, evidence from rs-fMRI studies examining regional brain function in adolescents with SAD remains limited, particularly with respect to studies integrating amplitude of low-frequency fluctuation (ALFF) and regional homogeneity (ReHo). This study aimed to investigate regional brain functional abnormalities in adolescents with SAD using ALFF and ReHo analyses of rs-fMRI data. Fifty-five adolescents diagnosed with SAD and thirty-six healthy controls (HC) recruited from the community were enrolled in the study. Clinical symptoms were assessed using the Social Anxiety Scale for Children (SASC), Screen for Child Anxiety Related Emotional Disorders (SCARED), and Social Avoidance and Distress Scale (SADS). Rs-fMRI data were acquired using a 3.0 T Siemens scanner. Amplitude of Low-Frequency Fluctuation (ALFF) and Regional Homogeneity (ReHo) values were compared between the two groups. ALFF/ReHo values extracted from brain regions with statistically significant between-group differences were subsequently correlated with clinical scale scores. Receiver operating characteristic (ROC) curve analysis with calculation of the area under the curve (AUC) was further conducted to explore the discriminative value of these regional indices in differentiating SAD from HC in the present sample, and a nested cross-validation was performed in which region selection was repeated within the training data of each fold. The SAD group exhibited significantly decreased ALFF in the right cerebellar lobule VI and increased ALFF in the left superior occipital gyrus, left middle occipital gyrus, and right superior parietal gyrus. Additionally, ReHo was significantly increased in the bilateral middle occipital gyri (Gaussian random field [GRF] correction, voxel-level P < 0.001, cluster-level P < 0.05). ROC analysis showed that ReHo in the right middle occipital gyrus (AUC = 0.854, 95% CI: 0.775–0.933, P < 0.001), ReHo in the left middle occipital gyrus (AUC = 0.813, 95% CI: 0.720–0.907, P < 0.001), and ALFF in the left middle occipital gyrus (AUC = 0.807, 95% CI: 0.711–0.903, P < 0.001) exhibited good discriminative performance in differentiating SAD from HC in the present sample. Moderate discriminative performance was observed for ALFF in the left superior occipital gyrus (AUC = 0.733, 95% CI: 0.630–0.835, P < 0.001), while ALFF in the right superior parietal gyrus showed relatively lower discriminatory performance (AUC = 0.673, 95% CI: 0.560–0.786, P = 0.006). In contrast, ALFF in the right cerebellar lobule VI was lower in the SAD group than in HC, and the corresponding AUC was below 0.5 (AUC = 0.342, 95% CI: 0.228–0.455), indicating discrimination in the inverse direction rather than an absence of discriminative information. In a nested cross-validation wit h region selection repeated within the training data of each fold, discriminative performance was similar (AUC = 0.839), and the same six regions were selected in all 91 folds, indicating that region identification was highly reproducible; when age was added to the model, the AUC increased to 0.947. No significant correlations were observed between any of the functional brain metrics and scores on the SASC, SCARED, or SADS (all P > 0.05). Adolescents with SAD exhibited increased amplitude of spontaneous low-frequency BOLD fluctuations (ALFF) in the left superior occipital gyrus, left middle occipital gyrus, and right superior parietal gyrus, as well as enhanced local synchronization (ReHo) in the bilateral middle occipital gyri. These findings suggest increased amplitude and local synchrony of spontaneous low-frequency BOLD fluctuations in occipital and parietal regions in adolescents with SAD. Although several regional measures showed moderate-to-good discriminative performance, neither a single region nor any combination of regions was sufficient for individual-level classification. Given the cross-sectional design, these findings should be interpreted as hypothesis-generating and warrant further validation in task-based and longitudinal studies. Not applicable.