Abnormal regional activity in the prefrontal‐limbic circuit at rest: Potential imaging markers and treatment predictors in drug‐naive anxiety disorders

Abstract Background Previous research has identified functional impairments within the prefrontal‐limbic circuit in individuals with anxiety disorders. However, the link between these deficiencies, clinical symptoms, and responses to antipsychotic treatment is still not fully understood. This study aimed to investigate abnormal regional activity within the prefrontal‐limbic circuit among drug‐naive individuals diagnosed with generalized anxiety disorder (GAD) and panic disorder (PD) and to analyze changes following treatment. Methods Resting‐state magnetic resonance imaging was performed on a cohort of 118 anxiety disorder patients (64 GAD, 54 PD) and 61 healthy controls (HCs) at baseline. Among them, 52 patients with GAD and 44 patients with PD underwent a 4‐week treatment regimen of paroxetine. Fractional amplitude of low‐frequency fluctuation (fALFF) measurements and pattern classification techniques were employed to analyze the data in accordance with the human Brainnetome atlas. Results Both patients with GAD and PD demonstrated decreased fALFF in the right cHipp subregion of the hippocampus and increased fALFF in specified subregions of the cingulate and orbitofrontal lobe. Notably, patients with PD exhibited significantly higher fALFF in the left A24cd subregion compared to patients with GAD, while other ROI subregions showed no significant variations between the two patient groups. Whole‐brain analysis revealed abnormal fALFF in both patient groups, primarily in specific areas of the cingulate and parasingulate gyrus, as well as the inferior and medial orbitofrontal gyrus (OFG). Following a 4‐week treatment period, specific subregions in the GAD and PD groups showed a significant decrease in fALFF. Further analysis using support vector regression indicated that fALFF measurements in the right A13 and right A24cd subregions may be predictive of treatment response among anxiety disorder patients. Conclusions Aberrant functional activity in certain subregions of the prefrontal‐limbic circuit appears to be linked to the manifestation of anxiety disorders. These findings suggest potential imaging indicators for individual responses to antipsychotic treatment.