Abstract
Generalized Anxiety Disorder (GAD) is characterized by excessive worry and physical symptoms of prolonged anxiety. Patients with subclinical GAD-states (sub-GAD) do not fulfill the diagnostic criteria of GAD, but they often show a disease burden similar to GAD, and the subclinical state may turn into a full syndrome. Neuroinflammation may contribute to changes in brain structures in sub-GAD, but direct evidence remains lacking. We investigated 73 newly recruited sub-GAD patients who had never received pharmacological or psychological treatment and 64 matched non-clinical individuals. We utilized magnetic resonance imaging (MRI) to assess putative neuroinflammatory markers (DBSI-RF, diffusion-based spectral imaging-based restricted fraction) in the hippocampus, amygdala, and neocortex. The patients completed the Hamilton Anxiety Rating Scale (HAM-A), the Generalized Anxiety Disorder 7-item scale (GAD-7), and the Beck Depression Inventory-II (BDI-II). Compared to controls, sub-GAD individuals had significantly elevated inflammatory MRI markers in the amygdala but not in the hippocampus and neocortex. The DBSI-RF values correlated with the severity of anxiety (HAM-A and GAD-7 scores), but not with BDI-II. These findings suggest that neuroinflammation in the amygdala may play a critical role in the development of anxiety in sub-GAD.