Neural mechanisms of aberrant self-referential processing in patients with generalized anxiety disorder

Massive theoretical studies in clinical psychology have implicated the self in understanding internalizing disorders (i.e., anxiety and mood disorders), in which self-related tasks were frequently used to investigate internalizing psychopathology. As one of the most frequently seen internalizing disorder in primary care, patients with generalized anxiety disorder (GAD) are characterized by inappropriate self-related processing such as negative self-referential thinking. However, relevant neural mechanisms remain unknown. In this study, participants underwent a self-related task which they were presented with several positive and negative trait words and were required to judge the extent to which these traits matched themselves when compared to their average peers. Aberrant brain activation and functional connectivity of GAD were detected during processing positive and negative traits. Compared to healthy controls (HCs), patients with GAD exhibited abnormal self-processing which manifested as lower biased self-rating scores particularly for negative traits and weaker brain activity in the left dorsomedial prefrontal cortex, inferior frontal gyrus, superior temporal sulcus (STS), and bilateral lingual gyrus when processing trait words. Abnormal functional connections between these hypoactive regions and regions associated with reward, emotion, and theory of mind were observed in subsequent psychophysiological interaction analysis. An attenuation of connectivity between the left insula and left STS was associated with greater severity of anxiety symptom in GAD patients. These findings provide insight into the abnormal neurocognitive mechanisms of biased self-related processing in GAD patients, which involves distorted self-schema accompanied by abnormal activation and functional connections of regions implicated in self-related and social cognition processing.