Differential alterations of resting-state functional connectivity in generalized anxiety disorder and panic disorder

Abstract

Generalized anxiety disorder (GAD) and panic disorder (PD) are most common anxiety disorders with high lifetime prevalence while the pathophysiology and disease-specific alterations still remain largely unclear. Few studies have taken a whole-brain perspective in the functional connectivity (FC) analysis of these two disorders in resting state. It limits the ability to identify regionally and psychopathologically specific network abnormalities with their subsequent use as diagnostic marker and novel treatment strategy. The whole brain FC using a novel FC metric was compared, that is, scaled correlation, which they demonstrated to be a reliable FC statistics, but have higher statistical power in two-sample t-test of whole brain FC analysis. About 21 GAD and 18 PD patients were compared with 22 matched control subjects during resting-state, respectively. It was found that GAD patients demonstrated increased FC between hippocampus/parahippocampus and fusiform gyrus among the most significantly changed FC, while PD was mainly associated with greater FC between somatosensory cortex and thalamus. Besides such regional specificity, it was observed that psychopathological specificity in that the disrupted FC pattern in PD and GAD correlated with their respective symptom severity. The findings suggested that the increased FC between hippocampus/parahippocampus and fusiform gyrus in GAD were mainly associated with a fear generalization related neural circuit, while the greater FC between somatosensory cortex and thalamus in PD were more likely linked to interoceptive processing. Due to the observed regional and psychopathological specificity, their findings bear important clinical implications for the potential treatment strategy.

Keywords: anxiety disorders; fear; functional magnetic resonance imaging (fMRI); generalization; interoception; whole brain functional connectivity analysis.

Figure 1

Altered functional connectivity of GAD (a, b) and PD (c). Abnormal FC in GAD were divided into two graphs (a, b) in order to display more clearly. Red line indicates increased FC in patient group with respective to matched controls, and blue line indicates the opposite. (Note that names and abbreviations of brain regions can be referred to Table S1, Supporting Information).

Figure 2

Distribution of scaled correlation (a) and Pearson correlation (b) for control and GAD group (for the first FC in Table II). As can be seen, the distribution of scaled correlation and Pearson correlation has similar mean (for both control and GAD group, with P > 0.05, see also Supporting Information Table S2), while the variance of the former is smaller than that of the latter (see Supporting Information Table S3).

Figure 3

Distribution of scaled correlation (a) and Pearson correlation (b) for control and PD group (for the first FC in Table III). As can be seen, the distribution of scaled correlation and Pearson correlation has similar mean (for both control and PD group, with P > 0.05, see Supporting Information Table S4), while the variance of the former is smaller than that of the latter (see Table S5, Supporting Information).