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Progressive brain structural alterations assessed via causal analysis in patients with generalized anxiety disorder.

ABSTRACT: Accumulating neuroimaging studies implicate widespread brain structural alterations in patients with generalized anxiety disorder (GAD), but little is known regarding the temporal information of these changes and their causal relationships. In this study, a morphometric analysis was performed on T1-weighted structural images, and the progressive changes in the gray matter volume (GMV) in GAD were simulated by dividing the patients into different groups from low illness duration to high illness duration. The duration was defined as the interval between the onset of GAD and the time for magnetic resonance imaging collection. Then, a causal structural covariance network analysis was conducted to describe the causal relationships of the brain structural alterations in GAD. With increased illness duration, the GMV reduction in GAD originated from the subgenual anterior cingulate cortex (sgACC) and propagated to the bilateral ventromedial prefrontal cortex, right dorsomedial prefrontal cortex, left inferior temporal gyrus, and right insula. Intriguingly, the sgACC and the right insula had positive causal effects on each other. Moreover, both sgACC and right insula exhibited positive causal effects on the parietal cortex and negative effects on the posterior cingulate cortex, dorsolateral prefrontal cortex, visual cortex, and temporal lobe. The opposite causal effects were noted on the somatosensory and the ventrolateral prefrontal cortices. In conclusion, patients with GAD show gradual GMV reduction with increasing ilness duration. Furthermore, the causal effects of the sgACC and the right insula GMV reduction with shifts of duration may provide an important new avenue for understanding the pathological anomalies in GAD.

SUBMITTER: Chen Y

PROVIDER: S-EPMC7419314 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Background: Generalized anxiety disorder (GAD) and panic disorder (PD) are the two severe subtypes of anxiety disorders (ADs), which are similar in clinical manifestation, pathogenesis, and treatment. Earlier studies have taken a whole-brain perspective on GAD and PD in the assumption that intrinsic fluctuations are static throughout the entire scan. However, it has recently been suggested that the dynamic alternations in functional connectivity (FC) may reflect the changes in macroscopic neural activity patterns underlying the critical aspects of cognition and behavior, and thus may act as biomarkers of disease. Methods: In this study, the resting-state functional MRI (fMRI) data were collected from 26 patients with GAD, 22 patients with PD, and 26 healthy controls (HCs). We investigated dynamic functional connectivity (DFC) by using the group spatial independent component analysis, a sliding window approach, and the k-means clustering methods. For group comparisons, the temporal properties of DFC states were analyzed statistically. Results: The dynamic analysis demonstrated two discrete connectivity "States" across the entire group, namely, a more segregated State I and a strongly integrated State II. Compared with HCs, patients with both GAD and PD spent more time in the weakly within-network State I, while performing fewer transitions and dwelling shorter in the integrated State II. Additionally, the analysis of DFC strength showed that connections associated with ADs were identified including the regions that belonged to default mode (DM), executive control (EC), and salience (SA) networks, especially the connections between SA and DM networks. However, no significant difference was found between the GAD and PD groups in temporal features and connection strength. Conclusions: More common but less specific alterations were detected in the GAD and PD groups, which implied that they might have similar state-dependent neurophysiological mechanisms and, in addition, could hopefully help us better understand their abnormal affective and cognitive performances in the clinic.

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Progressive brain structural alterations assessed via causal analysis in patients with generalized anxiety disorder.

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