Network abnormalities in generalized anxiety pervade beyond the amygdala-pre-frontal cortex circuit: Insights from graph theory

Abstract

Generalized anxiety disorder (GAD) has excessive anxiety and uncontrollable worry as core symptoms. Abnormal cerebral functioning underpins the expression and perhaps pathogenesis of GAD:. Studies implicate impaired communication between the amygdala and the pre-frontal cortex (PFC). Our aim was to longitudinally investigate whether such network abnormalities are spatially restricted to this circuit or if the integrity of functional brain networks is globally disrupted in GAD. We acquired resting-state functional magnetic resonance imaging data from 16 GAD patients and 16 matched controls at baseline and after 1 year. Using network modeling and graph-theory, whole-brain connectivity was characterized from local and global perspectives. Overall lower global efficiency, indicating sub-optimal brain-wide organization and integration, was present in patients with GAD compared to controls. The amygdala and midline cortices showed higher betweenness centrality, reflecting functional dominance of these brain structures. Third, lower betweenness centrality and lower degree emerged for PFC, suggesting weakened inhibitory control. Overall, network organization showed impairments consistent with neurobiological models of GAD (involving amygdala, PFC, and cingulate cortex) and further pointed to an involvement of temporal regions. Such impairments tended to progress over time and predict anxiety symptoms. A graph-analytic approach represents a powerful approach to deepen our understanding of GAD.

Risk of Death in Individuals Hospitalized for COVID-19 With and Without Psychiatric Disorders: An Observational Multicenter Study in France

“…We may hypothesize that individuals with intellectual disabilities are more likely to have genetic conditions linked to higher risk for other medical conditions. Individuals with intellectual disabilities or anxiety disorders may also be less likely to adequately communicate their symptoms and distress to care providers ( 58 , 59 , 60 , 61 ). Patient complaints may also be wrongly attributed to these conditions or considered as exaggerated in these patients, despite their elevated risk of death as suggested by our findings, which may lead to less thorough medical evaluation and worse prognosis.…”

White Matter Structural Brain Connectivity of Young Healthy Individuals With High Trait Anxiety

“…The amygdala is located on the medial dorsal side of the anterior temporal lobe and is a part of the limbic system. Functional brain imaging studies showed that the level of amygdala activation was higher in anxious patients than in healthy controls; moreover, increased amygdala response in clinical and healthy individuals was associated with trait anxiety (36). Makovac et al found reduced connections of the amygdala to the prefrontal cortex in people with generalized anxiety disorders (36).…”

“…Functional brain imaging studies showed that the level of amygdala activation was higher in anxious patients than in healthy controls; moreover, increased amygdala response in clinical and healthy individuals was associated with trait anxiety (36). Makovac et al found reduced connections of the amygdala to the prefrontal cortex in people with generalized anxiety disorders (36). Similarly, Xue et al found that high state anxiety level was associated with decreased connectivity of the amygdala to the precuneus/posterior cingulate cortex in adults with anxiety disorders (37).…”

Network analysis reveals abnormal functional brain circuitry in anxious dogs

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