Ricerc@Sapienza

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.

The Cognitive Avoidance Theory of Worry argues that worry is a cognitive strategy adopted to control the physiological arousal associated with anxiety. According to this theory, pathological worry, as in Generalized Anxiety Disorder (GAD), is verbal in nature, negative and abstract, rather than concrete. Neuroimaging studies link the expression of worry to characteristic modes of brain functional connectivity, especially in relation to the amygdala.

In Generalized Anxiety Disorder (GAD), fluctuations in ongoing thoughts (i.e., mind-wandering) often take the form of rigid and intrusive perseverative cognition, such as worry. Here, we sought to characterise the neural correlates of mind-wandering and perseverative cognition, alongside autonomic nervous system indices of central arousal, notably pupil dilation. We implemented a protocol incorporating the dynamic delivery of thought-probes within a functional neuroimaging task.

Generalized anxiety disorder (GAD) is associated with both autonomic dysfunction, notably decreased vagally-mediated heart rate variability (vmHRV), and neurostructural abnormalities. Regional differences in brain morphometry correlate with vmHRV in healthy individuals. Here, we tested the hypothesis that specific focal abnormalities in cortical structure in GAD underpin decreased vmHRV.

The ENIGMA group on Generalized Anxiety Disorder (ENIGMA-Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The group is actively conducting a mega-analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between-country transfer of subject-level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources.

Perseverative cognition represents a prototypical example of how our internal thoughts can impact our psychological and physical health, as if we were facing an actual environmental stressor (Brosschot et al., 2006). The mechanisms involved—together with other emblematic examples like the placebo effect—provide clear evidence for brain-body interaction.