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.

Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond

“…Furthermore, this inflammation-induced amygdala response may also contribute to the association between increased CRP levels and heightened psychophysiological hyperarousal in traumatized individuals with PTSD (Michopoulos et al, 2015b). The hippocampus is another brain structure within the medial temporal lobe whose function, structure, and functional connectivity with other regions is comprised in individuals with PTSD, GAD, and PD (Cui et al, 2016;Fani et al, 2012b;Woon et al, 2010). Hippocampal alterations, including smaller hippocampal volume, are associated with both emotional and cognitive deficits in individuals with PTSD (Bremner, 2006).…”

“…Regions of the medial prefrontal cortex (mPFC), including the rostral anterior cingulate cortex, subgenual ACC (sgACC, Brodmann's Area 25) and medial frontal gyrus, are all heavily connected to the amygdala and hippocampus, and critically involved in emotion regulation, attention bias, and fear extinction in individuals with PTSD and other anxiety disorders (Banich et al, 2009;Cui et al, 2016;Etkin and Wager, 2007;Fani et al, 2012a;Monk et al, 2008). Activation of the ventral mPFC (including the sgACC and the orbitofrontal cortex) due to a grief-elicitation task in women undergoing bereavement stress is associated with increased IL-1β and TNF receptor II (TNF-II;O'Connor et al, 2009).…”

Disruptions in cortico-subcortical covariance networks associated with anxiety in new-onset childhood epilepsy

“…The fusiform gyrus has been associated with cognitive load in a verbal working memory task in HC (Vogan et al, 2016). However, the fusiform gyrus has also been associated with abnormal resting-state functional connectivity (RS-FC) among anxious subjects compared to HC (Cui et al, 2016). Given that the right fusiform was found to be a highly central region in both groups with epilepsy, its development might be influential over other cortical/subcortical regions, however, it might be differentially affecting each group with epilepsy.…”

“…Specifically, working memory (Hopfinger et al, 2000) has been impaired in subjects suffering from anxiety along with sensory-perceptual processes (Cornwell et al, 2007), and processing efficiency (Eysenck and Calvo, 1992). Additionally, the anterior cingulate has been positively associated with cognitive load in HC (Cui et al, 2016) while the primary somatosensory cortex (located in the postcentral gyrus) is important for interoceptive awareness (Khalsa et al, 2009), which is commonly affected in patients suffering from panic disorder (a type of anxiety disorder). Given that these regions were found to be highly central areas in the group of patients with epilepsy and anxiety they might be contributing/spreading neurobiological disturbances given their strategic locations regarding cognition and behavior.…”

Complex network analysis of brain functional connectivity under a multi-step cognitive task

“…Its structural (or anatomic) and functional organization both behave complicated connectivity in the view of graph and have been widely investigated via complex network theory in the neuroscience community. Plenty of works focus on the topological properties of structural and functional brain networks derived from diffusion MRI, funcitonal MRI (fMRI), electroencephalograph (EEG), magnetoencephalography (MEG), and multielectrode array (MEA) data [1,2,3,4,6,5]. These networks show both the generic small-worldness [7] and scale-free characteristics [8] independent from the physiological and pathological states [9,10,11,12,13].…”