The Common Traits of the ACC and PFC in Anxiety Disorders in the DSM-5: Meta-Analysis of Voxel-Based Morphometry Studies

Abstract

BackgroundThe core domains of social anxiety disorder (SAD), generalized anxiety disorder (GAD), panic disorder (PD) with and without agoraphobia (GA), and specific phobia (SP) are cognitive and physical symptoms that are related to the experience of fear and anxiety. It remains unclear whether these highly comorbid conditions that constitute the anxiety disorder subgroups of the Diagnostic and Statistical Manual for Mental Disorders – Fifth Edition (DSM-5) represent distinct disorders or alternative presentations of a single underlying pathology.MethodsA systematic search of voxel-based morphometry (VBM) studies of SAD, GAD, PD, GA, and SP was performed with an effect-size signed differential mapping (ES-SDM) meta-analysis to estimate the clusters of significant gray matter differences between patients and controls.ResultsTwenty-four studies were eligible for inclusion in the meta-analysis. Reductions in the right anterior cingulate gyrus and the left inferior frontal gyrus gray matter volumes (GMVs) were noted in patients with anxiety disorders when potential confounders, such as comorbid major depressive disorder (MDD), age, and antidepressant use were controlled for. We also demonstrated increased GMVs in the right dorsolateral prefrontal cortex (DLPFC) in comorbid depression-anxiety (CDA), drug-naïve and adult patients. Furthermore, we identified a reduced left middle temporal gyrus and right precentral gyrus in anxiety patients without comorbid MDD.ConclusionOur findings indicate that a reduced volume of the right ventral anterior cingulate gyrus and left inferior frontal gyrus is common in anxiety disorders and is independent of comorbid depression, medication use, and age. This generic effect supports the notion that the four types of anxiety disorders have a clear degree of overlap that may reflect shared etiological mechanisms. The results are consistent with neuroanatomical DLPFC models of physiological responses, such as worry and fear, and the importance of the ventral anterior cingulate (ACC)/medial prefrontal cortex (mPFC) in mediating anxiety symptoms.

Working memory maintenance is sufficient to reduce state anxiety

“…Although the current results suggest that WM load-related anxiety reduction results from competition for resources among WM stores, rather than top-down central executive processes, it is difficult to rule out the latter hypothesis based on the current results alone. In either case, one candidate source for anxiety reduction is the dlPFC, which has been repeatedly shown to play a role in WM (Altamura et al, 2007; Barbey, Koenigs, & Grafman, 2013; Curtis & D’Esposito, 2003; Feredoes, Heinen, Weiskopf, Ruff, & Driver, 2011; Geier, Garver, & Luna, 2007), anxiety (Bishop, 2009; Forster, Nunez Elizalde, Castle, Bishop, & Elizalde, 2015; Nitschke, Sarinopoulos, Mackiewicz, Schaefer, & Davidson, 2006; Peers et al, 2013; Shang et al, 2014), and emotional learning (Carter, O’Doherty, Seymour, Koch, & Dolan, 2006). …”

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

“…Although most studies have focused on the role of mPFC and ACC in the etiology of PTSD, some studies indicate that the same regions are critical to the etiology of PD, GAD, social anxiety disorder, specific phobia, and agoraphobia. A meta-analysis indicates that reduced volume of the ventral ACC and the inferior frontal gyrus is common to anxiety disorders (social anxiety, GAD, PD, agoraphobia, and specific phobia; Shang et al, 2014). Finally, the dACC in the etiology of PD is suggested by data that indicate that surgery damage to the dACC can induce panic attacks (Shinoura et al, 2011).…”

Cortical thickness and subcortical structure volume abnormalities in patients with major depression with and without anxious symptoms

“…The prefrontal cortex is divided into ventromedial and dorsolateral areas, and the two parts are closely related to mood disorders. The ventromedial cortex of the prefrontal lobe is involved in emotion processing and motivation, and the dorsolateral prefrontal cortex is associated with cognitive processing (Brzezicka, 2013;Shang et al, 2014). The inferior temporal and superior temporal cortex are associated with the prefrontal cortex and are related to sensory integration, introspective functions, and visceral reactions to emotional stimuli (Drevets, Price, & Furey, 2008).…”