Neuroimaging in social anxiety disorder—A meta-analytic review resulting in a new neurofunctional model

Highlights

• Meta-analytic review of neuroimaging studies in social anxiety disorder since 2007.

• Functional studies add hyperactive parietal and occipital regions to model.

• Connectivity and network-based approaches are included.

• New model shows disconnection of medial parietal regions in SAD.

Abstract

Social anxiety disorder (SAD) is one of the most frequent anxiety disorders. The landmark meta-analysis of functional neuroimaging studies by Etkin and Wager (2007) revealed primarily the typical fear circuit as overactive in SAD. Since then, new methodological developments such as functional connectivity and more standardized structural analyses of grey and white matter have been developed. We provide a comprehensive update and a meta-analysis of neuroimaging studies in SAD since 2007 and present a new model of the neurobiology of SAD. We confirmed the hyperactivation of the fear circuit (amygdala, insula, anterior cingulate and prefrontal cortex) in SAD. In addition, task-related functional studies revealed hyperactivation of medial parietal and occipital regions (posterior cingulate, precuneus, cuneus) in SAD and a reduced connectivity between parietal and limbic and executive network regions. Based on the result of this meta-analysis and review, we present an updated model of SAD adopting a network-based perspective. The disconnection of the medial parietal hub in SAD extends current frameworks for future research in anxiety disorders.

Introduction

Anxiety disorders are the most frequent mental disorders, affecting 7–14% of the general population at any given time point (Baxter et al., 2013, Wittchen et al., 2011) and over 25% at least once in a lifetime (Kessler et al., 2005). Within anxiety disorders, social anxiety disorder (SAD) is the second largest group (Wittchen et al., 2011). Clinically, patients with SAD are afraid of and avoid situations associated with potential exposure to unfamiliar people or to possible scrutiny by others or endure such situations only with intense anxiety or distress (American Psychiatric Association, 2000).

In 2007, Etkin and Wager collated the then available functional magnetic resonance imaging (fMRI) studies in a meta-analysis and formulated a neurobiological model based on these studies (Etkin and Wager, 2007). This model comprised brain regions known as the “fear circuit” (e.g. Etkin, 2010, LeDoux, 2000, Marek et al., 2013), namely the amygdalar region, insula and the adjacent inferior frontal gyrus, in addition to the fusiform gyrus and superior temporal gyrus. Further neuroimaging methods such as Positron Emission Tomography (PET) and Single Positron Emission Tomography (SPECT) at that time were in agreement with this model reporting an increased blood flow in the amygdala (Tillfors et al., 2001, Tillfors et al., 2002), hippocampus (Tillfors et al., 2002) and insula (Warwick et al., 2006), which decreased (“normalized”) with psychopharmacological therapy (Fehm et al., 2005, Tillfors et al., 2002, Warwick et al., 2006) or exposure therapy (Van Ameringen et al., 2004).

Since this landmark meta-analysis of Etkin and Wager in 2007, a large number of studies have added important information regarding brain function in SAD. In addition, connectivity and network-based methods have extended the perspectives of understanding brain systems (Park and Friston, 2013). Recent reviews have covered specific issues relating to anxiety disorders and SAD. One meta-analysis addressed functional correlates of facial emotion recognition in SAD (Hattingh et al., 2013), other reviews focused on structural changes in SAD either in white matter (Ayling et al., 2012) or in grey matter (Ferrari et al., 2008), and the comprehensive review from Freitas-Ferrari (Freitas-Ferrari et al., 2010) has covered studies until 2009. But none of these reviews provided a new or updated model of the neurobiology of SAD integrating the findings of the different methodological approaches.

Therefore, this review aims at giving an overview of neuroimaging studies from the last six years, now also including methods which address: (a) connectivity as a new analytical method aiming at uncovering networks in addition to specific brain regions with more or less isolated dysfunctions, (b) structural methods showing differences between patients with SAD and healthy subjects in white and grey matter and (c) changes due to therapy or therapeutic strategies, which tend to uncover mechanisms of successful treatment and treatment prediction factors. Summarizing these results in an updated neurofunctional model of SAD, we aim to provide further insight into the psychopathological mechanisms of SAD and highlight open questions in this field.