Functional neuroimaging of anxiety: a meta-analysis of emotional processing in PTSD, social anxiety disorder, and specific phobia

Abstract

Objective: The study of human anxiety disorders has benefited greatly from functional neuroimaging approaches. Individual studies, however, vary greatly in their findings. The authors searched for common and disorder-specific functional neurobiological deficits in several anxiety disorders. The authors also compared these deficits to the neural systems engaged during anticipatory anxiety in healthy subjects.

Method: Functional magnetic resonance imaging and positron emission tomography studies of posttraumatic stress disorder (PTSD), social anxiety disorder, specific phobia, and fear conditioning in healthy individuals were compared by quantitative meta-analysis. Included studies compared negative emotional processing to baseline, neutral, or positive emotion conditions.

Results: Patients with any of the three disorders consistently showed greater activity than matched comparison subjects in the amygdala and insula, structures linked to negative emotional responses. A similar pattern was observed during fear conditioning in healthy subjects. Hyperactivation in the amygdala and insula were, of interest, more frequently observed in social anxiety disorder and specific phobia than in PTSD. By contrast, only patients with PTSD showed hypoactivation in the dorsal and rostral anterior cingulate cortices and the ventromedial prefrontal cortex-structures linked to the experience and regulation of emotion.

Conclusions: This meta-analysis allowed us to synthesize often disparate findings from individual studies and thereby provide neuroimaging evidence for common brain mechanisms in anxiety disorders and normal fear. Effects unique to PTSD furthermore suggested a mechanism for the emotional dysregulation symptoms in PTSD that extend beyond an exaggerated fear response. Therefore, these findings help refine our understanding of anxiety disorders and their interrelationships.

FIGURE 1. Patterns of Coactivation Correlations (Kendall’s tau b) Between Frontal, Thalamic, and Limbic Regions of Interest^a

^a (A) Three-dimensional rendering of the regions of interest and lines indicating significant coactivation correlations across the entire meta-analysis data set. (B) Patterns of coactivation correlations in either the positive (black lines) or inverse (blue lines) direction for the PTSD comparisons. (C) The same as for B, but for the combination of the social anxiety disorder and specific phobia data sets. For B and C, regions of interest are plotted along dimensions of the first two principal components on the x and y axes, respectively (axes not shown). Coactivation lines represent p<0.05, uncorrected.

FIGURE 2. Clusters in Which Significant Hyperactivation or Hypoactivation Were Found in Patients With PTSD, Social Anxiety Disorder, and Specific Phobia Relative to Comparison Subjects and in Healthy Subjects Undergoing Fear Conditioning^a

^a Results are shown for the amygdalae (A) and insular cortices (B). Note that within the left amygdala there were two distinct clusters for PTSD, a ventral anterior hyperactivation cluster and a dorsal posterior hypoactivation cluster. The right side of the image corresponds to the right side of the brain.

FIGURE 3. Significant Clusters of Hyperactivation or Hypoactivation in Medial Prefrontal Regions for Patients With PTSD, Social Anxiety Disorder, and Specific Phobia, and in Healthy Subjects Undergoing Fear Conditioning

FIGURE 4. Region-of-Interest-Based Comparisons Between Anxiety Disorders^a

^a (Left) Hyperactivation in patients, relative to comparison subjects, was observed more frequently in the amygdala and insula of patients with either social anxiety disorder or specific phobia than in patients with PTSD. (Right) Hypoactivation in the ventromedial prefrontal cortex, rostral and dorsal anterior cingulate cortices, and thalamus was specifically observed in patients with PTSD in relation to matched comparison subjects and not in patients with social anxiety disorder or specific phobia. *p<0.05. **p<0.01. ***p<0.005.