Induced Anxiety Provides Suitable Model for Pathological Anxiety, Especially Specific Phobia

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Researchers conducted a meta-analysis of 181 publications that contrasted the neural activity of subjects with anxiety with subjects in control groups or healthy subjects in a safe condition with healthy subjects in an unpredictable-threat condition.

While they say that further research that enables a direct comparison is necessary, induced anxiety is a “very good model” for specific phobia, and a “relatively good model” for panic disorder and posttraumatic stress disorder (PTSD) based on their functional neural activations, researchers said in a meta-analysis published in the American Journal of Psychiatry online.

The researchers sought to determine what neural activations 5 anxiety disorders (PTSD, social anxiety disorder, generalized anxiety disorder, panic disorder, and specific phobia) and induced anxiety had in common. They identified 181 publications (comprising 2,911 individuals with anxiety and 2,685 control participants) involving functional MRI whole-brain blood-oxygen-level-dependent activity that reported contrasts of patients with depression or anxiety and control participants or healthy individuals in unpredictable-threat and safe conditions. They divided the articles into the following groups: emotion, attention, decision, and memory. In the main analysis, they compared the neural activations of 2,554 individuals with pathological anxiety and 2,348 participants in control groups.

They found that the 414 individuals with specific phobia showed increased neural activity in the cingulate, left and right inferior frontal gyrus/insula and periaqueductal gray (bilaterally) while the 263 patients with panic disorder and 436 participants with PTSD showed more activation in the left and right insula/superior temporal gyrus.

The 805 individuals with social anxiety disorder showed activation in the right insula/inferior frontal gyrus/superior temporal gyrus and left amygdala. The 233 participants with generalized anxiety disorder showed deactivation in the left and right insula. The individuals with panic disorder, PTSD or social anxiety disorder did not show activation or deactivation in the mid and anterior cingulate cortex. Participants with generalized anxiety disorder showed deactivation in the cingulate cortex and the left and right insula.

The researchers found that the 693 individuals who experienced induced anxiety in threat conditions had experienced several areas of increased neural activity (compared to the non-threat condition) in common with the group of participants with pathological anxiety, including the anterior and midcingulate, the left middle gyrus, inferior frontal gyrus, and superior medial frontal gyrus.

The individuals with induced anxiety experienced more activation in the cingulate and medial frontal cortices (z=6.415) and bilaterally in the inferior frontal gyrus/anterior insula/Rolandic operculum (z=5.183 and z=5.067 for the right and left clusters, respectively), left and right supramarginal, right superior temporal, right middle frontal, right precentral gyri, BNST, and periaqueductal gray than they did when they were in safe conditions.

The researchers reported that Egger’s test did not indicate any significant publication bias for the left (bias=.34, P =.519) and right (bias=.46, P =.355) superior temporal gyrus/insula/inferior frontal gyrus clusters, the cingulate/medial frontal clusters (bias=0.25 [P =.666], bias=0.14 [P =.780], and bias=.05 [P =.927], respectively) or the cingulate/medial frontal (bias=1.5, P =.11) and the left (bias=1.3, P =.20) and right (bias=1.91, P =.15) inferior frontal gyrus/anterior insula clusters.

Induced anxiety and specific phobia had the most similar neural activity; both showed increased neural activity in the cingulate/medial prefrontal, the left and right insula/inferior gyrus/putamen/superior temporal gyrus pole, bilateral BNST and periaqueductal gray activation. Induced anxiety and panic disorder both indicated hyperactivation in the bilateral insula/inferior frontal gyrus. Induced anxiety had more limited neural activity in common with both PTSD (insula/inferior frontal gyrus opercular part) and social anxiety disorder (right insula/inferior frontal gyrus orbital and triangular parts).

The researchers said induced anxiety may therefore be an effective intermediate translational model of anxiety disorders.

Limitations included the inclusion of articles that may have presented confounding variables, differences between the groups included in the analyses, and the diversity of tasks in the studies.

“Conceptually, induction of anxiety via unpredictable threat spans both systems in humans: a conscious but diffuse feeling of anxiety as well as avoidance and physiological defensive arousal,” the researchers said. “The overlapping activity we observe may therefore be involved in both of these facets, but further work, ideally with identical cognitive tasks across both induced and pathological anxiety, is needed to truly disentangle these important distinctions.”

Disclosures: One study author declared affiliations with the industry. Please see the original reference for a full list of authors’ disclosures.


Chavanne AV, Robinson OJ. The overlapping neurobiology of induced and pathological anxiety: A meta-analysis of functional neural activation [published online October 15, 2020]. Am J Psychiatry. doi: 10.1176/appi.ajp.2020.19111153