Cognitive-behavior therapy (CBT) is a well-established first-line intervention for anxiety-related disorders, including specific phobia, social anxiety disorder, panic disorder/agoraphobia, generalized anxiety disorder, obsessive-compulsive disorder, and posttraumatic stress disorder. Several neural predictors of CBT outcome for anxiety-related disorders have been proposed, but previous results are inconsistent.

We conducted a systematic review and meta-analysis of task-based functional magnetic resonance imaging (fMRI) studies investigating whole-brain predictors of CBT outcome in anxiety-related disorders (17 studies, n = 442).

Across different tasks, we observed that brain response in a network of regions involved in salience and interoception processing, encompassing fronto-insular (the right inferior frontal gyrus-anterior insular cortex) and fronto-limbic (the dorsomedial prefrontal cortex-dorsal anterior cingulate cortex) cortices was strongly associated with a positive CBT outcome.

Our results suggest that there are robust neural predictors of CBT outcome in anxiety-related disorders that may eventually lead (probably in combination with other data) to develop personalized approaches for the treatment of these mental disorders.

A multitude of risk/protective factors for anxiety and obsessive-compulsive disorders have been proposed. We conducted an umbrella review to summarize the evidence of the associations between risk/protective factors and each of the following disorders: specific phobia, social anxiety disorder, generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder, and to assess the strength of this evidence whilst controlling for several biases.

Publication databases were searched for systematic reviews and meta-analyses examining associations between potential risk/protective factors and each of the disorders investigated. The evidence of the association between each factor and disorder was graded into convincing, highly suggestive, suggestive, weak, or non-significant according to a standardized classification based on: number of cases (>1000), random-effects p-values, 95% prediction intervals, confidence interval of the largest study, heterogeneity between studies, study effects, and excess of significance.

Nineteen systematic reviews and meta-analyses were included, corresponding to 216 individual studies covering 427 potential risk/protective factors. Only one factor association (early physical trauma as a risk factor for social anxiety disorder, OR 2.59, 95% CI 2.17–3.1) met all the criteria for convincing evidence. When excluding the requirement for more than 1000 cases, five factor associations met the other criteria for convincing evidence and 22 met the remaining criteria for highly suggestive evidence.

Although the amount and quality of the evidence for most risk/protective factors for anxiety and obsessive-compulsive disorders is limited, a number of factors significantly increase the risk for these disorders, may have potential prognostic ability and inform prevention.