Neural predictors of cognitive-behavior therapy outcome in anxiety-related disorders: a meta-analysis of task-based fMRI studies.

BACKGROUND: 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. METHODS: 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). RESULTS: 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. CONCLUSIONS: 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.

Risk and protective factors for anxiety and obsessive-compulsive disorders: an umbrella review of systematic reviews and meta-analyses.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Risk factors for posttraumatic stress disorder: An umbrella review of systematic reviews and meta-analyses.

Approximately one third of individuals who experience a severe traumatic event will develop posttraumatic stress disorder (PTSD). It is crucial to identify what factors may be associated with increased or decreased risk for PTSD. We conducted an umbrella review of systematic reviews and meta-analyses of risk/protective factors for PTSD and assessed and graded the evidence of the association between each factor and PTSD. Thirty-three systematic reviews and meta-analyses were included and 130 potential risk factors were identified. Of those, 57 showed a significant association with PTSD. Being female or being indigenous people of the Americas, among the sociodemographic factors; history of physical disease and family history of psychiatric disorder, among the pretrauma factors; and cumulative exposure to potentially traumatic experiences, trauma severity, and being trapped during an earthquake, among the peritrauma factors, showed convincing or highly suggestive evidence of an association with PTSD. Data from prospective studies were less conclusive. Our results have the potential of helping refine PTSD prediction models and contributing to the design of prevention strategies.

Are there glutamate abnormalities in subjects at high risk mental state for psychosis? A review of the evidence.

New approaches to underlying alterations in psychosis suggest increasing evidence of glutamatergic abnormalities in schizophrenia and an association between these abnormalities and certain core psychopathological alterations such as cognitive impairment and negative symptoms. Proton magnetic resonance spectroscopy ((1)H MRS) is an MR-based technique that enables investigators to study glutamate function by measuring in vivo glutamatergic indices in the brain. In this article we review the published studies of (1)H MRS in subjects with an at-risk mental state (ARMS) for psychosis. The primary aim was to investigate whether alterations in glutamate function are present before the illness develops in order to expand our understanding of glutamatergic abnormalities in prodromal phases. Three databases were consulted for this review. Titles and abstracts were examined to determine if they fulfilled the inclusion criteria. The reference lists of the included studies were also examined to identify additional trials. Eleven final studies were included in this review. Significant alterations in glutamate metabolites across different cerebral areas (frontal lobe, thalamus, and the associative striatum) in subjects with an ARMS for psychosis are reported in six of the trials. A longitudinal analysis in two of these trials confirmed an association between these abnormalities and worsening of symptoms and final transition to psychosis. Considering that five other studies found no significant differences across these same areas, we can conclude that more research is needed to confirm glutamatergic abnormalities in subjects with an ARMS for psychosis. However, future research must overcome the methodological limitations of existing studies to obtain reliable results.