The neurobiological basis of cognitive side effects of electroconvulsive therapy : a systematic review

Altres ajuts: M.C. is founded by the Sara Borrell postdoctoral contract [CD20/00189].Decades of research have consistently demonstrated the efficacy of electroconvulsive therapy (ECT) for the treatment of major depressive disorder (MDD), but its clinical use remains somewhat restricted because of its cognitive side effects. The aim of this systematic review is to comprehensively summarize current evidence assessing potential biomarkers of ECT-related cognitive side effects. Based on our systematic search of human studies indexed in PubMed, Scopus, and Web of Knowledge, a total of 29 studies evaluating patients with MDD undergoing ECT were reviewed. Molecular biomarkers studies did not consistently identify concentration changes in plasma S-100 protein, neuron-specific enolase (NSE), or Aβ peptides significantly associated with cognitive performance after ECT. Importantly, these findings suggest that ECT-related cognitive side effects cannot be explained by mechanisms of neural cell damage. Notwithstanding, S-100b protein and Aβ40 peptide concentrations, as well as brain-derived neurotrophic factor (BDNF) polymorphisms, have been suggested as potential predictive biomarkers of cognitive dysfunction after ECT. In addition, recent advances in brain imaging have allowed us to identify ECT-induced volumetric and functional changes in several brain structures closely related to memory performance such as the hippocampus. We provide a preliminary framework to further evaluate neurobiological cognitive vulnerability profiles of patients with MDD treated with ECT

Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the ENIGMA-Anxiety Working Group

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology

Focusing on Comorbidity A Novel Meta-Analytic Approach and Protocol to Disentangle the Specific Neuroanatomy of Co-occurring Mental Disorders

Background: In mental health, comorbidities are the norm rather than the exception. However, current meta-analytic methods for summarizing the neural correlates of mental disorders do not consider comorbidities, reducing them to a source of noise and bias rather than benefitting from their valuable information. Objectives: We describe and validate a novel neuroimaging meta-analytic approach that focuses on comorbidities. In addition, we present the protocol for a meta-analysis of all major mental disorders and their comorbidities. Methods: The novel approach consists of a modification of Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) in which the linear models have no intercept. As in previous SDM meta-analyses, the dependent variable is the brain anatomical difference between patients and controls in a voxel. However, there is no primary disorder, and the independent variables are the percentages of patients with each disorder and each pair of potentially comorbid disorders. We use simulations to validate and provide an example of this novel approach, which correctly disentangled the abnormalities associated with each disorder and comorbidity. We then describe a protocol for conducting the new meta-analysis of all major mental disorders and their comorbidities. Specifically, we will include all voxel-based morphometry (VBM) studies of mental disorders for which a meta-analysis has already been published, including at least 10 studies. We will use the novel approach to analyze all included studies in two separate single linear models, one for children/adolescents and one for adults. Discussion: The novel approach is a valid method to focus on comorbidities. The meta-analysis will yield a comprehensive atlas of the neuroanatomy of all major mental disorders and their comorbidities, which we hope might help develop potential diagnostic and therapeutic tools

Cortical and subcortical brain structure in generalized anxiety disorder: findings from 28 research sites in the enigma-anxiety working group

The goal of this study was to compare brain structure between individuals with generalized anxiety disorder (GAD) and healthy controls. Previous studies have generated inconsistent findings, possibly due to small sample sizes, or clinical/analytic heterogeneity. To address these concerns, we combined data from 28 research sites worldwide through the ENIGMA-Anxiety Working Group, using a single, pre-registered mega-analysis. Structural magnetic resonance imaging data from children and adults (5–90 years) were processed using FreeSurfer. The main analysis included the regional and vertex-wise cortical thickness, cortical surface area, and subcortical volume as dependent variables, and GAD, age, age-squared, sex, and their interactions as independent variables. Nuisance variables included IQ, years of education, medication use, comorbidities, and global brain measures. The main analysis (1020 individuals with GAD and 2999 healthy controls) included random slopes per site and random intercepts per scanner. A secondary analysis (1112 individuals with GAD and 3282 healthy controls) included fixed slopes and random intercepts per scanner with the same variables. The main analysis showed no effect of GAD on brain structure, nor interactions involving GAD, age, or sex. The secondary analysis showed increased volume in the right ventral diencephalon in male individuals with GAD compared to male healthy controls, whereas female individuals with GAD did not differ from female healthy controls. This mega-analysis combining worldwide data showed that differences in brain structure related to GAD are small, possibly reflecting heterogeneity or those structural alterations are not a major component of its pathophysiology

The contribution of brain imaging to the understanding of psychopathy

Psychopathy is a personality type characterized by both callous emotional dysfunction and deviant behavior that affects society in the form of actions that harm others. Historically, researchers have been concerned with seeking data and arguments to support a neurobiological foundation of psychopathy. In the past few years, increasing research has begun to reveal brain alterations putatively underlying the enigmatic psychopathic personality. In this review, we describe the brain anatomical and functional features that characterize psychopathy from a synthesis of available neuroimaging research and discuss how such brain anomalies may account for psychopathic behavior. The results are consistent in showing anatomical alterations involving primarily a ventral system connecting the anterior temporal lobe to anterior and ventral frontal areas, and a dorsal system connecting the medial frontal lobe to the posterior cingulate cortex/precuneus complex and, in turn, to medial structures of the temporal lobe. Functional imaging data indicate that relevant emotional flow breakdown may occur in both these brain systems and suggest specific mechanisms via which emotion is anomalously integrated into cognition in psychopathic individuals during moral challenge. Directions for future research are delineated emphasizing, for instance, the relevance of further establishing the contribution of early life stress to a learned blockage of emotional self-exposure, and the potential role of androgenic hormones in the development of cortical anomalies

Smartphone-based self-monitoring in bipolar disorder: evaluation of usability and feasibility of two systems

Abstract Background The aims of the present multicenter pilot study were to examine the feasibility and usability of two different smartphone-based monitoring systems (the Pulso system and the Trilogis-Monsenso system) from two IT companies in patients with bipolar disorder, developed and selected to be testes as a part of a European Union funded Pre-Commercial Procurement (the NYMPHA-MD project). Methods Patients with bipolar disorder (ICD-10), > 18 years of age during a remitted, partial remitted or mild to moderate depressive state (HDRS-17 < 25) from Italy, Spain and Denmark were included. Patients were randomized 1:1 to the use of one of two smartphone-based monitoring systems. The randomization was stratified according to study location (Italy, Spain, Denmark) and all patients were followed for a 4 weeks study period. Usability and feasibility were evaluated using the Computer System Usability Questionnaire, and the Usefulness, Satisfaction, and Ease of use Questionnaire. Results A total of 60 patients aged 18–69 years with bipolar disorder (ICD-10) recruited from Italy, Spain, Denmark were included—59 patients completed the study. In Denmark, the patients evaluated the Trilogis-Monsenso system with a statistically significant higher usability compared with the Pulso system. In Italy and Spain, the patients evaluated no statistically significant difference between the two systems in any of the categories, except for the usefulness category favoring the Trilogis-Monsenso system (z = 2.68, p < 0.01). Conclusions Both monitoring systems showed acceptable usability and feasibility. There were differences in patient-based evaluations of the two monitoring systems related to the country of the study. Studies investigating the usability and feasibility during longer follow-up periods could perhaps reveal different findings. Future randomized controlled trials investigating the possible positive and negative effects of smartphone-based monitoring systems are needed