Primary care plays a central role in the treatment of depression. Nonetheless, shortcomings in its management and suboptimal outcomes have been identified. Collaborative care models improve processes ...for the management of depressive disorders and associated outcomes. We developed a strategy to implement the INDI collaborative care program for the management of depression in primary health care centers across Catalonia. The aim of this qualitative study was to evaluate a trial implementation of the program to identify barriers, facilitators, and proposals for improvement.
One year after the implementation of the INDI program in 18 public primary health care centers we performed a qualitative study in which the opinions and experiences of 23 primary care doctors and nurses from the participating centers were explored in focus groups. We performed thematic content analysis of the focus group transcripts.
The results were organized into three categories: facilitators, barriers, and proposals for improvement as perceived by the health care professionals involved. The most important facilitator identified was the perception that the INDI collaborative care program could be a useful tool for reorganizing processes and improving the management of depression in primary care, currently viewed as deficient. The main barriers identified were of an organizational nature: heavy workloads, lack of time, high staff turnover and shortages, and competing demands. Additional obstacles were inertia and resistance to change among health care professionals. Proposals for improvement included institutional buy-in to guarantee enduring support and the organizational changes needed for successful implementation.
The INDI program is perceived as a useful, viable program for improving the management of depression in primary care. Uptake by primary care centers and health care professionals, however, was poor. The identification and analysis of barriers and facilitators will help refine the strategy to achieve successful, widespread implementation.
ClinicalTrials.gov identifier: NCT03285659 ; Registered 18th September, 2017.
Exposure to acute and chronic stress has a broad range of structural effects on the brain. The brain areas commonly targeted in the stress response models include the hippocampus, the amygdala, and ...the prefrontal cortex. Studies in patients suffering from the so-called stress-related disorders -embracing post-traumatic stress, major depressive and anxiety disorders- have fairly replicated animal models of stress response -particularly the neuroendocrine and the inflammatory models- by finding alterations in different brain areas, even in the early neurodevelopment. Therefore, this narrative review aims to provide an overview of structural neuroimaging findings and to discuss how these studies have contributed to our knowledge of variability in response to stress and the ulterior development of stress-related disorders. There are a gross number of studies available but neuroimaging research of stress-related disorders as a single category is still in its infancy. Although the available studies point at particular brain circuitries involved in stress and emotion regulation, the pathophysiology of these abnormalities -involving genetics, epigenetics and molecular pathways-, their relation to intraindividual stress responses -including personality characteristics, self-perception of stress conditions…-, and their potential involvement as biomarkers in diagnosis, treatment prescription and prognosis are discussed.
•Distinct brain connectivity patterns are associated with different clinical domains.•Mindfulness-based cognitive therapy may modulate brain networks in OCD patients.•Rumination may have a critical ...role in the neurobiology of mindfulness therapy.•Brain networks are potential predictive biomarkers for personalised OCD treatments.
Mindfulness-based cognitive therapy (MBCT) stands out as a promising augmentation psychological therapy for patients with obsessive-compulsive disorder (OCD). To identify potential predictive and response biomarkers, this study examines the relationship between clinical domains and resting-state network connectivity in OCD patients undergoing a 3-month MBCT programme. Twelve OCD patients underwent two resting-state functional magnetic resonance imaging sessions at baseline and after the MBCT programme. We assessed four clinical domains: positive affect, negative affect, anxiety sensitivity, and rumination. Independent component analysis characterised resting-state networks (RSNs), and multiple regression analyses evaluated brain-clinical associations. At baseline, distinct network connectivity patterns were found for each clinical domain: parietal-subcortical, lateral prefrontal, medial prefrontal, and frontal-occipital. Predictive and response biomarkers revealed significant brain-clinical associations within two main RSNs: the ventral default mode network (vDMN) and the frontostriatal network (FSN). Key brain nodes —the precuneus and the frontopolar cortex— were identified within these networks. MBCT may modulate vDMN and FSN connectivity in OCD patients, possibly reducing symptoms across clinical domains. Each clinical domain had a unique baseline brain connectivity pattern, suggesting potential symptom-based biomarkers. Using these RSNs as predictors could enable personalised treatments and the identification of patients who would benefit most from MBCT.
Pituitary adenylate cyclase-activating polypeptide (PACAP) receptor gene polymorphism has been postulated as a potential sex-specific diagnostic biomarker of trauma-related disorders. However, no ...research to date has evaluated whether the PACAPergic system may act as a vulnerability/resilience neuromechanism to trauma-induced psychopathology in healthy participants without heightened risk to experience traumatic events.
Here, we compared the amygdala and hippocampus response to fearful faces in participants with at-risk genotype versus non-risk participants from the Human Connectome Project (n = 991; 53.4% female).
Increased hippocampal response to fearful faces in the female risk group emerged in sex by genetic risk interaction.
Our findings revealed the first sex-specific neurogenetic vulnerability factor to trauma-related disorders, and emphasize the importance of prevention-based strategies to ameliorate neuropsychiatric pathophysiology.
The ENIGMA group on Generalized Anxiety Disorder (ENIGMA‐Anxiety/GAD) is part of a broader effort to investigate anxiety disorders using imaging and genetic data across multiple sites worldwide. The ...group is actively conducting a mega‐analysis of a large number of brain structural scans. In this process, the group was confronted with many methodological challenges related to study planning and implementation, between‐country transfer of subject‐level data, quality control of a considerable amount of imaging data, and choices related to statistical methods and efficient use of resources. This report summarizes the background information and rationale for the various methodological decisions, as well as the approach taken to implement them. The goal is to document the approach and help guide other research groups working with large brain imaging data sets as they develop their own analytic pipelines for mega‐analyses.
This report summarizes the background information and rationale for the various methodological decisions made by the ENIGMA—GAD group. The aim of this work is to help guide other research groups working with large brain imaging data sets.
•Survivors of intimate partner violence (IPV) present an increased risk of non-communicable diseases.•The link between IPV and disease is reviewed from a chronic stress framework.•The impact of IPV ...is evident at the level of neuroendocrine, immunology, neurocognition and neuroimaging.•Stress-response dysregulation is proposed as the neurobiological intermediary between IPV and disease.
A neurobiological framework of chronic stress proposes that the stress-response system can be functionally altered by the repeated presentation of highly stressful situations over time. These functional alterations mainly affect brain processing and include the dysregulation of the hypothalamic-pituitary-adrenal axis and associated processes. In the present critical review, we translate these results to inform the clinical presentation of women survivors of intimate partner violence (IPV). We approach IPV as a scenario of chronic stress where women are repetitively exposed to threat and coping behaviours that progressively shape their neurobiological response to stress. The changes at the central and peripheral levels in turn correlate with the phenotypes of non-communicable diseases. The reviewed studies clarify the extent of the impact of IPV on women’s health in large (N > 10,000) population-based designs, and provide observations on experimental neuroendocrine, immune, neurocognitive and neuroimaging research linking alterations of the stress-response system and disease. This evidence supports the prevention of violence against women as a fundamental action to reduce the prevalence of non-communicable diseases.
Electroconvulsive therapy (ECT) is considered the most effective treatment for major depressive disorder (MDD). In recent years, the pursuit of the neurobiological mechanisms of ECT action has ...generated a significant amount of functional magnetic resonance imaging (fMRI) research.
In this systematic review, we integrated all fMRI research in patients with MDD receiving ECT and, importantly, evaluated the level of convergence and replicability across multiple fMRI metrics.
While according to most studies changes in patients with MDD after ECT appear to be widely distributed across the brain, our multimetric review revealed specific changes involving functional connectivity increases in the superior and middle frontal gyri as the most replicated and across-modality convergent findings. Although this modulation of prefrontal connectivity was associated to ECT outcome, we also identified fMRI measurements of the subgenual anterior cingulate cortex as the fMRI signals most significantly linked to clinical response.
We identified specific prefrontal and cingulate territories which activity and connectivity with other brain regions is modulated by ECT, critically accounting for its mechanism of action.
•Multimetric reviews are the optimal approach for detecting neurofunctional findings.•Electroconvulsive therapy consistently modulates prefrontal functional connectivity.•Cingulate function is the best electroconvulsive therapy response biomarker.
•MDD participants have smaller GMV than HC in cerebellum and the frontal operculum.•ANX participants have less GMV than HC in temporal gyrus and pars orbitalis.•PTSD participants have smaller GMV in ...lingual gyrus and superior frontal gyrus.•As patients age, GMV reductions are more pronounced in fronto-temporal regions.•Higher proportion of females are related with GMV diminutions in temporal areas.
The high comorbidity of Major Depressive Disorder (MDD), Anxiety Disorders (ANX), and Posttraumatic Stress Disorder (PTSD) has hindered the study of their structural neural correlates. The authors analyzed specific and common grey matter volume (GMV) characteristics by comparing them with healthy controls (HC). The meta-analysis of voxel-based morphometry (VBM) studies showed unique GMV diminutions for each disorder (p < 0.05, corrected) and less robust smaller GMV across diagnostics (p < 0.01, uncorrected). Pairwise comparison between the disorders showed GMV differences in MDD versus ANX and in ANX versus PTSD. These results endorse the hypothesis that unique clinical features characterizing MDD, ANX, and PTSD are also reflected by disorder specific GMV correlates.
Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the ...neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA‐Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. This paper elaborates on the concepts and methods informing the work of the working group to date, and describes the initial approach of the four subgroups studying generalized anxiety disorder, panic disorder, social anxiety disorder, and specific phobia. At present, the ENIGMA‐Anxiety database contains information about more than 100 unique samples, from 16 countries and 59 institutes. Future directions include examining additional imaging modalities, integrating imaging and genetic data, and collaborating with other ENIGMA working groups. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA‐Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders.
Anxiety disorders are highly prevalent and disabling but seem particularly tractable to investigation with translational neuroscience methodologies. Neuroimaging has informed our understanding of the neurobiology of anxiety disorders, but research has been limited by small sample sizes and low statistical power, as well as heterogenous imaging methodology. The ENIGMA‐Anxiety Working Group has brought together researchers from around the world, in a harmonized and coordinated effort to address these challenges and generate more robust and reproducible findings. The ENIGMA consortium creates synergy at the intersection of global mental health and clinical neuroscience, and the ENIGMA‐Anxiety Working Group extends the promise of this approach to neuroimaging research on anxiety disorders.
It remains unexplored in the field of fear memory whether functional neuronal connectivity between two brain areas is necessary for one sex but not the other. Here, we show that chemogenetic ...silencing of centromedial (CeM)– Tac2 fibers in the lateral posterior BNST (BNSTpl) decreased fear memory consolidation in male mice but not females. Optogenetic excitation of CeM- Tac2 fibers in the BNSTpl exhibited enhanced inhibitory postsynaptic currents in males compared to females. In vivo calcium imaging analysis revealed a sex-dimorphic fear memory engram in the BNSTpl. Furthermore, in humans, the single-nucleotide polymorphism (SNP) in the Tac2 receptor (rs2765) ( TAC3R ) decreased CeM-BNST connectivity in a fear task, impaired fear memory consolidation, and increased the expression of the TAC3R mRNA in AA-carrier men but not in women. These sex differences in critical neuronal circuits underlying fear memory formation may be relevant to human neuropsychiatric disorders with fear memory alterations such as posttraumatic stress disorder.
Sex differences in neural projections of fear memory processing are unveiled.
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