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Despite achieving clinical remission, patients with depression encounter difficulties to return to their premorbid psychosocial functioning. Cognitive dysfunction has been proposed to be a primary mediator of functional impairment. Therefore, the new non-pharmacological procognitive strategy INtegral Cognitive REMediation for Depression (INCREM) has been developed with the aim of targeting cognitive and psychosocial functioning.This is a single-blind randomized controlled clinical trial with three treatment arms. Fifty-two depressed patients in clinical remission, with psychosocial difficulties and cognitive impairment, were randomly assigned to receive INCREM intervention, Psychoeducation programme, or treatment as usual. Patients were assessed before and after the study period, and six months after. The primary outcome was the change from baseline of patients' psychosocial functioning. Changes in cognitive functioning and other variables were considered secondary outcomes.The analysis showed a significant improvement in psychosocial functioning in the INCREM group, especially six months after the intervention, compared to patients who received the psychoeducation programme. An improvement in cognitive performance was also observed in the INCREM group.This study includes a small sample size due to the anticipated end of the clinical trial because of the COVID-19 pandemic.These results provide preliminary evidence on the feasibility and potential efficacy of the INCREM program to improve not only cognitive performance but also psychosocial functioning in clinically remitted depressed patients, and such improvement is maintained six months after. It can be speculated that the maintenance is mediated by the cognitive enhancement achieved with INCREM.

Contains fulltext : 288062.pdf (Publisher’s version ) (Closed access) There is limited convergence in neuroimaging investigations into volumes of subcortical brain regions in social anxiety disorder (SAD). The inconsistent findings may arise from variations in methodological approaches across studies, including sample selection based on age and clinical characteristics. The ENIGMA-Anxiety Working Group initiated a global mega-analysis to determine whether differences in subcortical volumes can be detected in adults and adolescents with SAD relative to healthy controls. Volumetric data from 37 international samples with 1115 SAD patients and 2775 controls were obtained from ENIGMA-standardized protocols for image segmentation and quality assurance. Linear mixed-effects analyses were adjusted for comparisons across seven subcortical regions in each hemisphere using family-wise error (FWE)-correction. Mixed-effects d effect sizes were calculated. In the full sample, SAD patients showed smaller bilateral putamen volume than controls (left: d = -0.077, pFWE = 0.037; right: d = -0.104, pFWE = 0.001), and a significant interaction between SAD and age was found for the left putamen (r = -0.034, pFWE = 0.045). Smaller bilateral putamen volumes (left: d = -0.141, pFWE

Altres ajuts: acords transformatius de la UAB Altres ajuts: Swiss National Science Foundation (SNSF) [NCCR Synapsy grant: 51NF40-158776 and − 185897] Posttraumatic stress disorder (PTSD) is a highly disabling psychiatric condition that may arise after exposure to acute and severe trauma. It is a highly prevalent mental disorder worldwide, and the current treatment options for these patients remain limited due to low effectiveness. The time window right after traumatic events provides clinicians with a unique opportunity for preventive interventions against potential deleterious alterations in brain function that lead to PTSD. Some studies pointed out that PTSD patients present an abnormal function of the hypothalamic-pituitary-adrenal axis that may contribute to a vulnerability toward PTSD. Moreover, glucocorticoids have arisen as a promising option for preventing the disorder's development when administered in the aftermath of trauma. The present work compiles the recent findings of glucocorticoid administration for the prevention of a PTSD phenotype, from human studies to animal models of PTSD. Overall, glucocorticoid-based therapies for preventing PTSD demonstrated moderate evidence in terms of efficacy in both clinical and preclinical studies. Although clinical studies point out that glucocorticoids may not be effective for all patients' subpopulations, those with adequate traits might greatly benefit from them. Preclinical studies provide precise insight into the mechanisms mediating this preventive effect, showing glucocorticoid-based prevention to reduce long-lasting behavioral and neurobiological abnormalities caused by traumatic stress. However, further research is needed to delineate the precise mechanisms and the extent to which these interventions can translate into lower PTSD rates and morbidity.

INTRODUCTION A high prevalence of obsessive-compulsive symptoms (OCSs) in anxiety-depressive disorders ranging from 30 to 67% has been described. OBJECTIVE This study aims to assess the presence and persistence of OCSs in an outpatient sample of subjects with anxiety and depressive disorders, as well as its relationship with recent life events (RLEs) and/or traumatic experiences (TEs). METHOD We conducted a prospective, observational, analytical study of 200 subjects with DSM-5 diagnoses of anxiety and/or depression. Participants were included by consecutive sampling and were evaluated at baseline and after 6-12 months (mean 8.5 months) of follow-up. The severity of the symptoms was assessed through the Hamilton Anxiety Scale (HARS) and Hamilton Scale for the evaluation of depression (HRSD-17), and comorbidity was assessed through the International Neuropsychiatric Interview (MINI). The Revised Inventory of Obsessions and Compulsions (OCI-R), the Recent Vital Changes Questionnaire (CVSV), and the Diagnostic Scale for Post-Traumatic Stress (PDS) were also administered. RESULTS 54% of the sample presented OCSs, and 30.5% presented one or more TEs throughout life. At the baseline visit, the presence of OCSs was associated with the severity of depressive symptoms (p=0.028), the presence of TEs (p

Objective Research suggests abnormalities in reward-based processes in anorexia nervosa (AN). However, few studies have explored if such alterations might be associated with different temporal activation patterns. This study aims to characterize alterations in time-dependent processes in the ventral striatum (VS) during social feedback in AN using functional magnetic resonance imaging (fMRI). Method Twenty women with restrictive-subtype AN and 20 age-matched healthy controls (HC) underwent a social judgment experimental fMRI task. Temporal VS hemodynamic responses were extracted in SPM for each participant and each social condition (acceptance/rejection). Results Compared with age-matched HC, patients with AN showed a significant time by group interaction of peak VS response throughout the task, with a progressive blunting of peak activation responses, accompanied by a progressive increase in baseline activity levels over time. Discussion The results suggest an attenuated response pattern to repetitive social rejection in the VS in patients with AN, together with a difficulty in returning to baseline. The information obtained from this study will guide future, design-specific studies to further explore alterations temporal dynamics.

Neuroimaging studies point to neurostructural abnormalities in youth with anxiety disorders. Yet, findings are based on small-scale studies, often with small effect sizes, and have limited generalizability and clinical relevance. These issues have prompted a paradigm shift in the field towards highly powered (i.e., big data) individual-level inferences, which are data-driven, transdiagnostic, and neurobiologically informed. Here, we built and validated neurostructural machine learning (ML) models for individual-level inferences based on the largest-ever multi-site neuroimaging sample of youth with anxiety disorders (age: 10-25 years, N=3,343 individuals from 32 global sites), as compiled by three ENIGMA Anxiety Working Groups: Panic Disorder (PD), Generalized Anxiety Disorder (GAD), and Social Anxiety Disorder (SAD). ML classifiers were trained on MRI-derived regional measures of cortical thickness, surface area, and subcortical volumes to classify patients and healthy controls (HC) for each anxiety disorder separately and across disorders (transdiagnostic classification). Modest, yet robust, classification performance was achieved for PD vs. HC (AUC=0.62), but other disorder-specific and transdiagnostic classifications were not significantly different from chance. However, above chance-level transdiagnostic classifications were obtained in exploratory subgroup analyses of male patients vs. male HC, unmedicated patients vs. HC, and patients with low anxiety severity vs. HC (AUC 0.59-0.63). The above chance-level classifications were based on plausible and specific neuroanatomical features in fronto-striato-limbic and temporo-parietal regions. This study provides a realistic estimate of classification performance in a large, ecologically valid, multi-site sample of youth with anxiety disorders, and may as such serve as a benchmark.

Background and objectives: The COVID-19 pandemic has forced universities to move the completion of university studies online. Spain's National Conference of Medical School Deans coordinates an objective, structured clinical competency assessment called the Objective Structured Clinical Examination (OSCE), which consists of 20 face-to-face test sections for students in their sixth year of study. As a result of the pandemic, a computer-based case simulation OSCE (CCS-OSCE) has been designed. The objective of this article is to describe the creation, administration, and development of the test. Materials and methods: This work is a descriptive study of the CCS-OSCE from its planning stages in April 2020 to its administration in June 2020. Results: The CCS-OSCE evaluated the competences of anamnesis, exploration, clinical judgment, ethical aspects, interprofessional relations, prevention, and health promotion. No technical or communication skills were evaluated. The CCS-OSCE consisted of ten test sections, each of which had a 12-minutes time limit and ranged from six to 21 questions (mean: 1.1 minutes/question). The CCS-OSCE used the virtual campus platform of each of the 16 participating medical schools, which had a total of 2,829 students in their sixth year of study. It was jointly held on two dates in June 2020. Conclusions: The CCS-OSCE made it possible to bring together the various medical schools and carry out interdisciplinary work. The CCS-OSCE conducted may be similar to Step 3 of the United States Medical Licensing Examination.

Some evidence suggests that patients with bipolar disorder (BD) have better Theory of Mind (ToM) skills than patients with schizophrenia/schizoaffective disorder (SCH). However, this difference is not consistently reported across studies, so rather than being global, it may be restricted to specific aspects of ToM. Our primary objective was to compare higher order ToM performance between BD and SCH patients using the Hinting Task (HT). Ninety-four remitted patients were recruited (BD = 47, SCH = 47). Intelligence quotient (IQ), attention, memory, executive functions, and processing speed were also assessed. Patients with BD performed better on the HT than patients with SCH, even when the analysis was adjusted for IQ and neurocognition (p

Psychotic major depression (PMD) is hypothesized to be a distinct clinical entity from nonpsychotic major depression (NPMD). However, neurobiological evidence supporting this notion is scarce. The aim of this study is to identify gray matter volume (GMV) differences between PMD and NPMD and their longitudinal change following electroconvulsive therapy (ECT). Structural magnetic resonance imaging (MRI) data from 8 independent sites in the Global ECT-MRI Research Collaboration (GEMRIC) database (n = 108; 56 PMD and 52 NPMD; mean age 71.7 in PMD and 70.2 in NPMD) were analyzed. All participants underwent MRI before and after ECT. First, cross-sectional whole-brain voxel-wise GMV comparisons between PMD and NPMD were conducted at both time points. Second, in a flexible factorial model, a main effect of time and a group-by-time interaction were examined to identify longitudinal effects of ECT on GMV and longitudinal differential effects of ECT between PMD and NPMD, respectively. Compared with NPMD, PMD showed lower GMV in the prefrontal, temporal and parietal cortex before ECT; PMD showed lower GMV in the medial prefrontal cortex (MPFC) after ECT. Although there was a significant main effect of time on GMV in several brain regions in both PMD and NPMD, there was no significant group-by-time interaction. Lower GMV in the MPFC was consistently identified in PMD, suggesting this may be a trait-like neural substrate of PMD. Longitudinal effect of ECT on GMV may not explain superior ECT response in PMD, and further investigation is needed. Funding Agencies|Keio University Medical Science Fund [99-095-0007]; AMED [JP20dm0307102h0003]; Research Foundation Flanders (FWO) grantFWO [G0C0319N]; KU Leuven Fund [C24/18/095]; Sequoia Fund for Research on Ageing and Mental Health; National Institute of HealthUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USA [MH125126, MH111826]; Carlos III Health InstituteInstituto de Salud Carlos III [CD20/00189]; Lundbeck FoundationLundbeckfonden; Western Norway Regional Health Authority [911986, 912238]

This cohort study quantifies the proportion of real-world individuals with schizophrenia spectrum disorders who would be ineligible for participation in randomized clinical trials and explores whether clinical outcomes differ between eligible and ineligible individuals., Key Points Question What percentage of patients with schizophrenia in the real world are represented in randomized clinical trials (RCTs) and do their outcomes differ from those not represented in RCTs? Findings In this study of 25 259 real-world individuals with diagnoses of schizophrenia spectrum disorders recorded in national patient registries in Finland and Sweden, about a fifth were represented in RCTs and their outcomes were better than of those individuals with schizophrenia not meeting RCT inclusion criteria. Meaning Future research should consider the heterogeneity of individuals with schizophrenia and the patient groups typically ineligible for participation; RCTs may become more inclusive by representing a broader spectrum of individuals with schizophrenia and by targeting specific currently underrepresented groups., Importance Most evidence about efficacy and safety of antipsychotics in schizophrenia spectrum disorders relies on randomized clinical trials (RCTs). However, owing to their strict eligibility criteria, RCTs represent only a part of the real-world population (ie, unselected patients seen in everyday clinical practice), which may result in an efficacy-effectiveness gap. Objective To quantify the proportion of real-world individuals with schizophrenia spectrum disorders who would be ineligible for participation in RCTs, and to explore whether clinical outcomes differ between eligible and ineligible individuals. Design, Setting, and Participants This study applied eligibility criteria typically used in RCTs for relapse prevention in schizophrenia spectrum disorders to real-world populations. Individuals with diagnoses of schizophrenia spectrum disorders recorded in national patient registries in Finland and Sweden were identified. Individuals who had used antipsychotics continuously for 12 weeks in outpatient care were selected. Individuals were followed up for up to 1 year while they were receiving maintenance treatment with any second-generation antipsychotic (excluding clozapine). Follow-up was censored at treatment discontinuation, initiation of add-on antipsychotics, death, and end of database linkage. Main Outcomes and Measures Proportions of RCT-ineligible individuals with schizophrenia spectrum disorders owing to any and specific RCT exclusion criteria. The risk of hospitalization due to psychosis within 1-year follow-up in ineligible vs eligible persons were compared using hazard ratios (HR) and corresponding 95% CIs. Results The mean (SD) age in the Finnish cohort (n = 17 801) was 47.5 (13.8) years and 8972 (50.4%) were women; the mean (SD) age in the Swedish cohort (n = 7458) was 44.8 (12.5) years and 3344 (44.8%) were women. A total of 20 060 individuals (79%) with schizophrenia spectrum disorders would be ineligible for RCTs (Finnish cohort: 14 221 of 17 801 [79.9%]; Swedish cohort: 5839 of 7458 [78.3%]). Most frequent reasons for ineligibility were serious somatic comorbidities and concomitant antidepressant/mood stabilizer use. Risks of hospitalization due to psychosis was higher among ineligible than eligible individuals (Finnish cohort: 18.4% vs 17.2%; HR, 1.14 [95% CI, 1.04-1.24]; Swedish cohort: 20.1% vs 14.8%; HR, 1.47 [95% CI, 1.28-1.92]). The largest risks of hospitalization due to psychosis were observed in individuals ineligible owing to treatment resistance, tardive dyskinesia, and history of suicide attempts. Finally, with more ineligibility criteria met, larger risks of hospitalization due to psychosis were observed in both countries. Conclusions and Relevance RCTs may represent only about a fifth of real-world individuals with schizophrenia spectrum disorders. Underrepresented (ineligible) patients with schizophrenia spectrum disorders have moderately higher risks of admission due to psychosis while receiving maintenance treatment than RCT-eligible patients. These findings set the stage for future studies targeting real-world populations currently not represented by RCTs.

Background Telomere length (TL) is one biomarker of cell aging used to explore the effects of the environment on age-related pathologies. Obesity and high body mass index have been identified as a risk factors for shortened TL. Objective To evaluate TL in different subtypes of obese patients, and to examine changes in TL in relation to weight loss after bariatric surgery. Setting University Hospital in Spain. Methods A cohort of 94 patients submitted to bariatric surgery were followed-up during 24 months (t24m: lost to follow-up = 0%). All patients were evaluated before surgery (t0) and during the postoperative period (t6m, t12m, and t24m) for body mass index and metabolic variables. We assessed TL at each timepoint using quantitative polymerase chain reactions and the telomere sequence to single-copy gene sequence ratio method. Results Patients with class III obesity showed significantly shorter TL at baseline than those patients with class II obesity (P = .027). No differences in TL were found between patients with or without type 2 diabetes or metabolic syndrome. Longitudinal analysis did not show an effect of time, type of surgery, age, or sex on TL. However, a generalized estimating equation model showed that TL was shorter amongst class III obesity patients across the time course (P = .008). Comparison between patients with obesity class II and class III showed differences in TL at t6m (adjusted P = .024), whereby class II patients had longer TL. However, no difference was observed at the other evaluated times. Conclusion Obesity severity may have negative effects on TL independently of type 2 diabetes or metabolic syndrome. Although TL is significantly longer in class II obesity patients relative to class III 6 months after bariatric surgery. This difference is not apparent after 24 months.

Background Emerging evidence suggests that the FK506 binding protein 51 (FKBP5/FKBP51), encoded by the FKBP5 gene, influences weight and metabolic regulation. The T allele of a functional polymorphism in FKBP5 (rs1360780), has been associated with the expression of FKBP51 and weight loss after bariatric surgery. Objective To examine the role of the FKBP5 rs1360780 polymorphism in relation to age, sex, and type of surgery in weight loss after bariatric surgery in patients with severe obesity. Setting University Hospital in Spain Methods A cohort of 151 obese patients submitted to Roux-en-Y gastric bypass (62.3%) and sleeve gastrectomy (37.7%) were followed-up during 24-months (t24m; loss to follow-up: 0%). During the postoperative period body mass index (BMI) and percentage of excess and total weight loss were evaluated. Results The BMI analysis showed an effect of the interaction FKBP5 genotype by sex (P = .0004) and a tendency to the interaction genotype by surgery (P = .048), so that men carrying the T allele had higher BMI at t24m than those without the T allele, and T-allele carriers that underwent sleeve gastrectomy had higher BMI at t24m than the noncarriers. Additionally, we found an interaction between FKBP5 and age for the percentage of excess weight loss and BMI (P = .0005 and P = 1.5e−7, respectively), whereby individuals >48 years with the T allele displayed significant differences for the analyzed variables at t24m compared with the homozygotes for the alternate C allele showing lower weight loss. Conclusion FKBP5 rs1360780 genotype has specific effects on weight loss outcomes after bariatric surgery depending on sex, age, and type of surgery, suggesting worse results in older males carrying the T allele who have undergone sleeve gastrectomy.

Introduction Continuation and maintenance electroconvulsive therapy (c/m-ECT) is a therapeutic option after an acute ECT course. Although it is widely used, both duration and the outcome of patients when ECT-c/m is discontinued is not yet well established. The aim of the study was to evaluate the recurrence rate and associated clinical factors when c/m-ECT is discontinued. Materials and methods Retrospective evaluation of 73 patients who were discontinued from c/m-ECT. The minimum evaluation time was one year. The need of hospital admission or a new acute course of ECT was considered a relapse. The recurrence rate was calculated as a percentage and the estimated time to recurrence was analyzed through a survival analysis. Possible associations between clinical variables and recurrence were analyzed by univariate and multivariate Cox analysis. Results Thirty-six patients (49.3%) relapsed: 61.1% of them relapsed during the first year after the c/m-ECT discontinuation (36.1% during the first 6 months). The estimated time to recurrence was 38.67 months. Fifty percent of patients who relapsed required a new acute course of ECT and 44.4% of them restarted c/m-ECT. Patients with an interval between sessions of less than one month and those with more previous episodes showed a higher risk of recurrence. Conclusions The risk of recurrence should be considered before the discontinuation of c/m-ECT. After the discontinuation, almost half of the patients relapsed, most of them within the first year. Close monitoring should be conducted in these patients and the discontinuation is not recommended when it is administered at intervals between sessions of less than a month. Further studies are required to identify risk groups for relapse.

Resumen Introduccion La terapia electroconvulsiva de continuacion/mantenimiento (TEC-c/m) es una opcion terapeutica tras la TEC aguda. Aunque es ampliamente usada, tanto su duracion como la evolucion de los pacientes tras su discontinuacion no estan bien establecidas. El objetivo del estudio fue evaluar la tasa de recidivas y los factores clinicos asociados a la misma tras discontinuar la TEC-c/m. Material y metodos Evaluacion retrospectiva de 73 pacientes a los que se les discontinuo la TEC-c/m. El tiempo de evaluacion minimo fue de un ano. Se considero recidiva la necesidad de ingreso o de nueva tanda aguda de TEC. La tasa de recidivas se determino como porcentaje y el tiempo estimado hasta la recidiva se analizo a traves de un analisis de supervivencia. Posibles asociaciones entre la recidiva y variables clinicas se analizaron mediante analisis univariado y multivariado de Cox. Resultados Treinta y seis pacientes (49,3%) recidivaron. El 61,1% lo hizo durante el primer ano tras la discontinuacion de la TEC-c/m (36,1% durante los primeros 6 meses). El tiempo estimado hasta la recidiva fue de 38,67 meses. El 50% de los pacientes que recayeron precisaron una nueva tanda aguda de TEC y el 44,4% reiniciaron TEC-c/m posteriormente. Los pacientes con un intervalo entre sesiones inferior a un mes y aquellos con mas episodios previos presentaron mayor riesgo de recidiva. Conclusiones Ante la discontinuacion de la TEC-c/m debe considerarse el riesgo de recidiva. Tras la discontinuacion, casi la mitad de los pacientes recidivaron, la mayoria en el primer ano. Es recomendable realizar un seguimiento estrecho tras la discontinuacion de la TEC-c/m y no es aconsejable su retirada cuando se administra con intervalos entre sesiones inferiores a un mes. Se requieren nuevos estudios para identificar grupos de riesgo para la recidiva.

Background: 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. Methods: 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. Results: 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.Conclusions: 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.Trial registration: ClinicalTrials.gov identifier: NCT03285659; Registered 18th September, 2017.

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.

Introduction Bipolar disorder (BD) has been reconceptualised as a progressive disorder that develops from mild to severe presentations. An empirical staging model – the Empirically Developed Clinical Staging Model for BD (EmDe-5) – was developed in a previous study. This study aims to further validate that model using a larger and more representative Spanish sample. Material and methods 183 BD outpatients were recruited at 11 sites in Spain. Assessment included clinical characteristics of the BD (number of hospitalisations, number of suicide attempts, comorbid personality disorders), physical health (BMI, metabolic syndrome, number of physical illnesses), cognition (SCIP), functioning (permanently disabled due to BD, FAST), and quality of life (SF-36). The CGI-S, VAS-S, and psychopharmacological treatment pattern were used as external validators. Results Ten patients (51.5%) were classified as stage 1, 33 (18%) as stage 2, 93 (50 8%) as stage 3, 37 (20 2%) as stage 4, and 10 (5 5%) as stage 5. All profilers, other than number of suicide attempts (p = 0.311) and comorbid personality disorder (p = 0.061), exhibited worse scores from stage 1 to 5. As expected, VAS-S and CGI-S scores were worse in the later stages. Regarding treatment, early stages (1–2) were associated with the use of one to three drugs while late stages (4–5) were associated with four or more drugs (p = 0.002). Conclusions We confirm the EmDe-5 staging model's construct validity. The ease of obtaining the profilers, together with the operational criteria provided to quantify them, will facilitate the use of the EmDe-5 staging model in daily clinical practice.

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.

Background and objective Low adherence to treatment is associated with poorer clinical outcome and greater healthcare resources utilization (HRU). Limited data are available on the extent of adherence to each individual antidepressant. The goal of this study was to compare the adherence rate to desvenlafaxine versus usual care with selective serotonin reuptake inhibitors (SSRI) and/or other serotonin-norepinephrine reuptake inhibitors (SNRI), in subjects with major depressive disorder (MDD). Methods Retrospective, multi-centric, observational study including 574 outpatients with MDD. Data were collected from mental and primary care centers. Adherence, persistence, effectiveness, and HRU was evaluated through multivariate regression models. Results At 12-months, adjusted adherence rate was higher with desvenlafaxine versus SNRI/SSRI, 67.9% versus 59.9% (OR 1.66, 95% CI 1.07-2.59, p = 0.024). Remission rate was numerically higher with desvenlafaxine versus SNRI/SSRI, 55.9% versus 50.1% (OR 1.35, 95% CI 0.93-1.98, p = 0.118), as well as treatment response, 76.5% in desvenlafaxine group versus 70.8% in SNRI/SSRI group (OR 1.25, 95% CI 0.82-1.90, p = 0.300). Medical visits use was higher in SNRI/SSRI than in desvenlafaxine group [9.8 (4.8) versus 9.1 (6.0), p = 0.019]. Conclusions Desvenlafaxine is significantly associated with a higher adherence rate at 12 months compared to usual care based on SSRI or other SNRI. This suggests that desvenlafaxine could improve disease management having a positive impact on disease-associated costs.

Background Patients with obesity show evidence of increased levels of inflammation, oxidative stress and premature ageing. Telomere length (TL) is a key marker of cellular ageing, and patients with obesity often present shorter TL. Bariatric surgery (BS) is currently the most effective treatment for severe obesity. The aim of this systematic review was to explore whether the beneficial health effects observed after surgery in obese patients correspond to a restoration in TL or slower rates of shortening. As a secondary aim, we evaluated, at baseline and post-surgery, the relationship between TL and different factors that could play a role in TL changes along time. Methods Searches for relevant articles were performed in MEDLINE, Web of Knowledge and SCOPUS. Prospective longitudinal studies that evaluated leukocyte TL in adult patients who had undergone BS were included. Data were extracted and evaluated by two independent researchers. The protocol was registered in PROSPERO with the number CRD42020197711. Results Seven studies based on independent samples that fulfilled our inclusion criteria were included. Obese patients showed shorter telomeres compared to healthy individuals. Long-term studies (>2 years) seem to suggest an improvement in TL after surgery presumably due to the improvement of the inflammatory and oxidative levels of the patients induced by weight loss. Conclusion Studies seem to point towards a beneficial long-term effect of BS on TL recovery. However, the scarce number of studies and the heterogeneity in the variables analysed in the different cohorts make it difficult to draw a firm conclusion. More studies are needed to evaluate long-term changes to TL following BS.

Imaging studies on neuronal network formation provide relevant information as to how the brain matures during adolescence. We used a novel imaging approach combining well-established MRI measures of local functional connectivity that jointly provide qualitatively different information relating to the functional structure of the cerebral cortex. To investigate the adolescent transition into adulthood, we comparatively assessed 169 preadolescents aged 8-12 years and 121 healthy adults. Whole-brain functional connectivity maps were generated using multi-distance measures of intracortical neural activity coupling defined within iso-distant local areas. Such Iso-Distant Average Correlation (IDAC) measures therefore represent the average temporal correlation of a given brain unit, or voxel, with other units situated at increasingly separated iso-distant intervals. The results indicated that between-group differences in the functional structure of the cerebral cortex are extensive and implicate part of the lateral prefrontal cortex, a medial frontal/anterior cingulate region, the superior parietal lobe extending to the somatosensory strip and posterior cingulate cortex, and local connections within the visual cortex, hippocampus, amygdala and insula. We thus provided detail of the cerebral cortex functional structure maturation during the transition to adulthood, which may serve to establish more accurate links between adolescent performance gains and cerebral cortex maturation. Remarkably, our study provides new information as to the cortical maturation processes in prefrontal areas relevant to executive functioning and rational learning, medial frontal areas playing an active role in the cognitive appraisal of emotion and anxiety, and superior parietal cortices strongly associated with bodily self-consciousness in the context of body image formation. This work was supported in part by the European Research Council under the ERC [grant number 268479] – the BREATHE project and the Carlos III Health Institute grants PI13/01958 and PI16/00889.

Cognitive behavioral therapy (CBT) including exposure and response prevention is a well-established treatment for obsessive-compulsive disorder (OCD) and is based on the principles of fear extinction. Fear extinction is linked to structural and functional variability in the ventromedial prefrontal cortex (vmPFC) and has been consistently associated with glutamate neurotransmission. The relationship between vmPFC glutamate and fear extinction and its effects on CBT outcome have not yet been explored in adults with OCD. We assessed glutamate levels in the vmPFC using 3T magnetic resonance spectroscopy, and fear extinction (learning and recall) using skin conductance responses during a 2-day experimental paradigm in OCD patients (n = 17) and in healthy controls (HC; n = 13). Obsessive-compulsive patients (n = 12) then received manualized CBT. Glutamate in the vmPFC was negatively associated with fear extinction recall and positively associated with CBT outcome (with higher glutamate levels predicting a better outcome) in OCD patients. Glutamate levels in the vmPFC in OCD patients were not significantly different from those in HC, and were not associated with OCD severity. Our results suggest that glutamate in the vmPFC is associated with fear extinction recall and CBT outcome in adult OCD patients.