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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.

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]

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.

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.

Background and objectives Healthy people with intact cognitive functioning may also experience subjective cognitive deficits (SCD). However, no study has thoroughly explored these symptoms in healthy Spaniards. Therefore, we aimed to: (i) describe the pattern of SCD in this population, (ii) report magnitude categories of SCD, and (iii) correlate SCD with age, gender and years of education. Methods 102 healthy Spaniards (51 men) were recruited. Men and women subgroups were matched by age and years of education. SCD were evaluated using the 20-item Perceived Deficits Questionnaire (PDQ-20). Magnitude categories of SCD were described as distribution-based quartiles of the total PDQ-20 score, with higher scores/quartiles indicating greater SCD. Participants with a total PDQ-20 score greater than 2 standard deviations (SD) above normal variation were considered at risk of clinically significant SCD. Results Mean total PDQ-20 score was 17.98 (SD = 8.29), with higher scores on “Attention/Concentration” and “Retrospective Memory” subscales than on “Planning/Organization” and “Prospective Memory” subscales. Total PDQ-20 score distribution by quartile was: 0–11 (1 st quartile), 12–17 (2 nd quartile), 18–23 (3 rd quartile) and 24–80 (4 th quartile). Only 1.96% of participants were at risk of clinically significant SCD. There was a marginal trend in the association between age and “Retrospective Memory” subscale ( r s = 0.256; p = 0.009). Conclusions Our findings may help health professionals interpret PDQ-20 scores more accurately in clinical settings. A total PDQ-20 score equal or greater to 35 may be a valid threshold for identifying people at risk of clinically significant SCD. Assessment of SCD may improve the ecological validity of research on human cognition.

Obsessive-compulsive disorder (OCD) has been consistently associated with structural and functional alteration of the orbitofrontal cortex (OFC) and its subcortical connections. In exploring these alterations, a neurodevelopmental basis to OCD has been suggested. While some studies have examined outcomes of early cortical maturation processes, such as global cortical thickness and gyrification, no work has specifically examined the OFC. Within the OFC, three types of sulcogyral patterns have been identified as a result of variance in cortical folding. The distribution of these patterns has been found to differ in patients of various neuropsychiatric disorders relative to the general population, however no study has yet investigated this distribution in individuals with OCD. Eighty OCD patients and 78 healthy controls were evaluated using magnetic resonance imaging, with identification of the sulcogyral pattern based on the method of Chiavaras and Petrides (2000). While gross changes in OFC sulcogyral patterning did not distinguish OCD patients from healthy controls, expression of both the Type II and Type III patterns was significantly associated with increased OCD illness severity. This finding indicates that early neurodevelopmental factors may influence illness severity.

Objective and subjective cognitive measures are altered in major depressive disorder (MDD), but there is a poor correlation between them. This study aims to explore such discrepancy and the characteristics explaining this phenomenon. 229 patients with MDD subdivided into remitted (n = 57), partially remitted (n = 90) and acute (n = 82) underwent a clinical interview, completed self-report questionnaires and a neuropsychological assessment. The association between objective and subjective cognition was evaluated in the areas of attention and memory. Also, dependent measures of concordance and self-appraisal were calculated for each patient. Potential predictors of these outcomes were evaluated through regression analysis. Depressive symptoms correlated negatively with objective but especially with subjective cognition. Patients in an acute episode showed a significant correlation between objective and subjective attention/ memory measures, but also the greatest underestimation of their cognitive performance. In those with fewer depressive symptoms, objective and subjective cognition showed poor correspondence between them. In the regression analyses with the full MDD sample, higher scores on depressive symptoms, intelligence quotient and executive functions predicted lower self-appraisal. Objective and subjective cognition show poor concordance in MDD patients, especially in those with residual mood symptoms. Higher executive functions also explain this discrepancy. Assessments of both subjective cognitive complaints and objective performance seem necessary as they may be measuring different aspects of cognitive functioning. (c) 2018 Elsevier B.V. and ECNP. All rights reserved.

Objectives: To characterize people who died by suicide after having previous contacts with public health system using the data available in a primary care setting. Method: A retrospective, population-based case-control study identified through autopsy reports subjects who died from suicide between 2010 and 2015 in Barcelona province. Those who had previous interaction with primary healthcare services were selected, and 20 controls per case with similar age, sex and residence area were randomly sampled from a primary healthcare medical database; the available medical data derived from routine primary care records were anonymised and retrieved for analysis in all subjects. Results: Of 2109 people deceased by suicide, 971 had previous primary healthcare interactions; 33.8% aged over 65 and 74% men. Of those with previous contact, 33% died during the week after and 58.5% within one month. A multivariable analysis identified several significant risk factors in the database, including previous suicide attempts, psychiatric diagnosis, number of primary healthcare visits, referrals to mental health, number of drugs prescribed, recent psychoactive drug prescriptions, and being on sick leave due to mental conditions in the previous year. Conclusions: Nearly half of suicide subjects contacted primary healthcare before dying but remained either undetected or not effectively managed for prevention. In cases who interacted, available data on risk factors included high frequentation and being on sick leave due to mental health disorders, in addition to other well-known factors. Routine electronic medical records represent an opportunity to provide clinical-decision support tools that could be implemented through automatized risk calculation.HIGHLIGHTSMost of suicide patients had a recent interaction with the healthcare systemWell known risk factors were available in the routine electronic medical recordsAdditional alerting tools could be implemented through automatized risk calculation.

Resumen Antecedentes y objetivos La pandemia de la COVID-19 ha obligado a completar los estudios universitarios online. La Conferencia Nacional de Decanos de Facultades de Medicina coordina una prueba de evaluacion de competencias clinicas objetiva y estructurada (ECOE) de 20 estaciones presenciales a los estudiantes de sexto del grado. Como consecuencia de la pandemia se ha disenado una ECOE sustitutoria con casos-clinicos computarizados simulados (ECOE-CCS). El objetivo del articulo es describir la elaboracion, la ejecucion y el desarrollo de la prueba. Materiales y metodos Estudio descriptivo de la ECOE-CCS conjunta desde su gestacion en abril 2020 hasta su ejecucion en junio 2020. Resultados La ECOE-CCS evaluo las competencias de anamnesis, exploracion, juicio clinico, aspectos eticos, relaciones interprofesionales, prevencion y promocion de la salud. No se evaluaron habilidades tecnicas ni de comunicacion. La ECOE-CCS consistio en 10 estaciones de 12 minutos de duracion, con un numero de preguntas de seis a 21 (media: 1,1 minutos/pregunta). En la ECOE-CCS se utilizo la plataforma virtual del campus de cada una de las 16 facultades de Medicina que participaron, con un total de 2.829 estudiantes de sexto curso. Se realizo de una forma conjunta en dos fechas de junio del 2020. Conclusiones La experiencia de la ECOE-CCS permitio llevar a cabo una integracion y el trabajo interdisciplinar de las diferentes facultades de Medicina. La ECOE-CCS realizada podria asemejarse al Step 3 CCS de la United States Medical Licensing Examination.

Background Offspring of patients diagnosed with bipolar disorder and schizophrenia (Off-BDSZ) have a high genetic risk of developing a mental illness. The aim of this project is to develop and investigate the efficacy of an intervention aimed at this population, based on the concept of cognitive reserve. Methods This is a multicenter randomized trial with an experimental test–retest design study with control group. Two groups will be included: a community comparison group (CC) and a Off-BDSZ group. A total of 108 Off-BDSZ and 65 CC aged between 6 and 25 years will be recruited. Off-BDSZ participants will be randomized to receive either Cognitive Reserve EnhAncement ThErapy (CREATE) (n = 54), or a supportive approach (n = 54). The CC group will be assessed at baseline. The duration of the intervention will be 3 months, with 12 weekly group sessions. The primary outcome will be the improvement in CR measured according to change in the Cognitive Reserve Assessment Scale in Health (CRASH) and Cognitive Reserve scale for Adolescents (CORE-A). All participants will be blindly evaluated using clinical, cognitive and neuroimaging measures at baseline, at three months (after the psychological intervention), and at twelve-month follow-up after treatment completion. Discussion The results will provide insight into whether the CREATE-Offspring version may enhance cognitive reserve (CR) in child, adolescent and young adult Off-BDSZ as well as advance knowledge about changes in clinical manifestations, neuropsychological performance and brain structure and function associated with improving CR. This novel and cost-effective intervention represents an advance in the framework of preventive interventions in mental health. Trial registration Clinicaltrials.gov, NCT03722082 . Registered on 26 October 2018.

[Background] Substantial evidence supports the existence of neurocognitive endophenotypes in bipolar disorder (BD), but very few longitudinal studies have included unaffected relatives. In a 5-year, follow-up, family study, we have recently suggested that deficits in manual motor speed and visual memory could be endophenotype candidates for BD. We aimed to explore whether this also applies to processing speed., [Methods] A sample of 348 individuals, including 163 BD patients, 65 unaffected first-degree relatives (BD-Rel) and 120 genetically unrelated healthy controls (HC), was assessed with the Digit Symbol Substitution Test (DSST) on two occasions over a 2-year period (T1, T2). DSST values were controlled for age, years of education, occupational status, and subsyndromic mood symptoms. Differences between groups were evaluated with ANCOVAs., [Results] At T1 BD performed significantly worse than HC (p < 0.001; Cohen's d = 1.38) and BD-Rel (p < 0.001; Cohen's d = 0.82). BD-Rel showed an intermediate performance with significant differences with HC (p < 0.01; Cohen's d = 0.50). Similarly, at T2 BD performed significantly worse than HC (p < 0.001; Cohen's d = 1.44) and BD-Rel (p < 0.01; Cohen's d = 0.51). BD-Rel performance was intermediate and significantly lower than that of HC (p < 0.01; Cohen's d = 0.97). A Repeated Measures ANOVA revealed no significant between-group differences in performance over time (p > 0.05)., [Conclusions] The results of this longitudinal, family study suggest that impaired processing speed may represent a suitable cognitive endophenotype for BD. Further research on the field is required to confirm these preliminary findings., Dr Vicent Balanzá-Martínez acknowledges the support from Instituto de Salud Carlos III (PI16/1770, PROBILIFE Study).

Background: Impairment of social cognition is documented in bipolar disorder (BD) and schizophrenia/schizoaffective disorder (SCH). In healthy individuals, women perform better than men in some of its sub-domains. However, in BD and SCH the results are mixed. Our aim was to compare emotion recognition, affective Theory of Mind (ToM) and first- and second-order cognitive ToM in BD, SCH and healthy subjects, and to investigate sex-related differences. Methods: 120 patients (BD = 60, SCH = 60) and 40 healthy subjects were recruited. Emotion recognition was assessed by the Pictures of Facial Affect (POFA) test, affective ToM by the Reading the Mind in the Eyes Test (RMET) and cognitive ToM by several false-belief stories. Group and sex differences were analyzed using parametric (POFA, RMET) and non-parametric (false-belief stories) tests. The impact of age, intelligence quotient (IQ) and clinical variables on patient performance was examined using a series of linear/logistic regressions. Results: Both groups of patients performed worse than healthy subjects on POFA, RMET and second-order falsebelief (p < 0.001), but no differences were found between them. Instead, their deficits were related to older age and/or lower IQ (p < 0.01). Subthreshold depression was associated with a 6-fold increased risk of first-order false-belief failure (p < 0.001). Sex differences were only found in healthy subjects, with women outperforming men on POFA and RMET (p

Background One common denominator to the clinical phenotypes of borderline personality disorder (BPD) and major depressive disorder (MDD) is emotion regulation impairment. Although these two conditions have been extensively studied separately, it remains unclear whether their emotion regulation impairments are underpinned by shared or distinct neurobiological alterations. Methods We contrasted the neural correlates of negative emotion regulation across an adult sample of BPD patients (n = 19), MDD patients (n = 20), and healthy controls (HCs; n = 19). Emotion regulation was assessed using an established functional magnetic resonance imaging cognitive reappraisal paradigm. We assessed both task-related activations and modulations of interregional connectivity. Results When compared to HCs, patients with BPD and MDD displayed homologous decreased activation in the right ventrolateral prefrontal cortex (vlPFC) during cognitive reappraisal. In addition, the MDD group presented decreased activations in other prefrontal areas (i.e., left dorsolateral and bilateral orbitofrontal cortices), while the BPD group was characterized by a more extended pattern of alteration in the connectivity between the vlPFC and cortices of the visual ventral stream during reappraisal. Conclusions This study identified, for the first time, a shared neurobiological contributor to emotion regulation deficits in MDD and BPD characterized by decreased vlPFC activity, although we also observed disorder-specific alterations. In MDD, results suggest a primary deficit in the strength of prefrontal activations, while BPD is better defined by connectivity disruptions between the vlPFC and temporal emotion processing regions. These findings substantiate, in neurobiological terms, the different profiles of emotion regulation alterations observed in these disorders.

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.

Fil: Wainsztein, Agustina E. Instituto de Neurociencias FLENI-CONICET. Grupo de Investigación en Neurociencias Aplicadas a las Alteraciones de la Conducta; Argentina Fil: Wainsztein, Agustina E. Fundación FLENI. Servicio de Psiquiatría; Argentina Fil: Castro, Mariana N. Instituto de Neurociencias FLENI-CONICET. Grupo de Investigación en Neurociencias Aplicadas a las Alteraciones de la Conducta; Argentina Fil: Castro, Mariana N. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Psiquiatría y Salud Mental; Argentina Fil: Castro, Mariana N. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Castro, Mariana N. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Fisiología; Argentina Fil: Goldberg, Ximena. Universitat Autònoma de Barcelona. Institut d'Investigació i Innovació Parc Taulí I3PT. Hospital Universitario Parc Taulí. Área de Investigación en Neurociencias y Salud Mental. Departamento de Salud Mental; España Fil: Camacho-Téllez, Vicente. Instituto de Neurociencias FLENI-CONICET. Grupo de Investigación en Neurociencias Aplicadas a las Alteraciones de la Conducta; Argentina Fil: Camacho-Téllez, Vicente. Fundación FLENI. Servicio de Psiquiatría; Argentina Fil: Camacho-Téllez, Vicente. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Vulcano, Mercedes. Fundación FLENI. Servicio de Psiquiatría; Argentina Fil: Vulcano, Mercedes. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Psiquiatría y Salud Mental; Argentina Fil: Abulafia, Carolina Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Abulafia, Carolina Andrea. Pontificia Universidad Católica Argentina. Instituto de Investigaciones Biomédicas; Argentina Fil: Abulafia, Carolina Andrea. Instituto de Neurociencias FLENI-CONICET. Grupo de Investigación en Neurociencias Aplicadas a las Alteraciones de la Conducta; Argentina Fil: Ladrón de Guevara, M. Soledad. Instituto de Neurociencias FLENI-CONICET. Grupo de Investigación en Neurociencias Aplicadas a las Alteraciones de la Conducta; Argentina Fil: Ladrón de Guevara, M. Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Cardoner, Narcís. Universitat Autònoma de Barcelona. Institut d'Investigació i Innovació Parc Taulí I3PT. Hospital Universitario Parc Taulí. Área de Investigación en Neurociencias y Salud Mental. Departamento de Salud Mental; España Fil: Nemeroff, Charles B.Universidad de Texas en Austin. Institute for Early Life Adversity Research, Dell Medical School; Estados Unidos Fil: Menchón, José M. Hospital Universitario de Bellvitge. Departamento de Psiquiatría. Instituto de Investigación Biomédica de Bellvitge-IDIBELL; España Fil: Soriano-Mas, Carles. Universidad de Texas en Austin. Institute for Early Life Adversity Research, Dell Medical School; Estados Unidos Fil: Villarreal, Mirta F. Instituto de Neurociencias FLENI-CONICET. Grupo de Investigación en Neurociencias Aplicadas a las Alteraciones de la Conducta; Argentina Fil: Villarreal, Mirta F. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Villarreal, Mirta F. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Física; Argentina Fil: Guinjoan, Salvador M. Universidad de Buenos Aires. Facultad de Medicina. Departamento de Salud Mental; Argentina Fil: Guinjoan, Salvador M. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Guinjoan, Salvador M. Laureate Institute for Brain Research; Estados Unidos Fil: Guinjoan, Salvador M. Universidad de Buenos Aires. Facultad de Psicología; Argentina Abstract: Adverse childhood experiences (ACEs) have lifelong effects on emotional behavior and are frequent in Borderline Personality Disorder (BPD) and Major Depressive Disorder (MDD). The Central Autonomic Network (CAN), which modulates heart rate variability (HRV), comprises brain regions that mediate emotion regulation processes. However, it remains unclear the effect of ACEs on CAN dynamics and its relationship with HRV in these disorders. We studied the effects of ACEs on the brain and HRV simultaneously, during regulation of psychological stress in 19 BPD, 20 MDD and 20 healthy controls (HC). Participants underwent a cognitive reappraisal task during fMRI with simultaneous ECG acquisition. ACEs exposure was associated with increased activity of CAN and salience network components in patients with MDD compared to BPD during cognitive reappraisal. A brain-autonomic coupling was found in BPD relative to HC during emotion regulation, whereby greater activity of left anterior cingulate and medial superior frontal gyrus areas was coupled with increased HRV. Results suggest that ACEs exposure is associated with a distinct activation of the CAN and salience network regions governing responses to psychological stress in MDD compared to BPD. These alterations may constitute a distinctive neurobiological mechanism for abnormal emotion processing and regulation related to ACEs in MDD.

Recent neurobiological models of obsessive-compulsive disorder (OCD) have highlighted the potential role of abnormalities in fear learning processes. We compared brain activation -as assessed with whole-brain functional magnetic resonance imaging- during fear conditioning, fear extinction learning, and fear extinction recall in patients with OCD (n = 18) and healthy controls (n = 18). We also investigated whether brain activation during any of these processes was associated with exposure-based cognitive-behavioral therapy (CBT) outcome in patients. Patients with OCD showed significantly lower brain activation in the right insulo-opercular region and the dorsal anterior cingulate cortex during fear conditioning in comparison to healthy controls. Moreover, brain activation in the right insula predicted CBT outcome, with lower activation predicting a better outcome. Brain activation during extinction learning or recall did not differ between patients and controls or predicted CBT outcome in patients. Our results suggest that neural activations during fear conditioning in patients with OCD are abnormal and predict CBT outcome.

Background Bariatric surgery is currently the most effective long-term treatment for severe obesity. However, interindividual variation in surgery outcome has been observed, and research suggests a moderating effect of several factors including baseline co-morbidities (e.g., type 2 diabetes [T2D] and genetic factors). No data are currently available on the interaction between T2D and variants in brain derived neurotrophic factor (BDNF) and its effect on weight loss after surgery. Objectives To examine the role of the BDNF Val66Met polymorphism (rs6265) and the influence of T2D and their interaction on weight loss after bariatric surgery in a cohort of patients with severe obesity. Setting University hospital in Spain. Methods The present study evaluated a cohort of 158 patients with obesity submitted to bariatric surgery (Roux-en-Y gastric bypass or sleeve gastrectomy) followed up for 24 months (loss to follow-up: 0%). During the postoperative period, percentage of excess body mass index loss (%EBMIL), percentage of excess weight loss (%EWL), and total weight loss (%TWL) were evaluated. Results Longitudinal analyses showed a suggestive effect of BDNF genotype on the %EWL (P = .056) and indicated that individuals carrying the methionine (Met) allele may experience a better outcome after bariatric surgery than those with the valine/valine (Val/Val) genotype. We found a negative effect of a T2D diagnosis at baseline on %EBMIL (P = .004). Additionally, we found an interaction between BDNF genotype and T2D on %EWL and %EBMIL (P = .027 and P = .0004, respectively), whereby individuals with the Met allele without T2D displayed a greater %EWL and greater %EBMIL at 12 months and 24 months than their counterparts with T2D or patients with the Val/Val genotype with or without T2D. Conclusion Our data showed an association between the Met variant and greater weight loss after bariatric surgery in patients without T2D. The presence of T2D seems to counteract this positive effect.

Background. This study aimed to identify clinical and cognitive factors associated with increased risk for difficult-to-treat depression (DTD) or treatment-resistant depression (TRD). Methods. A total of 229 adult outpatients with major depression were recruited from the mental health unit at a public hospital. Participants were subdivided into resistant and nonresistant groups according to their Maudsley Staging Model score. Sociodemographic, clinical, and cognitive (objective and subjective measures) variables were compared between groups, and a logistic regression model was used to identify the factors most associated with TRD risk. Results. TRD group patients present higher verbal memory impairment than the nonresistant group irrespective of pharmacological treatment or depressive symptom severity. Logistic regression analysis showed that low verbal memory scores (odds ratio [OR]: 2.02; 95% confidence interval [CI]: 1.38–2.95) together with high depressive symptom severity (OR: 1.29; CI95%: 1.01–1.65) were associated with TRD risk. Conclusions. Our findings align with neuroprogression models of depression, in which more severe patients, defined by greater verbal memory impairment and depressive symptoms, develop a more resistant profile as a result of increasingly detrimental neuronal changes. Moreover, our results support a more comprehensive approach in the evaluation and treatment of DTD in order to improve illness course. Longitudinal studies are warranted to confirm the predictive value of verbal memory and depression severity in the development of TRD.

BACKGROUND: Current brain-based theoretical models of generalized anxiety disorder (GAD) suggest a dysfunction of amygdala-ventromedial prefrontal cortex emotional regulatory mechanisms. These alterations might be reflected by an altered resting state functional connectivity between both areas and could extend to vulnerable non-clinical samples such as high worriers without a GAD diagnosis. However, there is a lack of information in this regard. METHODS: We investigated differences in resting state functional connectivity between the basolateral amygdala and the ventromedial prefrontal cortex (amygdala-vmPFC) in 28 unmedicated participants with GAD, 28 high-worriers and 28 low-worriers. We additionally explored selected clinical variables as predictors of amygdala-vmPFC connectivity, including anxiety sensitivity. RESULTS: GAD participants presented higher left amygdala-vmPFC connectivity compared to both groups of non-GAD participants, and there were no differences between the latter two groups. In our exploratory analyses, concerns about the cognitive consequences of anxiety (the cognitive dimension of anxiety sensitivity) were found to be a significant predictor of the left amygdala-vmPFC connectivity. LIMITATIONS: The cross-sectional nature of our study preclude us from assessing if functional connectivity measures and anxiety sensitivity scores entail an increased risk of GAD. CONCLUSIONS: These results suggest a neurobiological qualitative distinction at the level of the amygdala-vmPFC emotional-regulatory system in GAD compared to non-GAD participants, either high- or low-worriers. At this neural level, they question previous hypotheses of continuity between high worries and GAD development. Instead, other anxiety traits such as anxiety sensitivity might confer a greater proneness to the amygdala-vmPFC connectivity alterations observed in GAD.

Introduction: Suicide attempts represent an important public health burden. Centralised electronic health record (EHR) systems have high potential to provide suicide attempt surveillance, to inform public health action aimed at reducing risk for suicide attempt in the population, and to provide data-driven clinical decision support for suicide risk assessment across healthcare settings. To exploit this potential, we designed the Catalonia Suicide Risk Code Epidemiology (CSRC-Epi) study. Using centralised EHR data from the entire public healthcare system of Catalonia, Spain, the CSRC-Epi study aims to estimate reliable suicide attempt incidence rates, identify suicide attempt risk factors and develop validated suicide attempt risk prediction tools. Methods and analysis: The CSRC-Epi study is registry-based study, specifically, a two-stage exposure-enriched nested case-control study of suicide attempts during the period 2014-2019 in Catalonia, Spain. The primary study outcome consists of first and repeat attempts during the observation period. Cases will come from a case register linked to a suicide attempt surveillance programme, which offers in-depth psychiatric evaluations to all Catalan residents who present to clinical care with any suspected risk for suicide. Predictor variables will come from centralised EHR systems representing all relevant healthcare settings. The study's sampling frame will be constructed using population-representative administrative lists of Catalan residents. Inverse probability weights will restore representativeness of the original population. Analysis will include the calculation of age-standardised and sex-standardised suicide attempt incidence rates. Logistic regression will identify suicide attempt risk factors on the individual level (ie, relative risk) and the population level (ie, population attributable risk proportions). Machine learning techniques will be used to develop suicide attempt risk prediction tools. Ethics and dissemination: This protocol is approved by the Parc de Salut Mar Clinical Research Ethics Committee (2017/7431/I). Dissemination will include peer-reviewed scientific publications, scientific reports for hospital and government authorities, and updated clinical guidelines. This project was supported by ISCIII/FEDER PI17/00521, ISCIII/FEDER PI17/01205, and Generalitat de Catalunya (2017 SGR 452). The Catalonia Suicide Risk Code surveillance programme is an initiative of the Mental Health and Addictions Plan of the Department of Health of the Catalan Government. PM has a Sara Borrell research contract awarded by the ISCIII (CD18/00049). ME has a Juan de la Cierva research contract awarded by the ISCIII (FJCI-2017–31738). VPS and ME want to thank unrestricted research funding from Secretaria d′Universitats i Recerca del Departament d′Economia i Coneixement (2017 SGR 134 to ‘Mental Health Research Group’), and Generalitat de Catalunya (Government of Catalonia). BPG and ADIT received funding from ISCIII FI18/00012 and FPU2017-06447, respectively. LBC received funding by Ministerio de Educación, Cultura y Deporte (FPU15/05728). DP and JA received funding by ISCIII/FEDER PI17/01205.

Background Early improvement to antidepressant drugs predicts remission, but the predictive value of early improvement to electroconvulsive therapy (ECT) is still unclear. The main aim of this study was to determine the optimal definition of early improvement in the treatment of major depressive disorder (MDD) with ECT, by analyzing its value as a predictor of remission. Methods A naturalistic study was conducted in 87 adult MDD patients treated with acute ECT. ROC curves were generated to identify the best time point (week 1 or 2 of treatment) predicted remission. Sensibility, specificity, and predictive values were calculated for several definitions of early improvement previously proposed in the literature (20%, 25%, 30%, and 35%). Complementary, time to remission was analyzed and a logistic regression model was performed to further characterize the impact of the optimal definition of early improvement on remission while adjusting for other clinically relevant variables. Results A 30% reduction in the HAM-D score after 2 weeks was identified as the optimal definition of early improvement, with acceptable sensitivity (76%), and specificity (67%). Complementary analyses provided further support for this definition showing a shorter time to remission and a significant effect adjusted for the rest of variables. Limitations Relatively small sample size, ECT restricted to brief bilateral treatment. Conclusions Early improvement, defined as a 30% of reduction in the HAM-D21 score at week 2, is a good predictor of remission in MDD patients treated with bilateral ECT, with potential clinical impact. Lack of early improvement could indicate a need for further changes in treatment strategies.

Major Depressive Disorder (MDD) entails cognitive dysfunction in many cognitive domains, but it is still uncertain whether such deficits are present in the early stages. The purpose of the study is to determine the cognitive performance in first episode depression (FED) exploring the presence of different cognitive profiles, and the role of cognition in FED at baseline and long-term. Ninety subjects (18-50 years) were included, 50 patients with a FED and 40 healthy controls. Participants were assessed with a neuropsychological battery, covering language, attention, verbal memory, processing speed and executive domains. Neuropsychological group comparisons were performed with MANOVAs. A hierarchical cluster analysis was run to identify clusters of patients with similar neuropsychological performance. Two generalized linear models were built to predict baseline HDRS-17 and changes at 12 months. Patients performed significantly worse than healthy controls in language, attention/working memory, verbal memory, processing speed and executive functioning, with moderate to large effect sizes (0.5 - 1). Two clusters were found: cognitively preserved patients (n=37) and cognitively impaired patients (n=13). Large effect sizes of cognitive impairment in FED were observed between the two cognitive clusters (preserved and impaired). Depressive symptoms at baseline were predicted by verbal memory (p=0.003), while 12-month changes were predicted by executive function (p=0.041) and language (p=0.037). Cognitive performance predicted depressive symptoms at baseline and at follow-up, pointing to the usefulness of cognitive assessment even at the commencement of the illness. (C) 2018 Elsevier B.V. and ECNP. All rights reserved.

Objectives: This study had 2 objectives: First, to explore the gender-related differences in emotional processing (EP) and theory of mind—both cognitive (CToM) and affective (AToM)—in patients with schizophrenia and in a control group of healthy subjects; and, second, to examine, from a gender perspective, the possible association between EP and CToM in the AToM performance. Methods: Forty patients with schizophrenia/schizoaffective disorder were recruited and matched by gender, age and years of education with 40 healthy subjects. EP was measured by the pictures of facial affect (POFA) test. CToM was measured using first- and second-order false-belief (FB) stories. AToM was measured by the reading the mind in the eyes test (RMET). Group and gender differences in CToM were analysed using the X2 test, whereas EP and AToM were analysed using the non-parametric Mann–Whitney U Test and a general linear model. Results were adjusted by intelligence quotient and negative symptomatology. Results: Patients with schizophrenia underperformed against healthy subjects in the POFA test, second-order FB, and RMET, but not in first-order FB. No significant gender differences were found. However, there was a trend showing that females outperformed males in the POFA ( P = 0.056). Group ( P < 0.001), POFA ( P < 0.001) and second-order FB ( P = 0.022) were the best factors predicting RMET performance (adjusted R2 = 0.584). Conclusions: Our results suggest that the illness is the main factor related to the deficit in social cognition, except for the basic aspects of the CToM that were unimpaired in most patients. Nevertheless, the influence of female gender in EP should not be neglected in any group. Finally, the hierarchal interaction between these domains is discussed.

Few systematic evaluations have been performed of the efficacy of electroconvulsive therapy (ECT) as a relapse prevention strategy in major depressive disorder (MDD). This is a single-blind, multicenter, randomized controlled trial to compare the efficacy and tolerability of pharmacotherapy plus maintenance ECT (M-Pharm/ECT) versus pharmacotherapy alone (M-Pharm) in the prevention of MDD relapse. Subjects with MDD who had remitted with bilateral acute ECT (n = 37) were randomly assigned to receive M-Pharm/ECT (n = 19, 14 treatments) or M-Pharm (n = 18) for nine months. The subjects were followed up for 15 months. The main outcome was relapse of depression, defined as a score of 18 or more on the Hamilton Depression Rating Scale. At nine months, 35% of the subjects treated with M-Pharm/ECT relapsed as compared with 61% of the patients treated with M-Pharm. No statistically significant differences between groups were indicated by either Kaplan–Meier or Cox proportional hazards regression analyses. The subjects without psychotic features were at higher risk of relapse. There were no statistically significant differences in the MMSE scores of the two groups at the end of the study. Further studies are needed to better define the indications for M-ECT in order to improve its efficacy as a relapse prevention strategy.

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.

Background 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. Objective 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. Results 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. Conclusion 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.

Human functional magnetic resonance imaging (fMRI) studies suggest that the ventromedial prefrontal cortex (vmPFC) contributes to the learned discrimination of threat and safety signals, although its precise contribution to these processes remains unclear. One hypothesis is that the vmPFC supports the positive affective processing of safety signals linked to their implicit stress-relieving properties. We set out to test this hypothesis and to examine the specificity of vmPFC responses to safety signal processing versus its high level of 'default mode' activity. Sixty participants completed an fMRI conditioning task that involved the generation of a conditioned threat (CS+) and safety (CS-) signal following the completion of a pre-conditioning baseline. Confirming past findings, activation of the vmPFC and other midline cortical and parietal areas - broadly resembling the default mode network - robustly discriminated between the CS- and CS+. However, when adjusting for this network's characteristic 'baseline' activity, only a subset of regions, including the vmPFC, was activated by the CS-. Regional selectivity for safety signal processing was confirmed by demonstrating a significant correlation between the magnitude of vmPFC responses and self-rated positive affect evoked by the CS-. Taken together, our current findings confirm a link between human vmPFC activity and the positive affective processing of safety signals. We discuss these findings with regards a broader model of human vmPFC function and its suggested higher-order contribution to emotionally adaptive behavior.

Aim Schizoid (ScPD) and Schizotypal (SPD) personality disorders are rare and severe disorders. They are associated with high liability to schizophrenia and present an attenuated form of its negative symptoms, which are considered a putative endophenotype for schizophrenia. The trans-diagnostic study of negative symptoms in non-psychotic populations such as ScPD/SPD might provide useful markers of a negative-symptom domain; however, little is known about their neurobiological substrates. The aim of the study was to investigate differences in gray and white matter volumes in subjects with ScPD/SPD compared to a group of healthy controls. Methods Structural magnetic resonance images were obtained from 20 never-psychotic subjects with ScPD/SPD and 28 healthy controls. Resulting values from clusters of differences were correlated in patients with relevant clinical variables (O-LIFE scale). Results ScPD/SPD presented greater bilateral white matter volume compared to healthy controls in the superior part of the corona radiata, close to motor/premotor regions, which correlated with the O-LIFE subtest of cognitive disorganization. No differences were found in regional gray matter or global gray/white matter volumes. Conclusion Greater volumes in motor pathways might relate to cognitive symptoms and motor alterations commonly present in schizophrenia-related disorders. Given the established link between motor signs and psychosis, structural alterations in motor pathways are suggested as a putative biomarker of a negative-symptom domain in psychosis subject to further testing.

Given the limitation of pharmacological treatments to treat cognitive symptoms in patients with Major Depressive Disorder (MDD), cognitive remediation programs has been proposed as a possible procognitive intervention but findings are not conclusive. This study investigates the efficacy of an INtegral Cognitive REMediation (INCREM) that includes a combination of a Functional Remediation (FR) strategy plus a Computerized Cognitive Training (CCT) in order to improve not only cognitive performance but also the psychosocial functioning and the quality of life. A single blind randomized controlled clinical trial in 81 patients with a diagnosis of MDD in clinical remission or in partial remission. Participants will be randomized to one of three conditions: INCREM (FR + CCT), Psychoeducation plus online games and Treatment As Usual (TAU). Intervention will consist in 12 group sessions, of approximately 110 min once a week. The primary outcome measure will be % of change in psychosocial functioning after treatment measured by the Functional Assessment Short Test (FAST); additionally, number of sick leaves and daily activities will also be recorded as pragmatic outcomes. To our knowledge, this is the first randomized controlled clinical trial using a combination of two different approaches (FR + CCT) to treat the present cognitive deficits and to promote their improvements into a better psychosocial functioning. Clinical Trials NCT03624621 . Date registered 10th of August 2018 and last updated 24th August 2018.