Predictors of transition to schizophrenia and other long-lasting non-affective psychoses in first-episode patients with acute and transient psychotic disorders: A validation study

Background and objectives Almost half of the individuals with a first-episode of psychosis who initially meet criteria for acute and transient psychotic disorder (ATPD) will have had a diagnostic revision during their follow-up, mostly toward schizophrenia. This study aimed to determine the proportion of diagnostic transitions to schizophrenia and other long-lasting non-affective psychoses in patients with first-episode ATPD, and to examine the validity of the existing predictors for diagnostic shift in this population. Methods We designed a prospective two-year follow-up study for subjects with first-episode ATPD. A multivariate logistic regression analysis was performed to identify independent variables associated with diagnostic transition to persistent non-affective psychoses. This prediction model was built by selecting variables on the basis of clinical knowledge. Results Sixty-eight patients with a first-episode ATPD completed the study and a diagnostic revision was necessary in 30 subjects at the end of follow-up, of whom 46.7% transited to long-lasting non-affective psychotic disorders. Poor premorbid adjustment and the presence of schizophreniform symptoms at onset of psychosis were the only variables independently significantly associated with diagnostic transition to persistent non-affective psychoses. Conclusion Our findings would enable early identification of those inidividuals with ATPD at most risk for developing long-lasting non-affective psychotic disorders, and who therefore should be targeted for intensive preventive interventions. (AU)

Postbiotics of Lacticaseibacillus paracasei CECT 9610 and Lactiplantibacillus plantarum CECT 9608 attenuates store-operated calcium entry and FAK phosphorylation in colorectal cancer cells.

Store-operated Ca2+ entry (SOCE) is a major mechanism for Ca2+ influx in colorectal cancer (CRC) cells. This mechanism, regulated by the filling state of the intracellular Ca2+ stores, is mediated by the endoplasmic reticulum Ca2+ sensors of the stromal interaction molecules (STIM) family [stromal interaction molecule 1 (STIM1) and STIM2] and the Ca2+-release-activated Ca2+ channels constituted by Orai family members, with predominance of calcium release-activated calcium channel protein 1 (Orai1). CRC cells exhibit enhanced SOCE due to remodeling of the expression of the key SOCE molecular components. The enhanced SOCE supports a variety of cancer hallmarks. Here, we show that treatment of the colorectal adenocarcinoma cell lines HT-29 and Caco-2 with inanimate Lacticaseibacillus paracasei (CECT9610) and Lactiplantibacillus plantarum (CECT9608) attenuates SOCE, although no detectable effect is seen on SOCE in normal colon mucosa cells. The effect of Lacticaseibacillus paracasei and Lactiplantibacillus plantarum postbiotics was mediated by downregulation of Orai1 and STIM1, while the expression levels of Orai3 and STIM2 remained unaltered. Treatment of HT-29 and Caco-2 cells with inanimate Lacticaseibacillus paracasei and Lactiplantibacillus plantarum impairs in vitro migration by a mechanism likely involving attenuation of focal adhesion kinase (FAK) tyrosine phosphorylation. Cell treatment with the Orai1 inhibitor synta-66 attenuates SOCE and prevents any further effect of Lacticaseibacillus paracasei and Lactiplantibacillus plantarum postbiotics. Together, our results indicate for the first time that Lacticaseibacillus paracasei and Lactiplantibacillus plantarum postbiotics selectively exert negative effects on Ca2+ influx through SOCE in colorectal adenocarcinoma cell lines, providing evidence for an attractive strategy against CRC.

Proxy measures for the assessment of psychotic and affective symptoms in studies using electronic health records.

BACKGROUND: There is a lack of standardised psychometric data in electronic health record (EHR)-based research. Proxy measures of symptom severity based on patients' clinical records may be useful surrogates in mental health EHR research. AIMS: This study aimed to validate proxy tools for the short versions of the Positive and Negative Syndrome Scale (PANSS-6), Young Mania Rating Scale (YMRS-6) and Montgomery-Åsberg Depression Rating Scale (MADRS-6). METHOD: A cross-sectional, multicentre study was conducted in a sample of 116 patients with first-episode psychosis from 12 public hospitals in Spain. Concordance between PANSS-6, YMRS-6 and MADRS-6 scores and their respective proxies was evaluated based on information from EHR clinical notes, using a variety of statistical procedures, including multivariate tests to adjust for potential confounders. Bootstrapping techniques were used for internal validation, and an independent cohort from the Treatment and Early Intervention in Psychosis Program (TIPP-Lausanne, Switzerland) for external validation. RESULTS: The proxy versions correlated strongly with their respective standardised scales (partial correlations ranged from 0.75 to 0.84) and had good accuracy and discriminatory power in distinguishing between patients in and not in remission (percentage of patients correctly classified ranged from 83.9 to 91.4% and bootstrapped optimism-corrected area under the receiver operating characteristic curve ranged from 0.76 to 0.89), with high interrater reliability (intraclass correlation coefficient of 0.81). The findings remained robust in the external validation data-set. CONCLUSIONS: The proxy instruments proposed for assessing psychotic and affective symptoms by reviewing EHR provide a feasible and reliable alternative to traditional structured psychometric procedures, and a promising methodology for real-world practice settings.

Characterization of the immunosuppressive environment induced by larval Echinococcus granulosus during chronic experimental infection.

The larval stage of Echinococcus granulosus causes the chronic infection known as cystic echinococcosis, deploying strong inhibitory mechanisms on host immune responses. Using experimental intraperitoneal infection in C57BL/6 mice, we carried out an in-depth analysis of the local changes in macrophage populations associated with chronic infection. In addition, we analyzed T cells and relevant soluble mediators. Infected animals showed an increase in local cell numbers, mostly accounted for by eosinophils, T cells, and macrophages. Within macrophage populations, the largest increases in cell numbers corresponded to resident large peritoneal macrophages (LPM). Monocyte recruitment appeared to be active, as judged by the increased number of monocytes and cells in the process of differentiation towards LPM, including small (SPM) and converting peritoneal macrophages (CPM). In contrast, we found no evidence of macrophage proliferation. Infection induced the expression of M2 markers in SPM, CPM, and LPM. It also enhanced the expression of the co-inhibitor PD-L1 in LPM, SPM, and CPM and induced the co-inhibitor PD-L2 in SPM and CPM. Therefore, local macrophages acquire M2-like phenotypes with probable suppressive capacities. Regarding T cells, infection induced an increase in the percentage of CD4+ cells that are PD-1+, which represent a potential target of suppression by PD-L1+/PD-L2+ macrophages. In possible agreement, CD4+ T cells from infected animals showed blunted proliferative responses to in vitro stimulation with anti-CD3. Further evidence of immune suppression in the parasite vicinity arose from the observation of an expansion in FoxP3+ CD4+ regulatory T cells and increases in the local concentrations of the anti-inflammatory cytokines TGF-ß and IL-1Ra.

Effects of Inspiratory Muscle Training on Physiological Performance Variables in Women's Handball.

Inspiratory muscle training (IMT) has been used in different sports, although there is no consensus on its benefits. We investigated the effects of eight weeks of IMT in women's handball. Twenty-four players were randomly distributed into experimental (EXP; n = 13) and control (CON; n = 11) groups. Only the EXP group performed IMT using the POWERBreathe device, following indications of the manufacturers. Before and after the intervention, spirometric variables were evaluated at rest and during a graded test using direct analysis of respiratory gases. Perception of exertion at submaximal intensity was also determined. No significant differences were observed post- vs. pre-intervention (p ≥ 0.05) regarding forced vital capacity (FVC), forced expiratory volume in the 1st second (VEF1), FVC/VEF1, maximal expiratory flow at 50% of FVC or peak inspiratory flow. Post-intervention, only the CON group increased their absolute and relative VO2max (2.1 ± 0.2 L/min pre vs. 2.2 ± 0.3 L/min post; 33.6 ± 3.6 ml/kg∙min pre vs. 34.5 ± 3.2 ml/kg∙min post, respectively). No significant improvements (p ≥ 0.05) were observed in VO2 associated with ventilatory threshold 1 (VT1), nor in the intensity associated with VO2max and VT1. However, there was a tendency for the mentioned variables to decrease in the CON group, while in the EXP group the trend was to maintain or increase previous values. IMT did not determine an improvement in the perception of exertion at submaximal intensity. The use of POWERBreathe, as described in the present study, is feasible in terms of time and effort, although its benefits may not be significant.

Spatial patterns associated with the distribution of immature stages of Aedes aegypti in three dengue high-risk municipalities of Southwestern Colombia.

Aedes aegypti mosquitoes are the main vector of human arbovirosis in tropical and subtropical areas. Their adaptation to urban and rural environments generates infestations inside households. Therefore, entomological surveillance associated with spatio-temporal analysis is an innovative approach for vector control and dengue management. Here, our main aim was to inspect immature pupal stages in households belonging to municipalities at high risk of dengue in Cauca, Colombia, by implementing entomological indices and relating how they influence adult mosquitos' density. We provide novel data for the geographical distribution of 3,806 immature pupal stages of Ae. aegypti. We also report entomological indices and spatial characterization. Our results suggest that, for Ae. aegypti species, pupal productivity generates high densities of adult mosquitos in neighbouring households, evidencing seasonal behaviour. Our dataset is essential as it provides an innovative strategy for mitigating vector-borne diseases using vector spatial patterns. It also delineates the association between these vector spatial patterns, entomological indicators, and breeding sites in high-risk neighbourhoods.

The Ca2+ Sensor STIM in Human Diseases.

The STIM family of proteins plays a crucial role in a plethora of cellular functions through the regulation of store-operated Ca2+ entry (SOCE) and, thus, intracellular calcium homeostasis. The two members of the mammalian STIM family, STIM1 and STIM2, are transmembrane proteins that act as Ca2+ sensors in the endoplasmic reticulum (ER) and, upon Ca2+ store discharge, interact with and activate the Orai/CRACs in the plasma membrane. Dysregulation of Ca2+ signaling leads to the pathogenesis of a variety of human diseases, including neurodegenerative disorders, cardiovascular diseases, cancer, and immune disorders. Therefore, understanding the mechanisms underlying Ca2+ signaling pathways is crucial for developing therapeutic strategies targeting these diseases. This review focuses on several rare conditions associated with STIM1 mutations that lead to either gain- or loss-of-function, characterized by myopathy, hematological and immunological disorders, among others, and due to abnormal activation of CRACs. In addition, we summarize the current evidence concerning STIM2 allele duplication and deletion associated with language, intellectual, and developmental delay, recurrent pulmonary infections, microcephaly, facial dimorphism, limb anomalies, hypogonadism, and congenital heart defects.

Daily dataset of precipitation and temperature in the Department of Cauca, Colombia.

This study used the geostatistical Kriging methodology to reduce the spatial scale of a host of daily meteorological variables in the Department of Cauca (Colombia), namely, total precipitation and maximum, minimum, and average temperature. The objective was to supply a high-resolution database from 01/01/2015 to 31/12/2021 in order to support the climate component in a project led by the National Institute of Health (INS) named "Spatial Stratification of dengue based on the identification of risk factors: a pilot study in the Department of Cauca". The scaling process was applied to available databases from satellite information and reanalysis sources, specifically, CHIRPS (Climate Hazards Group InfraRed Precipitation with Station Data), ERA5-Land (European Centre for Medium-Range Weather Forecasts), and MSWX (Multi-Source Weather). The 0.1° resolution offered by both the MSWX and ERA5-Land databases and the 0.05° resolution found in CHIRPS, was successfully reduced to a scale of 0.01° across all variables. Statistical metrics such as Root Mean Squared Error (RMSE), Mean Absolute Error (MAE), Person Correlation Coefficient (r), and Mean Bias Error (MBE) were used to select the database that best estimated each variable. As a result, it was determined that the scaled ERA5-Land database yielded the best performance for precipitation and minimum daily temperature. On the other hand, the scaled MSWX database showed the best behavior for the other two variables of maximum temperature and daily average temperature. Additionally, using the scaled meteorological databases improved the performance of the regression models implemented by the INS for constructing a dengue early warning system.

Spatial patterns associated with the distribution of immature stages of Aedes aegypti in three high-risk dengue municipalities of Southwestern Colombia / Patrones espaciales asociados a la distribución de estadios inmaduros de Aedes aegypti en tres municipios de alto riesgo para el departamento del Cauca, Colombia

Aedes aegypti mosquitoes are the main vector of human arbovirosis in tropical and subtropical areas.  Its adaptation to urban and rural environments generates infestations inside households. Therefore, entomological surveillance in association with spatio-temporal analysis is an innovative approach to vector control and dengue management. The main aim was to inspect immature pupal stages in households belonging to municipalities at high risk of dengue in Cauca, Colombia by implementing entomological indices and relating how they influence adult mosquito density. Here, we provide novel data for the geographical distribution of 3,806 immature pupal stages of Ae. aegypti. We also report entomological indices and spatial characterization. The results suggest that for Ae. aegypti species, pupal productivity generates high densities of adults in neighbouring households, evidencing seasonal behaviour. This dataset is of great importance as it provides an innovative strategy for vector-borne disease mitigation using vector spatial patterns and their association with entomological indicators and breeding sites in high-risk neighbourhoods.

Los mosquitos Aedes aegypti son el principal vector de las arbovirosis humanas en zonas tropicales y subtropicales. Su adaptación a entornos urbanos y rurales genera infestaciones en el intradomicilio de las viviendas. De aquí que, la vigilancia entomológica en asociación con el análisis espacial y el análisis espacio-temporal sean un enfoque innovador para el control de vectores y la gestión del dengue.El objetivo principal de la investigación fue realizar una comparación de la vigilancia entomológica, mediante el uso de índices cuantitativos de pupas y de adultos en tres municipios de alto riesgo de dengue Patía (El Bordo), Miranda y Piamonte del departamento del Cauca, con el fin de examinar cómo influye la productividad de pupas, entre índices entomológicos, en la densidad de mosquitos adultos y otros patrones espaciales y temporales. Ae. aegypti , sus índices entomológicos y su caracterización espacial. Los resultados sugieren que, para las especies de Ae. aegypti , la productividad de pupas genera altas densidades de adultos en las viviendas vecinas, evidenciando un comportamiento estacional.Estos resultados son de gran importancia ya que proporciona una estrategia innovadora para la mitigación de enfermedades transmitidas por vectores utilizando patrones espaciales de los vectores y su asociación con indicadores entomológicos y lugares de cría en barrios de alto riesgo para la transmisión del dengue.

Transdiagnostic Study of Impulsivity and Self-Injurious Behaviour in Unstable and Impulsive Disorders.

High comorbidity between borderline personality disorder (BPD) and eating disorders (ED) shows the necessity of developing transdiagnostic models, where impulsivity could play a relevant role in the manifestations of self-injurious behaviour.

Estudio Transdiagnóstico de la Impulsividad y de la Conducta Autolítica en los Trastornos Impulsivos e Inestables / Transdiagnostic study of impulsivity and self-injurious behavior in unstable and impulsive disorders

Introducción. La elevada comorbilidad entre el trastorno límite de la personalidad (TLP) y los trastornos de la conducta alimentaria (TCA) pone de manifiesto la necesidad de establecer modelos transdiagnósticos, donde la impulsividad podría tener un papel relevante en las manifestaciones dela conducta autolítica. Objetivos: 1) Comparar los niveles de impulsividad y conducta autolítica entre personas con TLP, personas con TCA y controles. 2) Predecir la presencia de conductas autolíticas a partir de la impulsividad y otras variables clínicas relevantes, como la vivencia de acontecimientos traumáticos y la sensibilidad al rechazo. Método. 108 mujeres (23 controles; 29 con diagnóstico de TCA restrictivo (TCAr); 21 con diagnóstico de TCA purgativo (TCAp); y 35 con diagnóstico de TLP) fueron evaluadas a través de la Escala de Impulsividad de Barratt, el Cuestionario para Experiencias Traumáticas y el Cuestionario de Sensibilidad al Rechazo. La información sobre conducta autolítica fue recogida a través de entrevista e historia clínica. Resultados. Se encontraron diferencias en las puntuaciones de impulsividad y conducta autolítica entre los grupos, encontrándose mayor impulsividad en los grupos TLP y TCAp, y mayores índices de conducta autolítica en el grupo TLP seguido de ambos grupos de TCA. Por otro lado, la impulsividad predecía los intentos de suicidio, y junto con la sensibilidad al rechazo interpersonal predecía las autolesiones no suicidas (ANS).Conclusión. La impulsividad es una variable dimensional en el TLP y en los TCA, que a su vez juega un papel relevante en la predicción de las conductas autolíticas. (AU)

Introduction. High comorbidity between borderline personality disorder (BPD) and eating disorders (ED) shows the necessity of developing transdiagnostic models, where impulsivity could play a relevant role in the manifestations ofself-injurious behaviour. Objectives: 1) To compare the levelsof impulsivity and self-injurious behaviour among peoplewith BPD, people with ED and controls. 2) To predict the presence of self-injurious behaviour based on impulsivity andother relevant clinical variables, such as the experience oftraumatic events and sensitivity to rejection. Methods. 108 women (23 controls; 29 with a diagnosis of restrictive ACT (rED); 21 with a diagnosis of purgative ACT(pED); and 35 with a diagnosis of BPD) were assessed usingthe Barratt Impulsivity Scale, the Traumatic Experiences Questionnaire and the Sensitivity to Rejection Questionnaire. Information about self-injurious behaviour was collectedthrough interview and clinical history. Results. Differences in impulsivity and self-injurious behaviour scores were found between the groups, with higherimpulsivity in the BPD and pED groups, and higher rates ofself-injurious behaviour in the BPD group followed by both ED groups. On the other hand, impulsivity predicted suicideattempts, and together with sensitivity to interpersonal rejection predicted nonsuicidal self-harm (NSSH). Conclusion. Impulsivity is a dimensional variable in BPD and ED, which in turn plays a relevant role in the prediction of self-injurious behaviour. (AU)

Mucins Shed from the Laminated Layer in Cystic Echinococcosis Are Captured by Kupffer Cells via the Lectin Receptor Clec4F.

Cystic echinococcosis is caused by the larval stages (hydatids) of cestode parasites belonging to the species cluster Echinococcus granulosus sensu lato, with E. granulosus sensu stricto being the main infecting species. Hydatids are bladderlike structures that attain large sizes within various internal organs of livestock ungulates and humans. Hydatids are protected by the massive acellular laminated layer (LL), composed mainly of mucins. Parasite growth requires LL turnover, and abundant LL-derived particles are found at infection sites in infected humans, raising the question of how LL materials are dealt with by the hosts. In this article, we show that E. granulosus sensu stricto LL mucins injected into mice are taken up by Kupffer cells, the liver macrophages exposed to the vascular space. This uptake is largely dependent on the intact mucin glycans and on Clec4F, a C-type lectin receptor which, in rodents, is selectively expressed in Kupffer cells. This uptake mechanism operates on mucins injected both in soluble form intravenously (i.v.) and in particulate form intraperitoneally (i.p.). In mice harboring intraperitoneal infections by the same species, LL mucins were found essentially only at the infection site and in the liver, where they were taken up by Kupffer cells via Clec4F. Therefore, shed LL materials circulate in the host, and Kupffer cells can act as a sink for these materials, even when the parasite grows in sites other than the liver.

Fear-Avoidance Beliefs Are Associated with Pain Intensity and Shoulder Disability in Adults with Chronic Shoulder Pain: A Cross-Sectional Study.

Shoulder pain is one of the most common musculoskeletal conditions, and for people over 40 years old, it represents the musculoskeletal pain with the greatest impact on quality of life. Psychological factors, such as fear-avoidance beliefs, are associated with musculoskeletal pain, and several studies suggest that they can influence various treatment outcomes. Our objective was to explore the cross-sectional association between fear-avoidance beliefs and shoulder pain intensity and disability in subjects with chronic shoulder pain. A cross-sectional study was conducted, and 208 participants with chronic unilateral subacromial shoulder pain were recruited. The shoulder pain and disability index assessed pain intensity and disability. The Spanish fear-avoidance components scale assessed the presence of fear-avoidance beliefs. The association between fear-avoidance beliefs and pain intensity and disability was analyzed by means of multiple linear regression models and proportional odds models, reporting odds ratios and 95% confidence intervals. Shoulder and pain disability scores were significantly associated with fear-avoidance beliefs (p < 0.0001, adjusted R-square 0.93, multiple linear regression). There was no evidence of an association between sex and age in this study. The regression coefficient for shoulder pain intensity and disability score was 0.67446. The proportional odds model showed an odds ratio of 1.39 (1.29-1.50) for shoulder pain intensity and disability total score. This study suggests that greater levels of fear-avoidance beliefs are associated with greater levels of shoulder pain and disability in adults with chronic shoulder pain.

Immunology of a unique biological structure: the Echinococcus laminated layer.

The larval stages of the cestode parasites belonging to the genus Echinococcus grow within internal organs of humans and a range of animal species. The resulting diseases, collectively termed echinococcoses, include major neglected tropical diseases of humans and livestock. Echinococcus larvae are outwardly protected by the laminated layer (LL), an acellular structure that is unique to this genus. The LL is based on a fibrillar meshwork made up of mucins, which are decorated by galactose-rich O-glycans. In addition, in the species cluster termed E. granulosus sensu lato, the LL features nano-deposits of the calcium salt of myo-inositol hexakisphosphate (Insp6). The main purpose of our article is to update the immunobiology of the LL. Major recent advances in this area are (i) the demonstration of LL "debris" at the infection site and draining lymph nodes, (ii) the characterization of the decoy activity of calcium Insp6 with respect to complement, (iii) the evidence that the LL mucin carbohydrates interact specifically with a lectin receptor expressed in Kupffer cells (Clec4F), and (iv) the characterization of what appear to be receptor-independent effects of LL particles on dendritic cells and macrophages. Much information is missing on the immunology of this intriguing structure: we discuss gaps in knowledge and propose possible avenues for research.

Role of Orai-family channels in the activation and regulation of transcriptional activity.

Store operated Ca2+ entry (SOCE) is a cornerstone for the maintenance of intracellular Ca2+ homeostasis and the regulation of a variety of cellular functions. SOCE is mediated by STIM and Orai proteins following the activation of inositol 1,4,5-trisphosphate receptors. Then, a reduction of the endoplasmic reticulum intraluminal Ca2+ concentration is sensed by STIM proteins, which undergo a conformational change and activate plasma membrane Ca2+ channels comprised by Orai proteins. STIM1/Orai-mediated Ca2+ signals are finely regulated and modulate the activity of different transcription factors, including certain isoforms of the nuclear factor of activated T-cells, the cAMP-response element binding protein, the nuclear factor κ-light chain-enhancer of activated B cells, c-fos, and c-myc. These transcription factors associate SOCE with a plethora of signaling events and cellular functions. Here we provide an overview of the current knowledge about the role of Orai channels in the regulation of transcription factors through Ca2+ -dependent signaling pathways.

Longitudinal trajectories in negative symptoms and changes in brain cortical thickness: 10-year follow-up study.

BACKGROUND: Understanding the evolution of negative symptoms in first-episode psychosis (FEP) requires long-term longitudinal study designs that capture the progression of this condition and the associated brain changes. AIMS: To explore the factors underlying negative symptoms and their association with long-term abnormal brain trajectories. METHOD: We followed up 357 people with FEP over a 10-year period. Factor analyses were conducted to explore negative symptom dimensionality. Latent growth mixture modelling (LGMM) was used to identify the latent classes. Analysis of variance (ANOVA) was conducted to investigate developmental trajectories of cortical thickness. Finally, the resulting ANOVA maps were correlated with a wide set of regional molecular profiles derived from public databases. RESULTS: Three trajectories (stable, decreasing and increasing) were found in each of the three factors (expressivity, experiential and attention) identified by the factor analyses. Patients with an increasing trajectory in the expressivity factor showed cortical thinning in caudal middle frontal, pars triangularis, rostral middle frontal and superior frontal regions from the third to the tenth year after the onset of the psychotic disorder. The F-statistic map of cortical thickness expressivity differences was associated with a receptor density map derived from positron emission tomography data. CONCLUSIONS: Stable and decreasing were the most common trajectories. Additionally, cortical thickness abnormalities found at relatively late stages of FEP onset could be exploited as a biomarker of poor symptom outcome in the expressivity dimension. Finally, the brain areas with less density of receptors spatially overlap areas that discriminate the trajectories of the expressivity dimension.

Brain matrix metalloproteinase-9 activity is altered in the corticosterone mouse model of depression.

Major depressive disorder is a highly prevalent psychiatric condition. Metalloproteinase 9 (MMP-9), a gelatinase involved in synaptic plasticity, learning and memory processes, is elevated in both chronic stress animal models and human peripheral blood samples of depressed patients. In this study we have evaluated the MMP-9 activity and protein expression in brain areas relevant to depression using the chronic corticosterone mouse model of depression. These mice show a depressive- and anxious-like behaviour. The MMP-9 activity and protein levels are significantly elevated in both the hippocampus and the cortex, and nectin-3 levels are lower in these brain areas in this model. In particular, these mice display an increased gelatinase activity in the CA1 and CA3 subfields of the hippocampus and in the internal layer of the prefrontal cortex. Moreover, the immobility time in the tail suspension test presents a positive correlation with the cortical MMP-9 activity, and a negative correlation with nectin-3 levels. In conclusion, the chronic corticosterone model of depression leads to an increase in the protein expression and activity of MMP-9 and a reduction of its substrate nectin-3 in relevant areas implicated in this disease. The MMP-9 activity correlates with behavioural despair in this model of depression. All these findings support the role of MMP-9 in the pathophysiology of depression, and as a putative target to develop novel antidepressant drugs.

Executive dysfunction in eating disorders: Relationship with clinical features.

Eating disorders (ED) are severe mental disorders that may result in significant functional impairment and disability. Neuropsychological studies have consistently found impaired executive function (EF) among ED patients. EF is particularly involved in fundamental skills of daily living and in behavioral and emotional regulation. In this study, impairment of executive functioning is investigated in patients with eating disorders and the associations with clinical features and clinical subtypes are analyzed. METHOD: 75 female patients (m = 22.01 years, sd = 9.15) with eating disorder (43 restrictive anorexia, 30 binge-eating anorexia and 13 bulimia nervosa) and 37 healthy controls (m = 18.54 years, sd = 4.21) were included in the study. An extensive assessment of executive function domains (verbal fluency, set shifting, attention span, selective attention, working memory, inhibitory control and processing speed) was carried out in both groups. Clinical scales for food intake restriction, binge-eating/purging, depression, anxiety and impulsivity were also administered and correlated with scores on executive function tests. RESULTS: Patients with an ED had significantly lower scores than healthy controls in performance of several executive function tests, particularly in set shifting, interference control and processing speed (p < .01, in all three domains). Executive function impairment was related to anxious, depressive and eating disorder symptoms (p < .05), regardless of clinical subtype. CONCLUSIONS: Executive function impairment in eating disorders is associated with greater ED symptomatic severity and might involve a negative treatment outcome. Therefore, cognitive remediation techniques should probably be considered in a number of severe patients with ED.