Chitosan-based oral hydrogel formulations of ß-galactosidase to improve enzyme supplementation therapy for lactose intolerance.

ß-Galactosidase supplementation plays an important role in the life of people with lactose intolerance. However, these formulations are rendered ineffective by the low pH and pepsin in the stomach and pancreatic proteases in the intestine. Therefore, it is necessary to develop oral transport systems for carrying this enzyme in the active form up to the intestine, where the lactose digestion occurs. In this research, a new hydrogel was developed that could potentially be used for enzyme supplement therapy. In this regard, the chitosan-based ß-Gal formulations described in the manuscript are an alternative long-acting preparation to the so far available preparations that allow for enzyme protection and mucosal targeting. These hydrogels were prepared from chitosan and polyethylene glycol and contained a covalently immobilized ß-galactosidase from Aspergillus oryzae. The ß-galactosidase in the hydrogel was protected from degradation in a gastric medium at a pH of 2.5 and retained 75 % of its original activity under subsequent intestinal conditions. In the case of a simulated gastric fluid with a pH of 1.5, a copolymer containing methacrylic acid functional groups was sufficient to protect the hybrid hydrogel from the extremely acidic pH. In addition, the surface of the hydrogel was chemically modified with thiol and amidine groups, which increased the binding to intestinal mucin by 20 % compared with the unmodified hydrogel. These results represent a promising approach for oral transport as a reservoir for ß-galactosidase in the small intestine to reduce the symptoms of hypolactasia.

From the problem to the solution: Chitosan valorization cycle.

The problem of fisheries waste has increased in recent years and has become a global problem influenced by various biological, technical, operational and socioeconomic factors. In this context, the use of these residues as raw materials is a proven approach not only to reduce the crisis of unprecedented magnitude facing the oceans, but also to improve the management of marine resources and increase the competitiveness of the fisheries sector. However, the implementation of valorization strategies at the industrial level is being excessively slow, despite this great potential. Chitosan, a biopolymer extracted from shellfish waste, is a clear example of this because although countless chitosan-based products have been described for a wide variety of applications, commercial products are still limited. To address this drawback, it is essential to consolidate a "bluer" chitosan valorization cycle towards sustainability and circular economy. In this perspective we wanted to focus on the cycle of valorization of chitin, which allows to transform a waste product (chitin) into a material suitable for the development of useful products to solve the source of its origin as a waste product and pollutant; chitosan-based membranes for wastewater remediation.

Design of a biocatalytic cascade for the enzymatic sulfation of unsulfated chondroitin with in situ generation of PAPS.

Sulfation of molecules in living organisms is a process that plays a key role in their functionality. In mammals, the sulfation of polysaccharides (glycosaminoglycans) that form the proteoglycans present in the extracellular matrix is particularly important. These polysaccharides, through their degree and sulfation pattern, are involved in a variety of biological events as signal modulators in communication processes between the cell and its environment. Because of this great biological importance, there is a growing interest in the development of efficient and sustainable sulfation processes, such as those based on the use of sulfotransferase enzymes. These enzymes have the disadvantage of being 3'-phosphoadenosine 5'-phosphosulfate (PAPS) dependent, which is expensive and difficult to obtain. In the present study, a modular multienzyme system was developed to allow the in situ synthesis of PAPS and its coupling to a chondroitin sulfation system. For this purpose, the bifunctional enzyme PAPS synthase 1 (PAPSS1) from Homo sapiens, which contains the ATP sulfurylase and APS kinase activities in a single protein, and the enzyme chondroitin 4-O-sulfotransferase (C4ST-1) from Rattus norvegicus were overexpressed in E. coli. The product formed after coupling of the PAPS generation system and the chondroitin sulfation module was analyzed by NMR.

Fast and Sustained Axonal Growth by BDNF Released from Chitosan Microspheres.

Brain-derived neurotrophic factor (BDNF) regulates dendritic branching and dendritic spine morphology, as well as synaptic plasticity and long-term potentiation. Consequently, BDNF deficiency has been associated with some neurological disorders such as Alzheimer's, Parkinson's or Huntington's diseases. In contrast, elevated BDNF levels correlate with recovery after traumatic central nervous system (CNS) injuries. The utility of BDNF as a therapeutic agent is limited by its short half-life in a pathological microenvironment and its low efficacy caused by unwanted consumption of non-neuronal cells or inappropriate dosing. Here, we tested the activity of chitosan microsphere-encapsulated BDNF to prevent clearance and prolong the efficacy of this neurotrophin. Neuritic growth activity of BDNF release from chitosan microspheres was observed in the PC12 rat pheochromocytoma cell line, which is dependent on neurotrophins to differentiate via the neurotrophin receptor (NTR). We obtained a rapid and sustained increase in neuritic out-growth of cells treated with BDNF-loaded chitosan microspheres over control cells (p < 0.001). The average of neuritic out-growth velocity was three times higher in the BDNF-loaded chitosan microspheres than in the free BDNF. We conclude that the slow release of BDNF from chitosan microspheres enhances signaling through NTR and promotes axonal growth in neurons, which could constitute an important therapeutic agent in neurodegenerative diseases and CNS lesions.

[Summary PAPPS Childhood and Adolescence 2022]. / Resumen PAPPS Infancia y Adolescencia 2022.

Two important topics about children and adolescents in our primary care activity are presented in this update document: tobacco smoking prevention in adolescence and prophylaxis with vitamin K to prevent the hemorrhagic disease of the newborn.

What gypsy mothers say about breastfeeding.

OBJECTIVE: To know and deepen in the evaluation, and experience of gypsy women with breastfeeding. METHOD: Qualitative study with an interpretative phenomenological approach, through a focus group with the participation of six mothers of gypsy ethnicity, users of the Fuente de San Luis Health Center in the city of Valencia. RESULTS: The barriers described by these mothers regarding breastfeeding refer to a lack of family support, an association of breastfeeding to sacrifice and to the dependence of the baby to the breast. From the accounts of these mothers it is perceived, a disinterest in breastfeeding and a lack of confidence in their own bilogy, which together with a low participation in maternal education activities, have meant the barriers that have mostly limited and largely hindered breastfeeding in this group of mothers. CONCLUSIONS: It would be desirable to implement improvement actions that would pay more attention to promote, protect and support breastfeeding in this group.

Chitosan sulfate-lysozyme hybrid hydrogels as platforms with fine-tuned degradability and sustained inherent antibiotic and antioxidant activities.

The control of the properties and biological activities of chitosan-lysozyme hybrid hydrogels to exploit their interesting biomedical applications depends largely on the chitosan acetylation pattern, a difficult parameter to control. Herein, we have prepared sulfated chitosan-lysozyme hydrogels as versatile platforms with fine-tuned degradability and persistent bactericidal and antioxidant properties. The use of chitosan sulfates instead of chitosan has the advantage that the rate and mechanisms of lysozyme release, as well as antibacterial and antioxidant activities, depend on the sulfation profile, a structural parameter that is easily controlled by simple chemical modifications. Thus, while 6-O-sulfated chitosan hydrogels allow the release of loaded lysozyme in a short time (60% in 24 h), due to a high rate of degradation that allows rapid antibiotic and antioxidant activities, in 3-O-sulfated systems there is a slow release of lysozyme (80% in 21 days), resulting in long-lasting antibiotic and antioxidant activities.

Does COVID-19 psychological fatigue exist? Results of three online cross-sectional studies conducted in Spain from April 2020 to March 2021.

Background: A previously published meta-analysis found that about one-third of the general population experienced some mental health problem during the early phase of the COVID-19 pandemic, potentially leading to a late mental health crisis. We aimed to describe the acute, short-term, and long-term effects of the COVID-19 pandemic on mental health. Methods: A one-year online survey (S) was conducted in Spain (April 2020 - March 2021). We recruited 18 180 subjects using a virtual respondent-driven snowball sampling method (S1 April 2020, n = 6108; S2 October-November 2020, n = 6418; S3 March 2021, n = 5654). Participants completed the Spanish Depression, Anxiety, and Stress Scale (DASS-21). Results: Overall, our results suggest a progressive increase in the prevalence of anxiety and stress throughout the pandemic waves and relative stability of depression. Women had a greater probability of having depression, anxiety, or stress than men in each survey (P < 0.001). The youngest group (aged 18-24) reported a higher probability (P < 0.05) of having depression, anxiety, or stress than the older groups in S1 and S2. Middle-aged people (25-59) had a greater probability of being a case in the DASS-21 scales than the oldest group (60+), except for depression in men (P = 0.179). In S3, the trend changed: the youngest group showed a decrease in depression and stress while the oldest group showed a dramatic increase (anxiety: men = 664.5%, women = 273.52%; stress: men = 786%, women = 431.37%). Conclusions: It is plausible to conclude that COVID-19 psychological fatigue exists, especially in middle-aged and older adults. Strategies to assist people who have fewer coping skills should be implemented in the near future.

Early Impact of the COVID-19 Outbreak on Sleep in a Large Spanish Sample.

INTRODUCTION: Coronavirus disease 2019 (COVID-19) forced Spain to implement unprecedented lockdown restriction. In this context, different factors could worsen sleep quality, but the impact of the pandemic and lockdown on sleep is still mostly unknown. In this cross-sectional study, we describe self-reported sleep disturbances in people without mental health disorders from a large Spanish sample (n = 15,070). METHODS: During the early phase of the lockdown (19-26 March), an online survey was launched using a snowball sampling method and included sociodemographic and clinical data along with the Depression, Anxiety, and Stress Scale (DASS-21) and the Impact of Event Scale (IES). Two items of the IES were employed to assess sleep characteristics. Descriptive and bivariate analysis and logistic regression models were performed. RESULTS: Difficulty initiating or maintaining sleep were reported by 23.9% of the sample and was associated in the regression model with age (OR = 1.008, p = .003), female sex (OR = 1.344, p < .001), an income reduction >50% (OR = 1.248, p = .037), having one (OR = 1.208, p = .029) and two or more (OR = 1.299, p = .035) elderly dependents, drinking alcohol (OR = 1.129, p = .024), and a higher score on DASS-21 depression (OR = 1.148, p < .001), anxiety (OR = 1.218, p < .001), or stress (OR = 1.302, p < .001) subscales, whereas being able to enjoy free time (OR = 0.604, p < .001) and painting or listening to music (OR = 0.853, p = .012) were protective factors. Dreams related to COVID-19 were reported by 12.9% of the sample and were associated in the regression model with female sex (OR = 1.617, p < .001), being married (OR = 1.190, p = .015), self-employed (OR = 1.373, p = .032), or a civil servant (OR = 1.412, p = .010), having been tested for COVID-19 (OR = 1.583, p = .012), having infected family or friends (OR = 1.233, p = .001), reading news about coronavirus (OR = 1.139, p = .023), drinking alcohol (OR = 1.251, p < .001), and higher scores on DASS-21 depression (OR = 1.102, p < .001), anxiety (OR = 1.222, p < .001), or stress (OR = 1.213, p < .001) subscales, while protective factors were older age (OR = 0.983, p < .001) and being retired (OR = 0.625, p = .045). CONCLUSIONS: These findings could help clinicians and public health systems design and deliver tailored interventions, such as internet-delivered campaigns, to promote sleep quality in the general population.

Cognitive functioning after six months of follow-up in a sample of alcohol use disorder outpatients. / Funcionamiento cognitivo después de seis meses de seguimiento en una muestra de pacientes ambulatorios con trastorno por uso de alcohol.

Until now, no follow-up studies had simultaneously evaluated executive functions, other non-executive functions related cognitive functions, and impulsivity in a large enough sample of moderate to severe alcohol use disorder (AUD) patients. The main objective of the present study was to compare neuropsychological performance and its relation to alcohol use in patients with AUD and healthy controls, and to determine the evolution of cognitive impairment and alcohol use over time. For this purpose, a 6-month follow-up study was designed to compare a sample of 100 outpatients with AUD (DSM-5 criteria) with 100 matched healthy controls. The patient group was recruited from three different health centres in Spain located in Orense, Gijón and Barcelona. The assessment consisted of a systematic battery of cognitive tests to evaluate the following functions: attention, anterograde memory, processing speed, verbal fluency, executive function, and implicit attitude toward alcoholic beverages. We also compared clinical variables associated with alcohol use, such as alcohol craving and impulsivity. After 6 months, anterograde memory, working memory, and resistance to interference improved remarkably in AUD patients, although not enough to match the normal population. With regard to clinical variables, there was a small but significant cognitive improvement related to a reduction in alcohol use and impulsivity. Executive dysfunction and other non-executive functions related cognitive functions impairment can be considered prognostic factors in outpatients with moderate to severe AUD.

Hasta la fecha, ningún estudio de seguimiento había evaluado simultáneamente la función ejecutiva, otras funciones no ejecutivas relacionadas con funciones cognitivas y la impulsividad en una muestra suficientemente grande de pacientes con trastorno por uso de alcohol (TUA) entre moderado y grave. Este estudio tuvo como objetivo principal comparar el desempeño neuropsicológico y su relación con el uso de alcohol en pacientes con TUA y en controles sanos, y determinar la evolución del deterioro cognitivo y el uso de alcohol a largo plazo. Con este fin, se diseñó un estudio de seguimiento de seis meses para comparar una muestra de 100 pacientes ambulatorios con TUA (criterios del DSM-5) emparejados con 100 controles sanos. Los pacientes se reclutaron de tres centros sanitarios diferentes de España, Orense, Gijón y Barcelona. La evaluación consistió en una batería sistematizada de pruebas cognitivas para evaluar las siguientes funciones: atención, memoria anterógrada, velocidad de procesamiento, fluidez verbal, función ejecutiva y actitud implícita hacia bebidas alcohólicas. También se compararon variables clínicas asociadas al consumo de alcohol, como el craving y la impulsividad. Después de seis meses, la memoria anterógrada, memoria de trabajo y resistencia a la interferencia mejoraron notablemente en los pacientes con TUA, aunque no llegaron a igualar la población general. Respecto de las variables clínicas, hubo una pequeña pero significativa mejoría cognitiva relacionada con una reducción del consumo de alcohol y de la impulsividad. La disfunción ejecutiva y otras funciones no ejecutivas relacionadas con el deterioro cognitivo pueden considerarse factores pronósticos en pacientes ambulatorios con TUA entre moderado y grave.

Learning and verbal memory: A comparison between patients with alcohol use disorder and major depressive disorder. / Aprendizaje y memoria verbal: Comparación entre pacientes con trastorno por consumo de alcohol y trastorno de depresión mayor.

Brain damage related to alcohol consumption is associated with impairments in cognitive functions, among which memory and verbal learning stand out. The main objective is to evaluate memory and verbal learning in a sample of 111 patients with alcohol use disorder (AUD) versus 78 with major depressive disorder (MDD) and 100 healthy controls. The evaluation included sociodemographic and clinical variables, the Hamilton Depression Scale (HDRS) and the California Verbal Learning Test (CVLT). One-way ANOVA was used for comparisons between the 3 groups and two-way ANCOVAS including different covariates. The one-way ANOVA shows that patients with AUD and MDD had scores similar to each other and lower than those of the control group (p <0.001), with the exception of the Cued CVLT (worse scores in MDD vs AUD, p <0.001). After including age, sex and years of completed studies as covariates, the differences between the AUD and MDD groups persisted compared to the control group (p ≤ 0.003) in all indices except for the Immediate Free CVLT and the Cued CVLT (worse performance in MDD vs AUD, p = 0.022 and p = 0.035, respectively). In the second ANCOVA, after controlling for depression severity, differences were only detected between AUD patients and healthy controls (p ≤ 0.007). Patients with AUD present a significant impairment in learning and verbal memory when compared with patients with MDD and with healthy people.

El daño cerebral relacionado con el consumo de alcohol se asocia a alteraciones de las funciones cognitivas, entre las que destacan memoria y aprendizaje verbal. El objetivo principal es evaluar memoria y aprendizaje verbal en una muestra de 111 pacientes con trastorno por consumo de alcohol (TCA) versus 78 con trastorno de depresión mayor (TDM) y 100 controles sanos. La evaluación incluyó variables sociodemográficas y clínicas, la Escala de Hamilton para la Depresión (HDRS) y el Test de Aprendizaje Verbal de California (CVLT). Se utilizó ANOVA de un factor para comparaciones entre los 3 grupos y ANCOVAS bidireccionales incluyendo diferentes covariables. El ANOVA de un factor muestra que los pacientes con TCA y TDM obtienen puntuaciones similares entre sí e inferiores a las del grupo control (p < 0,001), con excepción del CVLT Guiado (peores puntuaciones en TDM vs TCA, p < 0,001). Tras incluir como covariables la edad, sexo y los años de estudios completados, persisten las diferencias entre los grupos de TCA y TDM frente al grupo control (p ≤ 0,003) en todos los índices con excepción del CVLT Libre Inmediato y del CVLT Guiado (peor rendimiento en TDM vs TCA, p = 0,022 y p = 0,035, respectivamente). En el segundo ANCOVA, tras controlar por gravedad de la depresión, únicamente se detectan diferencias entre los pacientes con TCA y los controles sanos (p ≤ 0,007). Los pacientes con TCA presentan una importante alteración en aprendizaje y memoria verbal al compararlos con pacientes con TDM y con personas sanas.

Heparanized chitosans: towards the third generation of chitinous biomaterials.

The functionalization of chitosans is an emerging research area in the design of solutions for a wide range of biomedical applications. In particular, the modification of chitosans to incorporate sulfate groups has generated great interest since they show structural similarity to heparin and heparan sulfates. Most of the biomedical applications of heparan sulfates are derived from their ability to bind different growth factors and other proteins, as through these interactions they can modulate the cellular response. This review aims to summarize the most recent advances in the synthesis, and structural and physicochemical characterization of heparanized chitosan, a remarkably interesting family of polysaccharides that have demonstrated the ability to mimic heparan sulfates as ligands for different proteins, thereby exerting their biological activity by mimicking the function of these glycosaminoglycans.

Preparation and Characterization of Aminoglycoside-Loaded Chitosan/Tripolyphosphate/Alginate Microspheres against E. coli.

Although aminoglycosides are one of the common classes of antibiotics that have been widely used for treating infections caused by pathogenic bacteria, the evolution of bacterial resistance mechanisms and their inherent toxicity have diminished their applicability. Biocompatible carrier systems can help sustain and control the delivery of antibacterial compounds while reducing the chances of antibacterial resistance or accumulation in unwanted tissues. In this study, novel chitosan gel beads were synthesized by a double ionic co-crosslinking mechanism. Tripolyphosphate and alginate, a polysaccharide obtained from marine brown algae, were employed as ionic cross-linkers to prepare the chitosan-based networks of gel beads. The in vitro release of streptomycin and kanamycin A was bimodal; an initial burst release was observed followed by a diffusion mediated sustained release, based on a Fickian diffusion mechanism. Finally, in terms of antibacterial properties, the particles resulted in growth inhibition of Gram-negative (E. coli) bacteria.

Deciphering Structural Determinants in Chondroitin Sulfate Binding to FGF-2: Paving the Way to Enhanced Predictability of their Biological Functions.

Controlling chondroitin sulfates (CSs) biological functions to exploit their interesting potential biomedical applications requires a comprehensive understanding of how the specific sulfate distribution along the polysaccharide backbone can impact in their biological activities, a still challenging issue. To this aim, herein, we have applied an "holistic approach" recently developed by us to look globally how a specific sulfate distribution within CS disaccharide epitopes can direct the binding of these polysaccharides to growth factors. To do this, we have analyzed several polysaccharides of marine origin and semi-synthetic polysaccharides, the latter to isolate the structure-activity relationships of their rare, and even unnatural, sulfated disaccharide epitopes. SPR studies revealed that all the tested polysaccharides bind to FGF-2 (with exception of CS-8, CS-12 and CS-13) according to a model in which the CSs first form a weak complex with the protein, which is followed by maturation to tight binding with k D ranging affinities from ~ 1.31 µM to 130 µM for the first step and from ~ 3.88 µM to 1.8 nM for the second one. These binding capacities are, interestingly, related with the surface charge of the 3D-structure that is modulated by the particular sulfate distribution within the disaccharide repeating-units.

Alcohol use and risk factors for self-harm behavior in Spanish adolescents. / Consumo de alcohol y factores de riesgo de conductas autolesivas en adolescentes españoles.

Self-harm behaviors in children and adolescents constitute an important public health problem with prevalence figures in the clinical population between 40 and 80%. The objectives of the study were to analyze and compare the Spanish sub-samples of two studies, SEYLE and WE-STAY to determine prevalence, self-harm patterns and factors associated with self-harm behaviors, notably the use of alcohol or drugs. The questionnaires used in both studies were the Global School Health Survey (GSHS), the Beck Depression Inventory (BDI-II), the Strengths and Difficulties Questionnaire (SDQ). The self-harm behaviors were evaluated with a modified 6-item version of s the Deliberate Self-Harm Inventory (DSHI). The independence of the study's categorical variables was assessed using the Chi-square test. The change in the relative risk of self-harm between the SEYLE study and WE-STAY was evaluated through the odds ratio (OR) calculation. Two different logistic regression models were calculated in order to establish the factors associated with self-harm behaviors in each study. In the present study, the rates of DSH vary according to study and sex, ranging from 0.58% to 2.08%, and different patterns of self-harm are evidenced by sex, with males self-injuring more frequently by self-inflicted blows and burns, while young women more often cut themselves. The presence of depressive symptoms and alcohol use were the factors most strongly associated with an increased risk of DSH.

Las conductas autolesivas en niños y adolescentes constituyen un importante problema de salud pública con cifras de prevalencia en la población clínica entre el 40 y 80%. Los objetivos del estudio son analizar y comparar las submuestras españolas de dos trabajos, SEYLE y WE-STAY, para conocer la prevalencia, los patrones de autolesión y los factores asociados a las conductas autolesivas, en particular el consumo de alcohol o drogas. Los cuestionarios utilizados en ambos estudios fueron la Encuesta Global de Salud Escolar (GSHS), el Inventario de Depresión de Beck (BDI-II), el Cuestionario de Fortalezas y Dificultades (SDQ). Los comportamientos autolesivos fueron evaluados con una versión modificada de 6 ítems basada en el Inventario de Autolesiones Deliberadas (DSHI). La independencia de las variables categóricas del estudio se evaluó mediante la prueba Ji-Cuadrado. El cambio en el riesgo relativo de autolesión entre el estudio SEYLE y WE-STAY, se evaluó a través del cálculo de odds ratio (OR). Se calcularon dos modelos de regresión logística diferentes con el fin de establecer los factores asociados con comportamientos autolesivos en cada estudio. En el presente estudio las tasas de DSH varían en función del estudio y del sexo en un rango entre 0,58% y 2,08%, presentando patrones de autolesiones diferentes según el sexo, los hombres se autolesionaron más frecuentemente mediante golpes autoinfligidos y quemaduras, mientras que las mujeres se hicieron más frecuentemente cortes. La presencia de síntomas depresivos y el consumo de alcohol fueron los factores asociados de forma más robusta a un mayor riesgo de DSH.

Suicidal behaviour and cognition: A systematic review with special focus on prefrontal deficits.

BACKGROUND: Suicide is a major health concern worldwide, thus, identifying risk factors would enable a more comprehensive understanding and prevention of this behaviour. Neuropsychological alterations could lead to difficulties in interpreting and managing life events resulting in a higher risk of suicide. METHOD: A systematic literature search from 2000 to 2020 was performed in Medline (Pubmed), Web of Science, SciELO Citation Index, PsycInfo, PsycArticles and Cochrane Library databases regarding studies comparing cognition of attempters versus non-attempters that share same psychiatric diagnosis. RESULTS: 1.885 patients diagnosed with an Affective Disorder (n = 1512) and Schizophrenia/ Schizoaffective Disorder (n = 373) were included. In general comparison, attention was found to be clearly dysfunctional. Regarding diagnosis, patients with Schizophrenia and previous history of suicidal behaviour showed a poorer performance in executive function. Patients with current symptoms of an Affective Disorder and a previous history of suicidal attempt had poorer performance in attention and executive function. Similarly, euthymic affective patients with history of suicidal behaviour had worse decision-making, attention and executive function performance compared to euthymic non-attempters. LIMITATIONS: The number of papers included in this review is limited to the few studies using non-attempter clinically-matched control group and therefore results regarding diagnosis, symptomatology and time of the attempt are modest and contradictory. CONCLUSIONS: Patients who have attempted suicide have a poorer neuropsychological functioning than non-attempters with a similar psychiatric disorder in attention and executive function. These alterations increase vulnerability for suicide.

The Mediating Role of Impulsivity in the Relationship Between Suicidal Behavior and Early Traumatic Experiences in Depressed Subjects.

Background: Depressed patients with early traumatic experiences may represent a clinically and biologically distinct subtype, with worse clinical outcomes and greater risk of suicide. Since early traumatic experiences alter development of systems that regulate the stress response, increasing sensitivity to stress and mood disorders later in life, certain personality features may influence coping strategies, putting individuals with depression and a history of early traumatic experiences at greater risk of suicidal behavior. Objective: To determine whether impulsivity mediates the relationship between early traumatic experiences and suicidal behavior in patients with major depressive disorder (MDD). Methods: The total sample consists of 190 patients [mean age (SD) = 53.71 (10.37); females: 66.3%], with current MDD (DSM-5 criteria). The Childhood Trauma Questionnaire-Short Form (CTQ-SF), the List of Threatening Experiences (LTE), and the Barratt Impulsiveness Scale-11 (BIS-11) were used to assess childhood and adulthood adverse life events and impulsivity, respectively. We developed mediation models by bootstrap sampling methods. Results: Eighty-one (42.6%) patients had a history of previous suicide attempts (SA). CTQ-SF-Total and BIS-11-Total scores were significantly higher in MDD patients with previous SA. Correlation analyses revealed significant correlations between the CTQ-SF-Total and BIS-11-Total, CTQ-SF-Total and HDRS-Total, and BIS-11-Total and HDRS-Total scores. Regression models found that CTQ-SF-Total, BIS-11-Total, and HDRS-Total scores were associated with SA. Mediation analyses further revealed the association between CTQ-SF-Total and SA was mediated by the indirect effect of the BIS-11-Total score (b = 0.007, 95% CI = 0.001, 0.015), after statistically controlling for sex, the HDRS-Total, and the LTE-Total. Discussion: Data suggest that impulsivity could mediate the influence of childhood trauma on suicidal behavior. This will help understand the role of risk factors in suicidal behavior and aid in the development of prevention interventions focused on modifiable mediators when risk factors are non-modifiable.

Early psychological impact of the 2019 coronavirus disease (COVID-19) pandemic and lockdown in a large Spanish sample.

BACKGROUND: Epidemic outbreaks have significant impact on psychological well-being, increasing psychiatric morbidity among the population. We aimed to describe the early psychological impact of COVID-19 and its contributing factors in a large Spanish sample, globally and according to mental status (never mental disorder NMD, past mental disorder PMD, current mental disorder CMD). METHODS: An online questionnaire was conducted between 19 and 26 March, five days after the official declaration of alarm and the lockdown order. Data included sociodemographic and clinical information and the DASS-21 and IES questionnaires. We analysed 21 207 responses using the appropriate descriptive and univariate tests as well as binary logistic regression to identify psychological risk and protective factors. RESULTS: We found a statistically significant gradient in the psychological impact experienced in five domains according to mental status, with the NMD group being the least affected and the CMD group being the most affected. In the three groups, the depressive response was the most prevalent (NMD = 40.9%, PMD = 51.9%, CMD = 74.4%, F = 1011.459, P < 0.001). Risk factors were female sex and classification as a case in any psychological domain. Protective factors were younger age and ability to enjoy free time. Variables related to COVID-19 had almost no impact except for having COVID-19 symptoms, which was a risk factor for anxiety in all three groups. CONCLUSIONS: Our results can help develop coping strategies addressing modifiable risk and protective factors for each mental status for early implementation in future outbreaks.

Glutamine and New Pharmacological Targets to Treat Suicidal Ideation.

Glutamate is the major excitatory neurotransmitter in the central nervous system, and it is linked with the amino acid glutamine through a metabolic relationship of enzymatic compound interconversion and transportation, also known as the glutamate-glutamine cycle.A growing body of evidence suggests involvement of the glutamatergic neurotransmitter system in suicidal behaviours. The initial evidence comes from the pathophysiology of neuropsychiatric disorders, as disruptions in glutamate neurotransmission have been found underlying pathology in multiple suicide-related psychiatric conditions such as major depressive disorder, schizophrenia, post-traumatic stress disorder, and bipolar disorder.Existing data from experimental animal models and human in vivo studies also demonstrate that glutamate plays a key role in suicide-related personality traits including aggression and impulsive aggression.Further studies on glutamate system dysfunction underlying suicidal behaviours have focused on the different steps of the glutamate-glutamine cycle: an inflammation-mediated reduction of glutamine synthetase activity has been found in depressed suicide attempters, phosphate-activated glutaminase genes are reduced in suicide completers, and gene expression abnormalities in NMDA receptors have also been discovered in suicide victims.Evidence of a role of the glutamate-glutamine cycle in suicidal behaviours unveils new targets for anti-suicide interventions. Lithium's mechanism to reduce the risk of suicide in people with mood disorders may be related to its ability to increase glutamine synthetase, whereas novel NMDA antagonists such as ketamine [or its S(+) enantiomer esketamine] have already demonstrated positive results in reducing suicidal ideation.