Depresión y ansiedad en la EPOC. Repercusión, identificación y manejo

La prevalencia de trastornos depresivos y de ansiedad es significativamente más elevada entre los pacientes con EPOC que en la población general, generando en estos altos niveles de incapacidad y de afectación del funcionamiento. La presencia de estas alteraciones afectivas se ve asociada a un peor curso evolutivo de la EPOC, expresado por ejemplo en una mayor gravedad clínica de la EPOC, una tendencia a presentar exacerbaciones, recaídas y reingresos, e incluso una mayor mortalidad. Otro aspecto a reseñar es el hecho de que la comorbilidad entre ambos factores afecta de manera significativa la adherencia al tratamiento y de manera especial la calidad de vida de los pacientes con EPOC. Finalmente es de destacar que el manejo de pacientes con dicha comorbilidad debe realizarse a través de un modelo integrado de cuidados, en el que participen de manera coordinada los sanitarios de las unidades de EPOC y los especialistas de psiquiatría y de salud mental. En él a su vez se ha de adoptar un esquema escalonado de cuidados que incluya intervenciones farmacológicas y psicológicas cuya intensidad y grado de especialización se deberá ajustar a la severidad clínic

Apnea during slow sub-anaesthetic infusion of intravenous ketamine for treatment-resistant depression

Ketamine's pharmacological profile makes it an interesting and useful drug to challenge treatment-resistant-depression (TRD). Emerging adverse events associated with single-slow-sub-anaesthetic doses for the treatment of depression are common, although generally transient and self-limited. Nevertheless, data on the safety of this practice are scarce. Thus, it seems timely before ketamine is used for clinical treatment of depression to recommend careful monitoring and reporting of all potential adverse events related to ketamine administration. Here, we describe a case of apnea during slow sub-anaesthetic infusion of intravenous ketamine for the treatment of resistant depression. As far as we are concerned, this is an uncommon, previously unreported, and potentially severe adverse event that clinicians should be aware of, and specific management measures should be implemented

Do patients diagnosed with a neurological disease present increased risk of suicide?

RESUMEN: Introducción: Las enfermedades neurológicas representan la principal causa de discapacidady la segunda causa de muerte a nivel mundial. El dolor físico y psicológico, la desesperanzay la desconexión con el medio están presentes tras el diagnóstico de numerosos procesosneurológicos y especialmente de las enfermedades neurodegenerativas.Desarrollo: Existe un mayor riesgo de suicidio en pacientes con enfermedades neurológicascomunes como la epilepsia, la migra?na y la esclerosis múltiple, así como en quienes padecentrastornos degenerativos como la enfermedad de Alzheimer, la enfermedad de Huntington, laesclerosis lateral amiotrófica o la enfermedad de Parkinson. En la mayoría de los casos, la idea-ción suicida aparece en la etapa próxima al diagnóstico, ante sintomatología invalidante, y/oen pacientes que presentan comorbilidad psiquiátrica (a menudo asociada con dichas dolenciasneurológicas).Conclusiones: Para una prevención efectiva del suicidio en este grupo de la población debeevaluarse el riesgo principalmente en pacientes recién diagnosticados, ante la expresión demarcada desesperanza, ante sintomatología invalidante y en pacientes que presentan comorbi-lidad psiquiátrica (especialmente síntomas depresivos). La formación de los especialistas paradetectar signos de alerta es fundamental tanto para que puedan hacer un correcto abordajecomo para que sean capaces de determinar cuándo es necesaria la valoración de un especialistaen psiquiatría.ABSTRACT: Introduction: Neurological diseases are the leading cause of disability and the second leading cause of death worldwide. Physical and psychological pain, despair, and disconnection with the environment are observed after the diagnosis of numerous neurological processes, particularly neurodegenerative diseases. Development: A higher risk of suicide is observed in patients with such common neurological diseases as epilepsy, migraine, and multiple sclerosis, as well as in those with such degenerative disorders as Alzheimer disease, Huntington disease, amyotrophic lateral sclerosis, and Parkinson's disease. In most cases, suicidal ideation appears in the early stages after diagnosis, in the presence of disabling symptoms, and/or in patients with psychiatric comorbidities (often associated with these neurological diseases). Conclusions: Effective suicide prevention in this population group requires assessment of the risk of suicide mainly in newly diagnosed patients, in patients showing unmistakable despair or disabling symptoms, and in patients presenting psychiatric comorbidities (especially depressive symptoms). It is essential to train specialists to detect warning signs in order that they may adopt a suitable approach and determine when psychiatric assessment is required

Association of Insulin Resistance With Schizophrenia Polygenic Risk Score and Response to Antipsychotic Treatment

This study examines the association between insulin resistance, schizophrenia polygenic risk, and treatment outcomes in first-episode, antipsychotic-naive patients with schizophrenia.Funding/Support: This work was supported by grants from the Stanley Medical Research Institute (Dr Bahn)

A Disrupted-in-Schizophrenia 1 Gene Variant is Associated with Clinical Symptomatology in Patients with First-Episode Psychosis

OBJECTIVE: DISC1 gene is one of the main candidate genes for schizophrenia since it has been associated to the illness in several populations. Moreover, variations in several DISC1 polymorphisms, and in particular Ser704Cys SNP, have been associated in schizophrenic patients to structural and functional modifications in two brain areas (pre-frontal cortex and hippocampus) that play a central role in the genesis of psychotic symptoms. This study tested the association between Ser704Cys DISC1 polymorphism and the clinical onset of psychosis. METHODS: Two hundred and thirteen Caucasian drug-naive patients experiencing a first episode of non-affective psychosis were genotyped for rs821616 (Ser704Cys) SNP of the DISC1 gene. The clinical severity of the illness was assessed using SAPS and SANS scales. Other clinical and socio-demographic variables were recorded to rule out possible confounding effects. RESULTS: Patients homozygous for the Ser allele of the Ser704Cys DISC1 SNP had significantly (p<0.05) higher rates at the positive symptoms dimension (SAPS-SANS scales) and hallucinations item, compared to Cys carriers. CONCLUSION: DISC1 gene variations may modulate the clinical severity of the psychosis at the onset of the disorde

Recovery of long-term paresis following resection of WHO grade II gliomas infiltrating the pyramidal pathway

Recent publications had reported high rates of preoperative neurological impairments in WHO grade II gliomas (GIIG) that significantly affect the quality of life. Consequently, one step further in the analysis of surgical outcome in GIIG is to evaluate if surgery is capable to improve preoperative deficits. Here are reported two cases of GIIG infiltrating the primary motor cortex and pyramidal pathway that had a long-term paresis before surgery. Both patients were operated with intraoperative electrical stimulation mapping, with identification and preservation of the primary motor cortex and pyramidal tract. Despite the long-lasting paresis, both cases had a significant improvement of motor function after surgery. Knowledge of this potential recovery before surgery is of major significance for planning the surgical strategy in GIIG. Two possible predictors of motor recovery were analyzed: 1) reconstruction of the corticospinal tract with diffusion tensor imaging tractography is indicative of anatomo-functional integrity, despite tract deviation and infiltration; 2) intraoperative identification of motor response by electrostimulation confirms the presence of an intact peritumoral tract. Thus, resection should stop at this boundary even in cases of long lasting preoperative hemiplegia

Peripheral lymphocyte signaling pathway deficiencies predict treatment response in first-onset drug-naïve schizophrenia

Despite being a major cause of disability worldwide, the pathophysiology of schizophrenia and molecular basis of treatment response heterogeneity continue to be unresolved. Recent evidence suggests that multiple aspects of pathophysiology, including genetic risk factors, converge on key cell signaling pathways and that exploration of peripheral blood cells might represent a practical window into cell signaling alterations in the disease state. We employed multiplexed phospho-specific flow cytometry to examine cell signaling epitope expression in peripheral blood mononuclear cell (PBMC) subtypes in drug-naïve schizophrenia patients (n = 49) relative to controls (n = 61) and relate these changes to serum immune response proteins, schizophrenia polygenic risk scores and clinical effects of treatment, including drug response and side effects, over the longitudinal course of antipsychotic treatment. This revealed both previously characterized (Akt1) and novel cell signaling epitopes (IRF-7 (pS477/pS479), CrkL (pY207), Stat3 (pS727), Stat3 (pY705) and Stat5 (pY694)) across PBMC subtypes which were associated with schizophrenia at disease onset, and correlated with type I interferon-related serum molecules CD40 and CXCL11. Alterations in Akt1 and IRF-7 (pS477/pS479) were additionally associated with polygenic risk of schizophrenia. Finally, changes in Akt1, IRF-7 (pS477/pS479) and Stat3 (pS727) predicted development of metabolic and cardiovascular side effects following antipsychotic treatment, while IRF-7 (pS477/pS479) and Stat3 (pS727) predicted early improvements in general psychopathology scores measured using the Brief Psychiatric Rating Scale (BPRS). These findings suggest that peripheral blood cells can provide an accessible surrogate model for intracellular signaling alterations in schizophrenia and have the potential to stratify subgroups of patients with different clinical outcomes or a greater risk of developing metabolic and cardiovascular side effects following antipsychotic therapy

Aripiprazole and Risperidone Present Comparable Long-Term Metabolic Profiles: Data From a Pragmatic Randomized Controlled Trial in Drug-Naïve First-Episode Psychosis

Objective: Aripiprazole and risperidone are 2 of the most used second-generation antipsychotics (SGAs) worldwide. Previous evidence shows a similar effect of these SGAs on weight and metabolic changes in the short term. However, a longer period is necessary for a better assessment of the SGA´s metabolic profile. We aimed to compare the long-term (1-year) metabolic profile of these 2 antipsychotics on a sample of drug-naïve first episode-psychosis (FEP) patients. Methods: A total 188 drug-naïve patients, suffering from a first episode of non-affective psychosis (FEP), were randomly assigned to treatment with either aripiprazole or risperidone. Weight and glycemic/lipid parameters were recorded at baseline and after 1-year follow-up. Results: We observed significant weight increments in both groups (9.2 kg for aripiprazole and 10.5 kg for risperidone) after 1 year of treatment. Despite this, weight and body mass index changes did not significantly differ between treatment groups (P > .05). Similarly, both treatment groups presented similar metabolic clinical impact with a comparable increase in the proportion of participants meeting criteria for metabolic disorders such as obesity or hypercholesterolemia, but not for metabolic syndrome (?9.2% vs ?4.3%) or hypertriglyceridemia (?21.9% vs ?8.0%), where aripiprazole showed worse outcomes than risperidone. Conclusion: This study shows that aripiprazole and risperidone share a similar long-term metabolic profile. After 1 year of antipsychotic treatment, drug-naïve FEP patients in both treatment groups presented a significant increase in weight and metabolic changes, leading to a greater prevalence of metabolic disorders

Aripiprazole as a Candidate Treatment of COVID-19 Identified Through Genomic Analysis

Background: Antipsychotics modulate expression of inflammatory cytokines and inducible inflammatory enzymes. Elopiprazole (a phenylpiperazine antipsychotic drug in phase 1) has been characterized as a therapeutic drug to treat SARS-CoV-2 infection in a repurposing study. We aim to investigate the potential effects of aripiprazole (an FDA approved phenylpiperazine) on COVID-19-related immunological parameters. Methods: Differential gene expression profiles of non-COVID-19 vs. COVID-19 RNA-Seq samples (CRA002390 project in GSA database) and drug-naïve patients with non-affective psychosis at baseline and after three months of aripiprazole treatment were identified. An integrative transcriptomic analyses of aripiprazole effects on differentially expressed genes in COVID-19 patients was performed. Findings: 82 out the 377 genes (21.7%) with expression significantly altered by aripiprazole have also their expression altered in COVID-19 patients and in 93.9% of these genes their expression is reverted by aripiprazole. The number of common genes with expression altered in both analyses is significantly higher than expected (Fisher?s Exact Test, two tail; p value = 3.2e-11). 11 KEGG pathways were significantly enriched with genes with altered expression both in COVID-19 patients and aripiprazole medicated non-affective psychosis patients (p adj<0.05). The most significant pathways were associated to immune responses and mechanisms of hyperinflammation-driven pathology (i.e.,?inflammatory bowel disease (IBD)? (the most significant pathway with a p adj of 0.00021), ?Th1 and Th2 cell differentiation? and ?B cell receptor signaling pathway?) that have been also associated with COVID19 clinical outcome. Interpretation: This exploratory investigation may provide further support to the notion that a protective effect is exerted by aripiprazole (phenylpiperazine) by modulating the expression of genes that have shown to be altered in COVID-19 patients. Along with many ongoing studies and clinical trials, repurposing available medications could be of use in countering SARS-CoV-2 infection, but require further studies and trials.Funding: The present study was part of a larger prospective longitudinal study, the “First Episode Psychosis Clinical Program 10” (PAFIP10) study. ClinicalTrials.gov Identifiers: NCT02200588, NCT03481465, and NCT03476473. No pharmaceutical industry or institutional sponsors participated in the study conception and design, data collection, analysis and interpretation of the results, or drafting of the manuscript. This work was supported by: SAF2016- 76046-R and SAF2013-46292-R (MINECO and FEDER) to B.C.F.Acknowledgments: We are highly indebted to the participants and their families for their cooperation in this study. We also thank IDIVAL biobank (Ines Santiuste and Jana Arozamena) for clinical samples and ́ data as well as the PAFIP members (Marga Corredera) for the data collection. We kindly thank all clinical staff at the Hospital Universitario Virgen del Rocio for support to collect clinical records and provide clinical care to COVID-19 patients. We also kindly thank Dra. Marisa Barrigon for helpful discussions regarding clinical data analysis, and Idalino Rocha for manuscript editing and formatting. This manuscript has been released as a pre-print at medRxiv. Available at: https://doi.org/ 10.1101/2020.12.05.20244590 (Crespo-Facorro et al., 2020)