RESUMEN
Schizophrenia (SZ) is a serious mental disorder that is typically treated with antipsychotic medication. Treatment-resistant schizophrenia (TRS) is the condition where symptoms remain after pharmacological intervention, resulting in long-lasting functional and social impairments. As the identification and treatment of a TRS patient requires previous failed treatments, early mechanisms of detection are needed in order to quicken the access to effective therapy, as well as improve treatment adherence. In this study, we aim to find a microRNA (miRNA) signature for TRS, as well as to shed some light on the molecular pathways potentially involved in this severe condition. To do this, we compared the blood miRNAs of schizophrenia patients that respond to medication and TRS patients, thus obtaining a 16-miRNA TRS profile. Then, we assessed the ability of this signature to separate responders and TRS patients using hierarchical clustering, observing that most of them are grouped correctly (~70% accuracy). We also conducted a network, pathway analysis, and bibliography search to spot molecular pathways potentially altered in TRS. We found that the response to stress seems to be a key factor in TRS and that proteins p53, SIRT1, MDM2, and TRIM28 could be the potential mediators of such responses. Finally, we suggest a molecular pathway potentially regulated by the miRNAs of the TRS profile.
Asunto(s)
Antipsicóticos , MicroARNs , Esquizofrenia , Humanos , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/genética , Esquizofrenia/diagnóstico , MicroARNs/genética , MicroARNs/uso terapéutico , Esquizofrenia Resistente al Tratamiento , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Resistencia a Medicamentos/genéticaRESUMEN
The Insulin-like growth factor 2 (IGF-2) has been recently proven to alleviate depressive-like behaviors in both rats and mice models. However, its potential role as a peripheral biomarker has not been evaluated in depression. To do this, we measured plasma IGF-2 and other members of the IGF family such as Binding Proteins (IGFBP-1, IGFBP-3, IGFBP-5 and IGFBP-7) in a depressed group of patients (n = 51) and in a healthy control group (n = 48). In some of these patients (n = 15), we measured these proteins after a period (19 ± 6 days) of treatment with antidepressants. The Hamilton Depressive Rating Scale (HDRS) and the Self-Assessment Anhedonia Scale (SAAS) were used to measure depression severity and anhedonia, respectively. The general cognition state was assessed by the Mini-Mental State Examination (MMSE) test and memory with the Free and Cued Selective Reminding Test (FCSRT). The levels of both IGF-2 and IGFBP-7 were found to be significantly increased in the depressed group; however, only IGF-2 remained significantly elevated after correction by age and sex. On the other hand, the levels of IGF-2, IGFBP-3 and IGFBP-5 were significantly decreased after treatment, whereas only IGFBP-7 was significantly increased. Therefore, peripheral changes in the IGF family and their response to antidepressants might represent alterations at the brain level in depression.
Asunto(s)
Trastorno Depresivo Mayor , Factor II del Crecimiento Similar a la Insulina , Humanos , Ratas , Animales , Ratones , Factor II del Crecimiento Similar a la Insulina/metabolismo , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina , Trastorno Depresivo Mayor/tratamiento farmacológico , Factor I del Crecimiento Similar a la Insulina/metabolismo , Anhedonia , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Proteína 2 de Unión a Factor de Crecimiento Similar a la InsulinaRESUMEN
The brain extracellular matrix (ECM) is involved in crucial processes of neural support, neuronal and synaptic plasticity, extrasynaptic transmission, and neurotransmission. ECM is a tridimensional fibrillary meshwork composed of macromolecules that determine its bioactivity and give it unique characteristics. The characterization of the brain ECM is critical to understand its dynamic in SZ. Thus, a comparative study was developed with 71 patients with schizophrenia (SZ) and 70 healthy controls. Plasma of participants was analysed by label-free liquid chromatography-tandem mass spectrometry, and the results were validated using the classical western blot method. Lastly, immunostaining of post-mortem human brain tissue was performed to analyse the distribution of the brain ECM proteins by confocal microscopy. The analysis identified four proteins: fibronectin, lumican, nidogen-1, and secreted protein acidic and rich in cysteine (SPARC) as components of the brain ECM. Statistical significance was found for fibronectin (P = 0.0166), SPARC (P = 0.0003), lumican (P = 0.0012), and nidogen-1 (P < 0.0001) that were decreased in the SZ group. Fluorescence imaging of prefrontal cortex (PFC) sections revealed a lower expression of ECM proteins in SZ. Our study proposes a pathophysiological dysregulation of proteins of the brain ECM, whose abnormal composition leads to a progressive neuronal impairment and consequently to neurodegenerative processes due to lack of neurophysiological support and dysregulation of neuronal homeostasis. Moreover, the brain ECM and its components are potential pharmacological targets to develop new therapeutic approaches to treat SZ.
Asunto(s)
Fibronectinas , Esquizofrenia , Encéfalo/metabolismo , Matriz Extracelular/metabolismo , Proteínas de la Matriz Extracelular/metabolismo , Fibronectinas/metabolismo , Humanos , Lumican/metabolismo , Osteonectina/metabolismo , Esquizofrenia/tratamiento farmacológico , Esquizofrenia/metabolismoRESUMEN
Insulin-like growth factor 2 (IGF-2) and IGF binding protein 7 (IGFBP-7) have been related to schizophrenia (SZ) due to their implication in neurodevelopment. The purpose of this study was to assess whether the alterations in IGF-2 and IGFBP-7 in SZ patients are intrinsically related to the psychiatric disorder itself or are a secondary phenomenon due to antipsychotic treatment. In order to test this hypothesis, we measured plasma IGF-2 and IGFBP-7 in drug-naïve first episode (FE) and multiple episodes or chronic (ME) SZ Caucasian patients who have been following treatment for years. A total of 55 SZ patients (FE = 15, ME = 40) and 45 healthy controls were recruited. The Positive and Negative Syndrome Scale (PANSS) and the Self-Assessment Anhedonia Scale (SAAS) were employed to check schizophrenic symptomatology and anhedonia, respectively. Plasma IGF-2 and IGFBP-7 levels were measured by Enzyme-Linked Immunosorbent Assay (ELISA). The FE SZ patients had much lower IGF-2, but not IGFBP-7, than controls. Moreover, both IGF-2 and IGFBP-7 significantly increased after atypical antipsychotic treatment (aripiprazole, olanzapine, or risperidone) in these patients. On the other hand, chronic patients showed higher levels of both proteins when compared to controls. Our study suggests that circulatory IGF-2 and IGFBP-7 increase after antipsychotic treatment, regardless of long-term conditions and being lower in drug-naïve FE patients.
Asunto(s)
Antipsicóticos , Esquizofrenia , Anhedonia , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Humanos , Proteína 2 de Unión a Factor de Crecimiento Similar a la Insulina , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor II del Crecimiento Similar a la Insulina/metabolismo , Esquizofrenia/metabolismoRESUMEN
The neurobiology of schizophrenia is multifactorial, comprising the dysregulation of several biochemical pathways and molecules. This research proposes a peripheral biomarker for schizophrenia that involves the second extracellular loop of norepinephrine transporter (NEText), the tropomyosin receptor kinase C (TrkC), and the neurotrophin-3 (NT-3) in T cells. The study of NEText, NT-3, and TrkC was performed in T cells and plasma extracted from peripheral blood of 54 patients with schizophrenia and 54 healthy controls. Levels of NT-3, TrkC, and NET were significantly lower in plasma and T cells of patients compared to healthy controls. Co-immunoprecipitation (co-IPs) showed protein interactions with Co-IP NEText-NT-3 and Co-IP NEText-TrkC. Computational modelling of protein-peptide docking by CABS-dock provided a medium-high accuracy model for NT-3-NEText (4.6935 Å) and TrkC-NEText (2.1365 Å). In summary, immunocomplexes reached statistical relevance in the T cells of the control group contrary to the results obtained with schizophrenia. The reduced expression of NT-3, TrkC, and NET, and the lack of molecular complexes in T cells of patients with schizophrenia may lead to a peripheral dysregulation of intracellular signaling pathways and an abnormal reuptake of norepinephrine (NE) by NET. This peripheral molecular biomarker underlying schizophrenia reinforces the role of neurotrophins, and noradrenergic and immune systems in the pathophysiology of schizophrenia.
Asunto(s)
Simulación del Acoplamiento Molecular , Neurotrofina 3/química , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/química , Receptor trkC/química , Esquizofrenia/etiología , Adulto , Biomarcadores/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neurotrofina 3/genética , Neurotrofina 3/metabolismo , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/genética , Proteínas de Transporte de Noradrenalina a través de la Membrana Plasmática/metabolismo , Estructura Secundaria de Proteína , Receptor trkC/genética , Receptor trkC/metabolismo , Esquizofrenia/genética , Esquizofrenia/metabolismoRESUMEN
BACKGROUND: We have shown that serotonin transporter (SERT) clustering in blood lymphocytes is altered in major depression and correlates with pharmacological therapeutic responses measured with the Hamilton scale. In the present report, we extend these results to the self-assessment anhedonia scale, as anhedonia is a cardinal symptom of major depression that is difficult to treat with first-line antidepressants. METHODS: We collected blood samples from 38 untreated depression patients at the time of enrolment and 8 weeks after pharmacological treatment. We used the self-assessment anhedonia scale to evaluate anhedonia symptoms before and after treatment. We also used quantitative immunocytochemistry to measure SERT clusters in blood lymphocytes. RESULTS: Evaluation of the distribution of SERT clusters size in the plasma membrane of lymphocytes identified two subpopulations of naive depression patients: Depression I (D-I) and Depression II (D-II). While naïve D-I and D-II patients initially showed similar anhedonia scores, D-II patients showed a good response in anhedonia symptoms after 8 weeks of psychopharmacological treatment, whereas D-I patients failed to show any improvement. Psychopharmacological treatment also induced an increase in the number of SERT clusters in lymphocytes in the D-II group, and this increase correlated with the improvement in anhedonia symptoms. CONCLUSIONS: SERT clustering in peripheral lymphocytes can be used to identify patient response to antidepressant therapy as ascertained by anhedonia scores.
RESUMEN
Functioning is a fundamental dimension across all aspects of life, frequently compromised or reduced in individuals with schizophrenia. However, the lack of a commonly agreed definition of functioning in schizophrenia makes it difficult to apply this concept in clinical practice. In this document, we make a detailed analysis of the literature to identify and define functioning and describe how it can be used in clinical practice today. We performed a preliminary literature search in the MEDLINE database (via PubMed) for articles discussing functioning in schizophrenia. The articles retrieved were then read and discussed by a panel of psychiatrists specialising in schizophrenia. The conclusions reached in this meeting formed the basis for a new exhaustive literature search for the purpose of synthesising the evidence published in the past 5 years. In this article, we show the importance a comprehensive, modern, homogeneous definition of functioning in schizophrenia, propose a definition of functioning, and put forward a series of recommendations for assessing functioning in clinical practice. We also review current unmet needs and highlight the need for a standardised tool for evaluating functioning.
Asunto(s)
Esquizofrenia , Humanos , Esquizofrenia/fisiopatología , Psicología del Esquizofrénico , Funcionamiento PsicosocialRESUMEN
Introduction: Bipolar disorder (BD) is a recurrent and disabling psychiatric disorder related to low-grade peripheral inflammation and altered levels of the members of the insulin-like growth factor (IGF) family. The aim of this study was to evaluate the plasma levels of IGF-2, insulin-like growth factor-binding protein 1 (IGFBP-1), IGFBP-3, IGFBP-5, IGFBP-7, and inflammatory markers such as tumor necrosis factor α (TNF-α), monocyte chemoattractant protein 1 (MCP-1), and macrophage inflammatory protein 1ß (MIP-1ß). Methods: We used the Young Mania Rating Scale (YMRS) to determine the severity of the symptomatology, while proteins were measured by enzyme-linked immunosorbent assay (ELISA). We included 20 patients with BD who suffered a manic episode and 20 controls. Some BD patients (n = 10) were evaluated after a period (17 ± 8 days) of pharmacological treatment. Results: No statistical difference was found in IGF-2, IGFBP-1, IGFBP-7, TNF-α, and MIP-1ß levels. However, IGFBP-3 and IGFBP-5 levels were found to be statistically decreased in BD patients. Conversely, the MCP-1 level was significantly increased in BD patients, but their levels were normalized after treatment. Intriguingly, only IGFBP-1 levels were significantly decreased after treatment. No significant correlation was found between the YMRS and any of the proteins studied either before or after treatment or between IGF proteins and inflammatory markers. Discussion: To some extent, IGFBP-3 and IGFBP-5 might be further explored as potential indicators of treatment responsiveness or diagnosis biomarkers in BD.
RESUMEN
The growth and development of the human brain is a long and complex process that requires a precise sequence of genetic and molecular events. This begins in the third week of gestation with the differentiation of neural progenitor cells and extends at least until late adolescence, possibly for life. One of the defects of this development is that we know very little about the signals that modulate this sequence of events. The first 3 years of life, during breastfeeding, is one of the critical periods in brain development. In these first years of life, it is believed that neurodevelopmental problems may be the molecular causes of mental disorders. Therefore, we herein propose a new hypothesis, according to which the chemical signals that could modulate this entire complex sequence of events appear in this early period, and the molecular level study of human breast milk and colostrum of mothers who give birth to children in different gestation periods could give us information on proteins influencing this process. In this work, we collected milk and colostrum samples (term, late preterm and moderate/very preterm) and exosomes were isolated. The samples of exosomes and complete milk from each fraction were analyzed by LC-ESI-MS/MS. In this work, we describe proteins in the different fractions of mature milk and colostrum of mothers with term, late preterm, or very preterm delivery, which could be involved in the regulation of the nervous system by their functions. We describe how they differ in different types of milk, paving the way for the investigation of possible new neuroregulatory pathways as possible candidates to modulate the nervous system.
Asunto(s)
Exosomas , Nacimiento Prematuro , Recién Nacido , Femenino , Embarazo , Adolescente , Niño , Humanos , Leche Humana/química , Leche Humana/metabolismo , Calostro/química , Calostro/metabolismo , Nacimiento Prematuro/metabolismo , Lactancia/fisiología , Exosomas/metabolismo , Proteómica , Espectrometría de Masas en TándemRESUMEN
Human milk is the biological fluid with the highest exosome amount and is rich in microRNAs (miRNAs). These are key regulators of gene expression networks in both normal physiologic and disease contexts, miRNAs can influence many biological processes and have also shown promise as biomarkers for disease. One of the key aspects in the regeneration of the nervous system is that there are practically no molecules that can be used as potential drugs. In the first weeks of lactation, we know that human breast milk must contain the mechanisms to transmit molecular and biological information for brain development. For this reason, our objective is to identify new modulators of the nervous system that can be used to investigate neurodevelopmental functions based on miRNAs. To do this, we collected human breast milk samples according to the time of delivery and milk states: mature milk and colostrum at term; moderate and very preterm mature milk and colostrum; and late preterm mature milk. We extracted exosomes and miRNAs and realized the miRNA functional assays and target prediction. Our results demonstrate that miRNAs are abundant in human milk and likely play significant roles in neurodevelopment and normal function. We found 132 different miRNAs were identified across all samples. Sixty-nine miRNAs had significant differential expression after paired group comparison. These miRNAs are implicated in gene regulation of dopaminergic/glutamatergic synapses and neurotransmitter secretion and are related to the biological process that regulates neuron projection morphogenesis and synaptic vesicle transport. We observed differences according to the delivery time and with less clarity according to the milk type. Our data demonstrate that miRNAs are abundant in human milk and likely play significant roles in neurodevelopment and normal function.
Asunto(s)
MicroARNs , Embarazo , Recién Nacido , Femenino , Humanos , Animales , MicroARNs/genética , MicroARNs/metabolismo , Leche Humana/metabolismo , Leche/metabolismo , Calostro/metabolismo , Lactancia/genética , Sinapsis/metabolismoRESUMEN
Background: One of the most significant risk factors for relapse and hospitalization in schizophrenia is non-adherence to antipsychotic medications, very common in patients with schizophrenia. The aim of this analysis was to evaluate the treatment persistence to aripiprazole once-monthly (AOM) and the factors affecting it in the pooled population of two similar studies performed previously in two different European countries. Methods: Pooled analysis of two non-interventional, retrospective, patient record-based studies: DOMINO and PROSIGO. Both analyzed treatment persistence after starting AOM treatment in the real-world setting. The primary variable was persistence with AOM treatment during the first 6 months after treatment initiation. A multivariate Cox regression model was used to evaluate the influence of several baseline characteristics on the persistence. Results: The study population comprised 352 patients included in the two studies, DOMINO (n = 261) and PROSIGO (n = 91). The overall persistence with AOM treatment at the end of the 6-month observation period was 82.4%. The multivariate analysis showed that patients with "secondary school" level of education present a 67.4% lower risk of discontinuation within 6 months after AOM initiation when compared with "no/compulsory education patients" (p = 0.024). In addition, patients with an occupation present a 62.7% lower risk of discontinuation when compared with unemployed patients (p = 0.023). Regarding clinical history, patients with a Clinical Global Impression-Severity scale (CGI-S) score ≤3 present a 78.1% lower risk of discontinuation when compared with patients with a CGI-S score ≥6 (p = 0.044), while patients with a time since schizophrenia diagnosis ≤8.4 years present a 52.9% lower risk of discontinuation when compared with the rest of patients (p = 0.039). Conclusion: The AOM persistence rate observed in this study was 82.4%, which was higher than that reported in clinical trials, aligned with other real-life studies and higher than reported for other long-acting injectable antipsychotics. The persistence rate was high in complex patients, although patients with higher level of education, active occupation, lower initial CGI-S score and shorter time since the diagnosis of schizophrenia appear to be more likely to remain persistent with AOM during the 6 months after initiation.
RESUMEN
Substance-related disorders (SRD) have been consistently associated with alterations both in cognitive and executive functions, which affect to patients' quality of life. The main objective of this work was to test the beneficial cognitive effects on patients with SRD after the implementation of "Trisquel," an intervention program in board game format. To check the effectiveness of Trisquel program, a group of people diagnosed with SRD was randomly assigned either to the experimental group or to the control group. The experimental group performed Trisquel structured sessions twice a week during 3 months, while the control group performed routinely conventional therapeutic activities with the same frequency and duration. Neuropsychological tests were done to both groups before and after the intervention. After the 3 months of intervention the experimental group showed the following statistically significant improvements for WAIS-III subtests: number key, symbol search, arithmetic, direct digits, inverse digits, total digits, letters-numbers in the processing speed index and in the working memory index. Regarding STROOP tests, statistically significant progress was observed in the phonetic fluency letter P, phonetic fluency letter M, phonetic fluency letter R subtests, word-reading and word-color subtests. The control group only obtained improvements for WAIS-III subtests of arithmetic, letters-numbers and in the working memory index. The results of this study confirm that "Trisquel" is an effective intervention program for people diagnosed with SRD, getting improvements in processing speed (psychomotor and reading), attentional subprocesses (focused and sustained) and executive functions (updating and inhibition).
RESUMEN
At the beginning of the pandemic, we observed that lithium carbonate had a positive effect on the recovery of severely ill patients with COVID-19. Lithium is able to inhibit the replication of several types of viruses, some of which are similar to the SARS-CoV-2 virus, increase the immune response and reduce inflammation by preventing or reducing the cytokine storm. Previously, we published an article with data from six patients with severe COVID-19 infection, where we proposed that lithium carbonate could be used as a potential treatment for COVID-19. Now, we set out to conduct a randomized clinical trial number EudraCT 2020-002008-37 to evaluate the efficacy and safety of lithium treatment in patients infected with severe SARS-CoV-2. We showed that lithium was able to reduce the number of days of hospital and intensive care unit admission as well as the risk of death, reduces inflammatory cytokine levels by preventing cytokine storms, and also reduced the long COVID syndromes. We propose that lithium carbonate can be used to reduce the severity of COVID-19.
RESUMEN
BACKGROUND: Poor adherence to antipsychotic drugs is a major problem in schizophrenia management and one of the most important risk factors for relapse and hospitalization. To date, there is little evidence on persistence predictors with long-acting injectable antipsychotics, especially with aripiprazole once-monthly (AOM). This study (NCT03130478) aimed to describe the impact of demographic and clinical characteristics on persistence with AOM treatment in real-world setting. METHODS: This was an observational, retrospective, non-interventional study that included adult patients with schizophrenia who were initiated on AOM during a schizophrenia-related hospitalization. Data were retrospectively collected from patients' medical records. The primary variable was persistence with AOM, measured as the number of days from AOM initiation up to all-cause AOM discontinuation during the first six months after treatment index. RESULTS: 140 patients were enrolled and 91 fulfilled the selection criteria. Six months after AOM initiation, 65 (71.4%) patients were still receiving AOM treatment, whereas 26 (28.6%) were not. The mean (standard deviation) time to AOM treatment discontinuation in the first six months was 138.1 (6.8) days, with most of the patients discontinuing at the first 28 days. The risk of AOM discontinuation in the first six months increases 1.05-fold annually since schizophrenia diagnosis (p=0.003); moreover, this risk increases 2.86-fold in patients with concomitant schizophrenia medication at AOM initiation compared to patients without concomitant schizophrenia treatments (p=0.02). CONCLUSIONS: Main factors predicting persistence with AOM treatment at six months in clinical practice are fewer years since schizophrenia diagnosis and not receiving concomitant schizophrenia treatments at AOM initiation.
Asunto(s)
Antipsicóticos , Esquizofrenia , Adulto , Antipsicóticos/uso terapéutico , Aripiprazol/uso terapéutico , Preparaciones de Acción Retardada/uso terapéutico , Humanos , Estudios Retrospectivos , Esquizofrenia/tratamiento farmacológicoRESUMEN
BACKGROUND: To obtain real-world evidence of functional improvements during atypical long-acting injectable (aLAI) therapy in recent-onset schizophrenia, an online survey was conducted to assess the impact of aripiprazole once-monthly injectable 400 mg (AOM 400; partial D2 receptor agonist) and paliperidone palmitate once-monthly (PP1M; injectable, full D2 receptor antagonist). METHODS: Psychiatrists provided data for their 2 most recent AOM 400 patients, 2 most recent PP1M patients. Survey included 2000 patient cases (1000 AOM 400; 1000 PP1M). Eligible patients were aged 18-35 years, had been diagnosed with schizophrenia within 5 years, received AOM 400 or PP1M continuously for ≥6 months according to approved labels (mean durations: 1.6 and 1.7 years with AOM 400 and PP1M, respectively). Assessments included Global Assessment of Functioning (GAF) Scale, Personal and Social Performance Scale, Positive and Negative Syndrome Scale, and Quality of Life Scale. GAF assessments were done retrospectively and also at the time of survey. RESULTS: Baseline mean GAF scores were 43.3 and 43.8 for AOM 400 and PP1M, respectively, indicating serious symptoms/functional impairment in both groups. Mean improvements following AOM 400 and PP1M therapy were 19.7 and 16.3 points, respectively (final scores in mild functional impairment category). Other measures assessing symptoms/functionality/quality of life demonstrated the benefits of long-term aLAI therapy. CONCLUSION: Schizophrenia patients with serious functional impairment prior to current aLAI treatment showed improvements in functional outcome after AOM 400 or PP1M therapy. These results suggest functional improvements with aLAIs are apparent not only in research but also real-world settings.
RESUMEN
The current use of combined antiretroviral therapy (cART) is leading to a significant decrease in deaths and comorbidities associated with human immunodeficiency virus type 1 (HIV-1) infection. Nonetheless, none of these therapies can extinguish the virus from the long-lived cellular reservoir, including microglia, thereby representing an important obstacle to curing HIV. Microglia are the foremost cells infected by HIV-1 in the central nervous system (CNS) and are believed to be involved in the development of HIV-1-associated neurocognitive disorder (HAND). At present, the pathological mechanisms contributing to HAND remain unclear, but evidence suggests that removing these infected cells from the brain, as well as obtaining a better understanding of the specific molecular mechanisms of HIV-1 latency in these cells, should help in the design of new strategies to prevent HAND and achieve a cure for these diseases. The goal of this review was to study the current state of knowledge of the neuropathology and research models of HAND containing virus susceptible target cells (microglial cells) and potential pharmacological treatment approaches under investigation.
RESUMEN
INTRODUCTION: Schizophrenia is a chronic illness often accompanied by metabolic disorders, diabetes, obesity and cardiovascular problems often associated with unhealthy lifestyles, as well as neuroendocrine problems caused by the disease itself. Lifestyle changes, such as regular physical exercise, have a positive effect on metabolic disorders and mental health, although the molecular changes that occur in this type of patient and how they explain the changes in their response are unknown. This study wants to analyze in a novel way the proteins and molecular pathways involved in critical plasmatic proteins in plasma to reveal the pathways involved in the implementation of physical exercise and the changes that occur among patients who participate in such programs with those who leave. METHODS: Twenty-one patients with chronic schizophrenia underwent a daily, 6-month aerobic training program. We divided them into a group that completed the program (12 patients) and a second group that left the training program (9 patients). The biochemical and clinical data of each patient were analyzed and the proteomic profile of the plasma was studied using ESI-LC-MS/MS. RESULTS: Proteomic analysis recognizes 21.165 proteins and peptides in each patient, of which we identified 1.812 proteins that varied between both groups linked to the metabolic and biological regulation pathways. After clinical analysis of each patient we found significant differences in weight, BMI, abdominal perimeter, diastolic blood pressure, and HDL cholesterol levels. The main change that vertebrates both groups is the Self-Assessment Anhedonia Scale, where we detected higher levels in the dropout group (no physical activity) compared to the active group. CONCLUSION: The benefits of physical exercise are clear in chronic patients with schizophrenia, as it substantially improves their BMI, as well as their clinical and biochemical parameters. However, our study reveals the biological and molecular pathways that affect physical exercise in schizophrenia, such as important metabolic proteins such as ApoE and ApoC, proteins involved in neuronal regulation such as tenascin and neurotrophins, neuroinflammatory regulatory pathways such as lipocalin-2 and protein 14-3-3, as well as cytoskeleton proteins of cells such as spectrins and annexines. Understanding these molecular mechanisms opens the door to future therapies in the chronicity of schizophrenia.
Asunto(s)
Esquizofrenia , Animales , Cromatografía Liquida , Ejercicio Físico , Humanos , Proyectos Piloto , Proteómica , Espectrometría de Masas en TándemRESUMEN
AIMS: Non-compliance is still an important problem in psychotic patients. Although antipsychotic (AP) treatment leads to a decrease in psychotic relapses, there are no clear recommendations about how long treatment should be maintained after first-episode psychosis (FEP) and no indication of the rates and causes of treatment withdrawal in this group. METHODS: We evaluated a large sample of patients with FEP for 2 years to compare the time to all-cause treatment discontinuation of AP drugs and the time to the first relapse. We collected the sociodemographic and psychopathological characteristics of the sample. The number of relapses was also recorded. RESULTS: A total of 310 FEP patients were assessed across seven early intervention teams (mean age = 30.2 years; SD = 11.2). The most prevalent diagnosis at baseline was psychotic disorder not otherwise specified (36.1%), and the most commonly used APs were risperidone (26.5%) and olanzapine (18.7%). A lack of efficacy was the most frequent reason for the withdrawal of the first AP prescribed, followed by non-compliance. There were no differences in the relapse rates between different APs. Patients treated with long-acting injectable (LAI) APs presented less disengagement from services than patients treated with oral APs. CONCLUSIONS: Although there were no differences between the different APs in terms of relapse rates, LAIs had higher retention rates than oral APs in early intervention services. Compliance is still an important issue in Psychiatry, so clinicians should use different strategies to encourage it, such as the use of LAI treatments.
Asunto(s)
Antipsicóticos , Trastornos Psicóticos , Adulto , Antipsicóticos/efectos adversos , Preparaciones de Acción Retardada/uso terapéutico , Humanos , Olanzapina/uso terapéutico , Prescripciones , Trastornos Psicóticos/diagnóstico , Risperidona/uso terapéuticoRESUMEN
Duloxetine is a serotonin-norepinephrine reuptake inhibitor approved for the treatment of patients affected by major depressive disorder (MDD), generalized anxiety disorder (GAD), neuropathic pain (NP), fibromyalgia (FMS), and stress incontinence urinary (SUI). These conditions share parallel pathophysiological pathways, and duloxetine treatment might be an effective and safe alternative. Thus, a systematic review was conducted following the 2009 Preferred Reporting Items (PRISMA) recommendations and Joanna Briggs Institute Critical (JBI) Appraisals guidelines. Eighty-five studies focused on efficacy, safety, and tolerability of duloxetine were included in our systematic review. Studies were subdivided by clinical condition and evaluated individually. Thus, 32 studies of MDD, 11 studies of GAD, 19 studies of NP, 9 studies of FMS, and 14 studies of SUI demonstrated that the measured outcomes indicate the suitability of duloxetine in the treatment of these clinical conditions. This systematic review confirms that the dual mechanism of duloxetine benefits the treatment of comorbid clinical conditions, and supports the efficacy, safety, and tolerability of duloxetine in short- and long-term treatments.
RESUMEN
Schizophrenia is a progressive disorder characterized by multiple psychotic relapses. After every relapse, patients may not fully recover, and this may lead to a progressive loss of functionality. Pharmacological treatment represents a key factor to minimize the biological, psychological and psychosocial impact of the disorder. The number of relapses and the duration of psychotic episodes induce a potential neuronal damage and subsequently, neurodegenerative processes. Thus, a comparative study was performed, including forty healthy controls and forty-two SZ patients divided into first-episode psychosis (FEP) and chronic SZ (CSZ) subgroups, where the CSZ sub group was subdivided by antipsychotic treatment. In order to measure the potential neuronal damage, plasma levels of ß-III tubulin, neurofilament light chain (Nf-L), and glial fibrillary acidic protein (GFAP) were performed. The results revealed that the levels of these proteins were increased in the SZ group compared to the control group (P < 0.05). Moreover, multiple comparison analysis showed highly significant levels of ß-III tubulin (P = 0.0002), Nf-L (P = 0.0403) and GFAP (P < 0.015) in the subgroup of CSZ clozapine-treated. In conclusion, ß-III tubulin, Nf-L and GFAP proteins may be potential biomarkers of neurodegeneration and progression in SZ.