RESUMO
A better understanding of the proteome profile after bipolar disorder (BD) and schizophrenia (SCZ) treatment, besides monitoring disease progression, may assist on the development of novel therapeutic strategies with the ability to reduce or control possible side effects. In this pilot study, proteomics analysis employing nano liquid chromatography coupled to mass spectrometry (nLC-MS) and bioinformatic tools were applied to identify differentially abundant proteins in serum of treated BD and SCZ patients. In total, 10 BD patients, 10 SCZ patients, and 14 healthy controls (HC) were included in this study. 24 serum proteins were significantly altered (p < 0.05) in BD and SCZ treated patients and, considering log2FC > 0.58, 8 proteins presented lower abundance in the BD group, while 7 proteins presented higher abundance and 2 lower abundance in SCZ group when compared against HC. Bioinformatics analysis based on these 24 proteins indicated two main altered pathways previously described in the literature; furthermore, it revealed that opposite abundances of the complement and coagulation cascades were the most significant biological processes involved in these pathologies. Moreover, we describe disease-related proteins and pathways associations suggesting the necessity of clinical follow-up improvement besides treatment, as a precaution or safety measure, along with the disease progression. Further biological validation and investigations are required to define whether there is a correlation between complement and coagulation cascade expression for BD and SCZ and cardiovascular diseases.
Assuntos
Transtorno Bipolar/patologia , Fatores de Coagulação Sanguínea/análise , Proteínas do Sistema Complemento/análise , Esquizofrenia/patologia , Adulto , Biomarcadores Farmacológicos , Transtorno Bipolar/sangue , Transtorno Bipolar/imunologia , Fatores de Coagulação Sanguínea/metabolismo , Proteínas Sanguíneas/análise , Cromatografia Líquida/métodos , Proteínas do Sistema Complemento/metabolismo , Biologia Computacional/métodos , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Masculino , Espectrometria de Massas/métodos , Projetos Piloto , Proteômica/métodos , Esquizofrenia/sangue , Esquizofrenia/imunologiaRESUMO
Objective: To determine whether changes in serum galectin-3 (gal-3) concentrations in schizophrenia patients have etiopathogenetic importance. Since very little research has assessed the connection between galectins and schizophrenia, we wanted to examine alterations in the inflammatory marker gal-3 in schizophrenia and investigate possible correlations between clinical symptomatology and serum concentrations. Methods: Forty-eight schizophrenia patients and 44 healthy controls were included in this study. The Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) were administered to determine symptom severity. Venous blood samples were collected, and serum gal-3 levels were measured. Results: Mean serum gal-3 levels were significantly lower in schizophrenia patients, and there were no significant differences in age or sex with the control group. There was also a significant positive correlation between serum gal-3 concentrations and negative schizophrenia symptoms according to the SANS. Conclusion: The results indicate that gal-3 is decreased in schizophrenia patients, which could contribute to inflammation in the pathogenesis of schizophrenia.
Assuntos
Humanos , Masculino , Feminino , Esquizofrenia/sangue , Galectina 3/sangue , Esquizofrenia/fisiopatologia , Biomarcadores/sangue , InflamaçãoRESUMO
OBJECTIVE: To evaluate the involvement of nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome in schizophrenia-like behaviour in young animals exposed to maternal immune activation (MIA). METHODS: To this aim, on the 15th gestational day, the females received an injection of lipopolysaccharides. When the animals completed 7, 14 and 45 postnatal days, they were killed and the whole brain was dissected for biochemical analysis. Animals with 45 postnatal days were submitted to behavioural tests of locomotor activity, social interaction and stereotyped movements. RESULTS: It was observed that the animals presented schizophrenia-like behaviour at 45 postnatal days associated with the increase of NLRP3 inflammasome expression and IL-1ß levels on 7, 14 and 45 postnatal days. CONCLUSION: This study shows that MIA may be associated with a schizophrenia-like behaviour. This behaviour can be induced to a neuroinflammatory profile in the brain. These evidences may base future studies on the relationship between neuroinflammation and psychiatric disorders.
Assuntos
Animais Recém-Nascidos/psicologia , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Esquizofrenia/diagnóstico , Animais , Animais Recém-Nascidos/metabolismo , Escala de Avaliação Comportamental/normas , Encéfalo/metabolismo , Feminino , Idade Gestacional , Comportamento de Doença/fisiologia , Imunidade Ativa/efeitos dos fármacos , Inflamassomos/imunologia , Injeções Intraperitoneais , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mães , Transtornos Neurocognitivos/imunologia , Esquizofrenia/sangueRESUMO
Schizophrenia (SZ) is a mental disorder characterized by neurocognitive dysfunctions and a reduction in occupational and social functioning. Several studies have provided evidence for mitochondrial dysfunction in the pathophysiology of SZ. In this sense, it is known that the addition of genetic variations in mitochondrial DNA (mtDNA) impairs oxidative phosphorylation of enzymatic complexes in mitochondria, resulting in ATP depletion and subsequent enhancement of reactive oxygen species; this is associated with cellular degeneration and apoptosis observed in some neuropsychiatric disorders. As a consequence of mitochondrial dysfunction, an increase in circulating cell-free mtDNA fragments can occur, which has been observed in individuals with SZ. Moreover, due to the bacterial origin of mitochondria, these cell-free mtDNA fragments in blood plasma may induce inflammatory and immunogenic responses, especially when their release is enhanced in specific disease conditions. However, the exact mechanism by which mtDNA could be released into blood plasma is not yet clear. Therefore, the aims of this review article were to discuss the participation of mtDNA genetic variations in physiopathologic mechanisms of SZ, and to determine the status of the disease and the possible ensuing changes over time by using circulating cell-free mtDNA fragments as a biomarker.
Assuntos
Disfunção Cognitiva/etiologia , DNA Mitocondrial/genética , Mitocôndrias/fisiologia , Esquizofrenia/genética , Biomarcadores , Disfunção Cognitiva/sangue , Replicação do DNA , DNA Mitocondrial/sangue , Progressão da Doença , Humanos , Microglia/fisiologia , Mitocôndrias/enzimologia , Fosforilação Oxidativa , Reconhecimento Automatizado de Padrão , Espécies Reativas de Oxigênio , Receptores de Reconhecimento de Padrão/fisiologia , Esquizofrenia/sangue , Esquizofrenia/complicações , Esquizofrenia/fisiopatologiaRESUMO
RATIONALE: A viable and accurate method based on high-power ultrasound-assisted microextraction and inductively coupled plasma mass spectrometry was developed to determine metals in human serum from patients with bipolar disorder and schizophrenia. METHODS: A simple and rapid sample preparation method using a cup-horn sonoreactor was developed. The acid concentration of HNO3 (10, 20, and 40% v/v) and HCl (1, 5, 15, and 30% v/v) of the extraction solution, the sonication time (1, 3, 6, and 10 min), and the sonication amplitude (20, 40, 60, and 80%) were evaluated. Cd, Cu, Fe, Li, Pb, and Zn were determined in serum samples from patients with bipolar disorder and schizophrenia, and from healthy controls. Quantitative metal recoveries using the proposed method were compared under the same conditions using an ultrasonic bath, magnetic stirring, and microwave-assisted digestion. RESULTS: Optimum extraction conditions were obtained using HNO3 (40% v/v) + HCl (30% v/v) as the extraction solution with 3 min sonication time and 60% sonication amplitude. Significant differences were observed among the methods compared. On application of the sample preparation method based on high-power ultrasound-assisted microextraction coupled with inductively coupled plasma mass spectrometry, Pb and Cd in all the studied samples were below the limit of detection of our method. Compared with healthy controls, the concentration of Cu, Li, Fe, and Zn was found to be significantly higher for the bipolar disorder group, while these metals and Li were found at a lower level for the group diagnosed with schizophrenia. CONCLUSIONS: Principal component analysis showed a significant separation for the groups studied based on their ionomic profiles after the application of high-power ultrasound-assisted microextraction as a sample preparation strategy.
Assuntos
Transtorno Bipolar/sangue , Análise Química do Sangue/métodos , Espectrometria de Massas/métodos , Metais/sangue , Esquizofrenia/sangue , Adulto , Estudos de Casos e Controles , Fracionamento Químico/instrumentação , Fracionamento Químico/métodos , Estudos de Viabilidade , Feminino , Humanos , Masculino , Micro-Ondas , Pessoa de Meia-Idade , Estudo de Prova de Conceito , Fatores de Tempo , Oligoelementos/sangue , UltrassomRESUMO
Atypical antipsychotics are widely used to manage schizophrenia symptoms. However, these drugs can induce deleterious side effects, such as MetS, which are associated with an increased cardiovascular risk to patients. Lipids play a central role in this context, and changes in lipid metabolism have been implicated in schizophrenia's pathobiology. Furthermore, recent evidence suggests that lipidome changes may be related to antipsychotic treatment response. The aim of this study was to evaluate the lipidome changes in blood plasma samples of schizophrenia patients before and after 6 weeks of treatment with either risperidone, olanzapine, or quetiapine. Liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis showed changes in the levels of ceramides (Cer), glycerophosphatidic acids (PA), glycerophosphocholines (PC), phosphatidylethanolamines (PE), phosphatidylinositols (PI), glycerophosphoglycerols (PG), and phosphatidylserines (PS) for all treatments. However, the treatment with risperidone also affected diacylglycerides (DG), ceramide 1-phosphates (CerP), triglycerides (TG), sphingomyelins (SM), and ceramide phosphoinositols (PI-Cer). Moreover, specific lipid profiles were observed that could be used to distinguish poor and good responders to the different antipsychotics. As such, further work in this area may lead to lipid-based biomarkers that could be used to improve the clinical management of schizophrenia patients.
Assuntos
Antipsicóticos/uso terapêutico , Lipidômica/métodos , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Estudos de Coortes , Feminino , Humanos , Lipidômica/tendências , Masculino , Pessoa de Meia-Idade , Esquizofrenia/diagnóstico , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To determine whether changes in serum galectin-3 (gal-3) concentrations in schizophrenia patients have etiopathogenetic importance. Since very little research has assessed the connection between galectins and schizophrenia, we wanted to examine alterations in the inflammatory marker gal-3 in schizophrenia and investigate possible correlations between clinical symptomatology and serum concentrations. METHODS: Forty-eight schizophrenia patients and 44 healthy controls were included in this study. The Scale for the Assessment of Positive Symptoms (SAPS) and the Scale for the Assessment of Negative Symptoms (SANS) were administered to determine symptom severity. Venous blood samples were collected, and serum gal-3 levels were measured. RESULTS: Mean serum gal-3 levels were significantly lower in schizophrenia patients, and there were no significant differences in age or sex with the control group. There was also a significant positive correlation between serum gal-3 concentrations and negative schizophrenia symptoms according to the SANS. CONCLUSION: The results indicate that gal-3 is decreased in schizophrenia patients, which could contribute to inflammation in the pathogenesis of schizophrenia.
Assuntos
Galectina 3/sangue , Esquizofrenia/sangue , Biomarcadores/sangue , Feminino , Humanos , Inflamação , Masculino , Esquizofrenia/fisiopatologiaRESUMO
BACKGROUND: Imbalances in metal concentrations have been suggested to contribute to the pathophysiology of different brain disorders, such as bipolar disorder (BD) and schizophrenia (SCZ). OBJECTIVES: The aim of this exploratory study is to evaluate the association between the concentrations of macro/trace elements in serum from BD and SCZ patients considering the effects from different treatments. METHODS: Eleven subjects with SCZ, seven with BD treated with lithium (BDL) and eight subjects with BD treated with other medications except lithium (BDN) were recruited for the study, as well as eleven healthy controls (HC). Serum concentrations of eleven macro/trace elements (Se, Zn, Fe, K, Ca, Mg, P, Al, Cu, Mn, and Ni) were determined using inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: Se and Zn concentrations were significantly lower for patients with SCZ and BD in comparison to HC by one-way ANOVA test. Moreover, serum concentrations for Fe were significantly higher (p < 0.05) in BDN (548 ± 92 µg L-1) and SCZ (632 ± 279 µg L-1) in comparison to HC (421 ± 121 µg L-1). A significant negative correlation was reported between Se and Fe in BDL group (r = -0.935, p < 0.05). In addition, a significantly higher Cu/Zn ratio was determined in SCZ group against HC (ratio = 2.4, p = 0.028). CONCLUSIONS: The obtained results suggest that the imbalance in Fe concentrations is an effect of BD treatment. Lithium is supposed to have an antagonist effect for Se in BDL patients. A negative correlation reported between Fe and BMI in SCZ group could be related to antipsychotic treatment and the Cu/Zn ratio reported could be considered as a suggesting parameter to relate oxidative stress to SCZ. Future studies including larger number of patients with SCZ and BD before and after treatment are necessary to confirm the investigative results presented herein.
Assuntos
Transtorno Bipolar/tratamento farmacológico , Lítio/farmacologia , Esquizofrenia/tratamento farmacológico , Oligoelementos/farmacologia , Adulto , Biomarcadores/sangue , Transtorno Bipolar/sangue , Transtorno Bipolar/diagnóstico , Estudos de Coortes , Feminino , Humanos , Lítio/administração & dosagem , Lítio/sangue , Masculino , Espectrometria de Massas , Metabolômica , Estresse Oxidativo/efeitos dos fármacos , Proteômica , Esquizofrenia/sangue , Esquizofrenia/diagnóstico , Oligoelementos/administração & dosagem , Oligoelementos/sangueRESUMO
Aims: Recent findings suggest that cognitive impairment can be associated with inflammation and immune changes in schizophrenia. We aimed to study possible associations between cytokine levels and cognitive performance in a sample of patients with schizophrenia.Methods: Cognition was assessed with the brief assessment of cognition in schizophrenia in 63 clinically stable outpatients with schizophrenia. Blood was collected and cytokines (IL-2, IL-4, IL-6, IL-10, IL-17A, TNF-α, IFN-γ) were measured by cytometric bead array method. Psychopathological scales were also applied.Results: IL-6 correlated negatively with general cognitive performance (rho = -0.395, p = .017) and positively with antipsychotic dose (rho = 0.412, p = .004). Multiple regression analysis showed that cognitive performance is associated with age and antipsychotic dose (p = .000 and p = .033).Conclusion: The association between IL-6 levels and cognitive performance is dependent on age and antipsychotic dose.
Assuntos
Antipsicóticos/uso terapêutico , Cognição/efeitos dos fármacos , Interleucina-6/sangue , Testes de Estado Mental e Demência , Esquizofrenia/sangue , Esquizofrenia/tratamento farmacológico , Adulto , Fatores Etários , Antipsicóticos/farmacologia , Biomarcadores/sangue , Cognição/fisiologia , Estudos Transversais , Citocinas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Psicologia do Esquizofrênico , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangueRESUMO
RATIONALE: An evaluation of bipolar disorder (BD) and schizophrenia (SCZ) was carried out, from a metallomics point of view, using native conditions, attempting to preserve the interaction between metals and biomolecules. METHOD: For this task, blood serum samples from healthy individuals and patients were compared. In addition, the profiles of metal ions and metalloids involved in the pathologies were quantified, and a comparison was carried out of the protein profile in serum samples of healthy individuals and diseased patients. RESULTS: After optimization and accuracy evaluation of the method, different concentrations of Li, Mg, Mn and Zn were observed in the samples of BD patients and high levels of copper for SCZ patients, indicating an imbalance in the homeostasis of important micronutrients. The treatment, especially with lithium, may be related to competition between metallic ions. BD-related metallobiomolecules were detected, preserving the binding between metal ions and biomolecules, with four fractions detected in the ultraviolet range (280 nm). Four fractions were collected by high-performance liquid chromatography/inductively coupled plasma mass spectrometry (HPLC/ICP-MS) and the proteins were identified by liquid chromatography/tandem mass spectrometry (LC/MS/MS). The Ig lambda chain V-IV region Hil, immunoglobulin heavy constant gama 1 (IGHG1) and beta-2-glycoprotein 1 (or ApoH) was identified in SCZ samples, suggesting its relationship with mood disorders. Surprisingly, Protein IGKV2D-28 was identified only in BD samples, opening up new possibilities for studies regarding the role of this protein in BD. CONCLUSIONS: This approach brings new perspectives to the comprehension of mood disorders, highlighting the importance of metallomics science in disease development. This strategy showed an innovative potential for evaluating mood disorders at the proteomic level, making it possible to identify proteins related to mood disorders and BD.