RESUMO
SUMMARY: Volume abnormalities in subcortical structures, including the hippocampus, amygdala, thalamus, caudate, putamen, and globus pallidus have been observed in schizophrenia (SZ) and bipolar disorder (BD), not all individuals with these disorders exhibit such changes. In addition, the specific patterns and severity of volume changes may vary between individuals and at different stages of the disease. The study aims to compare the volumes of these subcortical structures between healthy subjects and individuals diagnosed with SZ or BD. Volumetric measurements of lateral ventricle, globus palllidus, caudate, putamen, hippocampus, and amygdale were made by MRI in 52 healthy subjects (HS), 33 patients with SZ, and 46 patients with BD. Automatic segmentation methods were used to analyze the MR images with VolBrain and MRICloud. Hippocampus, amygdala and lateral ventricle increased in schizophrenia and bipolar disorder patients in comparison with control subjects using MRIcloud. Globus pallidus and caudate volume increased in patients with schizophrenia and bipolar disorder compared control subjects using Volbrain. We suggested that our results will contribute in schizophrenia and bipolar disorder patients that assessment of the sub-cortical progression, pathology, and anomalies of subcortical brain compositions. In patients with psychiatric disorders, VolBrain and MRICloud can detect subtle structural differences in the brain.
Se han observado anomalías de volumen en las estructuras subcorticales, incluidos el hipocampo, la amígdala, el tálamo, el núcleo caudado, el putamen y el globo pálido, en la esquizofrenia (SZ) y el trastorno bipolar (BD); no todos los individuos con estos trastornos presentan tales cambios. Además, los patrones específicos y la gravedad de los cambios de volumen pueden variar entre individuos y en diferentes etapas de la enfermedad. El estudio tuvo como objetivo comparar los volúmenes de estas estructuras subcorticales entre sujetos sanos e individuos diagnosticados con SZ o BD. Se realizaron mediciones volumétricas del ventrículo lateral, globo pálido, núcleo caudado, putamen, hipocampo y amígdala mediante resonancia magnética en 52 sujetos sanos (HS), 33 pacientes con SZ y 46 pacientes con BD. Se utilizaron métodos de segmentación automática para analizar las imágenes de resonancia magnética con VolBrain y MRICloud. El hipocampo, la amígdala y el ventrículo lateral aumentaron en pacientes con esquizofrenia y trastorno bipolar en comparación con sujetos de control que utilizaron MRIcloud. El globo pálido y el núcleo caudado aumentaron en pacientes con esquizofrenia y trastorno bipolar en comparación con los sujetos control que utilizaron Volbrain. Sugerimos que en pacientes con esquizofrenia y trastorno bipolar, nuestros resultados contribuirán a la evaluación de la progresión subcortical, la patología y las anomalías de las composiciones cerebrales subcorticales. En pacientes con trastornos psiquiátricos, VolBrain y MRICloud pueden detectar diferencias estructurales sutiles en el cerebro.
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Esquizofrenia/diagnóstico por imagem , Transtorno Bipolar/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Tamanho do Órgão , Esquizofrenia/patologia , Transtorno Bipolar/patologia , Estudos Transversais , Estudos Retrospectivos , Computação em NuvemRESUMO
Bipolar disorder shares symptoms and pathological pathways with other neurodegenerative diseases, including frontotemporal dementia (FTD). Since TAR DNA-binding protein 43 (TDP-43) is a neuropathological marker of frontotemporal dementia and it is involved in synaptic transmission, we explored the role of TDP-43 as a molecular feature of bipolar disorder (BD). Homogenates were acquired from frozen hippocampus of postmortem brains of bipolar disorder subjects. TDP-43 levels were quantified using an ELISA-sandwich method and compared between the postmortem brains of bipolar disorder subjects and age-matched control group. We found higher levels of TDP-43 protein in the hippocampus of BD (n = 15) subjects, when compared to controls (n = 15). We did not find associations of TDP-43 with age at death, postmortem interval, or age of disease onset. Our results suggest that protein TDP-43 may be potentially implicated in behavioral abnormalities seen in BD. Further investigation is needed to validate these findings and to examine the role of this protein during the disease course and mood states.
Assuntos
Transtorno Bipolar , Demência Frontotemporal , Transtorno Bipolar/patologia , Encéfalo/metabolismo , Proteínas de Ligação a DNA/metabolismo , Demência Frontotemporal/diagnóstico , Hipocampo/patologia , HumanosRESUMO
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: Bipolar disorder (BD) is highly heritable. The present study aimed at identifying brain morphometric features that could represent markers of BD vulnerability in non-bipolar relatives of bipolar patients. Methods: In the present study, structural magnetic resonance imaging brain scans were acquired from a total of 93 subjects, including 31 patients with BD, 31 non-bipolar relatives of BD patients, and 31 healthy controls. Volumetric measurements of the anterior cingulate cortex (ACC), lateral ventricles, amygdala, and hippocampus were completed using the automated software FreeSurfer. Results: Analysis of covariance (with age, gender, and intracranial volume as covariates) indicated smaller left ACC volumes in unaffected relatives as compared to healthy controls and BD patients (p = 0.004 and p = 0.037, respectively). No additional statistically significant differences were detected for other brain structures. Conclusion: Our findings suggest smaller left ACC volume as a viable biomarker candidate for BD.
Assuntos
Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Transtorno Bipolar/patologia , Giro do Cíngulo/patologia , Hipocampo/patologia , Transtorno Bipolar/genética , Imageamento por Ressonância Magnética , Família , Estudos de Casos e Controles , Endofenótipos , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Bipolar disorder (BD) is highly heritable. The present study aimed at identifying brain morphometric features that could represent markers of BD vulnerability in non-bipolar relatives of bipolar patients. METHODS: In the present study, structural magnetic resonance imaging brain scans were acquired from a total of 93 subjects, including 31 patients with BD, 31 non-bipolar relatives of BD patients, and 31 healthy controls. Volumetric measurements of the anterior cingulate cortex (ACC), lateral ventricles, amygdala, and hippocampus were completed using the automated software FreeSurfer. RESULTS: Analysis of covariance (with age, gender, and intracranial volume as covariates) indicated smaller left ACC volumes in unaffected relatives as compared to healthy controls and BD patients (p = 0.004 and p = 0.037, respectively). No additional statistically significant differences were detected for other brain structures. CONCLUSION: Our findings suggest smaller left ACC volume as a viable biomarker candidate for BD.
Assuntos
Transtorno Bipolar/patologia , Giro do Cíngulo/patologia , Hipocampo/patologia , Adulto , Transtorno Bipolar/genética , Estudos de Casos e Controles , Endofenótipos , Família , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The present study evaluated the effects of AR-A014418 on behavioral and oxidative stress parameters of rats submitted to the animal model of mania induced by ouabain (OUA). Wistar rats were submitted to stereotaxic surgery and received a single intracerebroventricular (ICV) injection of artificial cerebrospinal fluid (aCSF), OUA, or AR-A014418. After 7 days, the animals were submitted to open-field test. After behavioral analysis, the brains were dissected in frontal cortex and hippocampus to the evaluation of oxidative stress. The OUA induced manic-like behavior in rats, which was reversed by AR-A014418 treatment. The ICV administration of OUA increases the levels of superoxide in submitochondrial particles, lipid hydroperoxide (LPH), 4-hydroxynonenal (4-HNE), 8-isoprostane, protein carbonyl, 3-nitrotyrosine, and activity of superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione reductase (GR) in both structures evaluated. In general, the treatment with AR-A014418 reversed these effects of OUA on the submitochondrial particles, LPH, 4-HNE, 8-isoprostane, protein carbonyl, 3-nitrotyrosine levels, and SOD activity. Furthermore, the injection of OUA decreased the catalase activity, and AR-A014418 promoted an increase in activity of this enzyme in the brain structures. These results suggest that GSK-3ß inhibition can modulate manic-like behaviors. Also, it can be suggested that inhibition of GSK-3ß can be effective against oxidative stress. However, more studies are needed to better elucidate these mechanisms. Graphical Abstract The effects of AR-A014418 on the behavioral and oxidative stress parameters in the animal model of mania induced by ouabain. Superoxide = superoxide production in submitochondrial particles; LPH = lipid hydroperoxide; 4-HNE = 4-hydroxynonenal; SOD = superoxide dismutase; GPx = glutathione peroxidase; GR = glutathione reductase.
Assuntos
Comportamento Animal , Transtorno Bipolar/enzimologia , Transtorno Bipolar/patologia , Glicogênio Sintase Quinase 3 beta/antagonistas & inibidores , Estresse Oxidativo , Aldeídos/metabolismo , Animais , Antioxidantes/metabolismo , Comportamento Animal/efeitos dos fármacos , Transtorno Bipolar/fisiopatologia , Catalase/metabolismo , Dinoprosta/análogos & derivados , Dinoprosta/metabolismo , Modelos Animais de Doenças , Glutationa Peroxidase/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Atividade Motora/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Carbonilação Proteica/efeitos dos fármacos , Ratos Wistar , Partículas Submitocôndricas/efeitos dos fármacos , Partículas Submitocôndricas/metabolismo , Superóxido Dismutase/metabolismo , Superóxidos/metabolismo , Tiazóis/administração & dosagem , Tiazóis/farmacologia , Tirosina/análogos & derivados , Tirosina/metabolismo , Ureia/administração & dosagem , Ureia/análogos & derivados , Ureia/farmacologiaRESUMO
Accumulating evidence indicates that oxidative and nitrosative stress (O&NS) pathways play a key role in the pathophysiology of bipolar disorder (BD) and major depressive disorder (MDD). However, only a handful of studies have directly compared alterations in O&NS pathways among patients with MDD and BD types I (BPI) and BPII. Thus, the current study compared superoxide dismutase (SOD1), lipid hydroperoxides (LOOH), catalase, nitric oxide metabolites (NOx), malondialdehyde (MDA), and advanced oxidation protein products (AOPP) between mood disorder patients in a clinically remitted state. To this end 45, 23, and 37 participants with BPI, BPII, and MDD, respectively, as well as 54 healthy controls (HCs) were recruited. Z-unit weighted composite scores were computed as indices of reactive oxygen species (ROS) production and nitro-oxidative stress driving lipid or protein oxidation. SOD1, NOx, and MDA were significantly higher in MDD than in the other three groups. AOPP was significantly higher in BPI than in HCs and BPII patients. BPII patients showed lower SOD1 compared to all other groups. Furthermore, MDD was characterized by increased indices of ROS and lipid hydroperoxide production compared to BPI and BPII groups. Indices of nitro-oxidative stress coupled with aldehyde production or protein oxidation were significantly different among the three patient groups (BDII > BDI > MDD). Finally, depressive symptom scores were significantly associated with higher LOOH and AOPP levels. In conclusion, depression is accompanied by increased ROS production, which is insufficiently dampened by catalase activity, thereby increasing nitro-oxidative damage to lipids and aldehyde production. Increased protein oxidation with formation of AOPP appeared to be hallmark of MDD and BPI. In addition, patients with BPII may have protection against the damaging effects of ROS including lipid peroxidation and aldehyde formation. This study suggests that biomarkers related to O&NS could aid in the differentiation of MDD, BPI, and BPII.
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Transtorno Bipolar/patologia , Transtorno Depressivo Maior/patologia , Estresse Nitrosativo , Estresse Oxidativo , Adulto , Biomarcadores/metabolismo , Estudos de Casos e Controles , Fatores de Confusão Epidemiológicos , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Superóxidos/metabolismo , Adulto JovemRESUMO
An early stage of behavioral variant frontotemporal dementia (bvFTD) often displays a mix of behavioral disturbances and personality changes hindering a differential diagnosis from elderly bipolar disorder (BD), making this process a big challenge. However, no studies have compared these pathologies from neuropsychological and neuroanatomical perspectives. The aim of the present study was to compare the executive functions (EF) and social cognition profiles as well as the structural neuroimaging of bvFTD and elderly patients with BD. First, we compared the executive and social cognition performances of 16 bvFTD patients, 13 BD patients and 22 healthy controls. Second, we compared grey matter volumes in both groups of patients and controls using voxel-based morphometry. Lastly, we examined the brain regions where atrophy might be associated with specific impairments in bvFTD and BD patients. Compared to controls, bvFTD patients showed deficits in working memory, abstraction capacity, inhibitory control, cognitive flexibility, verbal fluency and theory of mind (ToM). Patients with BD showed lower performance than controls in terms of abstraction capacity and verbal inhibitory control. In bvFTD patients, atrophy of frontal, temporal and insular cortices was related to EF deficits. Atrophy of the amygdala, the hippocampus, the parahippocampal gyrus, the putamen, the insula, the precuneus, the right temporo-parietal junction and superior temporal pole was associated to ToM impairments. No significant associations between atrophy and EF performance were observed in BD patients. BvFTD patients showed greater EF and ToM deficits than BD patients. Moreover, compared to BD, bvFTD patients exhibited a significant decrease in GM volume in frontal, temporal and parietal regions. Our results provide the first comparison of EF, social cognition and neuroanatomical profiles of bvFTD and elderly BD patients. These findings shed light on differential diagnosis of these disorders and may have important clinical implications.
Assuntos
Transtorno Bipolar/patologia , Transtorno Bipolar/fisiopatologia , Córtex Cerebral/patologia , Função Executiva/fisiologia , Demência Frontotemporal/patologia , Demência Frontotemporal/fisiopatologia , Substância Cinzenta/patologia , Percepção Social , Teoria da Mente/fisiologia , Idade de Início , Idoso , Atrofia/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
INTRODUCTION: Bipolar disorder (BD) is a debilitating mood condition that affects approximately 1.3% of people worldwide, although some studies report up to 3.9% lifetime prevalence and 4-6% in adults when broad diagnostic criteria are applied. OBJECTIVE: To compare differences in total white matter (WM), corpus callosum (CC) and total gray matter (GM) volumes in patients with type I BD at early and late stages compared with controls. METHODS: Fifty-five subjects were enrolled in this study protocol. The double case-control design included 14 patients with BD at early stage; 15 patients at late stage; and their respective matched controls (14 and 12 subjects). RESULTS: CC and total WM volumes were significantly smaller in patients with BD at early and late stages vs. controls. There was no difference for total GM volume in the early stage group, but in patients at late stage total GM volume was significantly smaller than in controls. The total GM volume reduction in patients at late stage is in agreement with the neuroprogression theory of BD. The reduction of WM volumes in total WM and in the CC at early and late stages supports the possibility that an early demyelination process could occur underlying the clinical manifestation of BD. CONCLUSION: Our findings may direct to the investigation of WM abnormalities in populations at high risk to develop BD, perhaps as early biomarkers before the overt syndrome.
Assuntos
Transtorno Bipolar/diagnóstico por imagem , Substância Branca/diagnóstico por imagem , Adulto , Transtorno Bipolar/patologia , Estudos de Casos e Controles , Corpo Caloso/diagnóstico por imagem , Corpo Caloso/patologia , Progressão da Doença , Feminino , Substância Cinzenta/diagnóstico por imagem , Substância Cinzenta/patologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Substância Branca/patologiaRESUMO
Abstract Introduction: Bipolar disorder (BD) is a debilitating mood condition that affects approximately 1.3% of people worldwide, although some studies report up to 3.9% lifetime prevalence and 4-6% in adults when broad diagnostic criteria are applied. Objective: To compare differences in total white matter (WM), corpus callosum (CC) and total gray matter (GM) volumes in patients with type I BD at early and late stages compared with controls. Methods: Fifty-five subjects were enrolled in this study protocol. The double case-control design included 14 patients with BD at early stage; 15 patients at late stage; and their respective matched controls (14 and 12 subjects). Results: CC and total WM volumes were significantly smaller in patients with BD at early and late stages vs. controls. There was no difference for total GM volume in the early stage group, but in patients at late stage total GM volume was significantly smaller than in controls. The total GM volume reduction in patients at late stage is in agreement with the neuroprogression theory of BD. The reduction of WM volumes in total WM and in the CC at early and late stages supports the possibility that an early demyelination process could occur underlying the clinical manifestation of BD. Conclusion: Our findings may direct to the investigation of WM abnormalities in populations at high risk to develop BD, perhaps as early biomarkers before the overt syndrome.
Resumo Introdução: O transtorno do humor bipolar (THB) é uma condição debilitante que afeta aproximadamente 1,3% das pessoas em todo o mundo, embora alguns estudos relatem uma prevalência acumulada de até 3,9% e de 4-6% em adultos quando os critérios diagnósticos mais abrangentes são aplicados. Objetivo: Comparar as diferenças nos volumes totais de substância branca (SB), corpo caloso (CC) e volume total de substância cinzenta (SC) em pacientes com THB tipo I em estágios iniciais e tardios em comparação com controles. Métodos: Cinquenta e cinco sujeitos foram incluídos neste protocolo de estudo. O desenho de caso com duplo controle incluiu 14 pacientes com THB em estágio inicial; 15 pacientes com THB em fase tardia; e seus respectivos controles correspondentes (14 e 12 sujeitos). Resultados: Os volumes do CC e total de SB foram significativamente menores nos pacientes com THB nos estágios iniciais e tardios vs. controles. Não houve diferença para o volume total de SC no grupo em estágio inicial, mas em pacientes em fase tardia o volume total de SC foi significativamente menor do que nos controles. A redução do volume total de SC em pacientes em fase tardia está de acordo com a teoria da neuroprogressão do THB. A redução dos volumes de SB em SB total e no CC em fases precoces e tardias suporta a possibilidade de que um processo de desmielinização precoce poderia ocorrer subjacente à manifestação clínica de THB. Conclusão: Nossos achados podem direcionar a investigação de anormalidades da SB em populações de alto risco para o desenvolvimento de THB, talvez como biomarcadores precoces antes da síndrome aberta.