Resumo Introdução: O objetivo deste estudo foi comparar os pacientes com transtorno bipolar (TB), seus familiares de primeiro grau e um grupo de controles saudáveis em termos de uso de estratégias adaptativas e não adaptativas, explorando diferenças entre tipos específicos de estratégias e suas correlações com variáveis clínicas. Métodos: Estudo transversal, envolvendo 36 pacientes com TB eutímicos, 39 familiares de primeiro grau e 44 controles. As estratégias de enfrentamento foram avaliadas usando a escala Brief COPE. Resultados: Foram detectadas diferenças significativas no uso de estratégias adaptativas e não adaptativas por pacientes, seus familiares e controles. Os pacientes usaram estratégias adaptativas com menos frequência do que os familiares (p<0,001) e controles (p=0,003). Não houve diferença significativa entre familiares dos pacientes e controles (p=0,707). Por outro lado, os pacientes (p<0,001) e seus familiares (p=0,004) exibiram pontuações mais elevadas para coping não adaptativo em relação aos controles. Não houve diferença significativa quando os pacientes foram comparados com seus familiares (p=0,517). Conclusões: Familiares de primeiro grau estavam em um nível intermediário entre pacientes com TB e controles no que diz respeito ao uso de habilidades de enfrentamento. Esta descoberta apoia o desenvolvimento de intervenções psicossociais para incentivar o uso de estratégias adaptativas em vez de estratégias inadequadas nessa população.
Objective: Cardiovascular disease is the leading cause of death in patients with bipolar disorder. The aim of this study was to evaluate the factors associated with positive coronary calcium score (CCS) in individuals with bipolar disorder type 1. Methods: Patients from the Bipolar Disorder Program at Hospital de Clínicas de Porto Alegre, Brazil, underwent computed tomography scanning for calcium score measurement. Clinical and sociodemographic variables were compared between patients according to their CCS status: negative (CCS = 0) or positive (CCS > 0). Poisson regression analysis was used to examine the association of CCS with number of psychiatric hospitalizations. Results: Out of 41 patients evaluated, only 10 had a positive CCS. Individuals in the CCS-positive group were older (55.2±4.2 vs. 43.1±10.0 years; p = 0.001) and had more psychiatric hospitalizations (4.7±3.0 vs. 2.6±2.5; p = 0.04) when compared with CCS- negative subjects. The number of previous psychiatric hospitalizations correlated positively with CCS (p < 0.001). Conclusion: Age and number of psychiatric hospitalizations were significantly associated with higher CCS, which might be a potential method for diagnosis and stratification of cardiovascular disease in bipolar patients. There is a need for increased awareness of risk assessment in this population.
Objective: To assess cognitive performance and psychosocial functioning in patients with bipolar disorder (BD), in unaffected siblings, and in healthy controls. Methods: Subjects were patients with BD (n=36), unaffected siblings (n=35), and healthy controls (n=44). Psychosocial functioning was accessed using the Functioning Assessment Short Test (FAST). A sub-group of patients with BD (n=21), unaffected siblings (n=14), and healthy controls (n=22) also underwent a battery of neuropsychological tests: California Verbal Learning Test (CVLT), Stroop Color and Word Test, and Wisconsin Card Sorting Test (WCST). Clinical and sociodemographic characteristics were analyzed using one-way analysis of variance or the chi-square test; multivariate analysis of covariance was used to examine differences in neuropsychological variables. Results: Patients with BD showed higher FAST total scores (23.90±11.35) than healthy controls (5.86±5.47; p < 0.001) and siblings (12.60±11.83; p 0.001). Siblings and healthy controls also showed statistically significant differences in FAST total scores (p = 0.008). Patients performed worse than healthy controls on all CVLT sub-tests (p < 0.030) and in the number of correctly completed categories on WCST (p = 0.030). Siblings did not differ from healthy controls in cognitive tests. Conclusion: Unaffected siblings of patients with BD may show poorer functional performance compared to healthy controls. FAST scores may contribute to the development of markers of vulnerability and endophenotypic traits in at-risk populations.
Objectives:Staging models for medical diseases are widely used to guide treatment and prognosis. Bipolar disorder (BD) is a chronic condition and it is among the most disabling disorders in medicine. The staging model proposed by Kapczinski in 2009 presents four progressive clinical stages of BD. Our aim was to evaluate pharmacological maintenance treatment across these stages in patients with BD.Methods:One hundred and twenty-nine subjects who met DSM-IV criteria for BD were recruited from the Bipolar Disorders Program at Hospital de Clínicas de Porto Alegre, Brazil. All patients were in remission. The subjects were classified according to the staging model: 31 subjects were classified as stage I, 44 as stage II, 31 as stage III, and 23 as stage IV.Results:Patterns of pharmacological treatment differed among the four stages (p = 0.001). Monotherapy was more frequent in stage I, and two-drug combinations in stage II. Patients at stages III and IV needed three or more medications or clozapine. Impairment in functional status (Functioning Assessment Short Test [FAST] scale scores) correlated positively with the number of medications prescribed.Conclusions:This study demonstrated differences in pharmacological treatment in patients with stable BD depending on disease stage. Treatment response can change with progression of BD. Clinical guidelines could consider the staging model to guide treatment effectiveness.
INTRODUÇÃO:Níveis crescentes de evidência sugerem que o transtorno bipolar (TB) exibe um caráter progressivo, em nível tanto clínico, quanto bioquímico e neuroimagiológico. Este estudo revisa a literatura existente sobre a relação entre biomarcadores específicos e estágios do TB.MÉTODOS:Uma busca extensa da literatura nas bases de dados MEDLINE e PubMed foi conduzida para identificar estudos publicados em inglês e em português utilizando as palavras-chave biomarker (biomarcador), neurotrophic factors (fatores neurotróficos), inflammation (inflamação), oxidative stress (estresse oxidativo), neuroprogression (neuroprogressão) e staging models (modelos de estadiamento), em referência cruzada com o termo bipolar disorder (transtorno bipolar).RESULTADOS:Estudos morfométricos em doentes bipolares mostraram a existência de alterações neuroanatômicas, tais como o alargamento dos ventrículos, a perda de substância cinzenta no hipocampo e no cerebelo, a diminuição do volume de determinadas áreas do córtex pré-frontal e variações no tamanho da amígdala. Além disso, outros estudos apontam para a potencialidade do uso dos valores séricos dos fatores neurotróficos, de mediadores inflamatórios e de estresse oxidativo como biomarcadores do TB.CONCLUSÕES: O conhecimento das alterações neurobiológicas, associadas à progressão e atividade do TB, é fundamental para a identificação de biomarcadores. A incorporação de biomarcadores nos modelos de estadiamento do TB poderá permitir um aperfeiçoamento dos algoritmos terapêuticos, possibilitando a elaboração de esquemas de tratamento mais personalizados e eficazes, com destaque para a importância da intervenção precoce na atenuação da progressão da doença.
INTRODUCTION: A growing body of evidence suggests that bipolar disorder (BD) is a progressive disease according to clinical, biochemical and neuroimaging findings. This study reviewed the literature on the relationship between specific biomarkers and BD stages.METHODS: A comprehensive literature search of MEDLINE and PubMed was conducted to identify studies in English and Portuguese using the keywords biomarker, neurotrophic factors, inflammation, oxidative stress, neuroprogression and staging models cross-referenced with bipolar disorder.RESULTS: Morphometric studies of patients with BD found neuroanatomic abnormalities, such as ventricular enlargement, grey matter loss in the hippocampus and cerebellum, volume decreases in the prefrontal cortex and variations in the size of the amygdala. Other studies demonstrated that serum concentrations of neurotrophic factors, inflammatory mediators and oxidative stress may be used as BD biomarkers.CONCLUSIONS: The analysis of neurobiological changes associated with BD progression and activity may confirm the existence of BD biomarkers, which may be then included in staging models that will lead to improvements in treatment algorithms and more effective, individually tailored treatment regimens. Biomarkers may also be used to define early interventions to control disease progression.
Frequentemente, a compactação limita a produtividade das culturas anuais em solos mecanizados, sendo a sua distribuição na lavoura regionalizada. Em área manejada sob sistema plantio direto (SPD) por longo prazo, foi investigada a variabilidade espacial da resistência à penetração (RP), a eficiência de escarificadores mecânicos e o seu efeito na produtividade da soja. O solo foi Latossolo Vermelho argiloso localizado no planalto do RS. O clima é subtropical Cfa com precipitação pluvial anual de 1.750 mm e temperatura média anual de 18,7 ºC. O delineamento experimental foi de blocos casualizados com quatro tratamentos e duas repetições. Os tratamentos foram implantados em faixas paralelas de 100 × 20 m. Os tratamentos investigados foram: escarificador sítio-específico com profundidade de atuação variada em razão da RP (ESEV); escarificador convencional (EC) com profundidade fixa; escarificador sítio-específico com profundidade fixa (ESEF); e testemunha - sem escarificação (SE). Para avaliar a RP, utilizou-se um penetrômetro digital com leituras georrefenciadas em malha de 50 × 50 m realizadas manualmente em duas épocas. A produtividade da soja foi obtida por meio de uma colhedora equipada com sensor de produtividade e antena receptora de sinal de GPS. A RP apresentou valores médios de 1,4 e 2,1 MPa, para leituras realizadas após o manejo da cultura de cobertura e após a colheita, respectivamente. A RP determinada após o manejo da cultura de cobertura e a produtividade da soja apresentaram baixa correlação (r² = -0,297; p<0,05). Os valores de RP de 3,0 e 5,0 MPa resultaram em decréscimos de aproximadamente 10 e 38 % na produtividade da soja, respectivamente. A escarificação mecânica, independentemente do equipamento utilizado, não incrementou a produtividade da soja em relação à testemunha. Esse resultado foi atribuído à RP da área a ser classificada, quando da instalação dos tratamentos, como baixa/moderada, à ocorrência de frequente precipitação pluvial e às favoráveis condições físico-hídricas proporcionadas pelo SPD de longa duração.
Frequently, soil compaction limits the yield of grain crops in mechanized lands, and its spatial distribution in the cropland is usually regionalized. In an area managed under long-term no-tillage, we investigated the relationship between soil penetration resistance (PR) and soybean yield, the effectiveness of types of chisel plows, and their effect on soybean yield. The soil from the plateau region of the state of Rio Grande do Sul, Brazil, was classified as a clayey Oxisol. The climate is subtropical (Cfa - Köppen classification), with annual rainfall of 1,750 mm and mean annual temperature of 18.7 ºC. A completely randomized block experimental design was used with four treatments and two replications. The treatments, arranged in parallel strips of 100 × 20 m, were: a) site-specific chisel plow with variable depth according to soil penetration resistance (PR) (ESEV); b) conventional chisel plow (EC) with fixed depth; c) site-specific chisel plow with fixed depth (ESEF); d) control - without chisel plowing (SE). To evaluate PR, a digital penetrometer with georeferenced readings with a 50 × 50 m grid was used, with two evaluation periods. Soybean grain yield was obtained through a combine equipped with a yield sensor and GPS satellite receiver. A mean value of 1.4 MPa was observed for RP after cover crop management practices and a mean value of 2.1 after harvest. The RP reading after cover crop management and soybean grain yield exhibited poor correlation (r² = -0.297; p<0.05). The PR values of 3.0 and 5.0 MPa resulted in decreases of approximately 10 and 38 % of soybean grain yields, respectively. Chisel plowing, regardless of the piece type of equipment used, did not increase soybean yield compared to the control without soil tillage. This result was attributed to the frequent rainfall and good physical and hydraulic conditions of long-term no-till.
Objective: High cardiovascular mortality rates have been reported in patients with bipolar disorder (BD). Studies indicate that matrix metalloproteinases (MMPs) are implicated in cardiovascular diseases. We evaluated the expression pattern of MMP-2 and MMP-9 in blood from patients with BD during acute mania and after euthymia, in comparison with healthy controls. Methods: Twenty patients and 20 controls were recruited and matched for sex and age. MMP messenger RNA (mRNA) levels were measured using real-time quantitative polymerase chain reaction (PCR). Body mass index (BMI) was calculated for all subjects. Results: There were no significant differences in MMP-2 and MMP-9 mRNA expression between patients and controls. mRNA levels were not significantly different during mania and euthymia. However, MMP-2 mRNA levels were negatively associated with BMI in BD patients and positively associated with BMI in controls. There was no difference in the pattern of MMP-9 expression between patients and controls. Conclusions: Our results suggest a different pattern of association between MMP-2 and BMI in BD patients as compared with controls. Despite some study limitations, we believe that the role of MMPs in BD should be further investigated to elucidate its relationship with cardiovascular risk.
Objective: To evaluate serum levels of different biomarkers associated with cardiovascular disease in patients with bipolar disorder (BD). Patients were prospectively evaluated in two separate instances: during acute mania and after remission of manic symptoms. All measurements were compared with those of healthy controls. Methods: The study included 30 patients with BD and 30 healthy controls, matched for gender and age. Biochemical parameters evaluated included homocysteine (Hcy), folic acid, vitamin B12, ferritin, creatine kinase (CK) and C-reactive protein (CRP). Results: Hcy levels were significantly higher in the BD patients, both during mania and after achieving euthymia. When Hcy was adjusted for body mass index, there was no significant difference between patients and controls. Ferritin was the only marker that showed a significant decrease during mania when compared to both euthymic patients and controls. There were no significant differences for folate, vitamin B12, CK and CRP. Conclusions: These findings do not show an association between alterations of markers of cardiovascular risk during manic episodes. Further studies are necessary to determine factors and mechanisms associated with cardiovascular risk in patients with BD.
INTRODUCTION: The use of clinical staging models is emerging as a novel and useful paradigm for diagnosing severe mental disorders. The term "neuroprogression" has been used to define the pathological reorganization of the central nervous system along the course of severe mental disorders. In bipolar disorder (BD), neural substrate reactivity is changed by repeated mood episodes, promoting a brain rewiring that leads to an increased vulnerability to life stress. METHOD: A search in the PubMed database was performed with the following terms: "staging", "neuroprogression", "serum", "plasma", "blood", "neuroimaging", "PET scan", "fMRI", "neurotrophins", "inflammatory markers" and "oxidative stress markers", which were individually crossed with "cognition", "functionality", "response to treatments" and "bipolar disorder". The inclusion criteria comprised original papers in the English language. Abstracts from scientific meetings were not included. RESULTS: We divided the results according to the available evidence of serum biomarkers as potential mediators of neuroprogression, with brain imaging, cognition, functioning and response to treatments considered as consequences. CONCLUSION: The challenge in BD treatment is translating the knowledge of neuronal plasticity and neurobiology into clinical practice. Neuroprogression and staging can have important clinical implications, given that early and late stages of the disorder appear to present different biological features and therefore may require different treatment strategies.
OBJETIVO: Pesquisas sugerem as citocinas como potenciais mediadores da interação entre os sistemas imune e neuroendócrino, e que existe um estado pró-inflamatório associado com transtorno bipolar e esquizofrenia. O objetivo deste estudo é comparar os níveis de citocinas entre os dois distúrbios. MÉTODO: Vinte pacientes com transtorno bipolar eutímicos, 53 pacientes com esquizofrenia cronicamente estabilizados e 80 controles saudáveis foram recrutados. Todos os indivíduos são não-fumantes e não-obesos. As citocinas TNF-α, IL-6 e IL-10 foram examinadas por ELISA sanduíche. RESULTADOS: A IL-6 estava aumentada nos pacientes com esquizofrenia quando comparados aos controles (p < 0,0001) e aos pacientes bipolares eutímicos (p < 0,0001). Os níveis de IL-6 não foram diferentes nos controles em comparação com pacientes com transtorno bipolar eutímicos (p = 0,357). Os níveis de IL-10 foram menores nos controles quando comparados aos esquizofrenia (p = 0,001) ou aos bipolares (p = 0,004). Não houve diferença significativa nos níveis séricos de TNF-α entre os grupos (p = 0,284). A separação por sexo não mostrou diferenças significativas e não houve correlação entre a dose de antipsicóticos e os níveis de citocinas em pacientes com esquizofrenia. DISCUSSÃO: Estes resultados evidenciam uma ativação imune crônica na esquizofrenia. O transtorno bipolar parece apresentar um aumento da atividade inflamatória relacionado ao episódio de humor. Níveis maiores de IL-10 no transtorno bipolar e esquizofrenia sugerem diferentes padrões de equilíbrio inflamatório entre esses dois transtornos. Resultados fornecem apoio adicional para a investigação de citocinas como possíveis biomarcadores para a atividade da doença ou resposta ao tratamento.
OBJECTIVE: Previous reports suggest that cytokines act as potential mediators of the interaction between the immune and neuroendocrine systems, and that a proinflammatory state may be associated with bipolar disorder and schizophrenia. The aim is to compare cytokine levels in both disorders. METHOD: Twenty euthymic bipolar disorder patients, 53 chronic stabilized schizophrenia patients and 80 healthy controls were recruited. Subjects were all non-smokers and non-obese. Cytokines TNF-α, IL-6, and IL-10 were examined by sandwich ELISA. RESULTS: IL-6 levels were increased in schizophrenia patients when compared to controls (p < 0.0001) and euthymic bipolar disorder patients (p < 0.0001). IL-6 levels were no different in controls compared to euthymic bipolar disorder patients (p = 0.357). IL-10 was lower in controls compared to schizophrenia patients (p = 0.001) or to bipolar disorder patients (p = 0.004). There was no significant difference in TNF-α serum levels among the groups (p = 0.284). Gender-based classification did not significantly alter these findings, and no correlation was found between the antipsychotic dose administered and cytokine levels in patients with schizophrenia. DISCUSSION: These findings evidence a chronic immune activation in schizophrenia. Bipolar disorder seems to present an episode-related inflammatory syndrome. Increased anti-inflammatory factor IL-10 in bipolar disorder and schizophrenia suggests different patterns of inflammatory balance between these two disorders. Results further support the need to investigate cytokines as possible biomarkers of disease activity or treatment response.
CONTEXTO: O transtorno bipolar (TB) está associado a uma significativa morbi-mortalidade por causas metabólicas. Existem poucos dados sobre a prevalência de resistência à insulina (RI) e sua relação com a síndrome metabólica (SM) em pacientes com TB. OBJETIVO: Avaliar a prevalência de RI e SM em pacientes bipolares ambulatoriais e identificar os parâmetros clínicos associados à RI. MÉTODO: Estudo transversal em 65 pacientes com TB diagnosticados pelos critérios do DSM-IV-TR, avaliados de forma consecutiva no Programa de Transtorno Bipolar do Hospital de Clínicas de Porto Alegre, Brasil. RI foi diagnosticada utilizando o homeostatic model assessment - insulin resistance (HOMA-IR) e a SM foi diagnosticada utilizando três definições diferentes: do National Cholesterol Educational Program - Adult Treatment Panel III (NCEP-ATP III); do NCEP-ATP III modificado e da International Diabetes Federation (IDF). RESULTADOS: A prevalência de RI foi 43,1% (mulheres 40%, homens 44,4%). A prevalência de SM definida pelo NCEP ATP III foi 32,3%, pelo NCEP ATP III foi 40% e pela IDF foi 41,5%. Os critérios do NCEP ATP III modificado demonstrou a melhor relação entre sensibilidade (78,6%) e especificidade (89,2%) na detecção de RI. A circunferência da cintura foi o parâmetro clínico mais associado à RI. CONCLUSÃO: As definições atuais de SM podem identificar, com razoável sensibilidade e especificidade, RI em pacientes com TB. A obesidade abdominal é bastante associada à RI nessa população de pacientes.
BACKGROUND: Bipolar disorder (BD) is associated with significant morbidity and mortality from metabolic diseases. There is a paucity of data regarding insulin resistance (IR) and its relationship with the metabolic syndrome (MS) in bipolar patients. OBJECTIVE: To evaluate the prevalence of both IR and MS in BD outpatients and to assess clinical criteria associated with IR. METHOD: Cross-sectional study in 65 DSM-IV-TR BD patients consecutively assessed at the Bipolar Disorder Program at Hospital de Clínicas de Porto Alegre , Brazil. IR was diagnosed by the homeostatic model assessment - insulin resistance (HOMA-IR) and MS was diagnosed using three different definitions: National Cholesterol Educational Program - Adult Treatment Panel III (NCEP-ATP III); NCEP-ATP III modified criteria and International Diabetes Federation. RESULTS: IR was present in 43.1% of the sample (women 40%, men 44.4%). The prevalence of MS defined by the NCEP-ATP III criteria was 32.3%, NCEP-ATP III modified was 40% and IDF was 41.5%. NCEP-ATP III modified criteria showed the best trade-off between sensitivity (78.6%) and specificity (89.2%) to detect insulin resistance. Waist circumference was the clinical parameter most associated with IR. DISCUSSION: Current MS criteria may provide reasonable sensitivity and specificity for the detection of IR in BD patients. Abdominal obesity is closely related to IR in this patient population.