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.

Abstract Introduction: The objective of this study was to compare patients with bipolar disorder (BD), their first-degree relatives and a group of healthy controls in terms of use of adaptive and maladaptive coping strategies, exploring differences between specific types of strategies and their correlations with clinical variables. Methods: This was a cross-sectional study enrolling 36 euthymic patients with BD, 39 of their first-degree relatives and 44 controls. Coping strategies were assessed using the Brief COPE scale. Results: Significant differences were detected in the use of adaptive and maladaptive strategies by patients, their first-degree relatives and controls. Patients used adaptive strategies less often than the patients’ relatives (p<0.001) and controls (p = 0.003). There was no significant difference between first-degree relatives and controls (p=0.707). In contrast, patients (p<0.001) and their relatives (p=0.004) both exhibited higher scores for maladaptive coping than controls. There was no significant difference regarding the use of maladaptive strategies between patients and their relatives (p=0.517). Conclusions: First-degree relatives were at an intermediate level between patients with BD and controls regarding the use of coping skills. This finding supports the development of psychosocial interventions to encourage use of adaptive strategies rather than maladaptive strategies 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.

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.