Resumo Introdução: No Brasil, não existem instrumentos válidos para medir a disfunção cognitiva subjetiva no transtorno bipolar. O presente estudo analisou as propriedades psicométricas da Escala de Disfunções Cognitivas no Transtorno Bipolar (COBRA) em uma amostra brasileira de pacientes bipolares. Adicionalmente, investigamos a relação entre a COBRA, medidas cognitivas objetivas e curso da doença. Métodos: A amostra total (n=150) incluiu 85 pacientes com transtorno bipolar e 65 controles saudáveis. As propriedades psicométricas da COBRA (consistência interna, validade concorrente, validade discriminativa, análise fatorial, curva ROC e fidedignidade) foram analisadas. Resultados: A COBRA apresentou estrutura de um fator com alta consistência interna (alfa de Cronbach=0,890). A validade concorrente ficou demonstrada pela forte correlação com o domínio cognitivo da FAST (r=0,811, p<0,001). Pacientes bipolares tiveram mais queixas cognitivas [média=14,69; desvio padrão (DP)=10,03] que os controles (média=6,78; DP=5,49; p<0,001), sugerindo a validade discriminativa do instrumento. Não houve correlação significativa entre a COBRA e medidas cognitivas objetivas. Além disso, escores mais altos na COBRA estiveram associados com sintomas residuais depressivos (r=0,448; p<0,001) e maníacos (r=0,376; p<0,001), número de episódios depressivos (r=0,306; p=0,011), número de episódios totais (r=0.256; p=0.038) e tentativas de suicídio (r=0,356; p=0,003). Conclusão: A COBRA é um instrumento válido para avaliar queixas cognitivas, e o uso combinado das medidas cognitivas subjetivas-objetivas possibilita a correta identificação das disfunções cognitivas no transtorno bipolar.

Abstract Introduction: In Brazil, there is no valid instrument to measure subjective cognitive dysfunction in bipolar disorder. The present study analyzed the psychometric properties of the Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) in Brazilian bipolar patients. We further investigated the relationship between the COBRA, objective cognitive measures, and illness course variables. Methods: The total sample (N=150) included 85 bipolar disorder patients and 65 healthy controls. The psychometric properties of the COBRA (e.g., internal consistency, concurrent validity, discriminative validity, factor analyses, ROC curve, and feasibility) were analyzed. Results: The COBRA showed a one-factor structure with very high internal consistency (Cronbach's alpha=0.890). Concurrent validity was indicated by a strong correlation with the cognitive domain of the FAST (r=0.811, p<0.001). Bipolar patients experienced greater cognitive complaints (mean=14.69; standard deviation [SD]=10.03) than healthy controls (mean=6.78; SD=5.49; p<0.001), suggesting discriminative validity of the instrument. No significant correlations were found between the COBRA and objective cognitive measures. Furthermore, higher COBRA scores were associated with residual depressive (r=0.448; p<0.001) and manic (r=0.376; p<0.001) symptoms, number of depressive episodes (r=0.306; p=0.011), number of total episodes (r=0.256; p=0.038), and suicide attempts (r=0.356; p=0.003). Conclusion: The COBRA is a valid instrument to assess cognitive complaints, and the combined use of subjective-objective cognitive measures enables the correct identification of cognitive dysfunctions in bipolar disorder.

Resumo Introdução Células-tronco mesenquimais (CTMs) têm emergido como um promissor tratamento em diversas doenças neurodegenerativas devido a sua plasticidade e capacidade de regenerar tecidos. Estudos pré-clínicos, clínicos e de neuroimagem têm demonstrado a presença de atrofia hipocampal no transtorno bipolar (TB). Portanto, o desenvolvimento de tratamentos capazes de regenerar tecido lesado e estimular a neurogênese poderia ser útil. Objetivos Investigar mudanças comportamentais e neuroquímicas induzidas pelo transplante de CTMs no hipocampo de ratos em um modelo animal de mania induzido por dimesilato de lisdexanfetamina (LDX). Métodos Ratos Wistar (n=65) receberam LDX (10 mg/kg) ou solução salina por via oral durante 14 dias. No oitavo dia, os animais foram transplantados com injeção de CTMs ou solução salina (1 µL contendo 25.000 células) ou lítio (47,5 mg/kg) como controle interno do experimento. Duas horas após a última dose, foram realizadas análises comportamentais e neuroquímicas. Resultados Animais que receberam LDX tiveram um aumento da atividade locomotora comparados ao grupo que recebeu solução salina (p=0,004); já o lítio reverteu a hiperatividade locomotora desses animais (p<0,001). Os animais que receberam CTMs não apresentaram alterações no comportamento, indicando ausência de efeitos sobre hiperatividade locomotora. Os níveis de BDNF hipocampais não diferiram entre os grupos (p>0.05). Conclusão Não foi possível demonstrar efeitos neuroprotetores das CTMs, administradas em dose única, em um modelo animal de mania induzido por LDX. No entanto, não se pode descartar os possíveis efeitos terapêuticos das CTMs. Mais estudos são necessários para determinar os efeitos das CTMs em estruturas cerebrais e outros alvos fisiopatológicos relacionados ao TB.

Abstract Introduction The rationale of mesenchymal stem cells (MSCs) as a novel therapeutic approach in certain neurodegenerative diseases is based on their ability to promote neurogenesis. Hippocampal atrophy has been related to bipolar disorder (BD) in preclinical, imaging and postmortem studies. Therefore, the development of new strategies to stimulate the neurogenesis process in BD is crucial. Objectives To investigate the behavioral and neurochemical changes induced by transplantation of MSCs in a model of mania-like behavior induced by lisdexamfetamine dimesylate (LDX). Methods Wistar rats (n=65) received one oral daily dose of LDX (10 mg/kg) or saline for 14 days. On the 8th day of treatment, the animals additionally received intrahippocampal saline or MSC (1 µL containing 25,000 cells) or lithium (47.5 mg/kg) as an internal experimental control. Two hours after the last administration, behavioral and neurochemical analyses were performed. Results LDX-treated rats had increased locomotor activity compared to saline-saline rats (p=0.004), and lithium reversed LDX-related hyperactive behavior (p<0.001). In contrast, the administration of MSCs did not change hyperlocomotion, indicating no effects of this treatment on LDX-treated rats (p=0.979). We did not find differences between groups in BDNF levels (p>0.05) in the hippocampus of rats. Conclusion Even though these results suggest that a single intrahippocampal injection of MSCs was not helpful to treat hyperactivity induced by LDX and neither influenced BDNF secretion, we cannot rule out the possible therapeutic effects of MSCs. Further research is required to determine direct effects of LDX on brain structures as well as in other pathophysiological targets related to BD.

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.

Objective: Bipolar disorder (BD) has been associated with increased rates of age-related diseases, such as type II diabetes, metabolic syndrome, osteoporosis, and cardiovascular disorders. Several biological findings have been associated with age-related disorders, including increased oxidative stress, inflammation, and telomere shortening. The objective of this study was to compare telomere length among participants with BD at early and late stages and age- and gender-matched healthy controls. Methods: Twenty-six euthymic subjects with BD and 34 healthy controls were recruited. Genomic DNA was extracted from peripheral blood and mean telomere length was measured using real-time quantitative polymerase chain reaction. Results: Telomere length was significantly shorter in both the early and late subgroups of BD subjects when compared to the respective controls (p = 0.002 and p = 0.005, respectively). The sample size prevented additional subgroup analyses, including potential effects of medication, smoking status, and lifestyle. Conclusion: This study is concordant with previous evidence of telomere shortening in BD, in both early and late stages of the disorder, and supports the notion of accelerated aging in BD.

Recently, attention in the field of bipolar disorder (BD) has focused on prevention, including early detection and intervention, as these strategies have the potential to delay, lessen the severity, or even prevent full-blown episodes of BD. Although knowledge of the neurobiology of BD has advanced substantially in the last two decades, most research was conducted with chronic patients. The objective of this paper is to comprehensively review the literature regarding the early stages of BD, to explore recent discoveries on the neurobiology of these stages, and to discuss implications for research and clinical care. The following databases were searched: PubMed, PsycINFO, Cochrane Library, and SciELO. Articles published in English from inception to December 2015 were retrieved. Several research approaches were used, including examination of offspring studies, retrospective studies, prospective studies of clinical high-risk populations, and exploration of the progression after the first manic episode. Investigations with neuroimaging, cognition assessments, and biomarkers provide promising (although not definitive) evidence of alterations in the neural substrate during the at-risk stage. Research on BD should be expanded to encompass at-risk states and aligned with recent methodological progress in neuroscience.

Objectives: Depressive symptoms are associated with worse outcomes in patients with bipolar disorder (BD). However, scarce data are available regarding neurocognitive profiles across different areas of functioning among BD patients with moderate and severe depression. Our objective was to assess cognition and global functioning in a group of patients with bipolar depression. Methods: Data were available for 100 patients with bipolar depression (78% female) and 70 controls (64% female) paired by age and education level. Cognitive function was assessed with a neuropsychological test battery. Functioning was assessed with the Functioning Assessment Short Test. Results: In patients, severe depression was associated with poorer cognitive performance on measures of executive function. Patients with severe depression showed worse global functioning than those with moderate depression (z = 2.54, p = 0.011). In patients with severe depression, lower global functioning was associated with lower scores in working memory (r = -0.200, p = 0.010), and executive function (r = -0.210, p = 0.007; and r = 0.293, p < 0.001). Conclusion: Our findings suggest cognitive impairment and global functioning impairment are associated with the severity of depressive symptoms in bipolar depression. Intensive treatment of depressive symptoms in patients with BD is crucial to improve cognitive functioning and, consequently, functional outcomes.

Células tronco mesenquimais (CTMs) são células progenitoras multipotentes que têm a capacidade de se diferenciar em todas as linhagens de origem mesodérmica, como, cartilagem, ossos, e adipócitos. CTMs têm sido identificadas em diferentes fases do desenvolvimento, incluindo a idade adulta e em diferentes tecidos, tais como medula óssea, tecido adipose e cordão umbilical. Estudos recentes têm mostrado que as CTMs possuem a capacidade de migrar para locais de lesões. Nesse sentido, uma característica importante das CTMs são os seus efeitos imunomodulatórios e anti-inflamatórios. Por exemplo, há evidências que as CTMs podem regular o sistema imune por inibição da proliferação de células T e B. O interesse clínico no uso das CTMs tem aumentado consideravelmente nos últimos anos, especialmente devido às características ideais destas células para a medicina regenerativa. Terapias com CTMs têm mostrado resultados promissores em doenças neurodegenerativas, além de regular a inflamação, elas podem promover outros efeitos benéficos, tais como, crescimento neuronal, diminuição de radicais livres e reduzir a apoptose. No entanto, apesar de muitas pesquisas das CTMs em doenças neurodegenerativas, o mecanismo de ação das CTMs ainda não estão completamente esclarecidos, o que dificulta o desenvolvimento de tratamentos eficazes. Por outro lado, estudos em modelos de doenças psiquiátricas são escassos, apesar dos resultados promissores utilizando terapias com CTMs nesta área.

Mesenchymal stem cells (MSCs) are multipotent progenitor cells that have the capacity to differentiate into all lineages of mesodermal origin, e.g., cartilage, bone, and adipocytes. MSCs have been identified at different stages of development, including adulthood, and in different tissues, such as bone marrow, adipose tissue and umbilical cord. Recent studies have shown that MSCs have the ability to migrate to injured sites. In this regard, an important characteristic of MSCs is their immunomodulatory and anti-inflammatory effects. For instance, there is evidence that MSCs can regulate the immune system by inhibiting proliferation of T and B cells. Clinical interest in the use of MSCs has increased considerably over the past few years, especially because of the ideal characteristics of these cells for regenerative medicine. Therapies with MSCs have shown promising results neurodegenerative diseases, in addition to regulating inflammation, they can promote other beneficial effects, such as neuronal growth, decrease free radicals, and reduce apoptosis. Notwithstanding, despite the vast amount of research into MSCs in neurodegenerative diseases, the mechanism of action of MSCs are still not completely clarified, hindering the development of effective treatments. Conversely, studies in models of psychiatric disorders are scarce, despite the promising results of MSCs therapies in this field as well.

Resumo Ácaros do gênero Otodectes são parasitos encontrados frequentemente no ouvido de cães e gatos, sendo reconhecidos como os principais causadores de otite externa nesses animais. Trezentos e vinte cães, oriundos do município de Cuiabá, Mato Grosso, foram examinados através da otoscopia e do exame do swab parasitológico, com o objetivo de avaliar, através da análise bayesiana para a estimativa da prevalência, sensibilidade e especificidade destes métodos no diagnóstico da infestação causada pelo ácaro utilizando-se de dados a priori informativos e não informativos. Cada animal foi considerado uma unidade experimental. Do total de cães examinados, 142 (44,37%) apresentaram-se positivos para otocariose. Em 100 animais (31,25%) a infestação foi diagnosticada pelos dois métodos, em 31 (9,69%) apenas pelo exame do swab parasitológico, em 11 (3,44%) apenas pela otoscopia e em 178 (55,62%) animais o resultado foi negativo por ambos os métodos. A sensibilidade da otoscopia, quando comparada ao exame do swab parasitológico, foi considerada menor, a especificidade dos testes, porém, não difere estatisticamente. O modelo, a priori informativo, demonstrou ser o mais plausível e reduziu consideravelmente o intervalo de credibilidade das estimativas dos parâmetros. Conclui-se que a análise bayesiana é efetiva na estimativa da prevalência e características dos testes diagnósticos.

Abstract Mites of the genus Otodectes are parasites found frequently in the ear of dogs and cats, being recognized as the main causers of external otitis in these animals. Three hundred and twenty dogs, deriving of the city of Cuiabá, Mato Grosso, had been examined through the otoscopy and of the examination of parasitological swab, with the objective to evaluate through the bayes'analysis for the estimate of the prevalence, sensitivity and especificity of these methods in the diagnosis of the infestation caused for the mite, using dates informative and not informative a priori. Each animal was considered an experimental unit. Of the total of examined dogs, 142 (44.37%) had been presented positive for otocariosis. In 100 animals (31.25%) the infestation was diagnosed by the two methods, in 31 (9.69%) only for the examination of parasitological swab, in 11 (3.44%) only for the otoscopy and in 178 (55.62%) animal the result was negative for both the methods. The sensitivity of the otoscopy, when compared with the examination of parasitological swab, was considered lesser, however the especificity of tests they do not differ. The informative model with priori it demonstrated to be most reasonable and considerably reduced the interval of credibility of the estimates of the parameters. It can be concluded that Bayes'analysis is effective in the estimation of prevalence and characteristics of the diagnostic tests.

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.

OBJETIVO: Avaliar o funcionamento psicossocial de pacientes com subtipos restritivo e purgativo de transtorno alimentar (TA). MÉTODOS: Quarenta e quatro pacientes adultas com TA foram divididas em grupos restritivo (RP) e purgativo (PP) conforme a presença de sintomas purgativos. O funcionamento foi avaliado com a Functioning Assessment Short Test (FAST) e a Global Assessment of Functioning Scale (GAF). RESULTADOS: Não houve diferenças nos escores totais nem nos domínios da FAST entre os grupos RP (39,58±11,92) e PP (45,75±11,75) (p = 0,19). No entanto, o grupo PP demonstrou maior prejuízo funcional no domínio finanças (p < 0,01). RP e PP foram semelhantes em comorbidade com transtornos de humor, sintomas depressivos e sintomas psiquiátricos em geral. CONCLUSÕES: As semelhanças encontradas entre os grupos PP e RP no funcionamento geral e nos domínios autonomia, cognição, trabalho, relacionamentos interpessoais e lazer parecem refletir o uso de uma escala objetiva que corresponde à impressão clínica. De fato, é necessário cautela ao avaliar funcionamento psicossocial em pacientes com TA com escalas autoaplicáveis, porque estas costumam refletir a natureza egossintônica dos sintomas comumente observados nesses pacientes, especialmente no subtipo restritivo.

OBJECTIVE: To examine psychosocial functioning in eating disorder (ED) patients with restrictive and purgative subtypes. METHOD: Forty-four adult female patients with a diagnosis of ED were divided into restrictive (RP) and purgative (PP) groups according the presence of purgative symptoms. Functioning was assessed using the Functioning Assessment Short Test (FAST) and the Global Assessment of Functioning Scale (GAF). RESULTS: No differences were found in total FAST scores or in specific domains between the RP (39.58±11.92) and PP (45.75±11.75) groups (p = 0.19). However, PP showed more severe functional impairment than RP in the financial domain (p < 0.01). There were no differences in comorbidity with mood disorders, depressive symptoms, or general psychiatric symptoms between the two ED subtypes. CONCLUSIONS: The similarities found between PP and PR in overall functioning and in autonomy, cognition, work, interpersonal relationships, and leisure seem to reflect the use of an objective scale that corresponds to the clinical impression. In fact, the assessment of psychosocial functioning in ED patients using self-report instruments requires careful consideration because results may reflect the egosyntonic nature of symptoms commonly observed in these patients, particularly in the restrictive subtype.