Relative impact of diagnosis and clinical stage on response to electroconvulsive therapy: a retrospective cohort

Objectives: Electroconvulsive therapy (ECT) is commonly indicated for refractory psychiatric disorders. However, little research has compared response across diagnoses. Here, we aimed to evaluate the relative impact of diagnosis and clinical staging as response predictors in a cross-diagnostic sample. Methods: In a retrospective cohort of adult inpatients (n=287) who underwent at least six sessions of ECT, we investigated predictors of complete response (a clinical global impression of 1) to ECT. We use adjusted regression models to estimate the impact of clinical diagnosis and staging on complete response and dominance analysis to assess the relative importance of these predictors. Results: Those for whom a depressive episode was a primary indication for treatment were the most likely to have complete improvement, while those with psychosis were the least likely; clinical stage had a significant influence on outcome in all diagnoses. A diagnosis of psychosis was the strongest predictor of non-response. Conclusions: A diagnosis of psychosis (mainly schizophrenia) was the strongest predictor of non-response. We also found that clinical staging can aggregate information on ECT response that is independent of clinical diagnosis.

Barriers and facilitators perceived by people with bipolar disorder for the practice of exercise: a qualitative study / Barreiras e facilitadores percebidos por pessoas com transtorno bipolar para a prática de exercício físico: um estudo qualitativo

Abstract Introduction Exercising regularly has benefits for people with bipolar disorder. Nevertheless, as a group, these patients tend to be less physically active than the general population and little is known from the viewpoint of the patients about the barriers and facilitators to such a practice. Objective To know the barriers and facilitators perceived by people with bipolar disorder for the practice of exercise. Methods This study had a descriptive, qualitative, exploratory nature. The investigation method used for data collection was a semi-structured in-depth interview, using grounded theory as theoretical framework. Results The data analysis generated two main areas of interest: adherence to regular physical exercise (barriers and facilitators) and the participants' exercise history and perception of disease management, as described below. The main findings were: most of our sample did not exercise regularly, nor knew how exercise can positively influence their disorder; with regard to adherence to physical exercise, the presence of symptoms and stigma were the most important barriers to the practice of physical exercise. Social support, especially from family and friends, could be a facilitator to the practice of exercise. Conclusions Even considering the limitations for generalization of qualitative and exploratory studies, understanding perceived barriers and facilitators for the practice of exercise among people who suffer with bipolar disorder may contribute to the promotion of activities in which people with mental illness can participate.

Resumo Introdução A prática regular de exercício físico tem benefícios para pessoas com transtorno bipolar. No entanto, como grupo, esses pacientes tendem a ser mais sedentários do que a população geral, e pouco se sabe do ponto de vista dos pacientes sobre as barreiras e facilitadores para tal prática. Objetivo Conhecer as barreiras e facilitadores percebidos por pessoas com transtorno bipolar para a prática de exercício. Métodos Este foi um estudo descritivo, qualitativo e exploratório. O método de investigação utilizado na coleta de dados foi entrevista semiestruturada em profundidade, segundo a grounded theory. Resultados A análise dos conteúdos que surgiram nas entrevistas gerou duas principais áreas de interesse: adesão ao exercício físico regular (barreiras e facilitadores) e a história de exercícios dos participantes e a percepção do manejo da doença. Os principais achados foram: a maioria da nossa amostra não se exercitava regularmente, nem mesmo sabia como a prática regular podia influenciar positivamente sua doença; em relação à adesão ao exercício físico, a presença dos sintomas e do estigma foram as barreiras mais importantes para praticar o exercício físico. O apoio social, especialmente da família e dos amigos, pode ser um facilitador da adesão ao exercício. Conclusões Apesar das limitações de um estudo qualitativo e exploratório, conhecer as barreiras e os facilitadores percebidos para a prática de exercício entre pessoas que sofrem de transtorno bipolar pode facilitar a promoção de atividades onde essas pessoas possam participar e se beneficiar efetivamente.

Metabolic syndrome and psychiatric disorders: a population-based study

Objective: To identify the association of metabolic syndrome (MetS) and psychiatric disorders in young adults in southern Brazil. Methods: This population based cross-sectional study involved a total of 1,023 young adults between the ages of 21 and 32 years. Current episodes of psychiatric disorders were assessed using the Mini International Neuropsychiatric Interview - Plus version. MetS was evaluated using the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III). Results: Of the 1,023 participants, 24.3% were identified with MetS, 13.5% were diagnosed with anxiety disorders, 7.5% with current depression, 3.9% with bipolar disorders and 10.1% were at risk of suicide. MetS was associated with ethnicity (p = 0.022), excess weight (p < 0.001), current anxiety disorders (p < 0.001), current mood disorders (bipolar disorder in mood episode and current depression) (p < 0.001), and suicide risk (p < 0.001). Conclusions: MetS was associated with psychiatric disorders. Awareness of factors associated with MetS can help identify high-risk individuals and stimulate disease prevention and control programs, as well as lifestyle changes.

Frequency of brain tissue donation for research after suicide

Objectives: To describe the frequency of brain tissue donation for research purposes by families of individuals that committed suicide. Methods: All requests for brain tissue donation to a brain biorepository made to the families of individuals aged 18-60 years who had committed suicide between March 2014 and February 2016 were included. Cases presenting with brain damage due to acute trauma were excluded. Results: Fifty-six cases of suicide were reported. Of these, 24 fulfilled the exclusion criteria, and 11 others were excluded because no next of kin was found to provide informed consent. Of the 21 remaining cases, brain tissue donation was authorized in nine (tissue fragments in seven and the entire organ in two). Conclusions: Donation of brain tissue from suicide cases for research purposes is feasible. The acceptance rate of 42.8% in our sample is in accordance with international data on such donations, and similar to rates reported for neurodegenerative diseases.

Cognition and functioning in bipolar depression

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.

Association of interleukin-10 levels with age of onset and duration of illness in patients with major depressive disorder

Objective: To investigate peripheral levels of interleukin-10 (IL-10) in patients with major depressive disorder (MDD) and bipolar disorder (BD) and evaluate the relationship between IL-10, age of disease onset, and duration of illness. Methods: Case-control study nested in a population-based cohort of 231 individuals (age 18-24 years) living in Pelotas, state of Rio Grande do Sul, Brazil. Participants were screened for psychopathology using the Mini-International Neuropsychiatric Interview (MINI) and the Structured Clinical Interview for DSM-IV (SCID-I). Serum IL-10 was measured using commercially available immunoassay kits. Results: Peripheral levels of IL-10 were not significantly different in individuals with MDD or BD as compared to controls. However, higher IL-10 levels were found in MDD patients with a later disease onset as compared with controls or early-onset patients. In addition, IL-10 levels correlated negatively with illness duration in the MDD group. In the BD group, age of onset and duration of illness did not correlate with IL-10 levels. Conclusion: Higher levels of IL-10 are correlated with late onset of MDD symptoms. Moreover, levels of this cytokine might decrease with disease progression, suggesting that an anti-inflammatory balance may be involved in the onset of depressive symptoms and disease progression in susceptible individuals.

Quality of life, social functioning, family structure, and treatment history associated with crack cocaine use in youth from the general population

Objective:To assess the relationship between crack cocaine use and dimensions of quality of life and social functioning in young adults.Methods:This was a cross-sectional, population-based study involving 1,560 participants in Pelotas, Brazil. Crack cocaine use and abuse were investigated using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST) inventory. Outcomes of interest were quality of life, religiosity, and social functioning in terms of education, occupational status, family structure, and medical treatment history.Results:Lifetime crack cocaine use was associated with poor quality of life, worse functioning, impaired academic performance, and lower religious involvement. A greater maternal presence and higher paternal absence were more also more pronounced in crack cocaine users, who were also more likely to seek psychological and psychiatric treatment than the general population.Conclusion:Quality of life was severely impacted by crack cocaine use, especially in terms of general and physical health. Social functioning also differed between the general population and crack users, who had lower educational attainment and religious involvement. Maternal presence, paternal absence, and mental health-seeking behaviors were also more frequent among crack cocaine users, although these individuals reported lower rates of treatment satisfaction. Crack cocaine users also had significant social impairment, so that interventions involving family management and a greater focus on general health, quality of life, and functioning may make crucial contributions to the recovery of this group.

Cardiovascular risk factors in outpatients with bipolar disorder: a report from the Brazilian Research Network in Bipolar Disorder

Objective: Bipolar disorder (BD) is associated with significant morbidity and mortality due to comorbid general medical conditions, particularly cardiovascular disease. This study is the first report of the Brazilian Research Network in Bipolar Disorder (BRN-BD) that aims to evaluate the prevalence and clinical correlates of cardiovascular risk factors among Brazilian patients with BD. Methods: A cross-sectional study of 159 patients with DSM-IV BD, 18 years or older, consecutively recruited from the Bipolar Research Program (PROMAN) in São Paulo and the Bipolar Disorder Program (PROTAHBI) in Porto Alegre. Clinical, demographic, anthropometric, and metabolic variables were systematically assessed. Results: High rates of smoking (27%), physical inactivity (64.9%), alcohol use disorders (20.8%), elevated fasting glucose (26.4%), diabetes (13.2%), hypertension (38.4%), hypertriglyceridemia (25.8%), low HDL-cholesterol (27.7%), general (38.4%) and abdominal obesity (59.1%) were found in the sample. Male patients were more likely to have alcohol use disorders, diabetes, and hypertriglyceridemia, whereas female patients showed higher prevalence of abdominal obesity. Variables such as medication use pattern, alcohol use disorder, and physical activity were associated with selected cardiovascular risk factors in the multivariable analysis. Conclusion: This report of the BRN-BD provides new data regarding prevalence rates and associated cardiovascular risk factors in Brazilian outpatients with BD. There is a need for increasing both awareness and recognition about metabolic and cardiovascular diseases in this patient population. .

Staging and neuroprogression in bipolar disorder: a systematic review of the literature

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.

Marcadores periféricos e a fisiopatologia do transtorno bipolar / Peripheral markers and the pathophysiology of bipolar disorder

INTRODUÇÃO: O entendimento da fisiopatologia do transtorno bipolar vem tendo avanços consistentes nos últimos anos. Um enfoque na relação entre carga alostática e alterações sistêmicas vem tomando corpo, com o objetivo de se entender a frequente progressão da doença. Proeminentes entre os mediadores periféricos têm sido as moléculas que poderiam ser amplamente agrupadas em neurotrofinas, marcadores de estresse oxidativo e marcadores inflamatórios. OBJETIVO: Descrever achados recentes em relação à fisiopatologia sistêmica do transtorno bipolar, com enfoque especial em estudos brasileiros, tentando articular uma visão coerente do conhecimento atual do campo. MÉTODO: Revisão narrativa da literatura relacionada a neurotrofinas, estresse oxidativo e marcadores inflamatórios no transtorno bipolar. RESULTADOS: Diversas fontes de evidência, provenientes tanto de estudos pré-clínicos quanto clínicos, revelam consistentemente alterações sistêmicas no transtorno bipolar. Os achados são especialmente robustos em pacientes com múltiplos episódios. Nesses, alterações relacionadas a episódios de mania e depressão são notáveis em neurotrofinas e dano oxidativo a lipídeos. Um número menor de estudos mostra alterações no sistema imune, em particular estados pró-inflamatórios. CONCLUSÃO: Alterações sistêmicas que correlacionam o transtorno bipolar a comorbidade clínica, disfunção cognitiva, incapacidade e mortalidade precoce começam a ser traçadas. Estudos envolvendo desenhos longitudinais, amostras populacionais e ensaios clínicos envolvendo marcadores periféricos devem ser incorporados no futuro próximo e reforçar a validade de uma noção de envolvimento multissistêmico no transtorno bipolar.

INTRODUCTION: The understanding of the pathophysiology of bipolar disorder has steadily advanced in the past few years. Thereby, a focus on allostatic load and systemic changes has appeared, with the aim to understand illness progression. Amongst the peripheral markers, molecules that can be widely classified into neurotrophins, oxidadive stress markers, and inflammation markers have been elevated. OBJECTIVE: To describe recent findings regarding the systemic pathophysiology of bipolar disorder, with a special focus on Brazilian studies and to create a coherent view of the current knowledge in the field. METHOD: Narrative review of the literature regarding neurotrophins, oxidative stress, and inflammatory markers in bipolar disorder. RESULTS: A diverse body of evidence, based on both pre-clinical and clinical studies, reveals consistent systemic changes in bipolar disorder. The findings are particularly robust in patients after multiple episodes. Thereby, remarkable changes related to manic and depressive episodes were found in neurotrophins and oxidative damage to lipids. Regarding to immune system alterations, in particular pro-inflammatory states, the literature is less consistent. DISCUSSION: Systemic changes that link bipolar disorder to clinical comorbidity, cognitive dysfunction, disability and early mortality are becoming evident. In the near future, longitudinal studies with population-based samples and clinical trials incorporating biomarkers are needed to shed light upon the notion of a multisystem involvement in bipolar disorder.

N-acetylcysteine for major depressive episodes in bipolar disorder / N-acetilcisteína para o tratamento de episódios de depressão maior no transtorno bipolar

OBJECTIVE: In this report, we aimed to evaluate the effect of add-on N-acetylcysteine (NAC) on depressive symptoms and functional outcomes in bipolar disorder. To that end, we conducted a secondary analysis of all patients meeting full criteria for a depressive episode in a placebo controlled trial of adjunctive NAC for bipolar disorder. METHOD: Twenty-four week randomised clinical trial comparing adjunctive NAC and placebo in individuals with bipolar disorder experiencing major depressive episodes. Symptomatic and functional outcome data were collected over the study period. RESULTS: Seventeen participants were available for this report. Very large effect sizes in favor of NAC were found for depressive symptoms and functional outcomes at endpoint. Eight of the ten participants on NAC had a treatment response at endpoint; the same was true for only one of the seven participants allocated to placebo. DISCUSSION: These results indicate that adjunctive NAC may be useful for major depressive episodes in bipolar disorder. Further studies designed to confirm this hypothesis are necessary.

OBJETIVO: Neste relato, avaliamos o efeito da N-acetilcisteína (NAC) adjuvante em sintomas depressivos e desfechos funcionais no transtorno bipolar. Para isso, conduzimos uma análise secundária de todos os pacientes com critérios diagnósticos para um episódio depressivo em um ensaio clínico randomizado comparando NAC adjuvante com placebo no transtorno bipolar. MÉTODO: Ensaio clínico randomizado comparando NAC adjuvante com placebo para episódios depressivos no transtorno bipolar durante 24 semanas. Desfechos funcionais e sintomáticos foram coletados no período. RESULTADOS: Dezessete participantes estavam disponíveis para esta análise. Tamanhos de efeito grandes foram encontrados para sintomas depressivos e desfechos funcionais. Oito dos dez participantes no grupo da NAC tiveram resposta clínica ao fim do tratamento. O mesmo ocorreu em apenas um dos sete que receberam placebo. DISCUSSÃO: Esses resultados indicam que a NAC adjuvante pode ser útil para episódios de depressão maior no transtorno bipolar. Estudos desenhados para confirmar esta hipótese são necessários.