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 conduct a systematic review of the literature about the symptom of rumination in bipolar disorder (BD). Methods: We searched the MEDLINE (PubMed), ISI Web of Knowledge, PsycINFO, and SciELO databases using the descriptors “rumination” and “bipolar disorder” and no time limits. This strategy yielded 105 references, of which 74 were selected. Inclusion criteria were studies involving patients with BD and the use of at least one validated scale for the assessment of rumination. Review articles were excluded. Seventeen articles were ultimately analyzed and included in the review. Results: Rumination is present in all BD phases, is a stable interepisodic symptom, is associated with symptoms of depression, anxiety, and hypomania, and may occur in response to both positive and negative affect. There is no research on rumination and neurobiological findings in patients with BD. Conclusions: Rumination seems to be independent of mood state, but shows close relationship with it. It is possible that rumination has a negative impact on cognitive and executive functions, particularly inhibitory control. Finally, rumination is an important symptom in both phases of BD, and, therefore, may be a useful target for further exploration as a dimensional domain and a transdiagnostic phenomenon in Research Domain Criteria (RDoC) projects.

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.

Objective: In the present study, we aimed to examine the effects of repeated D-amphetamine (AMPH) exposure, a well-accepted animal model of acute mania in bipolar disorder (BD), and histone deacetylase (HDAC) inhibitors on locomotor behavior and HDAC activity in the prefrontal cortex (PFC) and peripheral blood mononuclear cells (PBMCs) of rats. Moreover, we aimed to assess brain-derived neurotrophic factor (BDNF) protein and mRNA levels in these samples. Methods: We treated adult male Wistar rats with 2 mg/kg AMPH or saline intraperitoneally for 14 days. Between the 8th and 14th days, rats also received 47.5 mg/kg lithium (Li), 200 mg/kg sodium valproate (VPT), 2 mg/kg sodium butyrate (SB), or saline. We evaluated locomotor activity in the open-field task and assessed HDAC activity in the PFC and PBMCs, and BDNF levels in the PFC and plasma. Results: AMPH significantly increased locomotor activity, which was reversed by all drugs. This hyperactivity was associated with increased HDAC activity in the PFC, which was partially reversed by Li, VPT, and SB. No differences were found in BDNF levels. Conclusion: Repeated AMPH administration increases HDAC activity in the PFC without altering BDNF levels. The partial reversal of HDAC increase by Li, VPT, and SB may account for their ability to reverse AMPH-induced hyperactivity.

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.

Mirtazapine is an antidepressant whose side effect profile differs from that of first-line agents (selective serotonin reuptake inhibitors) used in the treatment of panic disorder. The present study compared the effect of mirtazapine and fluoxetine in the treatment of panic disorder in a double-blind, randomized, flexible-dose trial conducted with outpatients. After a 1-week single-blind placebo run-in, 27 patients entered an 8-week double-blind phase in which they were randomly assigned to treatment with either mirtazapine or fluoxetine. Both groups improved significantly in all but one efficacy measure (P<=0.01). ANOVA showed no significant differences between the two treatment groups in number of panic attacks, Hamilton Anxiety Scale or Sheehan Phobic Scale, whereas measures of patient global evaluation of phobic anxiety were significantly different between groups (F1,20 = 6.91, P = 0.016) favoring mirtazapine. For the 22 patients who completed the study, the mean daily dose of mirtazapine was 18.3 ± 1.3 vs 14.0 ± 1.0 mg for fluoxetine at the endpoint. Weight gain occurred more frequently in the mirtazapine group (50 vs 7.7%, P = 0.04) and nausea and paresthesia occurred more often in the fluoxetine group (P = 0.01). Results suggest that mirtazapine has properties that make it attractive for the treatment of panic disorder.