Objective: Bipolar disorder (BD) is a major cause of disability-adjusted life years in young adults. Pregnancy complications have previously been associated with BD. The current study aimed to examine the association between perinatal factors and BD. Methods: We included 3,794 subjects from the 1993 Pelotas population-based birth cohort study. We assessed 27 variables at birth and modeled BD onset at 18 and 22 years. Bivariate analysis was performed by means of binomial logistic regression models. The variables with p-values less than 0.05 were included in a multiple regression with confounders. Results: Maternal smoking was associated with a 1.42-fold increased risk of BD at 18 or 22 years old (95%CI 1.091-1.841), and maternal passive exposure to tobacco with a 1.43-fold increased risk (95%CI 1.086-1.875). No association was found between other perinatal factors and BD after controlling for confounders. Conclusion: The results of the present cohort study corroborate previous reports in the literature indicating a negative effects of maternal smoking during pregnancy. These findings can be further tested and support the development of strategies to prevent the onset development of BD. Objective (BD disabilityadjusted disability adjusted adults Methods 3794 3 794 3,79 199 populationbased population based 2 1 models pvalues p values 005 0 05 0.0 confounders Results 1.42fold 142fold fold 1.42 42 95%CI 95CI CI 95 1.0911.841, 10911841 1.091 1.841 , 091 841 1.091-1.841) 1.43fold 143fold 1.43 43 1.0861.875. 10861875 1.086 1.875 . 086 875 1.086-1.875) Conclusion pregnancy 379 79 3,7 19 00 0. 42fold 142 1.4 4 9 0911 1.0911.841 1091184 1091 1.09 1841 1.84 09 84 1.091-1.841 43fold 143 0861 1.0861.875 1086187 1086 1.08 1875 1.87 08 87 1.086-1.875 37 7 3, 14 1. 1.0911.84 109118 109 1.0 184 1.8 8 1.091-1.84 1.0861.87 108618 108 187 1.086-1.87 1.0911.8 10911 10 1.091-1.8 1.0861.8 10861 1.086-1.8 1.0911. 1.091-1. 1.0861. 1.086-1. 1.0911 1.091-1 1.0861 1.086-1 1.091- 1.086-

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: 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.

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.