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Objectives: This study investigated behavioral self-regulation problems using the Children's Hostility Inventory (CHI) in pediatric bipolar disorder (PBD), healthy offspring of bipolar disorder patients (HOBD), and healthy controls (HC) without previous history of psychiatric disorders., Methods: The CHI was administered to 41 consecutive children and adolescents diagnosed with PBD, to 16 HOBD, and to 22 HC. The inventory assessed irritability, expression, hostility, and aggression and was completed by the children with the help of their mothers. Adolescents and their respective parents were interviewed separately using the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL)., Results: All subscales of the CHI presented statistically significant differences, except for the subscale assessing feelings of suspicion. Pairwise comparisons revealed consistently significant differences between the PBD group and controls, indicating more self-regulation difficulties in the PBD group, represented by high levels of hostility and aggressive behavior. There were no significant differences between the PBD and HOBD groups., Conclusions: Future studies should further investigate if such behavior is state-dependent or a trait of bipolar juvenile expression. Expression of hostility and irritability should be considered relevant targets in psychosocial approaches addressing this population., Competing Interests: The authors report no conflicts of interest.

Objectives: To examine the composition of self-regulation in pediatric bipolar disorder (PBD) through the relationship between executive functions, emotion processing, and family environmental factors., Methods: 58 participants (36 with PBD and 22 controls), ages 12-17, were assessed using the Barratt Impulsiveness Scale (BIS), Conners' Continuous Performance Test (CPT-II), Wisconsin Cards Sorting Test (WCST), Computerized Neurocognitive Battery Emotion Recognition Test-Facial Emotion Recognition Test (PENNCNB ER-40), and Expressed Emotion Adjective Checklist Questionnaire (EEAC)., Results: Adolescents with PBD displayed significant deficits in all three spheres when compared to the control group. Emotion processing correlated negatively with inhibition and attention, and correlated positively with mental flexibility/working memory. Family environmental factors correlated negatively with mental flexibility/working memory and emotion processing, and positively with attention and inhibition. These correlations indicate that better inhibitory control, attention, and mental flexibility/working memory are associated with greater emotion processing and a fitter family environment., Conclusion: This study is the first to investigate all of the components of self-regulation deficits simultaneously in patients with PBD. Results suggest that self-regulation is essential for a comprehensive perspective of PBD and should be assessed in an integrative and multifaceted way. Understanding that self-regulation is impacted by the abovementioned factors should influence treatment and improve the functional impairments of daily life observed in this population., Competing Interests: The authors report no conflicts of interest.

Social cognition has gained prominence in psychiatric research, beginning with schizophrenia and more recently in bipolar disorder. Considering the relevance of this domain to interpersonal relationships and functionality, we aimed to explore the fundamental research and clinical issues regarding social cognition and discuss future directions and challenges in the field of bipolar disorder., Competing Interests: The authors report no conflicts of interest.

Objective: To compare social skills and related executive functions among bipolar disorder (BD) patients with a family history of mood disorders (FHMD), BD patients with no FHMD and healthy control (HCs)., Methods: We evaluated 20 euthymic patients with FHMD, 17 euthymic patients without FHMD, and 31 HCs using the Social Skills Inventory (SSI) and a neuropsychological battery evaluating executive function, inhibitory control, verbal fluency and estimated intelligence., Results: Both BD groups had lower SSI scores than controls. Scores for one subfactor of the social skills questionnaire, conversational skills and social performance, were significantly lower among patients with FHMD than among patients without FHMD (p = 0.019). Both groups of BD patients exhibited significant deficits in initiation/inhibition, but only BD patients with FHMD had deficits in verbal fluency, both compared to HC. There were no associations between social skills questionnaire scores and measures of cognitive function., Conclusion: Euthymic BD patients have lower social skills and executive function performance than HC. The presence of FHMD among BD patients is specifically associated with deficits in conversational and social performance skills, in addition to deficits in verbal fluency. Both characteristics might be associated with a common genetically determined pathophysiological substrate.

Objective: Unaffected relatives of bipolar disorder (BD) patients have been investigated for the identification of endophenotypes in an attempt to further elucidate the pathophysiology of the disease. Brain-derived neurotrophic factor (BDNF) is considered to be implicated in the pathophysiology of BD, but its role as an endophenotype has been poorly studied. We investigated abnormal serum BDNF levels in BD patients, in their unaffected relatives, and in healthy controls., Methods: BDNF levels were obtained from 25 DSM-IV bipolar I disorder patients, 23 unaffected relatives, and 27 healthy controls. All BD patients were in remission. The unaffected subjects were first-degree relatives of the proband who had no lifetime DSM-IV diagnosis of axis I disorder. BDNF serum levels were determined by sandwich ELISA using monoclonal BDNF-specific antibodies., Results: There were no statistical differences in BDNF levels among BD patients, relatives, and healthy controls., Conclusion: Serum BDNF levels may not indicate high genetic risk for BD, possibly acting as state markers rather than trait markers of the disease.

Objective:: Rapid cycling (RC) is a feature of bipolar disorder (BD) that has been associated with worse outcome and more severe disability. Our goal was to investigate the association of demographic and clinical factors with RC., Methods:: We compared RC and non-rapid cycling (NRC) BD patients from the Brazilian Research Network in Bipolar Disorder (BRN-BD) regarding age at onset of BD; total number of episodes; previous number of manic, depressive, mixed, and hypomanic episodes; polarity of the first episode; gender; number of suicide attempts; number of lifetime hospitalizations and lifetime history of at least one hospitalization; family history of mood disorder; clinical comorbidities such as hypothyroidism, hyperthyroidism, seizures; and current use of medications such as lithium, anticonvulsants, antipsychotics, and antidepressants., Results:: We studied 577 patients and found that 100 (17.3%) met the criteria for RC in the year before the investigation. RC patients had earlier age at onset, longer duration of disease, more lifetime depressive and manic episodes, higher number of suicide attempts, and higher rate antidepressant use., Conclusion:: The presence of RC in the previous year was associated with specific clinical characteristics closely related to worse outcome in the course of BD.

Objective: Bipolar disorder (BD) is often left untreated for long periods, and this delay in treatment correlates with unfavorable prognosis. The present study sought to assess the magnitude of duration of untreated bipolar disorder (DUB) in Brazil. We hypothesized that DUB would be longer in Brazil than in developed countries, and would be associated with poor clinical outcomes., Methods: One hundred and fifty-two psychiatric outpatients were evaluated for BD diagnosis, demographics, DUB, and clinical outcomes., Results: The mean age and mean DUB were, respectively, 38.9±10.8 and 10.4±9.8 years. An extended DUB was associated with early onset of BD (p < 0.001), depression as first mood episode (p = 0.04), and presence of BD in a first-degree relative (p = 0.012). Additionally, a longer DUB was associated with poorer clinical outcomes, such as elevated rates of rapid cycling (p = 0.004) and anxiety disorders (p = 0.016), as well as lower levels of current full remission (p = 0.021)., Conclusion: As DUB may be a modifiable variable, better medical education regarding mental health, more structured medical services, and population-wide psychoeducation might reduce the time between onset and proper management of BD, thus improving outcome.

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.

Objective: This article reviews the evidence for the major risk factors associated with suicidal behavior in bipolar disorder., Method: Review of the literature studies on bipolar disorder, suicidal behavior and suicidal ideation., Results: Bipolar disorder is strongly associated with suicide ideation and suicide attempts. In clinical samples between 14-59% of the patients have suicide ideation and 25-56% present at least one suicide attempt during lifetime. Approximately 15% to 19% of patients with bipolar disorder die from suicide. The causes of suicidal behavior are multiple and complex. Some strong predictors of suicidal behavior have emerged in the literature such as current mood state, severity of depression, anxiety, aggressiveness, hostility, hopelessness, comorbidity with others Axis I and Axis II disorders, lifetime history of mixed states, and history of physical or sexual abuse., Conclusion: Bipolar disorder is the psychiatric condition associated with highest lifetime risk for suicide attempts and suicide completion. Thus it is important to clinicians to understand the major risk factors for suicidal behavior in order to choose better strategies to deal with this complex behavior.

Objective: Literature review of the controlled studies in the last 18 years in emotion recognition deficits in bipolar disorder., Method: A bibliographical research of controlled studies with samples larger than 10 participants from 1990 to June 2008 was completed in Medline, Lilacs, PubMed and ISI. Thirty-two papers were evaluated., Results: Euthymic bipolar disorder presented impairment in recognizing disgust and fear. Manic BD showed difficult to recognize fearful and sad faces. Pediatric bipolar disorder patients and children at risk presented impairment in their capacity to recognize emotions in adults and children faces. Bipolar disorder patients were more accurate in recognizing facial emotions than schizophrenic patients., Discussion: Bipolar disorder patients present impaired recognition of disgust, fear and sadness that can be partially attributed to mood-state. In mania, they have difficult to recognize fear and disgust. Bipolar disorder patients were more accurate in recognizing emotions than depressive and schizophrenic patients. Bipolar disorder children present a tendency to misjudge extreme facial expressions as being moderate or mild in intensity., Conclusion: Affective and cognitive deficits in bipolar disorder vary according to the mood states. Follow-up studies re-testing bipolar disorder patients after recovery are needed in order to investigate if these abnormalities reflect a state or trait marker and can be considered an endophenotype. Future studies should aim at standardizing task and designs.

Objective: Depression is a frequent, recurrent and chronic condition with high levels of functional disability. The Brazilian Medical Association Guidelines project proposed guidelines for diagnosis and treatment of the most common medical disorders. The objective of this paper is to present a review of the Guidelines Published in 2003 incorporating new evidence and recommendations., Method: This review was based on guidelines developed in other countries and systematic reviews, randomized clinical trials and when absent, observational studies and recommendations from experts. The Brazilian Medical Association proposed this methodology for the whole project. The review was developed from new international guidelines published since 2003., Results: The following aspects are presented: prevalence, demographics, disability, diagnostics and sub-diagnosis, efficacy of pharmacological and psychotherapeutic treatment, costs and side-effects of different classes of available drugs in Brazil. Strategies for different phases of treatment are also discussed., Conclusion: The Guidelines are an important tool for clinical decisions and a reference for orientation based on the available evidence in the literature.

Objective: Mixed episodes have been described as more severe than manic episodes, especially due to their longer duration and their association with higher rates of suicide attempts, hospitalization and psychotic symptoms. The purpose of this study was to compare the severity between mixed and pure manic episodes according to DSM-IV criteria, through the evaluation of sociodemographic data and clinical characteristics., Method: Twenty-nine bipolar I patients presenting acute mixed episodes were compared to 20 bipolar I patients with acute manic episodes according to DSM-IV criteria. We analyzed (cross-sectionally) episode length, presence of psychotic symptoms, frequency of suicide attempts and hospitalization, Young Mania Rating Scale scores, Hamilton Depression Rating Scale scores and the Clinical Global Assessment Scale scores., Results: Young Mania Rating Scale scores were higher in manic episodes than in mixed episodes. There were no differences in gender frequency, CGI scores and rates of hospitalization, suicide attempts and psychotic symptoms, when mixed and manic episodes where compared. Patients with mixed episodes were younger., Conclusion: In our sample, mixed states occurred at an earlier age than manic episodes. Contrary to previous reports, we did not find significant differences between manic and mixed episodes regarding severity of symptomatology, except for manic symptoms ratings, which were higher in acute manic patients. In part, this may be explained by the different criteria adopted on previous studies.

Objective: Treatment-emergent affective switch has been associated to cycle acceleration and poorer outcome, but there are few studies addressing this issue. The aim of this study was to prospectively compare the outcome of patients presenting treatment-emergent affective switch with patients with spontaneous mania, regarding presence and polarity of a new episode and time to relapse., Method: Twenty-four patients with bipolar disorder according to the DSM-IV were followed for 12 months. Twelve patients had treatment-emergent affective switch and twelve had spontaneous mania. Patients were evaluated weekly with the Young Mania Rating Scale and the Hamilton Depression Scale until remission of the index episode, and monthly until completion of the 12-month follow-up., Results: Eleven patients with treatment-emergent affective switch had a recurrence on follow-up, all of them with major depressive episodes. In the group with spontaneous mania, six patients had a recurrence: two had a depressive episode, and four had a manic episode (p = 0.069 for new episode, p = 0.006 for polarity of the episode). Patients with treatment-emergent affective switch relapsed in a shorter period than patients with spontaneous mania (p = 0.016)., Conclusions: In this first prospective study, treatment-emergent affective switch patients were at greater risk of relapses, especially depressive episodes, and presented a shorter duration of remission when compared with patients with spontaneous mania.

Objective: Systematic literature review of the controlled studies published in the last 15 years on neuropsychological deficits in Bipolar Disorder., Method: Bibliographical research was completed through Medline, Lilacs, PubMed and ISI, specifically for 1990 to 2005 period. Selected studies were organized beginning with the comparison among the selected sample (bipolar versus other pathology versus control healthy). We included only controlled studies with a patient sample larger than 10, and 73 papers were found, being that 53 selected for this systematic review., Results: Patients with Bipolar Disorder present difficulties in several cognitive domains which partially persist even after acute episodes acute episodes. The deficits impaired basically the executive functions. When compared to schizophrenia, bipolar patients present milder deficits in the neuropsychological tests, which may explain differences in terms of disease outcome and specific circuitry abnormalities. There was a positive correlation between cognitive deficits and number of episodes or hospitalizations. The medications used for mood stabilization can produce a negative impact on cognition., Conclusions: The abnormalities suggest a dysfunction in specific frontostriatal circuits, and may partially explain the difficulties in the psychosocial adaptation of these patients. Future studies should evaluate the effectiveness of neuropsychological rehabilitation programs, which seek through cognitive training to minimize the impact of these deficits in the every day life.

Objective: To study clinical and psychopathological features of obsessive-compulsive disorder (OCD) in women with bipolar disorder (BD)., Methods: Fifteen outpatients with concurrent bipolar disorder I (80.0%) or II (20.0%) and obsessive-compulsive disorder were studied. Most of them (80.0%) sought treatment for bipolar disorder. They were ascertained by means of the Structured Clinical Interview for DSM-IV (SCID/P), semi-structured interviews to investigate obsessions, compulsions and sensory phenomena that may precede compulsions and an additional module for the diagnosis of chronic motor and vocal tics. Severity of symptoms was assessed by the Yale-Brown Obsessive-Compulsive Rating Scale, Hamilton Depression Rating Scale and Young Mania Rating Scale., Results: Obsessive-compulsive disorder presented early onset (before the age of 10) in 9 (60%) cases, preceded bipolar disorder in 10 (66.7%) and displayed chronic waxing and waning course in 13 (86.7%) of them. There was wide overlap between types of obsessive-compulsive symptoms and all patients experienced sensory phenomena preceding the compulsions. There was no clear-cut impact of depressive and manic episodes on the intensity of obsessive-compulsive symptoms, which increased in depression and decreased in mania in 40.0% of the cases, had the opposite pattern in 26.7% of the patients and fluctuated inconsistently in the rest of them. Tics disorders were diagnosed in 5 (33.3%) patients., Conclusions: Our results suggest that in women with comorbid bipolar disorder and obsessive-compulsive disorder the latter presents features that may be typical of the association of the two disorders, such as early onset and sensory phenomena preceding compulsions. A prospective controlled study is necessary to confirm these observations, due to some limitations of our study: small exclusively female sample, heterogeneity concerning the type of bipolar disorder and the disorder that determined sought of treatment and retrospective non-controlled design.

Mixed States are described in the literature using based on different definitions resulting in different descriptions of the clinical and demographic characteristics, of these episodes, but although they are always asdeemed a severe form of Bipolar disorder with worse prognosis and more prevalent than previously described. The aim of this article is to present a review of these different definitions and their impact on the study of mixed states. Pharmacological treatment is also discussed.

High comorbidity between bipolar and anxiety disorders is frequently described in epidemiological and clinical studies. This association has important implications for diagnoses, clinical outcome, therapeutic intervention and prognoses of bipolar disorder that are presented in this review.

Objectives: To review the literature on antidepressant-induced mania, its incidence, clinical presentation, risk factors and treatment., Methods: A Medline search of studies published between 1970 and 2001 was carried out. Open and controlled studies as well as case series with data from more than five patients were included., Results: Antidepressant induced mania may differ clinically from spontaneous mania with a milder severity and shorter duration. The risk factors have not been established., Conclusion: A very limited number of prospective and controlled studies on antidepressant-induced mania have been published. Antidepressants have been associated with an increased risk of inducing mania. This risk may vary according to the drug utilized. Therefore antidepressants should be used in bipolar patients based on clinical efficacy as well as the potential effects on the course of the illness.

Objective: Depression is a frequent and chronic condition with high levels of functional disability. Brazilian Medical Association Guidelines project proposed guidelines for diagnosis and treatment of the most common medical disorders. The objective of this paper is to present the original document that originated the abbreviated version available at the electronic address of Brazilian Medical Association., Methods: This paper was based on guidelines developed in other countries and systematic reviews, randomized clinical trials and when absent, observational studies and recommendations from experts. Brazilian Medical Association proposed this methodology for the whole project., Results: The following aspects are presented: prevalence, demographics, disability, diagnostics and sub-diagnosis, efficacy of pharmacological and psychotherapeutic treatment, costs and side-effects of different classes of available drugs in Brazil. Planning of different phases of treatment is22 also discussed., Conclusions: Guidelines are a good tool helping clinical decisions and are a reference for an attitude based on levels of evidence.