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Objective: The term "mood stabilizer" is controversial in the literature and criticized for being imprecise and overly inclusive, having its retirement suggested to avoid misuse. Nevertheless, it continues to be employed as it may still carry important meaning. Methods: We employed document analysis for reviewing relevant definitions of mood stabilizer employed in the literature. Then, we clarify the meanings associated with the term by employing evolutionary concept analysis. Based on its results, we present a theoretical model for a mood stabilizer and further match it with evidence gathered from published meta‐analyses and other sources for drugs used in the treatment of bipolar disorder. Results: Concept analysis unearthed four attributes of a mood stabilizer that were nested into the following ascending hierarchy: "not worsening," "acute effects," "prophylactic effects," and "advanced effects." "Prophylactic effects" were often considered the core aspect of a legitimate mood stabilizer. Conclusion: The proposed model uses a hierarchy of attributes that take into account the complexity of the term and help to determine whether a drug is a mood stabilizer. Prophylaxis is pivotal to the concept, whose utility lies in implying a drug able to truly treat bipolar disorder, as opposed to merely targeting symptoms. Consistent use of the term could encourage investigation of drugs that modify long‐term outcomes and illness trajectory, instead of simply approaching symptom clusters. [ABSTRACT FROM AUTHOR]

The article discusses a study to examine the clinical effect of N-acetyl cysteine (NAC) in mania or hypomania. The study reveals the result using placebo-controlled, randomized, clinical trial a within-group efficacy for glutathione precursor as compared to placebo. It is concluded that future trials need to be designed to evaluate the efficacy of NAC in mania.

Objective: To verify the prevalence and clinical impact of excessive daytime sleepiness (EDS) in outpatients with bipolar disorder. Methods: Eighty‐one outpatients with bipolar disorder and 79 healthy control subjects were recruited. Patients were required not to be acutely manic or depressed. We used the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index and the Functioning Assessment Short Test to assess sleepiness, sleep problems and functioning, respectively. Results: Patients had a higher prevalence of sleepiness (40%) than the control group (18%). Sleepiness and sleep disturbance had independent impacts on disability in the multivariable model. Conclusions: This study suggests that EDS is a relevant clinical dimension in patients with bipolar disorder. It is a frequent symptom that often overlaps with other sleep disturbances. This study also reveals that once present it has the potential to increase functional impairment. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The objective of this report is to evaluate functioning in bipolar disorder in a population-based sample of young adults (18 to 24 years old). To this end, people with bipolar disorder were compared with matched participants with only depressive episodes and control subjects without a history of mood episodes. Methods: Case-control study nested in a population-based sample. Caseness was confirmed with the Structured Clinical Interview for DSM-IV. The Functioning Assessment Short Test was used as a measure of general functioning. A multivariate model was elaborated to account for potential confounders. Results: The sample consisted of 231 subjects. Both bipolar disorder (coef=0.60, SE=0.14, p<0.001) and major depression (coef=0.44, SE=0.14, p=0.001) were associated with functioning in the multivariate model. Current depressive symptoms appeared to influence functioning in those with major depression (Z=2.05, p=0.04), but not in those with bipolar disorder (Z=0.78, p=0.43). Limitation: Neuropsychological testing was not performed and we see it as an important limitation of this study. Conclusion: This population-based study further reinforces the notion that functional impairment is a fundamental characteristic of bipolar illness. It is present from early stages and is not completely explained by mood symptoms. [Copyright &y& Elsevier]

The article reports a study which used the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) Standard Care Pathways to test whether patients with multiple acute depressive episodes had a worse symptomatic and functional prognosis. The results revealed that patients with multiple previous episodes had consistently poorer cross-sectional and prospective outcomes. This indicates that bipolar disorder can be staged with prognostic validity

Abstract: Bipolar disorder is associated with a high rate of medical and psychiatric comorbidities. This burden of illness, along with cognitive impairment, is seen particularly in late cases, after multiple episodes. These changes in clinical presentation that take place over time have been recently conceptualized as “neuroprogression”. The concept of allostatic load is instrumental in understanding how the cumulative stress associated with psychiatric disorders translates into bodily wear and tear, thus providing an underlying explanation for illness progression. Allostatic load is engendered by several factors which interact in a nonlinear manner. Glucocorticoids are fundamental mediators; when chronically in excess, glucocorticoids initiate a series of bodily dysfunctions that may include cortisol-related mitochondrial dysfunction, oxidative stress, inflammation and decrease in the expression of neuroprotective factors. In the present review we examine the role of allostatic load in the illness progression that takes place in bipolar disorder. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

Abstract: Bipolar disorder (BD) is characterized by frequent recurrence, incomplete recovery, cognitive dysfunction and poor functioning. Impairment lingers in the interepisodic period and mechanisms leading to this dysfunctional state are not fully comprehended. To our knowledge the association of biological rhythm dysfunction with functioning in BD has not been assessed directly. The objective of this study was to measure and quantify the impact of rhythm dysfunction on interepisodic functioning in BD. We also tested the association between executive functioning and sleep and rhythm problems. Eighty-one outpatients with BD and 79 matched control subjects were consecutively recruited. Functional impairment was assessed with the Functioning Assessment Short Test (FAST) and biological rhythms with the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN). A subsample had their executive functioning assessed with the Wisconsin Card Sorting Test (WCST). Patients and control subjects were well matched. Functioning and rhythm scores were correlated in patients and control subjects. The BRIAN score was the strongest predictor of functioning in the regression model. Biological rhythms partially mediated the impairment associated with bipolar disorder. The rhythm score was also associated with executive functioning. Biological rhythm dysfunction was a potent predictor of functioning in interepisodic patients with bipolar disorder; it may also mediate much of the disorder-induced disability. These results further the notion that biological rhythms may be interesting targets for diverse interventions aiming to improve functioning and prevent relapse in interepisodic bipolar disorder. [Copyright &y& Elsevier]

Objective: Although bipolar disorder is a major contributor to functional impairment worldwide, an independent impact of bipolar disorder and ageing on functioning has yet to be demonstrated. The objective of the present study was to evaluate the effect of bipolar disorder on age-related functional status using matched controls as a standard. Method: One-hundred patients with bipolar disorder and matched controls were evaluated for disability. Age-related effects controlled for confounders were cross-sectionally evaluated. Results: Patients were significantly more impaired than controls. Regression showed effects for aging in both groups. The effect, size, however, was significantly stronger in patients. Conclusion: Bipolar disorder was an important effect modifier of the age impact on functioning. While a longitudinal design is needed to effectively demonstrate this different impact, this study further depicts bipolar disorder as a chronic and progressively impairing illness. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: As several lines of evidence point to irregular biological rhythms in bipolar disorder, and its disruption may lead to new illness episodes, having an instrument that measures biological rhythms is critical. This report describes the validation of a new instrument, the Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN), designed to assess biological rhythms in the clinical setting. Methods: Eighty-one outpatients with a diagnosis of bipolar disorder and 79 control subjects matched for type of health service used, sex, age and educational level were consecutively recruited. After a pilot study, 18 items evaluating sleep, activities, social rhythm and eating pattern were probed for discriminant, content and construct validity, concurrent validity with the Pittsburgh Sleep Quality Index (PSQI), internal consistency and test-retest reliability. Results: A three-factor solution, termed sleep/social rhythm factor, activity factor and feeding factor, provided the best theoretical and most parsimonious account of the data; items essentially loaded in factors as theoretically intended, with the exception of the sleep and social scales, which formed a single factor. Test–retest reliability and internal consistency were excellent. Highly significant differences between the two groups were found for the whole scale and for each BRIAN factor. Total BRIAN scores were highly correlated with the global PSQI score. Discussion: The BRIAN scale presents a consistent profile of validity and reliability. Its use may help clinicians to better assess their patients and researchers to improve the evaluation of the impact of novel therapies targeting biological rhythm pathways. [Copyright &y& Elsevier]

Objectives: As the use of functioning outcomes is increasingly being advocated in multinational clinical trials and comparative studies, making available instruments with known validity and reliability in several languages is required. Here we present data on the Portuguese validation of the Functioning Assessment Short Test (FAST), which was explicitly designed to gauge functioning dimensions empirically linked to bipolar disorder. Methods: One hundred patients with bipolar disorder and matched controls were assessed with the FAST, which was evaluated regarding discriminant, content and construct validity, concurrent validity with functioning instruments, internal consistency and test–retest reliability. Results: The FAST displayed a five-factor structure very similar to its conceptualization, successfully discriminated patient and control groups, and correlated highly with other functioning measures; it also showed excellent test–retest reliability and internal consistency. Conclusions: The FAST is a measure with sufficient validity and reliability, with potential for the use in international clinical trials and comparative studies. [ABSTRACT FROM AUTHOR]

Contraception has been little investigated in bipolar disorder, an illness associated with impulsive sexual behavior and use of medications that are unsafe during pregnancy. In this cross-sectional survey of 136 women with bipolar disorder, prevalence of contraception use was 58.8%. Use of any method was associated in the multivariable analysis with being married, younger than 40 and having had previous pregnancies. Women diagnosed with bipolar disorder and treated in a tertiary facility use contraceptive methods suboptimally. [ABSTRACT FROM AUTHOR]

Abstract: Neurotrophins are central to several aspects of central nervous system function, and emerging evidence links these growth factors to mood disorders. The purpose of this study was to investigate serum neurotrophin-4/5 (NT-4/5) levels in patients with bipolar disorder, both within mood episodes and in euthymia. Patients with bipolar I disorder (n =154) and controls (n =30) had their NT-4/5 serum levels assayed using an ELISA. Levels of NT-4/5 levels were significantly higher in bipolar disorder patients than in controls; NT-4/5 levels were increased in mania, depression and euthymia, but not significantly different between BD mood states. As far as are aware, this is the first study showing NT-4/5 immunocontent alterations in bipolar disorder. A tentative explanation would be that NT-4/5 increases is compensating for ongoing oxidative damage in dopaminergic neurons. [Copyright &y& Elsevier]

The recovery process in bipolar disorder is a subjective and multidimensional experience that seeks to develop new meanings and purposes for living a satisfying life despite the limitations imposed by the disorder. Thus, this qualitative study aimed to explore the perceptions of recovery and the meanings attributed by individuals undergoing treatment for bipolar disorder to the elements considered relevant in this process. Semi-structured interviews with open-ended questions were conducted to explore the experiences and perspectives of recovery in individuals undergoing treatment for bipolar disorder. Grounded Theory was used as the method for qualitative analysis. The study included 26 participants aged between 18 and 65 years. Based on the analysis of participant reports, we identified two main themes: living with the illness and what it means to be in recovery. The perception of recovery is an individual process and can differ from the medical model. Participants suggest that accepting the diagnosis of bipolar disorder and finding meaning in life are essential to their recovery. They also describe how mental health professionals can facilitate or hinder this process. Understanding patients' perceptions can facilitate access to healthcare services and treatment adherence. [ABSTRACT FROM AUTHOR]

The article presents a study on the effectiveness of N-acetyl cysteine (NAC) for the treatment of bipolar disorder. A total of 74 patients participated in a placebo-controlled trial and received NAC twice daily for 24 weeks to assess the relationship between functioning, quality of life, and bipolar disorder. The trial revealed that a considerable part of the impact of NAC on functioning has no relation with the change in depression.

The authors explore the reliability of the Portuguese version of the Bipolar Depression Rating Scale (BDRS) that has been developed to identify typical and atypical depressive symptoms as well as depressive mixed states. They note that BDRS was translated into Portuguese by two independent translators. Its structure has been evaluated using cluster analysis which involves sorting variables according to similarity on one or more dimensions. They believe that the reliability and the two-cluster solution demonstrates the validity of the scale.

A letter to the editor is presented regarding the article "Affective instability as rapid cycling: theoretical and clinical implications for borderline personality and bipolar spectrum disorders," by D. F. MacKinnon and R. Pies in the February 2006 issue.

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. [ABSTRACT FROM AUTHOR]

Abstract: Background: Relatively little is known about psychological predictors of the onset of mania among individuals with bipolar disorder, particularly during episodes of depression. In the present study we investigated attributional style as a predictor of onset of hypomanic, manic or mixed episodes among bipolar adults receiving psychosocial treatment for depression. We hypothesized that “extreme” (i.e., excessively pessimistic or optimistic) attributions would predict a greater likelihood of developing an episode of mood elevation. Method: Outpatients with DSM-IV bipolar I or II disorder (N = 105) enrolled in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) were randomly allocated to one of three types of intensive psychotherapy for depression or a brief psychoeducational intervention. Patients completed a measure of attributional style at baseline and were followed prospectively for up to one year. All analyses were by intent to treat. Results: Logistic regressions and Cox proportional hazards models indicated that extreme (both positively- and negatively-valenced) attributions predicted a higher likelihood of (and shorter time until) transition from depression to a (hypo)manic or mixed episode (ps < .04), independent of the effects of manic or depressive symptom severity at baseline. Extreme attributions were also retrospectively associated with more lifetime episodes of (hypo)mania and depression (ps < .05). Conclusions: Evaluating extreme attributions may help clinicians to identify patients who are at risk for experiencing a more severe course of bipolar illness, and who may benefit from treatments that introduce greater cognitive flexibility. [Copyright &y& Elsevier]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Gomes FA, Kauer-Sant’Anna M, Magalhães PV, Jacka FN, Dodd S, Gama CS, Cunha Â, Berk M, Kapczinski F. Obesity is associated with previous suicide attempts in bipolar disorder. Objective: There is a paucity of data about risk factors for suicide attempts in bipolar disorder. The aim of this study is to examine the association between suicide attempts and obesity in people with bipolar disorder. Methods: Two hundred fifty-five DSM-IV out-patients with bipolar disorder were consecutively recruited from the Bipolar Disorder Program at Hospital das Clínicas de Porto Alegre and the University Hospital at the Universidade Federal de Santa Maria, Brazil. Diagnosis and clinical variables were assessed with Structured Clinical Interview for DSM-IV-axis I (SCID I) and Program structured protocol. History of suicide attempts was obtained from multiple information sources including patients, relatives and review of medical records. Patients with body mass index (BMI) ≥ 30 were classified as obese. Results: Over 30% of the sample was obese and over 50% had a history of suicide attempt. In the multivariate model, obese patients were nearly twice (OR = 1.97, 95% CI: 1.06–3.69, p = 0.03) as likely to have a history of suicide attempt(s). Conclusion: Our results emphasise the relevance of obesity as an associated factor of suicide attempts in bipolar disorder. Obesity may be seen as correlate of severity and as such, must be considered in the comprehensive management of bipolar patients. [ABSTRACT FROM AUTHOR]

Objective: In the present study, we investigate the association between the val66met polymorphism of the brain-derived neurotrophic factor (BNDF) and the performance on the Wisconsin Card Sorting lest in a sample of Caucasian Brazilian patients with bipolar disorder. Method: Sixty-four patents with bipolar disorder were assessed and their performance on the Wisconsin Card Sorting Test was compared with the allele frequency and genotype of the val66met polymorphism of the brain-derived neurotrophic factor. Results: The percentage of non-perseverative errors was significantly higher among patients with the val/val genotype. There was no association between (BNDF) genotype frequency and other Wisconsin Card Sorting Test domains. Conclusion: Our results did not replicate previous descriptions of an association between a worse cognitive performance and the presence of the met allele of the val66met brain-derived neurotrophic factor gone polymorphism. [ABSTRACT FROM AUTHOR]

• Childhood trauma is much reported by subjects with bipolar disorder. • Worse clinical outcomes in bipolar with trauma as compared to bipolar without trauma. • Highest functional impairment in individuals with bipolar disorder and early trauma. Childhood trauma is a complex experience, much reported by subjects with bipolar disorder. There are still few studies that assess its consequences in a community sample of bipolar in early stage. The aim of the present study is to assess the association between childhood trauma and clinical outcomes, including the global functioning, in a community sample of young adults with bipolar disorder. This is a cross-sectional study with a community sample of subjects with bipolar disorder, from 23 to 30 years old, with and without childhood trauma. The trauma experiences during childhood were assessed by Childhood Trauma Questionnaire (CTQ). The functioning was assessed by Functioning Assessment Short Test (FAST). Ninety subjects with bipolar disorder were included in the study (30 with childhood trauma and 60 without childhood trauma). Young adults with bipolar disorder and childhood trauma showed higher prevalence of current suicide risk, higher severity of depressive symptoms, and higher functioning impairment as compared to subjects with bipolar disorder without childhood trauma. The childhood trauma experiences appear to be an environmental risk factor for worse clinical outcomes and higher functional impairment. [ABSTRACT FROM AUTHOR]

Highlights • BD patients presents a decrease in 1513C allele frequency compared to controls. • BD patients has a potential increase in 1513 A A and in 1513 A A/AC genotype frequency. • BD patients presents a state of disadvantage of pro-inflammatory receptor activity. • P2 × 7R is a possible important mediator to the pathophysiology of bipolar disorder. • P2 × 7R is a potential biomarker for prediction and diagnosis of BD. Abstract Although the etiology of Bipolar Disorder (BD) remains unknown, a strong genetic component to the pathogenesis and risk for this disorder has been widely hypothesized. Several risk genes for BD have been identified; of these, the purinergic P2 × 7 receptor (P2 × 7R) constitutes a pro-inflammatory receptor and a potential risk gene candidate. The purpose of the present study was to assess the frequency of the 1513 A > C P2RX7 polymorphism (rs3751143; Glu496Ala), which leads to receptor loss-of-function, in 154 BD patients versus 184 control subjects. The existence of a differential modulation of P2 × 7R was also analyzed in 22 euthymic BD patients, in comparison to 18 healthy controls. Our data show a decrease in 1513C allele frequency (p = 0.045) and a potential increase in 1513 A A/AC (p = 0.055) genotype frequency in BD patients, compared to controls, indicating an enhanced function of the pro-inflammatory P2 × 7 receptor in BD subjects. Interestingly, no differences in P2RX7 gene and protein expression were found between euthymic BD patients and matched healthy controls. In conclusion, our results suggest that P2 × 7R might play a role in the pathophysiology of BD and add new information regarding this receptor as a potential biomarker for the prediction and diagnosis of the disorder. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to explore effects of adjunctive treatment with N -acetyl cysteine (NAC) on markers of inflammation and neurogenesis in bipolar depression. Methods: This is a secondary analysis of a placebo-controlled randomised trial. Serum samples were collected at baseline, week 8, and week 32 of the open-label and maintenance phases of the clinical trial to determine changes in interleukin (IL)-6, IL-8, IL-10, tumour necrosis factor-α (TNF-α), C-reactive protein (CRP) and brain-derived neurotrophic factor (BDNF) following adjunctive NAC treatment, and to explore mediation and moderator effects of the listed markers. Results: Levels of brain-derived neurotrophic factor (BDNF), tumour necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukins (IL) -6, 8, or 10 were not significantly changed during the course of the trial or specifically in the open-label and maintenance phases. There were no mediation or moderation effects of the biological factors on the clinical parameters. Conclusion: The results suggest that these particular biological parameters may not be directly involved in the therapeutic mechanism of action of adjunctive NAC in bipolar depression. [ABSTRACT FROM AUTHOR]

Objective To assess the differences in the prevalence of the metabolic syndrome (MetS) and their components in young adults with bipolar disorder (BD) and major depressive disorder (MDD) in a current depressive episode. Methods This was a cross-sectional study with young adults aged 24–30 years old. Depressive episode (bipolar or unipolar) was assessed using the Mini International Neuropsychiatric Interview – Plus version (MINI Plus). The MetS was assessed using the National Cholesterol Education Program Adult Treatment Panel III (NCEP/ATP III). Results The sample included 972 subjects with a mean age of 25.81 (±2.17) years. Both BD and MDD patients showed higher prevalence of MetS compared to the population sample (BD = 46.9%, MDD = 35.1%, population = 22.1%, p < 0.001). Higher levels of glucose, total cholesterol and LDL cholesterol, Body Mass Index, low levels of HDL cholesterol, and a higher prevalence of abdominal obesity were observed in both BD and MDD individuals with current depressive episode compared to the general population. Moreover, there was a significant difference on BMI values in the case of BD and MDD subjects (p = 0.016). Conclusion Metabolic components were significantly associated with the presence of depressive symptoms, independently of the diagnosis. [ABSTRACT FROM AUTHOR]

Objective To assess the association between peripheral levels of inflammatory cytokines and functional impairment in subjects with Bipolar Disorder (BD), Major Depressive Disorder (MDD) and population controls. Methods This was a cross-sectional study with a matched sample of drug-free young adults with BD ( n = 48), MDD ( n = 48) and population controls ( n = 48). Mood disorder was confirmed by a certified psychologist using the Structured Clinical Interview for DSM-IV (SCID-I). Functional impairment was assessed using the Functional Assessment Short Test (FAST). Serum levels of IL-6 and IL-10 were measured by ELISA. Results Peripheral levels of IL-6 and IL-10 were not significantly different between subjects with BD, MDD compared to controls. Higher levels of functional impairment were verified in subjects with BD and MDD compared to population controls ( p ≤ 0.001). In addition, IL-6 and IL-10 levels were positively correlated with functional impairment in subjects with BD (IL-6: r = 0.349, p = 0.016; and IL-10: r = 0.351, p = 0.016). Conclusion Inflammatory dysregulation was associated with functional impairment among drug-free subjects with BD. This finding suggests that inflammatory dysregulation may be involved in the neuroprogression of BD. [ABSTRACT FROM AUTHOR]

The aim of this study was to compare the global functioning and cognitive performance in a community sample of young adults with mood disorders versus community controls. This was a cross-sectional study nested in a cohort study with a community sample. Data was collected from February 2012 to June 2014; specifically, at a mean of five years after the first phase, all young adults were invited to participate in a re-evaluation. Mini International Neuropsychiatric Interview - PLUS (MINI-PLUS) was used for the diagnosis of mood disorders. The Functional Assessment Short Test (FAST) and the Montreal Cognitive Assessment (MoCA) were used to assess the global functioning, and cognitive performance, respectively. Were included 1258 subjects. Functional impairment was greater in subjects with bipolar disorder when compared to community controls, and there were no differences between major depressive disorder and community controls. There were no significant differences in cognitive performance between young adults with mood disorders when compared to community controls. Functional impairment is a marker for bipolar disorder in young adults; however, gross cognitive impairment assessed by a screening test is not, possibly because cognition is impaired in more advanced stages of the disorder. [ABSTRACT FROM AUTHOR]

Bipolar disorder is a recurrent and highly incapacitating illness, related to inflammation and changes in the insulin-like growth factor 1 (IGF-1). The objective of this study was to evaluate serum levels of IGF-1 in bipolar disorder patients and its relation to inflammation. We included 31 patients with bipolar disorder and 33 healthy controls. Serum concentrations of IGF-1, growth hormone (GH), insulin and tumor necrosis factor α (TNF-α) were analyzed. The serum levels of IGF-1 seem to be increased in bipolar disorder patients (248.84±104.91 ng/mL) compared to controls (169.18±74.16 ng/mL). Comparing reference values of IGF serum concentrations between groups, we found that 32% of patients had increased IGF-1 serum concentrations while only 3% of subjects are above normal range. We did not find statistically significant differences between groups in the concentration of insulin, GH, and TNF-α. This study suggests an association between IGF-1 in the pathophysiology of bipolar disorder. It is possible that this peripheral increase is related to a central nervous system increased resistance to IGF-1, thus reducing its neuroprotective action. [ABSTRACT FROM AUTHOR]

Background It is known that sleep disturbance has been considered a trait-marker of mood disorders. However, the role of disruptions in biological rhythms, such as eating, activity, and social patterns, needs to be better understood. Aim To assess the differences in biological rhythms in subjects with bipolar disorder, major depressive disorder, and healthy controls. We also tested the association between disruptions of biological rhythms and circadian preferences. Methods A cross-sectional, population-based study with a representative sample of 1023 young adults. Bipolar disorder and depression were diagnosed using The Mini International Neuropsychiatric Interview – PLUS and DSM Structured Clinical Interview. Self-reported biological rhythms and circadian preference were assessed using the Biological Rhythm Interview of Assessment in Neuropsychiatry (BRIAN). Results Bipolar disorders and depression subjects presented higher rates of disruption in biological rhythms when compared to healthy controls even after adjusting for sex, socioeconomic status, alcohol, tobacco, illicit drug use, anxiety disorder and psychotropic medication use. Euthymic subjects showed higher biological rhythm disruption when compared to controls. Higher disruption in biological rhythms was observed in subjects with evening preferences. Conclusion Higher disruption in biological rhythms occurs in individuals with depression and bipolar disorder even on periods of euthymia. [ABSTRACT FROM AUTHOR]

Recent evidence points to the involvement of the purinergic signaling in the pathophysiology of bipolar disorder. The aim of this study was to assess the serum levels of adenosine and to evaluate its relation to functioning in 24 euthymic patients with bipolar disorder type I and in 25 matched healthy controls. Subjects were evaluated using the functioning assessment short test. Serum purine levels were measured by high pressure liquid chromatography. Our results show a decrease in serum adenosine levels in bipolar disorder patients compared with controls (t= −4.8, df= 43.96, p<0.001). Moreover, a significant negative correlation was found between patient adenosine levels and depression scale scores (r= −0.642, p= 0.001). Higher functional impairment was linked to lower levels of adenosine in patients (rho= −0.551, p= 0.008). Taken together, our results provide evidence for a purinergic imbalance in bipolar disorder, specifically an adenosinergic dysfunction. Our results also indicate a relation between adenosine levels and the functional impairment caused by the disorder, which could demonstrate a potential relation of adenosine levels in worsening of symptoms. [ABSTRACT FROM AUTHOR]

Objective To assess circadian preference among a community sample of people with bipolar disorder, major depression and without any mood disorders. Secondly, we investigated the association of circadian preference with cytokines interleukin-6 (IL-6), interleukin-10 (IL-10) and, tumor necrosis factor alpha (TNF-α) and oxidative stress assessed by thiobarbituric acid reactive substances (TBARS), uric acid and Protein Carbonyl Content (PCC). Method A cross-sectional study nested in a population-based sample. Caseness was confirmed with the Structured Clinical Interview for DSM-IV. A sample of 215 participants, in whom we measured circadian preferences, IL-6, IL-10, TNF-α, TBARS, uric acid, PCC. Biological rhythms were evaluated using the Biological Interview of Assessment in Neuropsychiatry. Results Bipolar group presented a higher alteration in biological rhythms (40.40 ± 9.78) when compared with the major depression group (36.35 ± 9.18) and control group (27.61 ± 6.89) p < 0.001. Subjects with bipolar disorder who were active at night and had a day/night cycle reverse showed decreased levels of IL-6 (t, 44 = 2.096; p = 0.042), (t, 44 = 2.213; p = 0.032), respectively. In the bipolar disorder group subjects who presented day/night cycle reverse had lower TBARS levels (t, 41 = 2.612; p = 0.013). TNF-α were decreased in subjects more active at night with bipolar disorder. Conclusion Lower serum levels of IL-6, TNF-α and TBARS were associated with evening preference in bipolar disorder group. These findings suggest that chronotype may alter the levels of interleukins and oxidative stress levels in bipolar and healthy subjects. A better understanding of the role of circadian preferences in levels of interleukins and oxidative stress are needed. [ABSTRACT FROM AUTHOR]

Background: Little is known about specific mood symptoms that may confer risk for suicidal ideation (SI) among patients with bipolar disorder (BD). We evaluated prospectively whether particular symptoms of depression and mania precede the onset or worsening of SI, among adults with or without a history of a suicide attempt.Methods: We examined prospective data from a large (N = 2,741) cohort of patients participating in the Systematic Treatment Enhancement Program for BD (STEP-BD). We evaluated history of suicide attempts at baseline, and symptoms of depression and mania at baseline and follow-up visits. Hierarchical linear modeling tested whether specific mood symptoms predicted subsequent levels of SI, and whether the strength of the associations differed based on suicide attempt history, after accounting for the influence of other mood symptoms and current SI.Results: Beyond overall current depression and mania symptom severity, baseline SI, and illness characteristics, several mood symptoms, including guilt, reduced self-esteem, psychomotor retardation and agitation, increases in appetite, and distractibility predicted more severe levels of subsequent SI. Problems with concentration, distraction, sleep loss and decreased need for sleep predicted subsequent SI more strongly among individuals with a suicide attempt history.Conclusions: Several specific mood symptoms may confer risk for the onset or worsening of SI among treatment-seeking patients with BD. Individuals with a previous suicide attempt may be at greater risk in part due to greater reactivity to certain mood symptoms in the form of SI. However, overall, effect sizes were small, suggesting the need to identify additional proximal predictors of SI. [ABSTRACT FROM AUTHOR]

Aim: To assess the functional impairment of young adults with bipolar disorder with substance abuse/dependence comorbidity.Method: Cross-sectional study within a community sample. Bipolar Disorder was assessed by qualified psychologists using The Mini International Neuropsychiatric Interview - PLUS (MINI-PLUS). Substance abuse and dependence was assessed using the "Alcohol, Smoking and Substance Involvement Screening Test" (ASSIST). Functional impairment was assessed using the Functional Assessment Short Test (FAST).Results: The sample included 1259 young adults. The prevalence of Bipolar Disorder (BD) without Substance Abuse/Dependence (SAD) comorbidity was 5.9% (n=74), and the prevalence of bipolar disorder with substance abuse/dependence comorbidity was 1.4% (n=17). Both groups showed higher impairment in overall functioning, interpersonal relationship, and leisure time as compared to controls. In addition, BD+SAD showed higher impairment in the cognitive functioning domain of FAST.Limitation: A battery of neuropsychological tests was not performed.Conclusion: Functional impairment is associated with BD, independently of substance abuse or dependence. In addition, BD+SAD present a more severe impairment in the cognitive domain of FAST as compared to controls. [ABSTRACT FROM AUTHOR]

Progression of bipolar disorder (BD) has been associated with cognitive impairment and changes in neuroplasticity, including a decrease in serum brain-derived neurotrophic factor (BDNF). However, no study could examine BDNF levels directly in different brain regions after repeated mood episodes to date. The proposed animal model was designed to mimic several manic episodes and evaluate whether the performance in memory tasks and BDNF levels in hippocampus, prefrontal cortex, and amygdala would change after repeated amphetamine (AMPH) exposure. Adult male Wistar rats were divided into subchronic (AMPH for 7 days) and chronic groups (35 days), mimicking manic episodes at early and late stages of BD, respectively. After open field habituation or inhibitory avoidance test, rats were killed, brain regions were isolated, and BDNF mRNA and protein levels were measured by quantitative real-time PCR and ELISA, respectively. AMPH impaired habituation memory in both subchronic and chronic groups, and the impairment was worse in the chronic group. This was accompanied by increased Bdnf mRNA levels in the prefrontal cortex and amygdala region, as well as reduced BDNF protein in the hippocampus. In the inhibitory avoidance, AMPH significantly decreased the change from training to test when compared to saline. No difference was observed between subchronic and chronic groups, although chronically AMPH-treated rats presented increased Bdnf mRNA levels and decreased protein levels in hippocampus when compared to the subchronic group. Our results suggest that the cognitive impairment related to BD neuroprogression may be associated with BDNF alterations in hippocampus, prefrontal cortex, and amygdala. [ABSTRACT FROM AUTHOR]

Background: Caregiver burden has been associated with caregivers' mental disorders and need for support and information. However, the lack of quantitative studies and formal interventions aiming to lower burden levels in this population reflect the current negligence regarding this important issue. Aim: To identify burden levels and associated factors in caregivers of young adults with bipolar and unipolar mood disorder. Method: This is a cross-sectional study nested within a population-based cross-sectional study with young adults. Caregiver burden was assessed through the Burden Interview. Information about caregiver mental disorders (Axis I) and alcohol abuse were obtained through the Mini International Neuropsychiatric Interview (MINI) and the Cut-Down, Annoyed, Guilty and Eye-Opener (CAGE) questionnaire, respectively. Results: Caregiver burden was associated to caregiver's mood and anxiety disorders, suicide risk and being the caregiver of young adults with depression disorder and bipolar disorder. Also, burden was higher among caregivers of bipolar individuals. When excluding the control group from the analysis, only mood and anxiety disorders remained associated to caregiver burden. Conclusions: Caregivers are affected by the young adult's disorder even before a diagnosis has been given, with serious impairments in their lives. Thus, this is a subject in need of designing relevant strategies aiming to provide them with care. [ABSTRACT FROM AUTHOR]

Objective: At least 50% of individuals with bipolar disorder have a lifetime anxiety disorder. Individuals with both bipolar disorder and a co-occurring anxiety disorder experience longer illness duration, greater illness severity, and poorer treatment response. The study explored whether comorbid lifetime anxiety in bipolar patients moderates psychotherapy treatment outcome. Method: In the Systematic Treatment Enhancement Program randomized controlled trial of psychotherapy for bipolar depression, participants received up to 30 sessions of intensive psychotherapy (family-focused therapy, interpersonal and social rhythm therapy, or cognitive-behavioral therapy) or collaborative care, a three- session comparison treatment, plus pharmacotherapy. Using the number needed to treat, we computed effect sizes to analyze the relationship between lifetime anxiety disorders and rates of recovery across treatment groups after 1 year. Results: A total of 269 patients (113 women) with a comorbid lifetime anxiety disorder (N=177) or without a comorbid lifetime anxiety disorder (N=92) were included in the analysis. Participants with a lifetime anxiety disorder were more likely to recover with psychotherapy than with collaborative care (66% compared with 49% recovered over 1 year; number needed to treat5.88, small to medium effect). For patients without a lifetime anxiety disorder, there was no difference between rates of recovery in psychotherapy compared with collaborative care (64% compared with 62% recovered; number needed to treat=50, small effect). Participants with one lifetime anxiety disorder were likely to benefit from intensive psychotherapy compared with collaborative care (84% compared with 53% recovered; number needed to treat=3.22, medium to large effect), whereas patients with multiple anxiety disorders exhibited no difference in response to the two treatments (54% compared with 46% recovered; number needed to treat=12.5, small effect). Conclusions: Depressed patients with bipolar disorder and comorbid anxiety may be in particular need of additional psychotherapy for treating acute depression. These results need to be replicated in studies that stratify bipolar patients to treatments based on their anxiety comorbidity status. [ABSTRACT FROM AUTHOR]

Abstract: Bipolar disorder (BD) is associated with considerable higher chronic medical comorbidities, overweight and obesity. Adipokines are adipocyte-derived secretory factors which have functions in immune response and seem to be associated with both BD and overweight. The aim of this study was to evaluate the plasma levels of adipokines (adiponectin, resistin and leptin) and TNF-α and its receptors (sTNFR1 and sTNFR2) in BD overweight patients in comparison with overweight controls. Thirty euthymic BD type-I patients and thirty controls matched by age, gender and body-mass index (BMI) were assessed by Mini-International Neuropsychiatric Interview, Young Mania and Hamilton Depression rating scales (YMRS and HDRS, respectively). Plasma levels of adiponectin, resistin, leptin, TNF-α and its soluble receptors were measured by ELISA. BD patients presented increased plasma levels of adiponectin (p < 0.001), leptin (p < 0.001) and sTNFR1 (p = 0.01). Plasma levels of adipokines were not correlated neither with clinical parameters nor TNF-α, sTNFR1 and sTNFR2 plasma levels. This study provides further support to the hypothesis of the immune/inflammatory imbalance in BD. [Copyright &y& Elsevier]

Abstract: Objective: To evaluate the prevalence of episodes of mania and hypomania, as well as associated factors and comorbidities among adults 18 to 24years old in the city of Pelotas, Brazil. Method: This is a cross-sectional population-based study. The sample was selected through conglomerates, and episodes of mania and hypomania were assessed using the Mini International Neuropsychiatric. Results: The sample consisted of 1560 subjects. The lifetime prevalence of manic and hypomanic episodes was 7.5% and 5.3%, respectively. Subjects with (hypo)manic episodes had a higher prevalence of anxiety disorders, substance abuse and suicidality. Limitation: The high rate of (hypo)mania may to some extent reflect diagnostic error. Conclusion: Such high prevalence of (hypo)mania may nonetheless be valid as it was associated with corresponding rates of comorbidity and suicidality. [Copyright &y& Elsevier]

• Mood disorders were associated with significant disability. • However, functioning significantly improved over the 5-year follow-up period. • There was a worsening of disability at follow-up for those in a depressive episode. • This worsening was independent of unipolar or bipolar depression severity. • Improvements in functioning in young people can be observed during euthymia. This study is aimed at assessing changes in functioning among young people from the general population with bipolar disorder and major depressive disorder over a period of five years. Specifically, we hypothesized that significant illness progression would take place during euthymia over time in bipolar disorder. We conducted a longitudinal study with 231 people, assessed at baseline and again at a five-year follow-up. A structured clinical interview was used to diagnose participants with mood disorders. A control group without mood disorders was also included. Functioning was assessed with the Functioning Assessment Short Test, and linear mixed models were used to analyze the effect of psychopathology on change in functioning. Mood disorders were associated with significant functional impairment, but functioning significantly improved in both groups over the 5-year follow-up period. Depressive episodes, however, were associated with worse functioning at follow-up, independently of depression severity. In contrast to our initial hypothesis, we found a worsening of functioning in a five-year period associated only with depressive episodes. This suggests that interventions focused on the prevention of mood episodes early in the course of illness may be particularly promising to reduce adverse functioning outcomes. [ABSTRACT FROM AUTHOR]

• Treatment of neuronal cells with ATP induces cellular death through apoptosis • Lithium is able to prevent the cellular toxicity induced by ATP • ATP activates microglial cells via P2 × 7R • Lithium couldn't prevent microglial M1-phenotype switch induced by ATP Lithium is the mainstay of pharmacotherapy for treating bipolar disorder (BD). However, despite its wide use for over 60 years in the clinic, its mechanisms of action are not yet well defined. Elucidating lithium's mechanism of action will not only shed light on the pathophysiology of BD, but also potentially uncover new treatment targets. Previous studies suggest that the purinergic system may be involved in lithium's neuroprotective action; thus, the specific aim of this study is to better understand the neuroprotective action of lithium against ATP-induced cellular effect in both neuronal and microglial cellular lineages. We used PC12 neuronal and N9 microglial cells, evaluating cell death by cell counting and Annexin/PI cytometry assay, P2 × 7R immunocontent and ectonucleotidases activity, together with cytokine and nitrite assessment for microglial activity determination. Our results indicate that cells of different neural origins are responsive to ATP, in the sense of neuronal excitotoxicity and microglial switch into an activated M1-like phenotype respectively. Lithium, in turn, modulates the response in neuronal PC12 cells, preventing ATP-induced cell death. On the other hand, in N9 microglial cells, lithium was unable to prevent ATP-induced activation via P2 × 7R, indicating that lithium protective action against the effects of ATP more likely occurs in neurons rather than in microglia. Further studies are needed to better characterize the involvement of the purinergic system in the mechanism of action of lithium against neuronal death and microglial activation, in order to uncover new therapeutic adjunctive targets, such as antagonism of P2 × 7R, as potential approach for bipolar disorder treatment. [ABSTRACT FROM AUTHOR]