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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.

Abstract Background Sunlight contains ultraviolet B (UVB) radiation that triggers the production of vitamin D by skin. Vitamin D has widespread effects on brain function in both developing and adult brains. However, many people live at latitudes (about > 40 N or S) that do not receive enough UVB in winter to produce vitamin D. This exploratory study investigated the association between the age of onset of bipolar I disorder and the threshold for UVB sufficient for vitamin D production in a large global sample. Methods Data for 6972 patients with bipolar I disorder were obtained at 75 collection sites in 41 countries in both hemispheres. The best model to assess the relation between the threshold for UVB sufficient for vitamin D production and age of onset included 1 or more months below the threshold, family history of mood disorders, and birth cohort. All coefficients estimated at P ≤ 0.001. Results The 6972 patients had an onset in 582 locations in 70 countries, with a mean age of onset of 25.6 years. Of the onset locations, 34.0% had at least 1 month below the threshold for UVB sufficient for vitamin D production. The age of onset at locations with 1 or more months of less than or equal to the threshold for UVB was 1.66 years younger. Conclusion UVB and vitamin D may have an important influence on the development of bipolar disorder. Study limitations included a lack of data on patient vitamin D levels, lifestyles, or supplement use. More study of the impacts of UVB and vitamin D in bipolar disorder is needed to evaluate this supposition.

Objective The importance of a healthy lifestyle in preventing morbidity and mortality is well-established. The COVID-19 pandemic brought about significant lifestyle changes globally, but the extent of these changes in the Brazilian population remains unclear. The objective of this study was to evaluate changes in lifestyle among the Brazilian general population during the first year of the pandemic.Design Three consecutive anonymous web surveys were carried out: survey 1 (S1)—April 2020, S2—August 2020 and S3—January 2021.Setting Brazil.Participants The study included 19 257 (S1), 1590 (S2) and 859 (S3) participants from the general population, who were ≥18 years, of both sexes, with access to the internet, self-reporting living in Brazil and who agreed to participate after reading the informed consent.Primary outcome Lifestyle changes were assessed using the Short Multidimensional Instrument for Lifestyle Evaluation—Confinement (SMILE-C). The SMILE-C assesses lifestyle across multiple domains including diet, substance use, physical activity, stress management, restorative sleep, social support and environmental exposures. We used a combination of bootstrapping and linear fixed-effect modelling to estimate pairwise mean differences of SMILE-C scores overall and by domain between surveys.Results In all the surveys, participants were mostly women and with a high education level. Mean SMILE-C scores were 186.4 (S1), 187.4 (S2) and 190.5 (S3), indicating a better lifestyle in S3 as compared with S1. The pairwise mean differences of the overall SMILE-C scores were statistically significant (p

Abstract Selecting a course of treatment in psychiatry remains a trial-and-error process, and this long-standing clinical challenge has prompted an increased focus on predictive models of treatment response using machine learning techniques. Electroencephalography (EEG) represents a cost-effective and scalable potential measure to predict treatment response to major depressive disorder. We performed separate meta-analyses to determine the ability of models to distinguish between responders and non-responders using EEG across treatments, as well as a performed subgroup analysis of response to transcranial magnetic stimulation (rTMS), and antidepressants (Registration Number: CRD42021257477) in Major Depressive Disorder by searching PubMed, Scopus, and Web of Science for articles published between January 1960 and February 2022. We included 15 studies that predicted treatment responses among patients with major depressive disorder using machine-learning techniques. Within a random-effects model with a restricted maximum likelihood estimator comprising 758 patients, the pooled accuracy across studies was 83.93% (95% CI: 78.90–89.29), with an Area-Under-the-Curve (AUC) of 0.850 (95% CI: 0.747–0.890), and partial AUC of 0.779. The average sensitivity and specificity across models were 77.96% (95% CI: 60.05–88.70), and 84.60% (95% CI: 67.89–92.39), respectively. In a subgroup analysis, greater performance was observed in predicting response to rTMS (Pooled accuracy: 85.70% (95% CI: 77.45–94.83), Area-Under-the-Curve (AUC): 0.928, partial AUC: 0.844), relative to antidepressants (Pooled accuracy: 81.41% (95% CI: 77.45–94.83, AUC: 0.895, pAUC: 0.821). Furthermore, across all meta-analyses, the specificity (true negatives) of EEG models was greater than the sensitivity (true positives), suggesting that EEG models thus far better identify non-responders than responders to treatment in MDD. Studies varied widely in important features across models, although relevant features included absolute and relative power in frontal and temporal electrodes, measures of connectivity, and asymmetry across hemispheres. Predictive models of treatment response using EEG hold promise in major depressive disorder, although there is a need for prospective model validation in independent datasets, and a greater emphasis on replicating physiological markers. Crucially, standardization in cut-off values and clinical scales for defining clinical response and non-response will aid in the reproducibility of findings and the clinical utility of predictive models. Furthermore, several models thus far have used data from open-label trials with small sample sizes and evaluated performance in the absence of training and testing sets, which increases the risk of statistical overfitting. Large consortium studies are required to establish predictive signatures of treatment response using EEG, and better elucidate the replicability of specific markers. Additionally, it is speculated that greater performance was observed in rTMS models, since EEG is assessing neural networks more likely to be directly targeted by rTMS, comprising electrical activity primarily near the surface of the cortex. Prospectively, there is a need for models that examine the comparative effectiveness of multiple treatments across the same patients. However, this will require a thoughtful consideration towards cumulative treatment effects, and whether washout periods between treatments should be utilised. Regardless, longitudinal cross-over trials comparing multiple treatments across the same group of patients will be an important prerequisite step to both facilitate precision psychiatry and identify generalizable physiological predictors of response between and across treatment options.

Abstract Objectives Evidence suggests that ketamine’s influence on brain-derived neurotrophic factor (BDNF) might be involved in its mechanism of rapid antidepressant action. We aimed to evaluate the differential impact of ketamine and esketamine on serum BDNF levels and its association with response patterns in treatment-resistant depression (TRD). Methods Participants (n = 53) are from a randomized, double-blind clinical trial comparing the efficacy of single-dose ketamine (0.5mg/kg, n = 27) and esketamine (0.25mg/kg, n = 26) in TRD. Depression severity was assessed before and 24 hours, 72 hours, and 7 days after the intervention, using the Montgomery-Åsberg Depression Rating Scale (MADRS). Blood samples were collected before infusion, 24 hours, and 7 days afterwards. Results There were no significant changes in BDNF levels at post-infusion evaluation points, and no difference in BDNF levels comparing ketamine and esketamine. Both drugs exhibited similar therapeutic effect. There was no association between BDNF levels and response to treatment or severity of depressive symptoms. Conclusion There was no significant treatment impact on BDNF serum levels – neither with ketamine nor esketamine – despite therapeutic response. These results suggest that ketamine or esketamine intervention for TRD has no impact on BDNF levels measured at 24 hours and 7 days after the infusion. This clinical trial is registered on the Japan Primary Registries Network: UMIN000032355.

Abstract Access to postmortem brain tissue can be valuable in refining knowledge on the pathophysiology and genetics of neuropsychiatric disorders. Obtaining postmortem consent for the donation after death by suicide can be difficult, as families may be overwhelmed by a violent and unexpected death. Examining the process of brain donation can inform on how the request can best be conducted. This is a qualitative study with in-depth interviews with forty-one people that were asked to consider brain donation—32 who had consented to donation and 9 who refused it. Data collection and analyses were carried out according to grounded theory. Five key themes emerged from data analysis: the context of the families, the invitation to talk to the research team, the experience with the request protocol, the participants’ assessment of the experience, and their participation in the study as an opportunity to heal. The participants indicated that a brain donation request that is respectful and tactful can be made without adding to the family distress brought on by suicide and pondering brain donation was seen as an opportunity to transform the meaning of the death and invest it with a modicum of solace for being able to contribute to research.

Abstract Introduction Neuroprogression has been proposed as the pathological rewiring of the brain that takes place in parallel with clinical and neurocognitive deterioration in the course of psychiatric disorders. This study aims to review the biological underpinnings and clinical outcomes related to neuroprogression in post-traumatic stress disorder (PTSD). Methods We performed a systematic review by searching PubMed, Embase, and Web of Science for articles published between January 1, 1960, and January 6, 2020. Inclusion criteria were met when articles assessed brain changes, neurocognition, functioning, inflammation, oxidative stress, and neurotrophins in patients with PTSD. Narrative review articles, case reports, and preclinical studies were excluded. Results A total of 965 abstracts were identified and 15 articles were included in our systematic review. It seems that for a subset of patients whose symptoms worsen or are maintained at a high intensity there is a progressive change in the frontal lobe, especially the prefrontal cortex, and worsening of both neurocognition (verbal memory and facial recognition) and functioning (physical, psychological, social and environmental). Conclusion Although current findings associate progressive reduction in frontal lobe size with neurocognitive impairment, further research is needed to characterize PTSD as a neuroprogressive disorder.

Objective: To assess whether the effects of oral administration of 300 mg of Cannabidiol (CBD) for 28 days on mental health are maintained for a period after the medication discontinuation.Methods: This is a 3-month follow-up observational and clinical trial study. The data were obtained from two studies performed simultaneously by the same team in the same period and region with Brazilian frontline healthcare workers during the COVID-19 pandemic. Scales to assess emotional symptoms were applied weekly, in the first month, and at weeks eight and 12.Results: The primary outcome was that, compared to the control group, a significant reduction in General Anxiety Disorder-7 Questionnaire (GAD-7) from baseline values was observed in the CBD group on weeks two, four, and eight (Within-Subjects Contrasts, time-group interactions: F1-125 = 7.67; p = 0.006; ηp2 = 0.06; F1-125 = 6.58; p = 0.01; ηp2 = 0.05; F1-125 = 4.28; p = 0.04; ηp2 = 0.03, respectively) after the end of the treatment.Conclusions: The anxiolytic effects of CBD in frontline health care professionals during the COVID-19 pandemic were maintained up to 1 month after the treatment discontinuation, suggesting a persistent decrease in anxiety in this group in the real world. Future double-blind placebo-controlled clinical trials are needed to confirm the present findings and weigh the benefits of CBD therapy against potential undesired or adverse effects.

Abstract Background Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p

Abstract Introduction Irritability has both mood and behavioral manifestations. These frequently co-occur, and it is unclear to what extent they are dissociable domains. We used confirmatory factor analysis and external validators to investigate the independence of mood and behavioral components of irritability. Methods The sample comprised 246 patients (mean age 45 years; 63% female) from four outpatient programs (depression, anxiety, bipolar, and schizophrenia) at a tertiary hospital. A clinical instrument rated by trained clinicians was specifically designed to capture irritable mood and disruptive behavior dimensionally, as well as current categorical diagnoses i.e., intermittent explosive disorder (IED); oppositional defiant disorder (ODD); and an adaptation to diagnose disruptive mood dysregulation disorder (DMDD) in adults. Confirmatory factor analysis (CFA) was used to test the best fitting irritability models and regression analyses were used to investigate associations with external validators. Results Irritable mood and disruptive behavior were both frequent, but diagnoses of disruptive syndromes were rare (IED, 8%; ODD, 2%; DMDD, 2%). A correlated model with two dimensions, and a bifactor model with one general dimension and two specific dimensions (mood and behavior) both had good fit indices. The correlated model had root mean square error of approximation (RMSEA) = 0.077, with 90% confidence interval (90%CI) = 0.071-0.083; comparative fit index (CFI) = 0.99; and Tucker-Lewis index (TLI) = 0.99, while the bifactor model had RMSEA = 0.041; CFI = 0.99; and TLI = 0.99 respectively). In the bifactor model, external validity for differentiation of the mood and behavioral components of irritability was also supported by associations between irritable mood and impairment and clinical measures of depression and mania, which were not associated with disruptive behavior. Conclusions Psychometric and external validity data suggest both overlapping and specific features of the mood vs. disruptive behavior dimensions of irritability.

Objective: To evaluate the association between childhood trauma (CT) and serum levels of brain-derived neurotrophic factor (BDNF) and thiobarbituric acid-reactive substances (TBARS) during crack-cocaine withdrawal. Method: Thirty-three male crack-cocaine users were recruited at admission to a public addiction treatment unit. Serum BDNF and TBARS levels were evaluated at intake and discharge. Information about drug use was assessed by the Addiction Severity Index-6th Version (ASI-6); CT was reported throughout the Childhood Trauma Questionnaire (CTQ). CTQ scores were calculated based on a latent analysis model that divided the sample into low-, medium-, and high-level trauma groups. Results: There was a significant increase in BDNF levels from admission to discharge, which did not differ across CT subgroups. For TBARS levels, we found a significant time vs. trauma interaction (F2,28 = 6.357, p = 0.005,ηp 2 = 0.312). In participants with low trauma level, TBARS decreased, while in those with a high trauma level, TBARS increased during early withdrawal. Conclusion: TBARS levels showed opposite patterns of change in crack-cocaine withdrawal according to baseline CT. These results suggest that CT could be associated with more severe neurological impairment during withdrawal.

Abstract Background Innate immune system dysfunction has been recognized as an important element in the pathophysiology of bipolar disorder (BD). We aimed to investigate whether there are differences in the response of macrophages derived from patients in the early stages and late stages of BD and healthy subjects. Methods Human monocytes purified from peripheral blood mononuclear cells (PBMCs) of patients with BD type I (n = 18)—further classified into early- and late stage BD patients according to their functioning- and from healthy individuals (n = 10) were differentiated into macrophages in vitro. Monocyte-derived macrophages (M) were exposed to IFNγ plus LPS-M(IFNγ + LPS)- or IL-4-M(IL-4)—to induce their polarization into the classical (also called M1) or alternative (also called M2) activation phenotypes, respectively; or either Mψ were not exposed to any stimuli characterizing the resting state (denominated M0). In vitro secretion of cytokines, such as IL-1β, IL-6, IL-10, and TNF-α, was used as an index of macrophage activity. Results M(IFNγ + LPS) from late-stage BD patients produced less amount of IL-1β, IL-6, and IL-10 when compared to early-stage BD patients and healthy controls. Following alternative activation, M(IL-4) derived from late-stage patients secreted less IL-6 compared to the other groups. TNFα was less secreted by all macrophage phenotypes derived from late-stage patients when compared to healthy controls only (p

Introduction Vaping behaviour has increased in popularity and is particularly important to examine how it effects health outcomes in vulnerable populations, including those with opioid use disorder (OUD). With polysubstance use including cigarette and cannabis use being highly prevalent in the OUD population and cannabis/nicotine increasingly being consumed by vaping, vaping may have an important contribution to health outcomes in these individuals. The primary objective of this review is to systematically assess the literature related to patients with OUD and the effects vaping has shown on their physical and mental health.Method and analysis A systematic search of databases including MEDLINE, Embase, PsycINFO, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library, Cochrane Clinical Trials Registry, the National Institutes for Health Clinical Trials Registry and the WHO International Clinical Trials Registry Platform from inception to 31 December 2020 will be conducted. Identified citations will be screened by two reviewers to determine eligibility at the title and abstract level, and then at the full text and data extraction phases. Any disagreements in inclusion will be resolved through unblinded discussion by these reviewers, with any remaining disagreements being resolved by a third reviewer. Data collection from eligible studies will be conducted according to the data extraction form tested prior to abstraction. Included studies will be examined for quality and bias and will be meta-analysed where applicable. This protocol is reported in keeping with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols guidelines.Ethics and dissemination The results for this review will be disseminated through publications in peer-reviewed journals, posters and presentations at scientific conferences. Additionally, we are collaborating with the Canadian Addiction Treatment Centre clinics to help disseminate the findings for this review. As this is a systematic review, no ethics approval is needed.Review registration number CRD42020178441.

ABSTRACT: Background: Bipolar disorder is associated with an increased burden of general medical conditions that might be related to a more severe illness course. Methods: This is a cross-sectional study that evaluated clinical correlates of general medical comorbidities in outpatients with bipolar disorder (BD) involving 203 adult patients with a DSM-IV diagnosis of BD, consecutively recruited from the Bipolar Research Program (PROTAHBI) in Porto Alegre, Brazil. Clinical, demographic and anthropometrical variables were systematically assessed, and general medical comorbidity was measured using the Cumulative Illness Rating Scale (CIRS). Results: The prevalence of one or more medical comorbidities was 90.1%. The most common were those from endocrine/metabolic/breast, neurologic and vascular categories. A high burden of general medical comorbidities (defined as CIRS total score ≥ 4) was related to increasing age and body mass index and longer duration of illness after controlling for confounding factors. Limitations: The cross-sectional design limits our ability to make causal conclusions. Also, our sample consisted of patients with longer illness duration from a tertiary clinic and may not generalize to the whole spectrum of bipolar disorder. Conclusions: BD was associated with a high burden of general medical conditions related to age, obesity and longer duration of illness. Medical comorbidities must be incorporated as a core feature in the development of effective treatment strategies for bipolar disorder.

Background: It has been reported that patients with bipolar disorder (BD) present changes in peripheral levels of the inflammatory cytokine CCL11, particularly at latestages. The aim of this study is to evaluate CCL11 levels in a population-based sample of drug-naive young adults. Methods: This is a cross-sectional study nested to a large population-based study. 29 drug-naive young adults with BD and 29 controls selected from this cohort were matched for sex, age, and years of education. The diagnosis of psychiatric disorders was performed using the Mini International Neuropsychiatric Interview PLUS. Serum levels of CCL11 were measured using sandwich-ELISA. Independent samples T-test was used to assess differences between groups regarding CCL11 levels. Multivariate linear regression analyses were used to evaluate the effect of independent factors on CCL11 levels. Results: There were no demographic differences between individuals with BD and controls. No significant differences were found regarding CCL11 levels between groups. The final multivariate model showed that the variables that remained independently associated with higher CCL11 levels were male sex (B:41.41 [CI95%: 15.66 - 67.15], p = 0.002) and tobacco use (B:22.71 [CI95%: 1.28 - 44.15], p = 0.038). Conclusions: The present study suggests that there is a possible influence of sex and tobacco use on CCL11 levels, as male sex and smoking status were associated with higher CCL11 levels in our sample. It also suggests that peripheral levels of CCL11 may not be involved in the pathophysiology of BD at early stages of the disorder.

Abstract Introduction The rationale of mesenchymal stem cells (MSCs) as a novel therapeutic approach in certain neurodegenerative diseases is based on their ability to promote neurogenesis. Hippocampal atrophy has been related to bipolar disorder (BD) in preclinical, imaging and postmortem studies. Therefore, the development of new strategies to stimulate the neurogenesis process in BD is crucial. Objectives To investigate the behavioral and neurochemical changes induced by transplantation of MSCs in a model of mania-like behavior induced by lisdexamfetamine dimesylate (LDX). Methods Wistar rats (n=65) received one oral daily dose of LDX (10 mg/kg) or saline for 14 days. On the 8th day of treatment, the animals additionally received intrahippocampal saline or MSC (1 µL containing 25,000 cells) or lithium (47.5 mg/kg) as an internal experimental control. Two hours after the last administration, behavioral and neurochemical analyses were performed. Results LDX-treated rats had increased locomotor activity compared to saline-saline rats (p=0.004), and lithium reversed LDX-related hyperactive behavior (p0.05) in the hippocampus of rats. Conclusion Even though these results suggest that a single intrahippocampal injection of MSCs was not helpful to treat hyperactivity induced by LDX and neither influenced BDNF secretion, we cannot rule out the possible therapeutic effects of MSCs. Further research is required to determine direct effects of LDX on brain structures as well as in other pathophysiological targets related to BD.

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

BACKGROUND:The present study analyzes the feasibility of text classification to predict individual suicidal behavior. Entries from Virginia Woolf's diaries and letters were used to assess whether a text classification algorithm could identify written patterns associated with suicide. METHODS:This is a text classification study. We compared 46 text entries from the two months before Virginia Woolf's suicide with 54 texts randomly selected from Virginia Woolf's work during other periods of her life. Letters and diaries were included, while books, novels, short stories, and article fragments were excluded. The data was analyzed using a Naïve-Bayes machine-learning algorithm. RESULTS:The model showed a balanced accuracy of 80.45%, sensitivity of 69%, and specificity of 91%. The Kappa statistic was 0.6, which means a good agreement, and the p-value of the model was 0.003. The area under the ROC curve (AUC) was 0.80. In other words, the model exhibited good performance when used for classifying Virginia Woolf's diaries and letters. DISCUSSION:The present study showed the feasibility of a machine-learning model coupled with text to identify individual written patterns associated with suicidal behavior. Our text signature was able to identify the period of two months preceding suicide with a high accuracy. This technique may be applied to subjects with psychiatric disorders by means of data captured from social media, e-mail, among others. The algorithm may then predict a specific outcome and enable early intervention by clinicians.

[This corrects the article DOI: 10.1371/journal.pone.0204820.].

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

We investigated the levels of brain derived-neurotrophic factor (BDNF), cytokines and oxidative parameters in serum and tried to correlate them with the age and functionality of patients with Progressive Muscle Dystrophies (PMD). The patients were separated into six groups (case and controls pared by age and gender), as follows: Duchenne Muscular Dystrophy (DMD); Steinert Myotonic Dystrophy (SMD); and Limb-girdle Muscular Dystrophy type-2A (LGMD2A). DMD patients (±17.9 years old) had a decrease of functionality, an increase in the IL-1β and TNF-α levels and a decrease of IL-10 levels and superoxide dismutase activity in serum. SMD patients (±25.8 years old) had a decrease of BDNF and IL-10 levels and superoxide dismutase activity and an increase of IL-1β levels in serum. LGMD2A patients (±27.7 years old) had an decrease only in serum levels of IL-10. This research showed the first evidence of BDNF involvement in the SMD patients and a possible unbalance between pro-inflammatory and anti-inflammatory cytokine levels, along with decreased superoxide dismutase activity in serum of DMD and SMD patients.

Objective:To investigate the effects of ethanol exposure in adolescent rats during adulthood by assesssing aggression and anxiety-like behaviors and measuring the levels of inflammatory markers.Methods:Groups of male Wistar rats (mean weight 81.4 g, n = 36) were housed in groups of four until postnatal day (PND) 60. From PNDs 30 to 46, rats received one of three treatments: 3 g/kg of ethanol (15% w/v, orally, n = 16), 1.5 g/kg of ethanol (12.5% w/v, PO, n = 12), or water (n = 12) every 48 hours. Animals were assessed for aggressive behavior (resident x intruder test) and anxiety-like behaviors (elevated plus maze) during adulthood.Results:Animals that received low doses of alcohol showed reduced levels of brain-derived neurotrophic factor (BDNF) in the hippocampus as compared to the control group. No significant difference was found in prefrontal cortex.Conclusions:Intermittent exposure to alcohol during adolescence is associated with lower levels of BDNF in the hippocampus, probably due the episodic administration of alcohol, but alcohol use did not alter the level agression toward a male intruder or anxiety-like behaviors during the adult phase.

Objective:To evaluate brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-α (TNF-α) blood levels as disease biomarkers of delirium in oncology inpatients.Methods:Seventeen oncology inpatients with delirium, 28 oncology inpatients without delirium, and 25 non-oncology controls (caregivers) were consecutively recruited from a Brazilian cancer center. This sample was matched by age, sex, and education level. The Confusion Assessment Method, the Mini-Mental State Examination, and the Digit Span Test were administered to ascertain delirium diagnosis. BDNF and TNF-α levels were measured by the Sandwich-ELISA method and flow cytometry, respectively. Blood samples were collected immediately after clinical evaluation.Results:Oncology inpatients (with and without delirium) showed significantly lower BDNF levels compared with non-oncology controls (F = 13.830; p = 0.001). TNF-α levels did not differ between the three groups.Conclusion:A cross-sectional relationship of BDNF and TNF-α blood levels with delirium in oncology inpatients was not demonstrated. The association between cancer and reduced serum BDNF levels may be mediated by confounding factors.

Mesenchymal stem cells (MSCs) are multipotent progenitor cells that have the capacity to differentiate into all lineages of mesodermal origin, e.g., cartilage, bone, and adipocytes. MSCs have been identified at different stages of development, including adulthood, and in different tissues, such as bone marrow, adipose tissue and umbilical cord. Recent studies have shown that MSCs have the ability to migrate to injured sites. In this regard, an important characteristic of MSCs is their immunomodulatory and anti-inflammatory effects. For instance, there is evidence that MSCs can regulate the immune system by inhibiting proliferation of T and B cells. Clinical interest in the use of MSCs has increased considerably over the past few years, especially because of the ideal characteristics of these cells for regenerative medicine. Therapies with MSCs have shown promising results neurodegenerative diseases, in addition to regulating inflammation, they can promote other beneficial effects, such as neuronal growth, decrease free radicals, and reduce apoptosis. Notwithstanding, despite the vast amount of research into MSCs in neurodegenerative diseases, the mechanism of action of MSCs are still not completely clarified, hindering the development of effective treatments. Conversely, studies in models of psychiatric disorders are scarce, despite the promising results of MSCs therapies in this field as well.

There is growing evidence showing that bipolar disorder is associated with persistent cognitive deficits. However, the exact meaning and impact of cognitive deficits in bipolar disorder is still not entirely known, even though they have been associated with poor psychosocial functioning. This study aims to summarize cognitive and psychosocial functioning findings of remitted bipolar patients. We conducted an extensive Medline search of the published English literature for the period January 2000– March 2014 using a variety of search terms to find relevant articles. Bibliographies of retrieved papers were further analysed for publications of interest. Our results showed that: (1) all mood states of bipolar disorder are associated with cognitive impairment. However, the euthymic state is associated with less impairment than the other states; (2) there is a strong association between clinical factors (i.e, duration of illness, number of episodes, residual mood symptoms, comorbidities) and cognitive impairment in euthymic bipolar patients, although these factors do not account fully for these deficits; (3) cognitive deficits, in particular, verbal learning and executive dysfunctions may contribute to poor functioning. In conclusion, our review suggests that cognitive deficits are strongly associated with mood episodes; such deficits persist, in lower degree, during remission. Impairment on cognitive performance may explain, in part, poor long–term functioning in remitted bipolar patients. It highlights that psychosocial interventions in combination with pharmacotherapy should be considered to improve cognition and enhance the level of functioning. Therefore, studies assessing the efficacy of novel strategies focused on cognitive and functional status are an important area of future investigation in bipolar disorder.

Objective: To evaluate behavioral changes and brain-derived neurotrophic factor (BDNF) levels in rats subjected to ketamine administration (25 mg/kg) for 7 days. Method: Behavioral evaluation was undertaken at 1 and 6 hours after the last injection. Results: We observed hyperlocomotion 1 hour after the last injection and a decrease in locomotion after 6 hours. Immobility time was decreased and climbing time was increased 6 hours after the last injection. BDNF levels were decreased in the prefrontal cortex and amygdala when rats were killed 6 hours after the last injection, compared to the saline group and to rats killed 1 hour after the last injection. BDNF levels in the striatum were decreased in rats killed 6 hours after the last ketamine injection, and BDNF levels in the hippocampus were decreased in the groups that were killed 1 and 6 hours after the last injection. Conclusion: These results suggest that the effects of ketamine on behavior and BDNF levels are related to the time at which they were evaluated after administration of the drug.

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.

Family history and traumatic experiences are factors linked to bipolar disorder. It is known that the lifetime risk of bipolar disorder in relatives of a bipolar proband are 5-10% for first degree relatives and 40-70% for monozygotic co-twins. It is also known that patients with early childhood trauma present earlier onset of bipolar disorder, increased number of manic episodes, and more suicide attempts. We have recently reported that childhood trauma partly mediates the effect of family history on bipolar disorder diagnosis. In light of these findings from the scientific literature, we reviewed the work of British writer Virginia Woolf, who allegedly suffered from bipolar disorder. Her disorder was strongly related to her family background. Moreover, Virginia Woolf was sexually molested by her half siblings for nine years. Her bipolar disorder symptoms presented a pernicious course, associated with hospitalizations, suicidal behavioral, and functional impairment. The concept of neuroprogression has been used to explain the clinical deterioration that takes places in a subgroup of bipolar disorder patients. The examination of Virgina Woolf’s biography and art can provide clinicians with important insights about the course of bipolar disorder.

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 is a severe, recurrent, and often chronic psychiatric illness associated with significant functional impairment, morbidity, and mortality. Creatine kinase is an important enzyme, particularly for cells with high and fluctuating energy requirements, such as neurons, and is a potential marker of brain injury. The aim of the present study was to compare serum creatine kinase levels between bipolar disorder patients, in the various phases (depressive, manic, and euthymic), and healthy volunteers. METHOD: Forty-eight bipolar patients were recruited: 18 in the euthymic phase; 17 in the manic phase; and 13 in the depressive phase. The control group comprised 41 healthy volunteers. The phases of bipolar disorder were defined as follows: euthymic-not meeting the DSM-IV criteria for a mood episode and scoring < 8 on the Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS); manic-scoring < 7 on the HDRS and > 7 on the YMRS; depressive-scoring > 7 on the HDRS and < 7 on the YMRS. Patients in mixed phases were excluded. Blood samples were collected from all participants. RESULTS: Creatine kinase levels were higher in the manic patients than in the controls. However, we observed no significant difference between euthymic and depressive patients in terms of the creatine kinase level. CONCLUSION: Our results suggest that the clinical differences among the depressive, manic, and euthymic phases of bipolar disorder are paralleled by contrasting levels of creatine kinase. However, further studies are needed in order to understand the state-dependent differences observed in serum creatine kinase activity.OBJETIVO: O transtorno do humor bipolar é uma doença psiquiátrica grave, recorrente e crônica associada a significativo prejuízo funcional, morbidade e mortalidade. A creatina quinase tem sido proposta como um marcador de dano cerebral. A creatina quinase é uma enzima importante principalmente para células que necessitam de uma grande quantidade de energia, como os neurônios. O objetivo do presente estudo foi comparar os níveis de creatina quinase entre as fases depressiva, maníaca e eutímica de pacientes com transtorno do humor bipolar. MÉTODO: Para avaliação dos níveis de creatina quinase no soro, 48 pacientes bipolares foram recrutados; 18 estavam eutímicos, 17 estavam em mania e 13 em episódio depressivo. Foi feita também uma comparação com um grupo controle que incluiu 41 voluntários saudáveis. Grupo eutimia: foram incluídos os pacientes que não cumpriam os critérios do DSM-IV para episódios de humor e deveriam ter a pontuação inferior a oito nas escalas de avaliação de mania (YMRS) e depressão (HDRS); grupo mania: foram incluídos os pacientes que apresentavam YMRS > 7 e HDRS < 7; grupo depressão: foram incluídos os pacientes que apresentavam HDRS > 7 e YMRS < 7. Os pacientes em episódios mistos não foram incluídos no estudo. Amostras de sangue foram coletadas de todos os participantes. RESULTADOS: Durante a mania, os níveis de creatina quinase foram aumentados em comparação com voluntários saudáveis. Entretanto, não houve diferença significativa nos níveis de creatina quinase em pacientes eutímicos e depressivos, quando comparados com o grupo controle. CONCLUSÃO: Nossos resultados sugerem que as fases maníaca, depressiva e eutímica do transtorno do humor bipolar, além de apresentarem sintomatologia distinta, também podem ser diferenciadas pelo nível de creatina quinase presente no sangue do paciente. Entretanto, mais estudos são necessários para entender as diferenças observadas na atividade da creatina quinase durante as fases do transtorno do humor bipolar.

OBJETIVO: Medicina translacional pode ser descrita como a aplicação integrada de ferramentas farmacológicas inovadoras, biomarcadores, métodos e tecnologias clínicas e delineamentos de pesquisa para aumentar o conhecimento a respeito das doenças. A pesquisa translacional oferece uma oportunidade para aplicar os achados de pesquisa básica na clínica cotidiana. O Instituto Nacional de Ciência e Tecnologia - Medicina Translacional foi criado com seis centros (Universidade Federal do Rio Grande do Sul, Universidade de São Paulo-Ribeirão Preto, Universidade Federal do Rio de Janeiro, Pontifícia Universidade Católica do Rio Grande do Sul, Universidade Estadual de Santa Catarina e uma core facility que serve a todos os centros). Os objetivos deste projeto são divididos em quatro dimensões: institucional, pesquisa, formação de recursos humanos e transferência de tecnologia para a comunidade e setor produtivo. MÉTODO: Neste artigo, são apresentadas algumas das estratégias utilizadas para atingir os objetivos do Instituto Nacional de Ciência e Tecnologia - Medicina Translacional: 1) Desenvolvimento de modelos animais para o transtorno bipolar; 2) Estratégias de investigação neurocomportamental e disfunções cognitivas dos transtornos cerebrais; 3) Modelos experimentais de funcionamento cerebral e comportamento, proliferação celular e câncer; 4)Teste de Simulação de Falar em Público e 5) Realidade Virtual para indução de Pânico e Agorafobia. CONCLUSÃO: O Instituto Nacional de Ciência e Tecnologia - Medicina Translacional possui como foco principal o desenvolvimento de metodologias mais úteis para aumentar a aplicabilidade dos conhecimentos da pesquisa básica em medicina.OBJECTIVE: Translational medicine has been described as the integrated application of innovative pharmacology tools, biomarkers, clinical methods, clinical technologies and study designs to improve the understanding of medical disorders. In medicine, translational research offers an opportunity for applying the findings obtained from basic research to every-day clinical applications. The National Science and Technology Institute for Translational Medicine is comprised of six member institutions (Universidade Federal do Rio Grande do Sul, Universidade de São Paulo-Ribeirão Preto, Universidade Federal do Rio de Janeiro, Pontifícia Universidade Católica do Rio Grande do Sul, Universidade Estadual de Santa Catarina and a core facility that serves all centers). The objectives of the project are divided into four areas: Institutional, Research, Human Resources and Technology for the Community and Productive Sector. METHOD: In this manuscript, we describe some of the approaches used to attain the main objectives of the National Science and Technology Institute for Translational Medicine, which include the development of 1) animal models for bipolar disorder; 2) strategies to investigate neurobehavioral function and cognitive dysfunction associated with brain disorders; 3) experimental models of brain function and behavior, neuropsychiatric disorders, cell proliferation, and cancer; 4) Simulated Public Speaking and 5) Virtual reality simulation for inducing panic disorder and agoraphobia. CONCLUSION: The main focus of the National Science and Technology Institute for Translational Medicine is the development of more useful methods that allow for a better application of basic research-based knowledge to the medical field.

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.OBJETIVO: O transtorno bipolar é responsável por importante parcela do prejuízo funcional ao redor do mundo. Um efeito independente do transtorno bipolar e da idade no funcionamento ainda não foi demonstrado. O presente estudo tem o objetivo de avaliar o efeito do transtorno bipolar no prejuízo funcional relacionado à idade, com controles pareados como padrão. MÉTODO: Cem pacientes com transtorno bipolar e controles pareados foram avaliados para incapacidade. Efeitos relacionados à idade, com controle para confundidores, foram investigados. RESULTADOS: Pacientes tiveram significativamente mais prejuízo que controles. A regressão mostrou efeito para a idade em ambos os grupos, e o efeito foi significativamente mais forte nos pacientes. CONCLUSÃO: O transtorno bipolar foi um importante modificador de efeito no impacto da idade no funcionamento. Enquanto um desenho de estudo longitudinal é necessário para efetivamente demonstrar este impacto diferencial, este estudo caracteriza o transtorno bipolar como uma doença crônica e incapacitante.

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 Test in a sample of Caucasian Brazilian patients with bipolar disorder. METHOD: Sixty-four patients 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 gene polymorphism.OBJETIVO: O presente estudo tem por objetivo investigar a associação entre o polimorfismo val66met do gene do fator neurotrófico derivado do cérebro (BDNF) e o desempenho cognitivo no Teste Wisconsin de Classificação de Cartas em uma amostra de pacientes bipolares brasileiros caucasianos. MÉTODO: Sessenta e quatro pacientes com transtorno bipolar foram avaliados em relação a sua cognição por meio do Teste Wisconsin de Classificação de Cartas que foi comparada com a freqüência alélica e genotípica do polimorfismo val66met do gene do fator neurotrófico derivado do cérebro. RESULTADOS: O percentual de erros não-perseverativos foi significativamente maior nos indivíduos com genótipo val/val. Não foi encontrada diferença significativa entre a freqüência genotípica do polimorfismo do BDNF e os outros domínios do Teste Wisconsin de Classificação de Cartas. CONCLUSÃO: O estudo do polimorfismo val66met em relação ao desempenho executivo em pacientes bipolares caucasianos de uma amostra brasileira não reproduziu achados anteriores que sugeriam um pior desempenho em indivíduos portadores do alelo met.

The Bipolar Mood Disorder is characterized by the alternation of depressive crises with episodes of mania or euphoria, having these patients 15 to 35 times more chances of suicide, as compared with people without this disorder. The pharmacotherapy is fundamental for this disease, aiming to decrease the frequency of episodes and disease severity. In these patients, the polypharmacy has recently increased and one of the main difficulties is the adherence to treatment. The objective of this study was to contribute for the improvement of bipolar patients health conditions, developing their respective pharmacotherapeutic follow-up. Twenty eight adult bipolar patients who were participants of a specialized clinic within a tertiary hospital in Porto Alegre have been randomly selected, and the Dader Method of pharmacotherapeutic follow-up has been applied. The more common clinical comorbidities were: hypertension (50%), obesity (46.43%), and hypothyroidism (36.29%). The bipolar patients are more susceptible to clinical comorbidities, and many of them could be due to pharmacotherapy. Only 1.43% of patients presented Drug Related Problems, being all of them resolved along the study. It was also observed that 32.14% of evaluated patients presented low adherence to treatment, and between these patients, 55.56% passed to have good adherence after pharmacotherapeutic follow-up. The pharmacotherapeutic follow-up is fundamental for the improvement of patient's health. New studies, with higher number of patients and longer duration, are necessary to evaluate the percentage of patients that could be beneficiary of Pharmaceutical Care.O Transtorno do Humor Bipolar é caracterizando pela alternância de crises depressivas com episódios de mania ou euforia, tendo estes pacientes 15-35 vezes mais chances de suicídio em comparação com pessoas sem este transtorno. A farmacoterapia é fundamental, visando diminuir a freqüência dos episódios e a gravidade da doença. Nestes pacientes, a polifarmácia tem aumentado ultimamente e uma das maiores dificuldades é a adesão ao tratamento. O objetivo do estudo foi contribuir para a melhoria das condições de saúde de pacientes bipolares, realizando o acompanhamento farmacoterapêutico dos mesmos. Foram selecionados aleatoriamente 28 pacientes bipolares adultos, participantes de um ambulatório especializado de um hospital terciário em Porto Alegre e aplicado o Método Dáder de acompanhamento farmacoterapêutico. As co-morbidades clínicas mais comuns foram: hipertensão (50%), obesidade (46,43%) e hipotiroidismo (39,29%). Os pacientes bipolares são mais suscetíveis a co-morbidades clínicas e muitas destas podem ser devidas a farmacoterapia. Apenas 1,43% dos pacientes apresentavam Problemas Relacionados a Medicamentos, sendo todos solucionados no decorrer do estudo. Também se observou que 32,14% dos pacientes avaliados apresentavam baixa adesão ao tratamento e entre estes, 55,56% passaram a ter boa adesão após o acompanhamento farmacoterapêutico. É fundamental para a melhoria da saúde do paciente o acompanhamento farmacoterapêutico. Novos estudos, com maior número de pacientes e maior duração, são necessários para avaliar o percentual de pacientes que poderão ser beneficiados pela Atenção Farmacêutica.

OBJECTIVE: The neurotrophins, antioxidant enzymes and oxidative markers have reciprocal interactions. This report verified in chronically stable medicated schizophrenic patients whether there are correlations between the serum levels of superoxide dismutase, a key enzyme in the antioxidant defense, thiobarbituric acid reactive substances, a direct index of lipid peroxidation, and brain-derived neurotrophic factor, the most widely distributed neurotrophin. METHOD: Sixty DSM-IV schizophrenic patients were included (43 males, 17 females). Mean age was 34.7 ± 10.8 years, mean age at first episode was 19.8 ± 7.9 years, and mean illness duration was 14.9 ± 8.5 years. Each subject had a blood sample collected for the determination of serum levels of brain-derived neurotrophic factor, thiobarbituric acid reactive substances and superoxide dismutase. RESULTS: Brain-derived neurotrophic factor levels showed a positive correlation with thiobarbituric acid reactive substances levels (r = 0.333, p = 0.009). Brain-derived neurotrophic factor levels were not correlated with superoxide dismutase levels (r = - 0.181, p = 0.166), and superoxide dismutase levels were not correlated with thiobarbituric acid reactive substances levels (r = 0.141, p = 0.284). CONCLUSIONS: The positive correlation between brain-derived neurotrophic factor and thiobarbituric acid reactive substances suggests the need of further investigation on intracellular interactions of neurotrophins, antioxidant enzymes and oxidative markers. In addition, this opens a venue for investigation on treatments for the prevention of neurotoxicity along the course of schizophrenia.OBJETIVO: As neurotrofinas, enzimas antioxidantes e marcadores de oxidação têm interações. Este estudo verificou se existem correlações entre os níveis séricos de superóxido-dismutase, uma enzima chave na defesa antioxidante, os produtos de reação com o ácido tiobarbitúrico, um indicador direto de peroxidação lipídica, e o fator neurotrófico derivado do cérebro, a neurotrofina mais amplamente distribuída. MÉTODO: Sessenta pacientes portadores de Esquizofrenia pelo DSM-IV foram incluídos (43 homens, 17 mulheres), com idade média de 34,7 ± 10,8 anos, idade média no primeiro episódio de 19,8 ± 7,9 anos, e tempo médio de duração da doença de 14,9 ± 8,5 anos. Foi coletado sangue de cada sujeito para a determinação dos níveis séricos de fator neurotrófico derivado do cérebro, superóxido-dismutase e ácido tiobarbitúrico. RESULTADOS: Os níveis de fator neurotrófico derivado do cérebro se correlacionaram positivamente aos de ácido tiobarbitúrico (r = 0,333, p = 0,009) e não mostraram correlação com os de superóxido-dismutase (r = - 0,181, p = 0,166). Este último também não se correlacionou aos níveis de ácido tiobarbitúrico (r = 0,141, p = 0,284). CONCLUSÕES: A correlação positiva entre fator neurotrófico derivado do cérebro e ácido tiobarbitúrico direciona para investigações na interação intracelular entre neurotrofinas, enzimas antioxidantes e marcadores de oxidação, além de abrir perspectives para pesquisa em tratamentos para a prevenção da neurotoxicidade ao longo do curso da esquizofrenia.

OBJECTIVE: Persistent neurocognitive deficits have been described in bipolar mood disorder. As far as we are aware, no study have examined whether the cognitive impairment is presented in the same way in a Brazilian sample. METHOD: Cognitive function of 66 patients with bipolar disorder (32 with depressive symptoms and 34 euthymic) and 28 healthy subjects was examined using a complete cognitive battery. RESULTS: Patients with bipolar disorder presented a significantly poorer performance in eight of the 12 subtests when compared to healthy subjects. There was no significant difference between the subgroups of patients. These patients showed impairment in both verbal and non-verbal cognitive function. CONCLUSION: Cognitive impairment was found in both groups of patients with bipolar disorder. The findings described here suggest an overall impairment of cognitive function, independent of mood symptoms. This is in line with data showing that cognitive deficits may be a persistent characteristic of bipolar disorder.OBJETIVO: Déficits neurocognitivos persistentes têm sido descritos no transtorno do humor bipolar; entretanto, não há estudos em amostras brasileiras para avaliar se o prejuízo se apresenta da mesma forma. MÉTODO: Foi realizada uma avaliação cognitiva em 66 pacientes bipolares (32 com sintomas depressivos e 34 eutímicos) e 28 controles, utilizando-se uma bateria cognitiva completa. RESULTADOS: Em oito dos 12 subtestes avaliados os pacientes apresentaram desempenho significativamente inferior em relação aos controles. Não houve diferença significativa entre os grupos de pacientes. Foram encontrados prejuízos cognitivos tanto na área verbal como na área não verbal da cognição. CONCLUSÃO: Foi observada uma performance inferior em ambos os grupos de pacientes com transtorno bipolar. As dificuldades cognitivas encontradas apontam para um prejuízo global no funcionamento cognitivo, independente da presença de sintomas, sugerindo estabilidade ou cronicidade dos déficits cognitivos.

OBJECTIVE: The aim of this study was to assess the association between suicide attempts and the use of multiple drugs in patients with bipolar disorder. METHOD: One hundred sixty-nine bipolar disorder outpatients diagnosed using the DSM-IV Structured Clinical Interview were included. Demographic and socioeconomic data, number of medications currently in use, history of suicide attempts, number of years undiagnosed, age of onset and current psychiatric co-morbidities were assessed using a structured questionnaire and DSM-IV criteria. The main outcome measure was the number of psychotropic drugs currently in use. RESULTS: Approximately half of all patients (48.5%) presented a history of suicide attempt; 84% were using more than one medication, and 19% were using more than three drugs. The most frequent combinations of drugs used by these patients were: lithium + valproate (17%); lithium + antipsychotics (10%); lithium + valproate + antipsychotics (9%); and antidepressants + any drug (6%). The number of suicide attempts was associated with the use of multiple drugs. CONCLUSIONS: Our findings support the notion that the use of combination therapy in bipolar disorder may be related to severity of the BD, such as number of suicide attempts.OBJETIVO: O objetivo deste trabalho foi verificar associação entre tentativas de suicídio e uso de múltiplas drogas em pacientes com transtorno do humor bipolar. MÉTODO: Cento e sessenta e nove pacientes ambulatoriais com transtorno do humor bipolar, diagnosticados pela entrevista clínica estruturada do DSM-IV, foram incluídos. Dados demográficos e socioeconômicos, número de medicações em uso, história de tentativas de suicídio, número de anos sem diagnóstico, idade de início e comorbidades psiquiátricas foram avaliados através de um questionário estruturado e pelos critérios do DSM-IV. A principal medida de desfecho foi o número de medicamentos psicotrópicos usados correntemente. RESULTADOS: Cerca de metade dos pacientes (48,5%) apresentou uma história de tentativas de suicídio; 84% estavam usando mais do que uma medicação e 19% estavam usando mais do que três medicações. As combinações de fármacos mais utilizadas por estes pacientes foram: lítio + valproato (17%); lítio + antipsicóticos (10%); lítio + valproato + antipsicóticos (9%); e antidepressivos + outros fármacos (6%). O número de tentativas de suicídio mostrou-se associado ao uso de polifarmácia, na análise ajustada. CONCLUSÕES: Nossos resultados sugerem que a polifarmácia em pacientes bipolares pode estar relacionada a indicadores de gravidade, como número de tentativas de suicídio.

OBJETIVO: Este trabalho estudou a eficácia e a tolerabilidade da fluvoxamina no tratamento, de forma aberta, sem comparação com placebo ou outros agentes, por 6 semanas, de pacientes com o diagnóstico de transtorno depressivo maior (TDM). Constitui-se em objetivo secundário do estudo avaliar os efeitos da fluvoxamina sobre o sono dos pacientes. MÉTODOS: Foram incluídos 104 pacientes, maiores de 18 anos, com o diagnóstico de TDM, de acordo com os critérios do Manual Diagnóstico e Estatístico de Transtornos Mentais, 4ª edição (DSM-IV), e com escores, na Escala de Hamilton para Depressão, versão de 17 itens (HAM-D 17), de 17 pontos ou mais. Avaliou-se a eficácia da fluvoxamina por meio das Escalas HAM-D 17 e da CGI (Impressão Clínica Global). A análise dos itens 4, 5 e 6 da HAM-D 17 foi utilizada para a avaliação do sono dos pacientes. Avaliaram-se a segurança e a tolerabilidade da fluvoxamina ao longo das 6 semanas, registrando-se quaisquer eventos adversos. A fluvoxamina foi inicialmente ministrada em doses de 50 ou 100 mg/dia, podendo haver aumentos progressivos até 300 mg/dia. RESULTADOS: Dos 104 pacientes incluídos, 81 (78%) concluíram o estudo. Obtiveram resposta favorável (diminuição de 50% ou mais na HAM-D 17) 69% dos pacientes, e a taxa de remissão (HAM-D 17 < 7) foi de 52%. A análise da CGI indicou ter havido melhora significante (p < 0,001) em relação aos escores de base. A análise específica dos itens relativos ao sono, na HAM-D 17, revelou melhora significativa já na segunda visita, mantendo-se ao longo das 6 semanas. Os eventos adversos foram os esperados para inibidores seletivos de recaptação da serotonina, predominando as queixas gastrointestinais, em sua maioria transitórias e de pequena intensidade. CONCLUSÃO: O estudo vem confirmar a eficácia e a tolerabilidade da fluvoxamina no tratamento do transtorno depressivo maior, assim como sua eficácia no tratamento das alterações do sono encontradas nos pacientes deprimidos. O perfil de eventos adversos foi o esperado para os ISRS, ressaltando-se o fato de que poucos pacientes relataram disfunção sexual (2,5% dos pacientes).OBJECTIVE: This research studied the efficacy and tolerability of fluvoxamine in the treatment of major depressive disorder (MDD), during 6 weeks, in an open trial, without placebo or active comparator. A secondary objective was the evaluation of the effects of fluvoxamine on the sleep of the pacients. METHODS: 104 patients were inicially included, with the diagnosis of MDD in accordance to the criteria of the Diagnostic and Statistical Manual for Mental Disorders, 4th edition (DSM-IV). Patients should have scores > 17 in the Hamilton Depression Scale for Depression 17 itens (HAM-D 17). The efficacy of fluvoxamine was studied through the HAM-D 17 and CGI (Clinical Global Impression). The analysis of the HAM-D 17 itens 4, 5, and 6 was used for the evaluation of the quality of sleep of the patients. Security and tolerability of fluvoxamine was assessed throughout the six weeks, being registered any adverse event. Fluvoxamine was inicially administered at the doses of 50 or 100 mg/day; the doses could be progressively increased until 300 mg/day. RESULTS: From the 104 included patients, 81 (78%) concluded the study. Sixty nine percent (69%) of the patients obtained favorable response (defined as 50% improvement in the HAM-D 17) and the remission rate (HAM-D 17 < 7) was 52%. The specific analysis of CGI showed significant improvement (p < 0.001) comparing to the baseline scores. The speficic analysis of the sleep itens of the HAM-D 17 showed significant improvement from the 2nd week; the improvement was sustained until the end of the 6 weeks study. The adverse events were those expected for the serotonin selective reuptake inhibitors (SSRI), predominantly gastrointestinal complaints, transitory and of low intensity in most of the cases. CONCLUSION: This study confirms the efficacy and tolerability of fluvoxamine in the treatment of MDD, and also its efficacy in the treatment of sleep disturbs among depressed patients. The profile of adverse events were those expected for SSRI. It should be emphasized that few patients reported sexual disfunction (2.5% of the patients).

OBJECTIVE: The aim of the present study is to compare quality of life among currently depressed, subsyndromal and remitted patients with bipolar disorder (BD) and to assess whether the level of depression correlates with the scores of quality of life in BD patients. METHOD: Sixty bipolar outpatients diagnosed using the Structured Clinical Interview for DSM-IV who met criteria for diagnosis of BD type I, II or not otherwise specified (BD-NOS), and who were not currently on a manic or mixed episode were included. The main variables of interest were quality of life (QOL) assessed using the 26-item World Health Organization QOL instrument (WHOQOL-BREF) and depression assessed using the 17-item Hamilton Depression Rating Scale (HDRS). RESULTS: A linear trend test showed a dose response association between patients' current mood state and all domains of quality of life. Higher quality of life scores were found among remitted patients, followed by subsyndromal patients; depressed patients presented lower scores of quality of life, except for the social domain. The four domains of the WHOQOL scale correlated negatively with the HDRS. CONCLUSIONS: Our findings suggest that bipolar depression and residual symptoms of depression are negatively correlated with QOL in BD patients.OBJETIVO: O objetivo deste estudo é o de comparar a qualidade de vida entre pacientes com transtorno bipolar que estão atualmente deprimidos, com depressão subsindrômica e com remissão de sintomas, e avaliar se o nível de depressão tem correlação com os escores de qualidade de vida em pacientes com transtorno bipolar. MÉTODO: Sessenta pacientes bipolares tratados ambulatorialmente, diagnosticados pela Entrevista Clínica Estruturada do DSM-IV, que preencheram critérios diagnósticos de transtorno bipolar tipo I, tipo II ou sem outra especificação (TB-SOE), e que não estavam atualmente em um episódio maníaco ou misto foram incluídos. As principais variáveis de interesse foram qualidade de vida, avaliada utilizando-se o instrumento de 26 questões de qualidade de vida da Organização Mundial de Saúde (WHOQOL-BREF) e depressão avaliada utilizando a Escala de 17 itens de Hamilton. RESULTADOS: O teste de tendência linear mostrou uma associação dose-reposta entre o estado de humor atual do paciente e todos os domínios da qualidade de vida. Escores maiores de qualidade de vida foram encontrados entre pacientes com remissão completa dos sintomas, seguidos pelos pacientes com sintomas subsindrômicos. Os pacientes deprimidos apresentaram escores de qualidade de vida mais baixos que os demais, exceto no domínio social. Os quatro domínios da escala WHOQOL tiveram uma correlação negativa com a Escala de 17 itens de Hamilton para avaliação de depressão. CONCLUSÕES: Nossos achados sugerem que a depressão bipolar e os sintomas residuais de depressão estão negativamente correlacionados com qualidade de vida em pacientes com transtorno bipolar.

OBJECTIVE: To investigate the efficacy and acceptability of antidepressants in the treatment of generalized anxiety disorder. METHODS: All randomized controlled trials assessing the use of antidepressants in generalized anxiety disorder up to may 2002 were included. Non randomized trials and those that included patients with both generalized anxiety disorder and another Axis I co-morbidity were excluded. Relative risks, weighted mean difference and number needed to treat were estimated. People who died or dropped out were regarded as having had no improvement. RESULTS: Antidepressants (imipramine, venlafaxine and paroxetine) were found to be superior to placebo in treating generalized anxiety disorder. The calculated number needed to treat for antidepressants in generalized anxiety disorder was 5.15. Dropout rates did not differ between antidepressants and placebo. CONCLUSION: The available evidence suggests that antidepressants would probably be a reasonable treatment for generalized anxiety disorder patients in the clinical context.OBJETIVOS: Investigar a eficácia e tolerabilidade dos antidepressivos no tratamento do Transtorno de ansiedade generalizada (TAG). MÉTODOS: Todos os ensaios clínicos randomizados que investigavam o uso de antidepressivos para Transtorno de ansiedade generalizada até maio de 2002 foram incluídos nesta revisão. Ensaios clínicos não randomizados e aqueles que incluíram pacientes com Transtorno de ansiedade generalizada e outra comorbidade de Eixo I foram excluídos. Riscos relativos, diferenças de médias e número necessário para tratar (NNT) foram estimados. Pessoas que morreram ou saíram dos estudos foram considerados como sem melhora. RESULTADOS: Antidepressivos (imipramina, venlafaxina e paroxetina) foram superiores ao placebo no tratamento do Transtorno de ansiedade generalizada. O número necessário para tratar para os antidepressivos em Transtorno de ansiedade generalizada foi 5,15. Taxas de abandono não diferiram entre antidepressivos e placebo. CONCLUSÃO: A evidência disponível sugere que os antidepressivos são um tratamento adequado para pacientes com Transtorno de ansiedade generalizada.

Apesar dos crescentes esforços para o entendimento da neurobiologia do transtorno afetivo bipolar (TAB), sua exata fisiopatologia permanece indeterminada. Inicialmente, a pesquisa estava voltada para o estudo das aminas biogênicas, devido aos efeitos dos diversos agentes psicofarmacológicos. Mais recentemente, evidências apontam que disfunções nos sistemas de sinalização intracelular e de expressão gênica podem estar associadas ao TAB. Estas alterações podem estar associadas a interrupções nos circuitos reguladores do humor, como sistema límbico, estriado e córtex pré-frontal, sendo que os efeitos neuroprotetores do uso crônico dos estabilizadores de humor podem reverter este processo patológico. Este artigo tem como objetivo trazer uma atualização dos achados recentes sobre a neuroquímica do TAB.Despite recent efforts to understand the neurobiology of Bipolar Disorder (BD), the exact pathophysiology remains undetermined. Due to the effects of various psychopharmacological agents, initial research focused on the study of biogenic amines. Recent evidence has shown that dysfunction in intracellular signaling systems and gene expression may be associated with BD. These alterations may cause interruptions in mood regulating circuits such as the limbic system, striatum and prefrontal cortex, and the neuroprotective effects of mood stabilizers may reverse this pathological process. This study aims to update the recent findings relative to the neurochemistry of BD.

OBJETIVOS: Estudos pós-mortem, farmacológicos, de neuroimagem e em modelos animais têm demonstrado uma possível associação de mecanismos de sinalização intracelular na fisiopatologia do transtorno afetivo bipolar (TAB). Esse trabalho tem como objetivo revisar os achados em neuropatologia e bioquímica celular. MÉTODOS: Foi realizada uma pesquisa ao MEDLINE, entre 1980 e 2003, tendo sido utilizados os unitermos: bipolar disorder, signaling, second messengers e postmortem, além de referências cruzadas dos artigos selecionados. RESULTADOS: uropatológicos demonstraram uma diminuição do número de células neuronais e gliais, principalmente no córtex pré-frontal de pacientes bipolares. Estudos neuroquímicos demonstraram alterações nas vias do AMPc, fosfatidilinositol, Wnt/GSK-3beta e Ca++ intracelular nesses pacientes. CONCLUSÃO: Os achados de alterações neuropatológicas e neuroquímicas no TAB podem estar relacionados com a fisiopatologia deste transtorno e com os efeitos dos estabilizadores de humor. No entanto, mais estudos são necessários para esclarecer o papel das cascatas de sinalização intracelular na patogênese deste transtorno.OBJECTIVES: Postmortem, pharmacological, neuroimaging, and animal model studies have demonstrated a possible association of intracellular signaling mechanisms in the pathophysiology of bipolar disorder. The objective of this paper is to review the findings in neuropathology and cellular biochemistry. METHODS: We performed a MEDLINE research, between 1980-2003, using bipolar disorder, signaling, second messengers, and postmortem as keywords, and cross-references. RESULTS: Neuropathological studies reported a decrease in neuronal and glial cells, mainly in the prefrontal cortex of bipolar patients. Neurochemical studies reported dysfunction in cAMP, phosphoinositide, Wnt/GSK-3b, and intracellular Ca++ pathways in these patients. CONCLUSION: The neuropathological and neurochemical abnormalities demonstrated in BD may be related to the pathophysiology of this disorder and the effects of mood stabilizers. However, further studies are needed to clarify the role of the intracellular signaling cascade in the pathogenesis of this disorder.

OBJECTIVE: To describe the demographic characteristics of gender, age, and presence of repetitive movements, intake of alcohol and non-steroid anti-inflammatories (NSAI), medical specialties that referred patients to nerve conduction studies and electromyography (NCS-EMG), school attainment, and seasonal distribution in patients with a neurophysiological diagnosis of carpal tunnel syndrome (CTS) in the State of Rio Grande do Sul, Brazil. METHOD: A series of 1039 patients (1549 hands) with neurophysiologically defined CTS was studied. Patients were referred for NCS-EMG in 3 universities and 2 private services, from August 2001 to January 2003. All patients completed a questionnaire containing demographic information. The diagnosis of CTS was established following a pre-established protocol, with defined diagnostic criteria. RESULTS: Around one fourth of patients had already performed NCS-EMG; the greatest frequency of CTS was observed in women (5.6:1) and in patients above the age of 40. Most patients reported performing repetitive movements in their daily routine (69.7%); 12.9% reported use of NSAI and 14.9% regular intake of alcoholic beverages. A greater frequency of CTS was observed in the months of July and August, when compared to the other months of the year. Around 2/3 of the study population had completed at least secondary school. Most requests of nerve conduction studies did not provide a diagnostic hypothesis (59.9%) and neurophysiologic studies were requested mostly by traumatology/orthopedics (71.1%). CONCLUSION: We have concluded that, in our environment, CTS shows some demographical characteristics that are similar to what the literature describes. Also, we have found that most of our sample concluded at least secondary school, and was referred to neurophysiologic studies by orthopedists. To be pointed out is the seasonal distribution of CTS, which demonstrates a significant association with winter months.OBJETIVO: Descrever as características demográficas de gênero, idade e presença de movimentos repetitivos, uso de álcool e antiinflamatórios não-esteróides (AINE), especialidades médicas de encaminhamento para eletroneuromiografia (ENMG), nível de escolaridade, e distribuição sazonal em pacientes com síndrome do túnel do carpo (STC) diagnosticada neurofisiologicamente no Estado do Rio Grande do Sul, Brasil. MÉTODO: Foi estudada uma série de 1039 pacientes (1549 mãos), com STC definida neurofisiologicamente, que foram encaminhados para realização de ENMG, em 3 serviços universitários e 2 privados, entre agosto de 2001 a janeiro de 2003. Todos os pacientes responderam questionário com informações demográficas. O diagnóstico da STC foi realizado seguindo protocolo pré-estabelecido, com critérios diagnósticos definidos. RESULTADO: Cerca de um quarto dos pacientes já havia realizado ENMG prévia, sendo observada maior freqüência da STC em mulheres (5,6:1) e em pacientes acima de 40 anos. A maioria relatava esforços repetitivos na sua atividade diária (69,7%), 12,9% estava em uso de AINE e 14,9% relatavam ingesta regular de bebidas alcoólicas. Observamos maior freqüência da STC nos meses de julho e agosto em relação aos outros meses do ano. Cerca de 2/3 da nossa população apresentava pelo menos o primeiro grau completo. Na maior parte dos pedidos de ENMG não era descrita uma hipótese diagnóstica (69,9%), sendo a traumatologia/ortopedia a especialidade que mais solicitou exames neurofisiológicos (71,1%). CONCLUSÃO: Concluímos que a STC, em nosso meio, apresenta características demográficas semelhantes às descritas na literatura. A maior parte de nossa amostra apresenta pelo menos o 1º. grau completo e foi encaminhada para realização de ENMG por traumatologistas. Salientamos a distribuição sazonal da STC que demonstra uma associação significativa com os meses de inverno.

OBJETIVOS: O objetivo deste estudo é verificar a efetividade do tratamento psicodinâmico em grupo de pacientes com fobia social generalizada. MÉTODOS: 30 pacientes foram incluídos em um estudo randomizado, simples-cego, comparando Terapia Psicodinâmica de Grupo (TPG) com um Grupo de Controle Placebo com Credibilidade (CPC). A TPG foi conduzida em 12 sessões de terapia de orientação psicodinâmica em grupo. Os pacientes do grupo controle receberam um pacote de aulas-discussões e tratamento de apoio por 12 semanas, que foi comparado à TPG. Todos os participantes preencheram a Escala de Liebowitz para Ansiedade Social (LSAS), a Escala Hamilton de Ansiedade (HAM-A) e a Escala de Impressão Clínica Global (CGI), na entrevista inicial e na 12ª semana de tratamento. Os dados foram analisados com uma ANOVA de medidas repetidas. Pacientes em vigência de tratamento farmacológico ou psicoterápico foram excluídos. RESULTADOS: Ambos os grupos apresentaram melhora na maioria das medidas. Na LSAS, os pacientes da TPG obtiveram melhora superior aos do grupo controle, ao cabo de 12 semanas (F1,28=4.84, p=0.036). Nas medidas basais dos sujeitos que completaram o estudo, não houve diferença entre os grupos em variáveis demográficas e de desfecho. CONCLUSÃO: Neste estudo, a TPG foi superior ao tratamento placebo com credibilidade no tratamento da fobia social generalizada, em um ensaio clínico randomizado, simples-cego, de 12 semanas.OBJECTIVES: The aim of this study is to assess the effectiveness of psychodynamic group therapy in patients with generalized social phobia. METHODS: Thirty patients were included in a randomized single-blind clinical trial comparing psychodynamic group treatment (PGT) with a credible placebo control group (CPC). PGT was carried out within a 12-session psychodynamically-oriented group psychotherapy. Control patients received a treatment package of lecture-discussion and support group for 12 weeks which was compared to PGT. Each participant completed the Liebowitz Social Anxiety Scale (LSAS), the Hamilton Anxiety Scale (HAS) and the Clinical Global Impression Scale(CGI) at pretreatment assessment and after 12 weeks of treatment. Data analysis was carried out using a repeated measures ANOVA. Patients were excluded if they were under any kind of pharmacotherapy or psychotherapic treatment. RESULTS: Both groups demonstrated significant pretreatment-to-posttreatment change on most measures. On the LSAS, PGT patients were rated as more improved than controls at posttest assessment (F1,28=4.84, p=0.036). Baseline data of completers did not show differences between both groups in the demographic variables and outcome variables used. CONCLUSIONS: The present study showed that PGT was superior to a credible placebo control group in the treatment of generalized social phobia, in a 12-week randomized single-blind clinical trial.

Este artigo revisa aspectos da definição da síndrome clínica do transtorno de estresse pós-traumático (TEPT). São apresentados os critérios diagnósticos empregados no DSM-IV e CID-10. Define-se a reação aguda ao estresse (RAE) e contrasta-se a mesma com os critérios que definem o TEPT, salientando-se a importância da expressão parcial dos sintomas de TEPT em vítimas de trauma. Estudos sistemáticos na população de pacientes são caracterizados como uma necessidade a ser endereçada em saúde pública, com vistas ao estabelecimento de protocolos adequados para o diagnóstico e tratamento dessa síndrome clínica.This article reviews aspects of the clinical characterization of the Postttraumatic Stress Disorder (PTSD). The disgnostic criteria used in DSM-IV and ICD-10 are presented. The Acute Reaction to Stress is defined and contrasted to the operational criteria which define the PTSD. The importance of the partial expression of the PTSD syndrome in victims of trauma is highlighted. Systematic studies within this patient population is characterized as a unmet need in public health. Addressing such a need is a major step towards the proper diagnosis and treatment of this clinical syndrome.