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Background: This study aimed to evaluate the effect of two different types of physical intervention on sedentary behavior and clinical changes in people with schizophrenia. Method: This is a clinical trial including people with schizophrenia in regular outpatient care who realized a 3-month exercise protocol and were separated into two groups: aerobic physical intervention (API) and postural physical intervention (PPI). All participants performed an assessment of (a) functional capacity through a 6 min walk test (6MWT), (b) flexibility using Well’s bench, (c) disease severity using the Brief Psychiatric Rating Scale (BPRS), (d) quality of life using the SF-36 Questionnaire and (e) physical activity using the Simple Physical Activity Questionnaire (SIMPAQ). Results: Thirty-eight patients with schizophrenia completed the intervention (24 patients in API and 14 patients in PPI). Regarding sedentary behavior, there was an improvement in the API group in the time exercising and in the PPI group concerning time in bed, time walking and exercising. Regarding quality of life, there was an improvement in the API group (functional capacity) and in the PPI group, there was an improvement in physical limitation, pain and emotional limitations. In the API group, there was an improvement in BMI (body mass index), diastolic blood pressure and systolic blood pressure. Functional capacity was improved only in the PPI group. There was no change in flexibility and disease severity. Conclusions: The study demonstrated a change response in the physical and mental aspects in people with schizophrenia after a change in sedentary behavior.

Background: Schizophrenia has disabling effects over mental and physical integrity involving changes in posture and flexibility, which reduce mobility, autonomy, and quality of life. Physical activity has been tested with uncertain effects in schizophrenia, mostly due to trial design, methodology, comparison groups, intervention length, and attrition. Inconsistency led to poor dissemination of active interventions in this population, which may benefit these individuals’ health. Objective: To evaluate the response of two different protocols: Aerobic and Functional exercises, in two groups of sedentary adults—patients with the diagnosis of schizophrenia and healthy controls.Methods: A clinical trial of two standardized physical interventions in adults diagnosed with schizophrenia and healthy controls. Posture was assessed by digital photogrammetry with the aid of a software and the flexibility by the Wells Fargo’s Test. Results: A total of 38 individuals completed the intervention, with 24 in Aerobic group and 14 in Functional group. The groups were homogeneous for gender, weight, and body mass index, with small differences in age and height. Posture and Flexibility changed according to group and intervention. In this study, guided physical activity improved posture and flexibility in both groups, with higher effect of the Functional protocol than the Aerobic protocol in cases and controls. Conclusions: Despite a preliminary and relatively small sample size, the study evidences the feasibility and clinical utility of physical intervention in schizophrenia. Additional data about specific adaptations in schizophrenia are needed to improve outcomes, such as individualized assistance, support, instructions and intensity. Trial registration: Clinical trial registration: Brazilian Registry of Clinical Trials (ReBEC) under No. RBR-2h2hjy; date: 09/29/2020, retrospectively registered (https://ensaiosclinicos.gov.br/rg/RBR-2h2hjy).

Objective: Clozapine is underprescribed due to neutropenia risk. Blood tests every 3 months in those on continuous treatment for > 1 year who have never had an absolute neutrophil count (ANC) < 2,000/µL has been proposed as a monitoring strategy; however, there are no South American data to support this recommendation. This study sought to investigate whether clozapine use and other variables could explain the occurrence of ANC < 1,000/µL in patients with severe mental disorders. Methods: A total of 5,847 subjects were included, 1,038 on clozapine. We performed a Cox regression considering the outcome as ANC < 1,000/µL at any time point. Predictors were sex, age, ethnicity, clozapine use, ANC > 2,000/µL during the first year of blood monitoring, and presence of a severe medical condition. Results: In the Cox regression model, ethnicity (white) (hazard ratio [HR] 0.53; 95%CI 0.29-0.99, p < 0.05) and ANC > 2,000/µL (HR 0.04; 95%CI 0.01-0.10, p < 0.001) were protective factors, while presence of a severe medical condition (HR 69.35; 95%CI 37.45-128.44, p < 0.001) was a risk factor for ANC < 1,000/µL. Other variables were not significant, including clozapine use (HR 1.33; 95%CI 0.74-2.39, p > 0.05). Conclusions: These findings suggest that clozapine does not increase the risk of neutropenia in subjects with ANC > 2,000/µL during the first year of use and in the absence of a severe medical condition. These results could help guide clinical and public-health decisions regarding clozapine blood monitoring guidelines.

The present study sought to assess biomarkers of inflammation in stable patients with schizophrenia (SZ) on clozapine therapy. We recruited 60 outpatients with SZ and 60 healthy controls, matched for sex and age. Compared with controls, patients had significantly increased concentrations of interleukin-6 and tumor necrosis factor-α. Interestingly, patients on simvastatin had lower interleukin-6 levels compared with patients not on simvastatin and controls. This study corroborated previous evidence for increased inflammatory biomarkers in SZ and detected a potential anti-inflammatory action of simvastatin in patients with a clinical diagnosis of SZ on clozapine therapy.

O transexualismo (CID-10) é uma condição caracterizada por forte e persistente dissociação com o gênero atribuído. A cirurgia de redesignação sexual (CRS) e a terapia hormonal (TH) permitem que indivíduos transexuais se sintam mais congruentes com seu gênero e, por isso, têm desempenhado papel importante nos últimos 70 anos. O fator neurotrófico derivado do cérebro (BDNF) parece desempenhar um papel fundamental na recuperação do trauma cirúrgico agudo e vulnerabilidade ambiental à psicopatologia. Nós hipotetizamos que o BDNF pode ser um biomarcador de alívio do sofrimento de incongruência de gênero pós-CRS. Objetivos: Mensurar os níveis séricos de BDNF no pré e pós-operatório em indivíduos transexuais como biomarcador de alívio de estresse relacionado à incongruência de gênero após a CRS. Métodos: Trinta e duas pessoas transexuais masculino para feminino submetidas a cirurgia e tratamento hormonal foram selecionadas de nossa amostra inicial. O nível sérico de BDNF foi avaliado antes e depois da CRS pela técnica ELISA. O tempo decorrido entre as coletas de sangue pré e pós-CRS foi medido. Resultados: Não houve diferença significativa nos níveis de BDNF pré e pós-CRS ou em relação ao tempo decorrido entre a CRS e a coleta. Conclusão: O alívio do sofrimento relacionado à incongruência de gênero pós-CRS não pode ser avaliado apenas pelo BDNF. Soluções cirúrgicas podem não fornecer uma solução rápida para o sofrimento associado ao transexualismo, e a CRS pode servir como um passo em direção à, em vez de conclusão da, construção da identidade de gênero de uma pessoa. Transsexualism (ICD-10) is a condition characterized by a strong and persistent dissociation with one’s assigned gender. Sex reassignment surgery (SRS) and hormone therapy provide a means of allowing transsexual individuals to feel more congruent with their gender and have played a major role in treatment over the past 70 years. Brain-derived neurotrophic factor (BDNF) appears to play a key role in recovery from acute surgical trauma and environmentally mediated vulnerability to psychopathology. We hypothesize that BDNF may be a biomarker of alleviation of gender incongruence suffering. Objectives: To measure preoperative and postoperative serum BDNF levels in transsexual individuals as a biomarker of alleviation of stress related to gender incongruence after SRS. Methods: Thirty-two male-to-female transsexual people who underwent both surgery and hormonal treatment were selected from our initial sample. BDNF serum levels were assessed before and after SRS with sandwich enzyme linked immunosorbent assay (ELISA). The time elapsed between the pre-SRS and post- -SRS blood collections was also measured. Results: No significant difference was found in pre-SRS or post- -SRS BDNF levels or with relation to the time elapsed after SRS when BDNF levels were measured. Conclusion: Alleviation of the suffering related to gender incongruence after SRS cannot be assessed by BDNF alone. Surgical solutions may not provide a quick fix for psychological distress associated with transsexualism and SRS may serve as one step toward, rather than as the conclusion of, construction of a person’s gender identity.

In patients with schizophrenia, obsessive-compulsive symptoms (OCS) are associated with lower rates of quality of life and polypharmacy. No previous controlled studies have tested the efficacy of repetitive transcranial magnetic stimulation (rTMS) on the treatment of OCS in this population. The present study examined the therapeutic effects of rTMS applied to the supplementary motor area (1Hz, 20min, 20 sessions) on OCS and general symptoms in patients with schizophrenia or schizoaffective disorder, and whether this intervention can produce changes in plasma levels of brain derived neurotrophic factor (BDNF). A double-blind randomized controlled trial was conducted. Active and sham rTMS were delivered to 12 patients (6 on each group). Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) and Brief Psychiatric Rating Scale (BPRS) scores, as well as BDNF levels, were assessed before, after, and 4 weeks after treatment. rTMS did not significantly change the outcomes after treatment and on the follow-up (Y-BOCS: Wald's X(2)=3.172; p=0.205; BPRS: X(2)=1.629; p=0.443; BDNF: X(2)=2.930; p=0.231). There seemed to be a trend towards improvement of BPRS scores 4 weeks after rTMS treatment comparing with sham (Cohen's d=0.875, with 32.9% statistical power). No side effects were reported. Future studies with larger sample sizes are needed.

Objective: To evaluate trends in psychiatric bed occupancy by elderly inpatients in the Brazilian public health care system between 2000 and 2010 and to determine the leading psychiatric diagnosis for hospital admissions. Methods: Data from all 895,476 elderly psychiatric admissions recorded in the Brazilian Public Health Care Database (DATASUS) between January 2000 and February 2010 were analyzed. Polynomial regression models with estimated curve models were used to determine the trends. The number of inpatient days was calculated for the overall psychiatric admissions and according to specific diagnoses. Results: A moderate decreasing trend (p < 0.001) in the number of inpatient days was observed in all geriatric psychiatric admissions (R2 = 0.768) and in admissions for organic mental disorders (R2 = 0.823), disorders due to psychoactive substance use (R2 = 0.767), schizophrenia (R2 = 0.680), and other diagnoses (R2 = 0.770), but not for mood disorders (R2 = 0.472). Most admissions (60 to 65%) were due to schizophrenia. Conclusion: There was a decreasing trend in inpatient days for elderly psychiatric patients between 2000 and 2010. The highest bed occupancy was due to schizophrenia, schizotypal, and delusional disorders.

Objective To describe the case of a patient with schizophrenia on clozapine treatment who had an episode of heat stroke. Case description During a heat wave in January and February 2014, a patient with schizophrenia who was on treatment with clozapine was initially referred for differential diagnose between systemic infection and neuroleptic malignant syndrome, but was finally diagnosed with heat stroke and treated with control of body temperature and hydration. Comments This report aims to alert clinicians take this condition into consideration among other differential diagnoses, especially nowadays with the rise in global temperatures, and to highlight the need for accurate diagnosis of clinical events during pharmacological intervention, in order to improve treatment decisions and outcomes.

Although the identification of reliable predictors of methylphenidate response in adults with attention-deficit/hyperactivity disorder (ADHD) is necessary to guide treatment decisions, very few data exist on this issue. Here, we assessed the predictors of clinical response to immediate-release methylphenidate hydrochloride (IR-MPH) in a naturalistic setting by analyzing the influence of demographic factors, severity, and a wide range of comorbid psychiatric disorders. Two hundred fifty adult patients with ADHD were evaluated and completed a short-term treatment with IR-MPH. Mental health diagnoses were based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria through the use of standard structured interviews. The Swanson, Nolan, and Pelham Rating Scale, version 4, adapted to adults was used to assess the severity of ADHD. In the linear regression model, only higher severity of ADHD was associated to a better IR-MPH response (b = 0.770; P < 0.001). Treatment of comorbidities in a subsample (n = 62) did not modify this pattern. Our findings suggest that in clinical settings, patients with more severe ADHD symptoms have a good response to treatment independently from the presence of mild or stabilized comorbidities and their treatments. For adults with ADHD, differently from other common psychiatric disorders such as depression and anxiety, higher severity is associated with better treatment response.

The dopamine transporter (SLC6A3/DAT1) plays a key role in the regulation of dopaminergic neurotransmission and is the major site of action for methylphenidate, a first-line medication for attention deficit hyperactivity disorder (ADHD). Most genetic association studies with ADHD have investigated a 40-bp variable number of tandem repeats (VNTR) polymorphism in the 3'-untranslated region (UTR) of the DAT1, but these investigations have reported heterogeneous findings. The few studies focused on the 5' region have reported promising results. Despite rs2652511 not being included, nor having any proxy SNP available in GWAS, the few candidate gene studies that analyzed it suggested an association with ADHD and schizophrenia. Here, we analyzed the -839 C/T (rs2652511) promoter variant and the 3'-UTR and intron 8 (Int8) VNTR polymorphisms in 522 adults with ADHD and 628 blood donor controls. The diagnostic procedures followed the DSM-IV criteria. A significant association was detected (P = 0.002) between the rs2652511 C-allele with ADHD. In addition, the 6-repeat allele of Int8 VNTR was associated with higher inattention scores (P = 0.034). The haplotype analysis including DAT1 3'-UTR and Int8 VNTR polymorphisms did not reveal associations with ADHD susceptibility or severity dimensions. These findings extend to adult samples previous findings from children samples on the role of the rs2652511 polymorphism in the promoter region of DAT1 as a risk factor for ADHD susceptibility.

To assess the relationship between posture and inflammatory response markers (C-reactive protein [CRP] and von Willebrand factor [vWF]) in schizophrenics.Forty patients with stable schizophrenia were divided into early-stage (10 years since first episode, n = 15) and late-stage (≥10 years since first episode, n = 25) groups. Both groups were compared to controls (n = 26). All participants underwent postural assessment by biophotogrammetry. Cases alone underwent blood collection. The significance level was set at 5%, and analyses were carried out in SPSS 18.0.In the early-stage group, 15 postural angles were significantly different from their reference ranges, whereas in the late-stage group, only seven angles were significantly different. In comparison with the control group, only six angles were significantly different. There was no difference in inflammation markers between the early- and late-stage groups. However, CRP levels were higher in cases with greater disease severity, and vWF was associated with forward head posture. Pain correlated with five postural angles, and late-stage patients reported more pain than early-stage cases.CRP was associated with disease severity, while vWF and pain were associated with forward head posture, hyperlordosis and scoliosis, suggesting an association between vascular inflammation and pain, with an influence on posture.

One monozygotic male twin pair discordant for transsexualism is described. Both twins were interviewed and tested with the Wechsler Adult Intelligence Scale battery for cognitive functions and they underwent magnetic resonance imaging to measure the volumes of specific cerebral structures. Interviews with the twins and their mother indicated no unusual medical or life history events that could have had a causal role in the emergence of the disorder. Both cognitive function testing and neuroimaging detected differences between the twins that could be related to unexplained epigenetic effects and exogenous hormone usage.

ObjectiveMany studies have documented the high rates of functional impairment among patients with schizophrenia. The majority of the available instruments used to assess functioning, however, focus on global measures of functional recovery rather than specific domains of psychosocial functioning. Most of these instruments have important limitations regarding use in psychiatry. The aim of the present study was to evaluate the psychometric properties of the Brazilian version of the Functioning Assessment Short Test (FAST) in patients with schizophrenia.MethodsA convenience sample of 107 chronic outpatients with schizophrenia and 108 controls was assessed in a university hospital (Hospital de Clínicas de Porto Alegre, Brazil). Psychometric properties of FAST (internal consistency, concurrent validity, and test-retest reliability) were analyzed.ResultsThe internal consistency obtained was high; the Cronbach’s alpha was 0.89. FAST total score was higher in patients than in the control group (Z = 11.95; P

Background: Schizophrenia is associated with psychotic experiences and cognitive deficits. Therefore, cognitive function is one of the most critical determinants of quality of life in this pathology. Resveratrol has been related with neuroprotective action but there are no studies evaluating resveratrol in schizophrenia. The objective of this study was to determine the efficacy of resveratrol supplementation on cognition in individuals with schizophrenia. Methods: This is a 1-month randomized, double-blind controlled trial (NCT 02062190), in which 19 men with diagnosis of schizophrenia, aged 18 to 65 years, were assigned to a resveratrol supplement group (200mg) or placebo group (200mg), with a 1-month follow-up. Applying a series of cognitive tests assessed neuropsychology performance (Hopkins Verbal Learning Test, Stroop Color and Word Test, Weschler Adult Intelligence Scale) and Brief Psychiatric Rating Scale assessed psychopathology severity. Results: There were no significant improvement in neuropsychology performance (episodic memory, working memory, attention and concentration capacity, inhibitory control, interference measures, selective attention and mental flexibility) and psychopathology severity after 1-month of resveratrol supplementation (p>0.05). Conclusion: In conclusion, we have shown that 1-month of a resveratrol supplementation (200 mg/day) did not improve episodic memory, working memory, attention and concentration capacity, inhibitory control, interference measures, selective attention and mental flexibility as compared with placebo in patients with schizophrenia.

Introduction: Schizophrenia is a severe, debilitating mental disorder that affects both the physical health and the functional capacity of patients, causing great impairment throughout the life course. Although physical and cognitive impairments may represent different expressions of a single systemic inflammatory process, little is known about the relationship between motor function and schizophrenia. Objective: To evaluate physical functional capacity in patients with schizophrenia and ascertain whether it correlates with markers of inflammation, disease severity, and pharmacotherapy. Methods: Cross-sectional study using a convenience sampling strategy. Forty patients with stable schizophrenia, undergoing treatment, were recruited from the Outpatient Program of Hospital de Clinicas de Porto Alegre, University Hospital linked to Public Health System. Physical functional capacity was assessed by the 6-minute walk test (6MWT), and inflammatory markers were measured by C - reactive protein (CRP) and Von Willebrand Factor (VWF). Results: Mean functional capacity and clinical variables differed among patients and Brazilian population regarding heart rate (p=0.004), diastolic (p=0.001) and systolic (p

Background: Patients with schizophrenia (SZ) are generally overweight or obese and have several metabolic disorders. Additionally, such patients have a lower life expectancy and the main cause of their increased mortality is cardiovascular disease (CVD). The objective of this study was to determine the efficacy of resveratrol supplementation on serum glucose and CVD risk factors in individuals with SZ. Methods and Results: This is a four-week randomized, double-blind controlled trial (registration No.: NCT 02062190) in which 19 men with a diagnosis of SZ, aged 18 to 65, were assigned to either a resveratrol supplement group (200 mg/day) or a placebo group (200 mg/day). In short, we did not observe significant changes after resveratrol supplementation. In the placebo group, we found a significant increase in total cholesterol levels (p = 0.024) and in LDL-cholesterol (p = 0.002), as well as a decrease in body fat percentage (p = 0.038). The placebo group also showed an increase in triglycerides (9.19%) and a reduction in HDL-cholesterol (4.88%). In the resveratrol group, triglycerides decreased (7.64%). Conclusion: In summary, oral resveratrol in reasonably low dosages (200 mg daily) brought no differences to body weight, waist circumference, glucose, and total cholesterol. It was possible to note that the lipid profile in the placebo group worsened and, although no significant differences were found, we can assume that resveratrol might prevent lipid profile damage and that the intervention affected the lipoprotein metabolism at various levels.

The consideration of age of onset of impairment as part of the ADHD diagnosis is controversial and has been a revisited issue with the emergence of the new classifications in Psychiatry. The aim of this study is to compare patients with early and late onset of ADHD impairment in terms of neuropsychological and personality characteristics. Adult patients with ADHD (n = 415) were evaluated in the ADHD outpatient program at Hospital de Clinicas de Porto Alegre, Brazil. The diagnostic process for ADHD and comorbidities was based on DSM-IV criteria. The comparison between the two ages of onset groups (before 7; n = 209 or from 7 to 12 years; n = 206) was performed with ANOVA, followed by Stepwise forward regression analyses to restrict the number of comparisons and access the possible effect of multiple confounders. Patients with early onset ADHD present higher scores in novelty seeking in both analyses (respectively P = 0.016 and P = 0.002), but similar cognitive and attention features as compared with the late onset group. These data add to previous evidence that despite a more externalizing profile of early onset ADHD, the overall performance is similar reinforcing the need for awareness and inclusion of the late onset group in DSM-V diagnostic criteria. Language: en

Since approximately 70% of adult patients with attention-deficit/hyperactivity disorder (ADHD) have at least one comorbid disorder, rating of impairment specifically attributable to ADHD is a hard task. Despite the evidence linking environmental adversities with negative outcomes in ADHD, life events measures have not been used to rate the disorder impairment. The present study tested for the first time the hypothesis that increased ADHD severity is associated with an increase in negative recent life events, independently of comorbidity status. The psychiatric diagnoses of 211 adult ADHD outpatients were based on DSM-IV criteria assessed through structured interviews (K-SADS-E for ADHD and ODD, MINI for ASPD and SCID-IV-R for other comorbidities). ADHD severity was evaluated with the Swanson, Nolan and Pelham rating scale (SNAP-IV) and recent life events with the Life Experience Survey. Higher SNAP-IV inattention and hyperactivity scores, female gender, lower socioeconomic status and the presence of comorbid mood disorders were associated with negative life events. Poisson regression models with adjustment for possible confounders confirmed the effect of inattention and hyperactivity severity on negative life events. Our results suggest that the negative life events experienced by these patients are associated to the severity of ADHD independently from comorbid psychiatric disorders.

IntroductionAttention-deficit/hyperactivity disorder (ADHD), oppositional defiant disorder (ODD), and conduct disorder (CD) are frequently co-occurring disorders in children and adolescents. However, their clinical status among adults is still under discussion. This study analyzes how the current clinical presentation of adult ADHD might be influenced by a lifetime history of CD and ODD.MethodsWe compared three groups of patients: ADHD without history of CD/ODD (n = 178), ADHD + history of ODD (n = 184), and ADHD + history of CD (n = 96).ResultsA history of CD (and to a lower extent ODD) is associated with a more severe and externalizing profile.ConclusionPast CD and ODD entail a significant negative mental health impact on persistent ADHD, reinforcing the importance of actively assessing the developmental history of adult ADHD patients.

Schizophrenia (SZ) is a chronic severe mental disorder. Increased inflammatory processes have been shown in acute and chronic SZ. Apoptotic processes may alter the neuronal network and are involved in the pathogenesis of several neurodegenerative diseases, such as SZ. Annexin-V seems to have a role on inhibition of pro-inflammatory activities during apoptosis. Tumor necrosis factor (TNF-alpha) is a cytokine involved in systemic inflammation and is a member of a group of cytokines which stimulate acute phase reactions. A chronic immune activation in SZ has been shown. The aim of this study was to compare annexin-V and TNF-alpha serum levels in chronic medicated patients with SZ and healthy controls. Thirty-eight outpatients from the HCPA Schizophrenia Program and 38 healthy controls were enrolled to this study protocol. Annexin-V and TNF-alpha serum levels were measured with ELISA. Serum annexin-V levels were significantly higher in patients with SZ than in controls (p

A obesidade mórbida está relacionada a muitos transtornos psiquiátricos e possui como opção terapêutica a cirurgia bariátrica. Objetivo: caracterizar a prevalência de transtornos depressivos e de ansiedade em pacientes submetidos à cirurgia bariátrica no Hospital Universitário Regional de Maringá e do Centro de Cirurgia de Obesidade de Maringá. Métodos: o estudo foi realizado com 50 pacientes obesos mórbidos submetidos à Cirurgia Bariátrica em diferentes períodos: pré-operatório, um mês de pós-operatório, três meses de pós-operatório e seis meses de pós-operatório. A avaliação do Transtorno Depressivo foi realizada pela aplicação do Inventário de Depressão de Beck, sendo outro instrumento utilizado neste trabalho a Escala Hospitalar de Ansiedade e Depressão (HAD). Resultados: a prevalência de quadros sugestivos de ansiedade foi: 40% (20 pacientes) no pré-operatório, 18% no primeiro mês pós-operatório, 8% no terceiro mês pós-operatório e 14% no sexto mês pós-operatório. Quadros sugestivos de depressão foram encontrados em: 26% (13 pacientes) no pré-operatório, 10% no primeiro mês pós-operatório e no terceiro mês pós-operatório e 8% no sexto mês pós-operatório. Conclusão: Os níveis de Ansiedade foram altos no pré-operatório, diminuíram no 1º e 3º mês pós-operatório e voltaram a subir no sexto mês, atingindo níveis mais altos que no terceiro mês.Morbid obesity is associated to several psychiatric disorders and bariatric surgery is a therapeutic option. Current research characterizes the prevalence of depression and anxiety disorders in patients who underwent bariatric surgery at the Regional Hospital of Maringá and at the Obesity Surgery Center of Maringá, Maringá PR Brazil. Study was undertaken with 50 morbid obese patients who underwent bariatric surgery and comprised different periods, namely, pre-surgery, one month after surgery, three months after surgery and six months after surgery. Depressive disorder was evaluated by Beck’s Depression Inventory and by the Hospital Scale of Anxiety and Depression (HAD). Results show prevalence of anxiety in 40% (20) of patients during the pre-surgery period; 18% during the 1st post-surgery month; 8% during the 3rd post-surgery month and 14% during the 6th post-surgery month. High rates of depression were found in 26% (13) of patients in the pre-surgery period; 10% in the 1st and 3rd post-surgery month and 8% in the 6th post-surgery month. Levels of anxiety were actually high in the pre-operative period but they decreased in the 1st and 3rd months after surgery. However, a rise during the 6th month was reported which reached higher levels than that during the 3rd month.

Objective The prevalence of smoking is significantly increased among adults with Attention-Deficit/Hyperactivity Disorder (ADHD), and this association has a significant impact in both disorders, ascribed to either self-medication or behavioral disinhibition hypotheses. However, little is known about clinical variables associated with cigarette smoking among patients with ADHD. The present study evaluates comorbidity, demographic and personality profiles of patients with ADHD in relation to smoking status. Methods Patients (n 422) were evaluated in the adult ADHD outpatient clinic of Hospital de Clinicas de Porto Alegre. Diagnoses were based on DSM-IV criteria and interviews were performed with Portuguese version of K-SADS-E for ADHD and Oppositional-Defiant Disorder. Axis I psychiatric comorbidities were evaluated with the SCID-I and smoking behavior with Fagerstrom Test for Nicotine Dependence (FTND). Personality was evaluated with Cloninger’s Temperament and Character Inventory (TCI). Results: The presence of smoking was strongly associated with externalizing characteristics as antisocial personality disorder (OR 4.2) and substance dependence (OR 6.5), but not with internalizing disorders. Moreover, smoking was associated with higher novelty seeking and lower harm avoidance scores. Conclusions Smoking initiation among patients with ADHD is consistent with a behavioral disinhibition profile beyond the possible role of self-medication in smoking persistence. Smoking in these patients is strongly associated with externalizing comorbid disorders.

article i nfo Several studies have tested for the association between polymorphisms in the ADRA2A gene and childhood ADHD. A meta-analysis of these results, however, has pointed towards a significant heterogeneity, raising the need for explanatory studies. As the effect of other relevant clinical characteristics could be a possible source, we studied three polymorphisms in the ADRA2A gene (−1291 CNG-MspI or rs1800544; −262 GNA-HhaI or rs1800544; 1780 CNT-DraI or rs553668) in 403 adult patients with ADHD assessed in relation to comorbidity and personality characteristics, as well as in 232 controls. The diagnosis followed DSM-IV criteria, and personality dimensions were evaluated with the Temperament and Character Inventory (TCI). There were no significant differences in allele and genotype frequencies between cases and controls. Patients carrying the G allele of rs1800544 presented lower scores in harm avoidance, and carriers of the T allele of rs553668 had more novelty seeking and less harm avoidance and persistence. Additionally, the haplotype carrying the G-G- T alleles (rs1800544-rs1800545-rs553668) was associated with lower scores in harm avoidance and persistence, and higher scores in novelty seeking compared to other haplotypes. These findings suggest that the conflicting findings obtained in association studies between ADRA2A polymorphisms and ADHD might be related to temperament profiles, and support additional studies addressing these effects in larger samples. © 2010 Elsevier Ireland Ltd. All rights reserved.

Brain-derived neurotrophic factor (BDNF) plays a critical role in neurodevelopment and neuroplasticity. Altered BDNF signaling is thought to contribute to the pathogenesis of schizophrenia (SZ) especially in relation to cognitive deficits. Clozapine (CLZ) has been shown a beneficial effect on cognition in SZ in some studies and a detrimental effect in others. To examine serum BDNF, two groups of chronically medicated DSM-IV SZ patients (n = 44), on treatment with clozapine (n = 31) and typical antipsychotics (n = 13) had 5 ml blood samples collected by venipuncture. Serum BDNF levels were significantly correlated with CLZ daily dose (r = 0.394, p = 0.028), but not with typical antipsychotic daily dose (r = 0.208, p = 0.496). This study suggests that serum BDNF levels are correlated with CLZ daily dose, and this may lead to the cognitive enhancement as seen in patients with SZ under CLZ. Despite the strong evidence that chronic administration of CLZ is effective for patients with SZ, it is still unknown whether atypical antipsychotic drugs regulate BDNF expression. Serum BDNF levels concentration in SZ merits further investigations with regard to the role of neurotrophins in the cognitive response to treatment with CLZ and other atypical antipsychotics.

Schizophrenia is a severe mental illness affecting around 1% of adults with a high degree of morbidity and mortality. Affected individuals are at increased risk for unemployment, handicap, obesity, diabetes mellitus, hearth attack and suicide. Antipsychotic drugs are the best treatment for this disease, but about 20% of patients display drug resistance, or refractoriness, and may receive a special neuroleptic named Clozapine. Despite its superiority from other neuroleptics, only 30-60% of drug-resistant patients are responsive to clozapine. Clozapine's action results from interactions between dopaminergic and serotonergic neurotransmitter systems and since clozapine appears to exert its effect strongly through the serotonergic systems, alterations in serotonin synaptic levels may influence antipsychotic response. The serotonin transporter (5-HTT) is responsible for pre-synaptic re-uptake of serotonin, making this transporter a logical candidate gene for prediction of clozapine response and to increase understanding about mechanisms of refractoriness. Therefore, we investigated the influence of two polymorphisms in the 5-HTT gene (HTTLPR/rs25531 and VNTR Stin2) in clozapine response in a sample of 116 schizophrenic individuals of European descent from South-Brazil. Significant differences between responders and non-responders to clozapine were observed for the HTTLPR/rs25531 polymorphism. Nonresponders to clozapine showed a higher frequency of S'-allele (P = 0.01) and also were more likely to be S'/S' homozygous or S'/L' heterozygous than those who did respond (P = 0.04). After controlling for confounding variables, logistic regression analyses confirmed this association (OR = 3.15; 95% CI: 1.13-8.80). The observed association suggests that increased availability of extracellular serotonin concentrations at all synapses may reduce clozapine effect.

Adrenergic α2A receptor gene (ADRA2A) is one of the most promising candidate genes for ADHD pharmacogenetics. Thus far, three studies have investigated the association between the ADRA2A −1291 C>G polymorphism and the therapeutic response to methylphenidate (MPH) in children with ADHD, all of them with positive results. The aim of this study is to investigate, for the first time, the association between three ADRA2A polymorphisms (−1291 C>G, −262 G>A, and 1780 C>T) and the response to MPH in adults with ADHD. The sample comprises 165 Brazilians of European descent evaluated in the adult ADHD outpatient clinic of the Hospital de Clinicas de Porto Alegre. The diagnostic procedures followed the DSM-IV criteria. Drug response was assessed by both categorical and dimensional approaches, through the scales Swanson, Nolan, and Pelham Rating scale version IV and the Clinical Global Impression-Severity Scale, applied at the beginning and after the 30th day of treatment. We found no evidence of association between the three ADRA2A polymorphisms and the therapeutic response to MPH treatment. Our findings do not support a significant role for the ADRA2A gene in ADHD pharmacogenetics, at least among adult patients.

Mental health policies throughout the world are being subjected to several changes due to increased pressure from the public and from health administrators. Mental health policies in the developing world experienced changes following advice and consultation from the World Health Organization (WHO). This was the case with Brazil, which enacted several laws and policies affecting community care and the closure of beds in psychiatric hospitals (the deinstitutionalization movement). Rio Grande do Sul, the southeast state in Brazil, adopted this policy in 1992, but still suffers from a shortage of psychiatric beds in both general hospitals (GHs) and psychiatric hospitals (PHs), despite advances in the provision of community care. As a result, Rio Grande do Sul (RS) can be studied as an example of “what actually happens” in mental health care in the developing world. The study analyzed online administrative data from 2000 to 2007 for three main parameters of mental health care (i.e. hospital use rate, length of stay, and hospital bed capacity). These were used to evaluate differences in psychiatric care among GHs and PHs. The number of existing and required psychiatric beds in RS was also calculated. GHs had very low hospital use rates, while PHs had a very high length of stay (200% higher than GH). The number of admissions to GHs grew by 170% over the 8 year period, and psychiatric bed availability was 1.5 per 10,000 inhabitants. The study provided evidence for the need of 30–50% more psychiatric beds in GHs. Also, additional staff training is needed to increase use rates in GHs and decrease the length of stay in PHs. Additional studies covering national data must be carried out to assess the extent of these problem in other Brazilian mental health care services.

Objective To assess long-lasting effects of childhood trauma on the functional outcome of adult patients diagnosed with schizophrenia. Method Ninety-nine stable patients with schizophrenia followed in an outpatient program at a public university hospital in Porto Alegre, southern Brazil, were investigated for childhood traumatic experiences by the Childhood Trauma Questionnaire (CTQ) and for functional impairment by the World Health Organization Disability Assessment Schedule (WHO/DAS). The schizophrenia diagnosis was assessed by ICD-10 and DSM-IV criteria according to the Operational Criteria Checklist for Psychotic Illness (OPCRIT). Results Childhood trauma in general was associated with increased disability in adulthood, reflected by impaired Overall Behavior ( p = .023) and Global Evaluation ( p = .032). Analysis of specific traumatic domains revealed that increased childhood physical neglect was associated with functional impairment in Overall Behavior ( p p = .037) and Global Evaluation ( p = .014). Higher emotional abuse was associated with impaired Overall Behavior ( p = .026), and higher emotional neglect with poor Global Evaluation ( p = .047). Additionally, earlier onset of illness was associated with lower level of functioning evidenced by impairment in Overall Behavior ( p = .042). Linear regression using WHO/DAS sections (Overall Behavior, Social Role Performance and Global Evaluation) as dependent variables and CTQ subscales indicated that only physical neglect had an effect on adult functionality. Conclusions Childhood trauma was associated with functional and social impairment in adult patients with schizophrenia. Specific types of abuse and neglect, such as physical neglect and emotional abuse and neglect, influenced disability, and the most robust association was physical neglect. Studies involving more patients, with normal controls and additional measurements of biological liability, should be conducted to confirm this association and to increase the understanding of gene-environment relationship in schizophrenia and pathways to disability. Practice implications Further investigation is warranted to clarify the association between childhood trauma and disability in schizophrenia, as well as to develop standardized instruments for the assessment of trauma and earlier detection of risk along with education of patients and families about adequate care, in an effort to reduce the incidence of disability in schizophrenia.

Aims: The delineation of allele distribution and frequency is required to effectively translate pharmacogenetics to the clinic and given the paucity of CYP2D6 data in the Brazilian population, the purpose of this research was to characterize CYP2D6 alleles and genotype frequencies in Brazilians of European and African ancestries. Moreover, since it is suggested in the literature that CYP2D6 poor metabolism might be involved with susceptibility to schizophrenia, we included data from Brazilian schizophrenic patients to verify if CYP2D6 poor metabolism phenotypes are associated with susceptibility to schizophrenia. Materials & methods: We investigated 24 CYP2D6 polymorphisms, gene deletions and gene multiplications in 179 healthy individuals from Brazil, 92 of European descent and 87 African Brazilians. CYP2D6 gene polymorphisms were genotyped by a MassARRAY® SNP genotyping system. Results: A total of 19 different alleles and five allele duplications were identified in African and European Brazilians. No significant differences in CYP2D6 allele function or poor metabolizer predicted phenotype frequencies were observed between healthy controls and schizophrenic patients, but the predicted metabolic phenotype distribution showed a significant higher frequency of intermediate metabolizers in African Brazilians than in European Brazilians (p = 0.001). Conclusions: CYP2D6 poor metabolizer genotype seems not to be a determining factor of schizophrenia susceptibility in Brazilians. The characterization of CYP2D6 variability will be very useful for future pharmacogenetic studies in the Brazilian population.

OBJETIVO: A eficácia da eletroconvulsoterapia em tratar sintomas depressivos está estabelecida por meio de inúmeros estudos desenvolvidos durante as últimas décadas. A eletroconvulsoterapia é o tratamento biológico mais efetivo para depressão atualmente disponível. O objetivo deste estudo foi demonstrar o papel da eletroconvulsoterapia no tratamento da depressão e destacar aspectos atuais relativos à sua prática. MÉTODO: Foram revisados na literatura estudos de eficácia, remissão de sintomas, fatores preditores de resposta, assim como aspectos atuais acerca da qualidade de vida, percepção dos pacientes, mecanismo de ação, técnica e prejuízo cognitivos. RESULTADOS: Os principais achados desta revisão foram: 1) a eletroconvulsoterapia é mais efetiva do que qualquer medicação antidepressiva; 2) a remissão da depressão com a eletroconvulsoterapia varia, em geral, de 50 a 80%; 3) Ainda é controverso o efeito da eletroconvulsoterapia nos níveis de fator neurotrófico derivado do cérebro (acho que aqui pode colocar entre parenteses o "BNDF"); 4) a eletroconvulsoterapia tem efeito positivo na melhora da qualidade de vida; 5) os pacientes submetidos à eletroconvulsoterapia, em geral, têm uma percepção positiva do tratamento. CONCLUSÃO: A eletroconvulsoterapia permanece sendo um tratamento altamente eficaz em pacientes com depressão resistente. Com o avanço da sua técnica, a eletroconvulsoterapia tornou-se um procedimento ainda mais seguro e útil tanto para a fase aguda, quanto para a prevenção de novos episódios depressivos. OBJECTIVE: The efficacy of electroconvulsive therapy in treating depressive symptoms has been established by means of innumerable studies developed along the last decades. Electroconvulsive therapy is the most effective biological treatment for depression currently available. The objective of this study was to demonstrate the role of electroconvulsive therapy in the treatment of depression and highlight present aspects related to its practice. METHOD: We reviewed in the literature studies on efficacy, symptom remission, predictive response factors as well as current aspects regarding quality of life, the patients' perception, mechanism of action, technique and cognitive impairment. RESULTS: The main results found in the this revision were: 1) electroconvulsive therapy is more effective than any antidepressant medication; 2) the remission of depression with electroconvulsive therapy varies, in general, from 50 to 80%; 3) The effect of electroconvulsive therapy in brain-derived neurotrophic factor levels is still controversial; 4) electroconvulsive therapy has a positive effect in the improvement of quality of life; 5) patients submitted to electroconvulsive therapy have, in general, a positive perception about the treatment. CONCLUSION: Electroconvulsive therapy remains a highly efficacious treatment in treatment-resistant depression. With the improvement of its technique, electroconvulsive therapy has become an even safer and more useful procedure both for the acute phase and for the prevention of new depressive episodes.

Background: Previous studies have suggested that individuals with ADHD have high scores in novelty seeking and harm avoidance. However, it is not known whether personality is associated with specific subtypes and dimensions of the disorder. The aim of this study is to test for associations between scores in the temperament and character inventory of C.R. Cloninger with adult ADHD subtypes and severity. Sampling and Methods: The diagnostic interviews of 296 adult ADHD patients followed the DSM-IV criteria. ADHD dimensions were evaluated with the SNAP-IV scores, and personality dimensions were assessed using the Temperament and Character Inventory. Results: The combined subtype (n = 168) was associated with higher scores in novelty seeking (p < 0.001) and lower scores in cooperativeness (p = 0.006) than the inattentive subtype (n = 128). Higher inattention scores were associated with decreased self-directedness (p < 0.001) and increased harm avoidance (p = 0.02), whereas higher hyperactivity/impulsivity scores correlated positively with novelty seeking (p < 0.001) and persistence (p = 0.03). Conclusions: These findings suggest that personality dimensions are strongly correlated with ADHD subtypes and severity dimensions, pointing to the need for studies evaluating the mechanisms behind this association.

There is an increasing body of evidence suggesting that oxidative stress may play a role in the pathophysiology of both schizophrenia (SZ) and bipolar disorder (BD). Methods We compared the antioxidant enzyme, serum superoxide dismutase (SOD) and the lipid peroxidation product, thiobarbituric acid reactive substances (TBARS) as assessed in depressed (N = 21), manic (N = 32) and euthymic (N = 31) bipolar patients, and in chronically medicated patients with schizophrenia (N = 97), all fulfilling DSM-IV diagnostic criteria, and a group of healthy controls (N = 32). Results Serum SOD (U/mg protein) activity was significantly increased (p

This study aimed to explore the influence of variation in DRD2, DRD3, CYP2D6, CYP3A4, and CYP3A5 genes on treatment resistance to typical neuroleptics in a Brazilian sample of patients with schizophrenia.One polymorphism at DRD2 gene, five at DRD3, 24 at CYP2D6, nine at CYP3A4 gene, and one at CYP3A5 gene were genotyped in a sample of 186 patients with schizophrenia.From the nine studied CYP3A4 single nucleotide polymorphisms, only the -392AG was polymorphic, and significant associations were observed between this single nucleotide polymorphism and efficacy of neuroleptic treatment. Homozygous individuals for the -392A variant [P=0.014, odds ratio (OR)=3.32] were more frequent in the treatment-resistant group, compared with carriers of one copy of the -392G variant. The CYP3A5 low expressor genotype (CYP3A5*3/CYP3A5*3) was found to be associated with refractoriness to neuroleptic treatment (P=0.003, OR=3.16). Among the haplotypes observed in DRD3 gene, the T/A/G/A/C haplotype showed an association with refractoriness to neuroleptics (chi=5.342, P=0.021, OR=1.75). This association showed that carriers of one copy of this haplotype presented intermediate values between noncarriers and homozygous individuals for the haplotype. No association was observed with polymorphisms in DRD2 and CYP2D6 genes. Multiple logistic regression analyses showed that the number of copies of DRD3 T/A/G/A/C haplotype and CYP3A5 low expressor genotype were predictors of refractoriness to neuroleptic after controlling for selected risk factors. CYP3A5*3 individuals carrying at least one copy of the T/A/G/A/C haplotype showed a higher risk to be refractory to neuroleptics than CYP3A5*3 homozygotes+non-T/A/G/A/C carriers (chi=5.533, P=0.019, OR=2.32, 95% confidence interval=1.08-5.02). No significant associations were observed with DRD2 and CYP2D6 polymorphisms.Our results suggest a role for CYP3A5 and DRD3 gene variants on refractoriness to neuroleptic treatment in Brazilians with schizophrenia.