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Aims: Clozapine treatment of schizophrenia is effective only in 30–60% of individuals. Since genetic factors are believed to play a significant role in the variation of response to antipsychotics, the aim of the present study was to verify the effect of a G-protein gene polymorphism on clozapine response and clozapine-induced generalized seizures in Brazilian patients with schizophrenia. Patients & methods: In total, 121 schizophrenic patients in treatment with clozapine were genotyped for the 825C>T polymorphism it the GNB3 gene using PCR. Results: Homozygosity for the T825 allele was more frequent among nonresponders (χ2 = 7.708; p = 0.021), and carriers of this allele had a higher risk to present a convulsion episode (χ2 = 7.279; p = 0.007). These results were confirmed after controlling for covariates by logistic regression. Conclusion: Our data suggest an influence of the 825C>T polymorphism on clozapine response in persons with schizophrenia and also on a specific neurological side effect (generalized seizures) under clozapine treatment.

There is evidence that major psychiatric disorders such as schizophrenia (SZ) are associated with deregulation of synaptic plasticity with downstream alterations of neurotrophins. NT3 is an important neurotrophin in the central nervous system, and performs key biological functions, such as promoting the survival, differentiation, and plasticity of neurons. NT3 has a central role in the early neuronal development; enhancing the survival of dopaminergic neurons, suggesting possible involvement in the physiopathology of dopamine related neuropsychiatric disorders such as SZ. Variations in the NT3 gene increase the risk of SZ. Three groups of chronically medicated DSM-IV patients with SZ, on treatment with clozapine (n=12), haloperidol (n=12), risperidone (n=12) and 10 healthy controls had 5 ml blood samples collected by venipuncture. NT3 serum levels were assessed using sandwich-ELISA and were significantly lower in SZ patients (p, Clarissa Severino Gama is funded by CNPq (PDE #200310/ 2007-0), Brazil, and Endeavour Awards Programme (#539/2008), Australia.

Objective The requirement in classificatory systems that some impairment from attention-deficit/hyperactivity disorder (ADHD) symptoms starts before 7 years of age (age of onset of impairment criteria – AOC) has been harshly criticized. Although there is evidence that late-onset ADHD is a valid diagnosis, little is known about the role of age of onset of impairment on the clinical profile of adult patients. Methods The diagnoses of 349 adults with ADHD followed DSM-IV criteria. ADHD and oppositional defiant disorder (ODD) were evaluated with the K-SADS-E, and other comorbidities with the SCID-IV and the MINI. Subjects were divided in early and late-onset groups (age of onset of impairment between 7 and 12 years old). The effect of age of onset over clinical and demographic characteristics was tested by regression models. Results Late-onset subjects were diagnosed later ( P = 0.04), had a lower frequency of problems with authority and discipline ( P = 0.004), and lower scores in SNAP-IV ( P P = 0.03). On the other hand, late-onset patients presented a higher prevalence of comorbid general anxiety disorder (GAD) ( P = 0.01). Both groups had a similar profile in the remaining comorbidities and sociodemographic characteristics. Conclusions This study provides initial evidence that adults with late-onset ADHD have less severity, lower frequency of externalizing symptoms and increased comorbidity with GAD, but similar profile in other comorbidities. In addition, the data suggest that late-onset patients have a higher probability of delayed diagnosis despite the significant impairment of their condition.

Despite the implication of fronto-striatal circuits in attention-deficit/hyperactivity disorder (ADHD), there is a lack of information on the role of these regions, especially the thalamus, in the heterogeneity of ADHD. We assessed the (1)H-magnetic resonance spectroscopy profile in ventromedial prefrontal cortex (VMPFC)-thalamic-striatal regions bilaterally in three groups of subjects (age range 18-24 years old): ADHD inattentive type (ADHD-I; n = 9), ADHD combined type (ADHD-C; n = 10) and non-ADHD controls (n = 12). The peaks of N-acetylaspartate, Choline (Cho), myo-inositol (mI), creatine (Cr) and glutamate-glutamine-GABA (Glx) to Cr were calculated. Subjects with ADHD-C showed lower mI/Cr ratio in the right VMPFC than controls, higher Cho/Cr ratio in the left thalamus-pulvinar than the ADHD-I group and higher Glx/Cr ratio in left putamen than individuals with ADHD-I and controls. This metabolic profile suggests a disruption of fronto-striato-thalamic structures in the ADHD-C as a result of lower neuronal energetic metabolism.

Dietary factors influence BDNF in animal studies, but there is no comparable data in clinical populations. We examined the effect of a dietary intervention on BDNF serum levels in 67 DSM-IV schizophrenic outpatients (51 males and 16 females). Two groups were assessed in a cross-sectional study: one on a hypocaloric diet (HD) and the other not on a hypocaloric diet. Weight, height and BMI data were collected concurrently with 5-ml blood sampling of each subject. BDNF levels were measured with a sandwich-ELISA. The blood sample was obtained a minimum of one month after the exposure to dietary intervention. Serum BDNF levels were significantly higher in patients on the HD (p=0.023). Additional research examining the interaction among patterns of nutritional food behavior and underlying physiopathology may result in insights upon which evidence-based decisions regarding dietary interventions can be made in people identified with major psychiatric disorders, such as schizophrenia.

The neurogranin (NRGN) gene produces a postsynaptic brain-specific protein that regulates calmodulin-Ca(2+) availability in neurons. Acting downstream of the NMDA receptor and upstream of calcineurin and other proteins implicated in schizophrenia, NRGN is a good candidate for association studies in schizophrenia. NRGN expression is regulated during development and is modulated by thyroid hormones and retinoids, molecules essential for the proper development of the central nervous system. Given the genetic complexity of schizophrenia and the potential genetic heterogeneity in different populations, we studied a possible association of NRGN with schizophrenia in 73 Azorean proband-parent triads and in two independent case-control samples from the Portuguese-mainland (244 schizophrenic and 210 controls) and Brazil (69 schizophrenic and 85 mentally healthy individuals). Genotype distribution showed association of the rs7113041 SNP with schizophrenia in males of Portuguese origin, which was confirmed by the analysis of the proband-parent triads. This evidence, implicating NRGN in schizophrenia, introduces another player into the glutamatergic hypothesis of schizophrenia., Fundação para a Ciência e Tecnologia/FEDER (Portugal) grant POCTI/35837/MGI/2000 and POCI/SAU-ESP/58757/2004. D. Ruano is a recipient of a fellowship (SFRH/BD/8659/2002) from Fundação para a Ciência e a Tecnologia (FCT), Portugal

Impaired antioxidant defenses are suggested to participate in the pathophysiology of schizophrenia. Altered superoxide dismutase (SOD) and increased lipid peroxidation, measured by the thiobarbituric acid reactive substances (TBARS), are increased in schizophrenia. The aim of this study was to determine the effects of clinical course and subtype on oxidative stress parameters. In this study, 68 male patients, classified according to DSM-IV schizophrenia subtypes and clinical course (partial remission, marked symptoms, and deteriorated), were studied, and TBARS and SOD measured. Mean serum SOD and mean serum TBARS concentrations were similarly not significantly different among different subtypes (paranoid, disorganized and undifferentiated). However, marked symptoms status was associated with higher TBARS levels compared to the deteriorated group. This suggests a possible relationship between symptom acuity and oxidative stress in males.

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.

Several observations point to the involvement of disturbed lipid biology in schizophrenia. Reduced response to niacin flushing test, which involves vasodilatation induced by prostaglandin D2 (PGD2), is among the evidences, together with decreased CSF levels of lipocalin-type prostaglandin D2 synthase (PTGDS), the enzyme responsible for the synthesis of PGD2 in the brain. Since PTGDS is also a carrier for lipophilic molecules such as retinoids and thyroid hormones, altered PTGDS levels might influence both PGD2-mediated signaling, and vitamin A and thyroid hormone availability. To test whether genetic variants of PTGDS are involved in the etiology of schizophrenia, we searched for variants in the coding and regulatory regions of the gene. We identified four previously described polymorphisms. Using two case-control samples from Portugal and Brazil, none of the polymorphisms tested was associated with the disease. In addition, no transmission distortion was observed in an independent parents-offspring sample from the Azorean Islands. Our data do not support the involvement of the PTGDS gene in the etiology of schizophrenia., FEDER and Fundação para a Ciência e a Tecnologia (Portugal). Grant Number: POCTI/SAU‐ESP/58757/2004 and POCTI/35837/MGI/2000

Objectives: The present study was designed to evaluate the effect of twelve weekly sessions of the cognitive-behavioral program originally known as the Integriertes Psychologisches Therapieprogramm für Schizophrene Patienten, designated the Integrated Psychological Therapy (IPT) program in English, on cognition, social adjustment and quality of life in schizophrenic outpatients, comparing it to the effect of treating such patients as usual. Method: Fifty-six adult outpatients (from 18 to 65 years of age) with ICD-10-based diagnoses of schizophrenia were randomly assigned to two different groups: active intervention (IPT group); and treatment as usual (control group). Outcome measures were quality of life (as determined using the WHOQOL-Bref), cognition (Mini- Mental State Examination and Word Recall Test), global functioning (DSM-IV Global Assessment of Functioning Scale),social functioning (Social and Occupational Functioning Assessment Scale)and social adjustment (Social Adjustment Scale). Results: The findings suggest that, in comparison with treatment as usual (control group), the twelve-session IPT program had a positive effect on several outcome measures: cognition in the domains of spatiotemporal orientation (p = 0.051) and memory (p = 0.031); overall social adjustment (p = 0.037),leisure/social life (p = 0.051) and family relations (p = 0.008); overall functioning (p = 0.000); social-occupational functioning (p = 0.000); and quality of life in the psychological domain(p = 0.021). Conclusion: The twelve- session cognitive-behavioral IPT intervention demonstrated superiority over treatment as usual in its effects on cognition, social adjustment and quality of life. Studies involving larger samples, longer follow-up periods and additional outcome measures are needed in order to assess the specific effects on dimensions of social functioning, cognitive functioning and quality of life in patients with schizophrenia. Objetivos: O presente estudo foi designado para avaliar o efeito de 12 sessões semanais do programa cognitivo-comportamental IPT (Integrated Psychological Therapy – Integriertes psychologisches Therapieprogramm für schizophrene Patienten – Terapia Psicológica Integrada), comparado ao tratamento usual sobre o funcionamento cognitivo, ajustamento social e qualidade de vida em pacientes ambulatoriais com esquizofrenia.Método: Cinqüenta e seis pacientes ambulatoriais adultos(idade entre 18 e 65 anos)com diagnóstico de esquizofrenia pela CID-10, foram aleatoriamente designados para dois grupos: intervenção ativa (IPT) e tratamento usual(grupo controle). As diferenças de medidas de resultados foram em qualidade de vida (WHOQOL-bref), cognição (Mini-Mental State Examination e word-span),funcionamento global (Global Assessment of Functioning-DMS-IV), funcionamento social (Social and Occupational Functioning Assessment Scale-DSM-IV) e ajustamento social(Social Adjustment Scale). Resultados: Os achados sugerem que 12 sessões do programa IPT mostraram um efeito positivo sobre várias medidas de resultado comparado ao grupo controle(tratamento usual): cognição nos domínios de orientação no tempo e no espaço (p = 0,045) e memória (p = 0,031); ajustamento social geral(p=0,037), lazer e vida social (p = 0,051), relações familiares(p=0,008); funcionamento global (p = 0,000); funcionamento sócio-ocupacional (p = 0,000); e qualidade de vida no domínio psicológico (p = 0,021). Conclusão: A intervenção cognitivo-comportamental de 12 sessões do IPT demonstrou superioridade de efeito sobre cognição,ajustamento social e qualidade de vida comparado ao tratamento usual. Estudos com amostras maiores, maior tempo de seguimento (follow-up) e medidas adicionais de desfechos são necessários para avaliar efeitos específicos sobre dimensões de funcionamento cognitivo, social e qualidade de vida em esquizofrênicos.

There is evidence that major psychiatric discords such as schizophrenia (SZ) and bipolar disorder (BD) are associated with dysregulation of synaptic plasticity with downstream alterations of neurotrophins. Brain-derived neurotrophic factor (BDNF) is the most widely distributed neurotrophin in the central nervous system (CNS), and performs many biological functions such as promoting the survival, differentiation, and plasticity of neurons. Variants in the BDNF gene increase the risk of SZ and bipolar disorder. Chronic administration of drugs used to treat SZ and BD, such as lithium, valproate, quetiapine, clozapine, and olanzapine, increases BDNF expression in rat brain. To examine serum BDNF, three groups of chronically medicated DSM-IV SZ patients, on treatment with clozapine (n=27), typical (n=14), and other atypical antipsychotics (n=19), 30 euthymic BD patients, and 26 healthy control had 5 ml blood samples collected by venipuncture. Serum BDNF levels were significantly higher in SZ patients (p

O presente artigo tem como objetivo sintetizar estudos sobre os testes neuropsicológicos que estão sendo mais utilizados em esquizofrenia. Foi realizada uma revisão sistemática da literatura, consultando-se: PubMed, MEDLINE (via PubMed) e LILACS, no período entre 1995 e 2006. As palavras-chave foram: cognition and schizophrenia; evaluation and cognition and schizophrenia; functioning and cognition and schizophrenia. Foi feita uma pesquisa manual de referências dos artigos mais citados, incluindo estudos de metanálise, revisão teórica e da Measurement and Treatment Research to Improve Cognition in Schizophrenia. Critérios de inclusão: estudos com pacientes com esquizofrenia que mencionaram a utilização de testes neuropsicológicos. Foi feita uma revisão sobre os testes mais citados, para verificação de nomenclatura, indicações e quais estavam validados para o Brasil. Foram identificados 98 estudos: 77 empíricos, oito metanálises, seis revisões teóricas e sete da Measurement and Treatment Research to Improve Cognition in Schizophrenia. Foram encontrados 102 diferentes nomes de testes neuropsicológicos, com citação de 10 baterias de testes, na maioria compostas por subtestes já padronizados. Entre os 77 estudos empíricos, 22 (28,57%) foram sobre validação de instrumentos ou baterias de testes. Entre os 10 testes mais citados, apenas três possuem validação para o Brasil (WCST; Wechsler Adult Intelligence Scale; Mini-Mental Status Examination). Esses achados evidenciam uma ampla heterogeneidade nos critérios de seleção dos testes neuropsicológicos, divergências na nomenclatura e certa tendência para a criação de novos testes e baterias para avaliação de funções cognitivas. A relevância e características dos prejuízos cognitivos na esquizofrenia revelam a urgente necessidade de identificação específica e padronizada de métodos de avaliação neuropsicológica para pacientes brasileiros. This article aims at summarizing studies on the most commonly used neuropsychological tests in schizophrenia. A systematic literature review was performed on PubMed, MEDLINE (via PubMed) and LILACS, from 1995 through 2006. The keywords were cognition and schizophrenia; evaluation and cognition and schizophrenia; functioning and cognition and schizophrenia. A manual research of references in most frequently cited articles was performed, including meta-analysis studies, theoretical reviews, and the Measurement and Treatment Research to Improve Cognition in Schizophrenia. Inclusion criteria were studies on schizophrenia patients that reported use of neuropsychological tests. A review of the most frequently cited tests was performed to check nomenclature, indications, and which were validated for Brazil. A total of 98 studies were identified: 77 empirical studies, eight meta-analyses, six theoretical reviews and seven from the Measurement and Treatment Research to Improve Cognition in Schizophrenia. There were 102 different names of neuropsychological tests; 10 batteries of tests were cited, most of them composed by previously standardized subtests. Of the 77 empirical studies, 22 (28.57%) were about validation of instruments or batteries of tests. Of the 10 most frequently cited tests, only three had been validated for Brazil (WCST; Wechsler Adult Intelligence Scale; Mini-Mental Status Examination). These findings show a wide heterogeneity in the selection criteria of neuropsychological tests, disagreement as to the nomenclature, and a certain trend toward creation of new tests and batteries for evaluating cognitive functions. The relevance and characteristics of cognitive impairments in schizophrenia confirm the urgent necessity of specific and standardized identification of neuropsychological evaluation methods for Brazilian patients.

It has been proposed that schizophrenia results from an environmental insult in genetically predisposed individuals. Environmental factors capable of modulating transcriptional activity and their carriers could link the genetic and environmental components of schizophrenia. Among these is transthyretin (TTR), a major carrier of thyroid hormones and retinol-binding protein (RBP). Retinoids and thyroid hormones regulate the expression of several genes, both during development and in the adult brain. Decreased TTR levels have been reported in the cerebrospinal fluid of patients with depression and Alzheimer's disease, and the absence of TTR influences behavior in mice. DNA variants capable of altering TTR ability to carry its ligands, either due to reduced transcription of the gene or to structural modifications of the protein, may influence development of the central nervous system and behavior. In the present study we searched for variants in the regulatory and coding regions of the TTR gene, and measured circulating levels of TTR and RBP. We found a novel single nucleotide polymorphism (SNP), ss46566417, 18 bp upstream of exon 4. Neither this SNP nor the previously described rs1800458 were found associated with schizophrenia. In addition, serum TTR and RBP levels did not differ between mentally healthy and schizophrenic individuals. In conclusion, our data does not support an involvement of the TTR gene in the pathophysiology of schizophrenia., This work was supported by Grant POCTI/35837/MGI/2000 from Fundação para a Ciência e a Tecnologia/FEDER. Dina Ruano is a recipient of a fellowship (SFRH/BD/8659/2002) from Fundação para a Ciência e a Tecnologia (FCT), Portugal.

OBJECTIVE: First and second generation antipsychotics are associated with metabolic disturbances. A cross-sectional study was designed to follow outpatients at the Schizophrenia and Dementia Program at a major teaching hospital in Porto Alegre, Brazil (Hospital de Clinicas de Porto Alegre) in order to verify whether second generation antipsychotics were associated with higher glucose and lipid levels regardless of age and gender. METHOD: Four metabolic parameters (cholesterol and fractions, glucose and triglycerides) and anthropometric measures were obtained from 124 consecutive adult outpatients diagnosed with schizophrenia by DSM-IV and ICD-10 with the Operational Criteria Checklist for Psychotic Disorders system using the same antipsychotic drug for at least 9 weeks. RESULTS: Most patients had elevated BMI (76.6%) and dyslipidemia (84.7%). Clozapine users had lower HDL levels compared to first generation antipsychotics users. Both groups had elevated body mass index (p = 0.033; OR = 3.3; 95%CI = 1.1-9.8) and second generation antipsychotics (p = 0.021; OR = 3.5; 95%CI = 1.1-11.2) showed significant effect, adjusted for age and gender in the logistic regression for dyslipidemia, and significant age effect for hyperglycemia (p = 0.030; OR = 1.1; 95%CI = 1.0-1.1). DISCUSSION: There was statistically significant association between the use of second generation antipsychotics and dyslipidemia. It raises the issue of increased vulnerability of second generation antipsychotics-treated patients, regardless of age, as well as the need for assertive treatment for overweight and dyslipidemia in schizophrenia in order to reduce the risk of diabetes and cardiovascular disease.

The present study investigates possible associations between the 5-HTT control region polymorphism (5-HTTLPR) with adult ADHD, including subtypes, severity, temperament profile and comorbidities. The polymorphic site was genotyped in 312 adult patients with ADHD and 236 controls, all of them Brazilians of European descent. The interviews followed the DSM-IV criteria, using the K-SADS-E for ADHD and oppositional defiant disorder, SCID-I and MINI for comorbidities and the TCI for temperament dimensions. The 5-HTTLPR polymorphism was not associated with ADHD. Carriers of the S allele presented slightly higher inattention and novelty seeking scores, and a higher frequency of drug dependence. These differences do not persist after correction for multiple comparisons. These results suggest that the 5-HTTLPR polymorphism does not have a direct role in the predisposition to adult ADHD. There is suggestive evidence for a small effect in some behavioral phenotypes related to ADHD.

To describe the construction and testing of a routine to assess psychiatric hospitalizations in the Brazilian Health System based on its database (DATASUS), and to assess characteristics and trends of these hospitalizations.Data were extracted from hospital admission authorizations in the state of Rio Grande do Sul, Southern Brazil, from 2000 to 2004. Data from 91,233 admissions were processed through a routine (syntaxes) using SPSS program and their reliability was tested. Hospitalization rates in general and psychiatric hospitals and main diagnoses were described, and trends were analyzed using polynomial regression models.Intra and inter-rater reliabilities were 100%. There was seen a trend of increasing hospitalization rates due to mood disorders and decreasing rates due to schizophrenia and organic disorders. Hospitalization rates due to substance use disorders remained stable. There was an increasing trend in the number of psychiatric hospitalizations in general hospitals with a 97.7% growth in the period studied.Routines proved to be reliable and feasible, suggesting the use of data from Hospital Information System database as a source of information for continuous evaluation of psychiatric hospitalizations in Brazilian Health System. Psychiatric hospitalization rates may have changed due to changes in the type of patients; diagnostic patterns, known as treatment-oriented diagnostic bias; and legislation.

Introdução: O uso de antipsicóticos tem sido fundamental no tratamento de portadores de esquizofrenia. Entretanto, tanto a clozapina quanto a maior parte dos antipsicóticos atípicos podem induzir um maior ganho de peso corporal e alterações metabólicas. Objetivo: Comparar a freqüência de sobrepeso e obesidade em pacientes esquizofrênicos expostos à clozapina com a dos expostos a demais antipsicóticos. Método: Foram estudados 121 pacientes esquizofrênicos, com idade de 18 anos ou mais, de ambos os sexos, atendidos no Ambulatório de Esquizofrenia e Demências do Hospital de Clínicas de Porto Alegre, encaminhados de forma consecutiva. Foram avaliadas medidas antropométricas de 53 pacientes em uso de clozapina e de 68 usando outros antipsicóticos, e todos preencheram os critérios diagnósticos de esquizofrenia do DSM-IV e CID-10. Resultados: Não houve diferença significativa na freqüência do IMC entre os esquizofrênicos em uso de clozapina, quando comparado com o dos que usam os demais antipsicóticos. As análises mostraram uma elevada prevalência de pacientes (72,7%) com excesso de peso (sobrepeso + obesidade). Discussão: Devido à maior freqüência de excesso de peso na população esquizofrênica, pode-se evidenciar na amostra um indicativo de maior risco para transtornos vasculares e metabólicos. A ausência de diferença significativa em relação ao uso de clozapina, comparada com os demais antipsicóticos, demonstra a necessidade da montagem de estudos prospectivos determinando a magnitude de ganho de peso e o aumento de risco relativo à exposição específica de cada antipsicótico. Background: The use of antipsychotics has been crucial in the treatment of schizophrenic patients. However, clozapine, as well as most atypical antipsychotics, may lead to higher weight gain and metabolic changes. Objective: To compare the frequency of overweight and obesity between schizophrenic patients exposed to clozapine to the prevalence of patients exposed to other antipsychotics. Method: This study assessed 121 schizophrenic outpatients aged 18 years or older, both genders, consecutively referred to an outpatient clinic for schizophrenia and dementia at Hospital de Clínicas de Porto Alegre, a public hospital in Porto Alegre, Brazil. Anthropometric measures of 53 patients taking clozapine and of 68 taking other antipsychotics were assessed. All patients met DSM-IV and ICD-10 diagnostic criteria for schizophrenia. Results: There was no significant difference in body mass index between schizophrenic patients taking clozapine and patients taking other antipsychotics. Analyses showed high frequency of overweight and obesity (72.7%). Discussion: Due to higher frequency of overweight in the schizophrenic population, it was possible to confirm a higher risk of vascular and metabolic disorders in the sample. Absence of a significant difference with regard to the use of clozapine, compared to other antipsychotics, provides evidence for the need of prospective studies in order to determine the magnitude of weight gain and risk increase related to specific exposure to each antipsychotic drug.

Objetivo: Antipsicóticos de primeira e de segunda geração estão implicados em alterações metabólicas. Foi elaborado este estudo transversal para verificar se os antipsicóticos de segunda geração estavam associados a maiores níveis de glicose e lipídeos, independente de idade e sexo, em pacientes atendidos no Programa de Esquizofrenia e Demência do Hospital de Clínicas de Porto Alegre. Método: Foram obtidos colesterol e frações, glicose e triglicerídeos séricos, e medidas antropométricas em 124 pacientes esquizofrênicos, encaminhados consecutivamente, diagnosticados pelo DSM-IV e CID-10 pelo sistema Operational Criteria Checklist for Psychotic Disorders, e em uso do mesmo antipsicótico por, no mínimo, nove semanas. Resultados: A maioria dos pacientes apresentou IMC elevado (76,6%) e dislipidemia (84,7%). Os usuários de clozapina apresentaram níveis de colesterol-HDL mais baixos que os de antipsicóticos de primeira geração. O índice de massa corporal elevado (p = 0,033; OR = 3,3; IC95% = 1,1-9,8) e antipsicóticos de segunda geração (p = 0,021; OR = 3,5; IC95% = 1,1-11,2) mostraram efeito significante, ajustado para idade e sexo, na regressão logística para dislipidemia, e efeito significativo de idade para hiperglicemia (p = 0,030; OR = 1,1; IC95% = 1,0-1,1). Discussão: Houve associação estatisticamente significante entre o uso de antipsicóticos de segunda geração e dislipidemia. Isto levanta a questão da vulnerabilidade aumentada dos usuários de antipsicóticos de segunda geração, independente de idade, e a necessidade do tratamento adequado de sobrepeso e dislipidemia em esquizofrenia para reduzir o risco de diabete e doenças cardiovasculares. Objective: First and second generation antipsychotics are associated with metabolic disturbances. A cross-sectional study was designed to follow outpatients at the Schizophrenia and Dementia Program at a major teaching hospital in Porto Alegre, Brazil (Hospital de Clínicas de Porto Alegre) in order to verify whether second generation antipsychotics were associated with higher glucose and lipid levels regardless of age and gender. Method: Four metabolic parameters (cholesterol and fractions, glucose and triglycerides) and anthropometric measures were obtained from 124 consecutive adult outpatients diagnosed with schizophrenia by DSM-IV and ICD-10 with the Operational Criteria Checklist for Psychotic Disorders system using the same antipsychotic drug for at least 9 weeks. Results: Most patients had elevated BMI (76.6%) and dyslipidemia (84.7%). Clozapine users had lower HDL levels compared to first generation antipsychotics users. Both groups had elevated body mass index (p = 0.033; OR = 3.3; 95%CI = 1.1-9.8) and second generation antipsychotics (p = 0.021; OR = 3.5; 95%CI = 1.1-11.2) showed significant effect, adjusted for age and gender in the logistic regression for dyslipidemia, and significant age effect for hyperglycemia (p = 0.030; OR = 1.1; 95%CI = 1.0-1.1). Discussion: There was statistically significant association between the use of second generation antipsychotics and dyslipidemia. It raises the issue of increased vulnerability of second generation antipsychotics-treated patients, regardless of age, as well as the need for assertive treatment for overweight and dyslipidemia in schizophrenia in order to reduce the risk of diabetes and cardiovascular disease.

There is strong evidence that oxygen free radicals may play an important role in the pathophysiology of schizophrenia. Impaired antioxidant defense and increased lipid peroxidation have been previously reported in drug-naive, first episode and chronically medicated schizophrenic patients using typical neuroleptics. We measured serum SOD and TBARS in two groups of chronic medicated DSM-IV schizophrenic patients, under haloperidol (n = 10) or clozapine (n = 7) and a group of healthy controls (n = 15). Serum SOD and TBARS were significantly higher (p = 0.001) in schizophrenic patients (7.1 +/- 3.0 and 3.8 +/- 0.8) than in controls (4.0 +/- 1.6 and 2.5 +/- 0.7). Among patients, serum TBARS was significantly higher (p = 0.008) in those under clozapine (4.4 +/- 0.7) than in those under haloperidol treatment (3.4 +/- 0.7). For SOD levels the difference between groups was not found. It is reasonable to argue that the difference found in TBARS levels might be due to the course of the disease, instead of medication. Further investigation on the role of oxidative tonus and lipid peroxidation in different schizophrenia subtypes and different outcome patterns in this disorder is warranted. Additionally it could also address questions concerning a possible oxidant/antioxidant imbalance in schizophrenia.

The diagnosis of attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) in adults lacks adequate assessment instruments. The aim of this investigation is to evaluate the interrater reliability of the sections of K-SADS-E adapted for the diagnosis of these disorders among adults. The adaptations were limited to asking questions directly to the patient, investigation of a later onset of symptoms, and asking for adult specific symptoms. Six trained raters scored 16 recorded interviews. Kappa coefficients were 1.00 for ADHD diagnosis in the past, 0.91 for subtype in the past, 1.00 for ADHD diagnosis in the present, 0.95 for subtype in the present, 1.00 and 0.89 for ODD diagnosis in the past and present, respectively (all with p0.001). These results reveal excellent agreement for the ADHD and ODD diagnosis in adults using the adapted form of the Portuguese version of K-SADS-E.

In the p50 suppression paradigm, when two auditory stimuli are presented 500 ms apart, the amplitude of the second response (S2), compared with the first (S1), is markedly attenuated in healthy subjects. This is an index of sensory gating. Most schizophrenic patients fail to inhibit the p50 response to the second stimulus, which is assumed to reflect an inhibitory deficit. Adenosine is a neuromodulator with mostly inhibitory activity which is released by physiological stimuli. Since this inhibitory pattern resembles the phenomenon of sensory gating, the contribution of adenosine to p50 suppression was investigated in normal volunteers after treatment with the adenosine antagonist theophylline or placebo. P50 recordings were conducted in thirteen healthy subjects at baseline and 5, 30, 60, and 90 min after oral administration of theophylline (0.66 mg/kg, maximum dose of 500 mg) or placebo in a cross-over design. Baseline results from 17 drug-treated schizophrenic patients were included for comparison. Compared with placebo, theophylline treatment significantly increased P50 ratio (S2/S1) from 0.28 +/- 0.03 to 0.82 +/- 0.11 at 30 min and 0.61 +/- 0.07 at 60 min (mean +/- SEM), which were not significantly different from the schizophrenia group (0.74 +/- 0.05). The increased p50 ratio by theophylline was due to a combined decrease in S1 and increase in S2 amplitude. The impairment of p50 suppression by theophylline in normal subjects suggests a modulatory role of adenosine in sensory gating, which may be related to p50 suppression deficit in schizophrenia and is in agreement with a hypoadenosinergic model of schizophrenia.

Adenosine has been proposed to contribute to the pathophysiology of schizoprenia and as a target for therapeutic intervention. In the lack of direct adenosine agonists, allopurinol may indirectly elevate adenosine levels by inhibiting degradation of purines. We report two cases of poorly responsive schizophrenic patients who improved considerably with add-on allopurinol 300 mg/day. Their clear clinical improvement warrant further investigation of allopurinol, as well as other purinergic strategies, for the treatment of schizophrenia.

Schizophrenia is a complex genetic disorder. The lack of concordance on disease manifestation in monozygotic twins provides clear evidence that environmental factors are key determinants in disease aetiology. In accordance, various environmental modulators such as hormones and vitamins may well contribute to the altered expression pattern of several genes identified in post-mortem brain tissue of patients. We constructed a microarray platform containing 1,808 human genes, where 142 belong to vitamin A, thyroid hormone and estrogens’ metabolic pathways, to specifically address whether these could contribute to a molecular signature of schizophrenia in peripheral lymphocytes. We found that the genes encoding for PLP1, UGT1A6, NTRK1, THRAP1, ESR2, TRIP13, MAPK8, TGFB2, IGFBP4 are differentially expressed in lymphocytes of patients under treatment with clozapine, risperdal or haloperidol. Some of these genes have been previously reported by others to be altered in brain regions of schizophrenic patients, and all are implicated in pathways suggested to be involved in the disease. These observations further support that:1.studies in peripheral blood lymphocytes may contribute to reveal candidate genes in schizophrenia;2.transcription modulation of several genes may occur through the mediation of vitamin and hormones, therefore linking genes and environment in schizophrenia.In order to understand the involvement of these genes in schizophrenia, future studies should investigate whether some of the observed changes are replicated in animal models of the disease, and how antipsychotic treatment interferes with their expression.

a b s t r a c t Introduction: Growing evidence suggests that oxidative stress (OS) may be associated with the pathophys- iology underlying schizophrenia (SZ). Some studies indicate that nutritional supplements offer protection from OS, but there is no data about the effect of a hypocaloric diet on OS in this population. Therefore, we aimed to study the effect of a hypocaloric dietary intervention on OS in subjects with SZ. Methods: A cross-sectional study of 96 participants in outpatient treatment for SZ comprised patients separated into two groups: one group of subjects followed a hypocaloric diet (HD) program (n = 42), while the other group followed a regular diet (RD) with no nutritional restrictions (n = 54). The serum total radical-trapping antioxidant parameter (TRAP), total antioxidant reactivity (TAR) and thiobarbituric acid reactive species (TBARS) levels were assessed. Results: TRAP levels were lower and TBARS levels were higher in the HD group than in the RD group (p = 0.022 and p = 0.023, respectively). There were no differences in TAR levels between the groups. Addi- tionally, there was a positive correlation between TRAP and TBARS levels after adjusting for BMI and clozapine dose (partial correlation = 0.42, p < 0.001). There were no correlations among the length of illness or diet and the levels of TRAP, TBARS, and TAR. Conclusions: Subjects with SZ on a hypocaloric diet displayed different OS parameters than those not following a HD. Serum TRAP levels were lower and TBARS levels were higher among SZ subjects with HD compared to SZ subjects without HD. Lower TRAP levels may reflect decreased oxidative stress, whereas higher TBARS levels most likely reflect a biochemical reaction to the decreased TRAP levels. Additionally, TAR levels were similar between groups, suggesting a similar quality of antioxidant defenses, despite quantitative differences between the two dietary protocols in SZ patients under outpatient care. © 2012 Elsevier Ireland Ltd. All rights reserved.

Skin biopsies were collected from three male patients (age 45, 44 and 44) with clinically diagnosed schizophrenia. The patients were diagnosed according to DSM-5 criteria by a trained psychiatrist. Dermal fibroblast cell lines were established and expanded for subsequent reprogramming procedures. Induced pluripotent stem (iPS) cells were derived using the integration-free CytoTune®-iPS 2.0 Sendai Reprogramming Kit, containing Sendai virus particles of the four Yamanaka factors Oct3/4, Sox2, Klf4 and c-Myc.

Today, more than ever, aggressiveness is an issue of concern due to its widespread manifestations within several levels of society. Its origins, its future, and the individual’s relationship to and use of it have been extensively discussed elsewhere [1, 2]. It is known to be part of our daily life and when appropriately oriented to external reality, it can help an individual be more fulfilled and satisfied in this world.

Objective Since DSM-IV criteria for attention-deficit/hyperactivity disorder (ADHD) require that some symptoms causing impairment must be present before 7 years of age, clinicians are faced with a diagnostic and treatment dilemma on how to proceed with late-onset ADHD patients. We aimed to compare the response to methylphenidate between a group of patients fulfilling all DSM-IV ADHD criteria (full ADHD diagnosis) and a group of patients fulfilling all DSM-IV criteria except the age-at-onset criterion (late-onset ADHD). Method We evaluated 180 children and adolescents (4-17 years old) and 111 adults from our ADHD unit. All ADHD diagnoses were assessed using DSM-IV criteria. Methylphenidate was administered twice daily (8 a.m. and noon), but an extra dose was allowed between 5 and 6 p.m. for children and adolescents needing extra coverage in the evening. The minimum dose was 0.30 mg/kg/day. Response to treatment was assessed in methylphenidatenaive subjects using the Swanson, Nolan, and Pelham Scale-version IV (SNAP-IV) at baseline and after 1 month of treatment. Data were collected from January 2000 to January 2006. Results In both samples, subjects with the full ADHD diagnosis did not have a better response to methylphenidate at doses around 0.5 mg/kg/day than the late-onset ADHD subjects. In fact, adults with late-onset ADHD had a better response to methylphenidate than adults with the full diagnosis, even after adjustment for confounders (baseline SNAP-IV total score and ADHD types) (children and adolescents: F = 0.865, p = .354; adults: F = 5.760, p = .018). Conclusion These results concur with recent literature questioning the validity of the DSM-IV age-at-onset criterion for the diagnosis of ADHD and suggest that clinicians should consider implementing methylphenidate treatment for subjects with late-onset ADHD.