Bipolar disorder: an association between body mass index and cingulate gyrus fractional anisotropy not mediated by systemic inflammation

Abstract Objective To investigate associations between body mass index (BMI), white matter fractional anisotropy (FA), and C-reactive protein (CRP) in a group of individuals with bipolar disorder (BD) during euthymia and compare them with a control group of healthy subjects (CTR). Methods The sample consisted of 101 individuals (BD n = 35 and CTR n = 66). Regions of interest (ROI) were defined using a machine learning approach. For each ROI, a regression model tested the association between FA and BMI, controlling for covariates. Peripheral CRP levels were assayed, correlated with BMI, and included in a mediation analysis. Results BMI predicted the FA of the right cingulate gyrus in BD (AdjR2 = 0.312 F(3) = 5.537 p = 0.004; β = -0.340 p = 0.034), while there was no association in CTR. There was an interaction effect between BMI and BD diagnosis (F(5) = 3.5857 p = 0.012; Fchange = 0.227 AdjR2 = 0.093; β = -1.093, p = 0.048). Furthermore, there was a positive correlation between BMI and CRP in both groups (AdjR2 = 0.170 F(3) = 7.337 p < 0.001; β = 0.364 p = 0.001), but it did not act as a mediator of the effect on FA. Conclusion Higher BMI is associated with right cingulate microstructure in BD, but not in CTR, and this effect could not be explained by inflammatory mediation alone.

Clozapine use decreases the number of hospitalizations per year in patients with treatment-resistant schizophrenia

For years, the management of schizophrenia has represented a challenge for clinicians, with antipsychotic treatments usually resulting in relapses and new hospitalizations. Clozapine has been shown to be an effective medication for treatment-resistant schizophrenia (TRS), but is currently underused due to its potential side effects. Nevertheless, research has suggested that clozapine reduces future hospitalizations in patients with TRS. This study aims to verify the rates of hospitalizations in patients with TRS under long-term use of clozapine. We retrospectively analyzed clinical data from 52 individuals with TRS before and after the use of clozapine. The mean duration of treatment with and without clozapine was 6.6 (± 3.9) and 8.5 years (± 6.6), respectively. Patients had a median of 0.5 (0.74) hospitalizations per year before the use of clozapine and 0 (0.74) hospitalizations after it (p = 0.001). Therefore, the use of clozapine resulted in an expected reduction in the number of hospitalizations per year in individuals with TRS. (AU)

Perda significativa de peso em pacientes com esquizofrenia na dieta hipocalórica de longo prazo: estudo piloto / Significant weight loss in patients with schizophrenia in long-term hypocaloric diet: a pilot study

Objetivo: A esquizofrenia está associada ao aumento da obesidade e morbidade por doença cardiovascular. O objetivo do presente estudo foi avaliar alterações no peso e índice de massa corporal (IMC) de pacientes com esquizofrenia após tratamento nutricional de longo prazo. Método: Estudo piloto retrospectivo envolvendo 42 indivíduos com esquizofrenia em tratamento nutricional entre 2004 e 2010. Os prontuários médicos foram revisados após aprovação institucional e coleta de dados para peso, índice de massa corporal (IMC), idade, gênero e dieta. O peso e o IMC foram avaliados no início do tratamento nutricional, após seis meses, após 12 meses e no momento da coleta de dados. Resultados: Houve perda significativa de peso e diminuição significativa do IMC quando comparados a cada grupo com o valor basal (p<0,001). Conclusões: Demonstramos que as intervenções nutricionais podem promover uma significativa perda de peso na esquizofrenia. Estes resultados suportam a importância da intervenção nutricional na esquizofrenia e trazem evidências de que a perda de peso permanece ao longo do tempo.(AU)

Objective: Schizophrenia is associated with increased obesity and morbidity from cardiovascular disease. The aim of the present study was to evaluate changes in weight and body mass index (BMI) of patients with schizophrenia following a long-term nutritional treatment. Methods: Retrospective pilot study involving 42 individuals with schizophrenia on nutritional treatment from 2004 to 2010. Medical charts were reviewed after institutional approval and data collection was conducted for weight, body mass index (BMI), age, gender and diet prescription. Weight and BMI were evaluated at baseline of nutrition treatment, after six months, after 12 months and at the time of data collection. Results: There was a significant weight loss and significant decreased in BMI when compared each group to baseline (p<0.001). Conclusions: We demonstrate that nutritional interventions can promote a significant weight loss in schizophrenia. These results support the importance of nutritional intervention in schizophrenia and bring evidences that weight loss remains along the time.(AU)

Pinocembrin Provides Mitochondrial Protection by the Activation of the Erk1/2-Nrf2 Signaling Pathway in SH-SY5Y Neuroblastoma Cells Exposed to Paraquat.

Pinocembrin (PB; 5,7-dihydroxyflavanone; C15H12O4) is a flavonoid found in propolis and exerts antioxidant, anti-inflammatory, and antimicrobial effects. Furthermore, PB has been studied as a neuroprotective agent. However, it remains to be understood whether and how PB would induce mitochondrial protection in mammalian cells. Therefore, we investigated here the mechanism involved in the protective effects elicited by PB in paraquat (PQ; 100 µM)-treated SH-SY5Y neuroblastoma cells. PB (25 µM) pretreatment (for 4 h) downregulated the levels of Bcl-2-associated X protein (Bax), blocked the release of cytochrome c to the cytosol, and inhibited the PQ-induced activation of caspase-9 and caspase-3. Besides, PB prevented mitochondrial dysfunction by suppressing the PQ-elicited inhibition of complexes I and V. Moreover, PB abrogated the loss of mitochondrial membrane potential (MMP) and the decline in ATP levels in the cells exposed to PQ. PB exerted antioxidant effects on mitochondria by decreasing the levels of redox impairment markers in mitochondrial membranes. Importantly, PB enhanced the levels of mitochondrial reduced glutathione (GSH). Upregulation of enzymes involved in the synthesis of GSH was seen in the cells exposed to PB. PB afforded mitochondrial protection by activating the extracellular signal-regulated kinase/nuclear factor erythroid 2-related factor 2 (Erk1/2-Nrf2) axis, since inhibition of Erk1/2 or silencing of Nrf2 abrogated these effects. Therefore, PB exerted mitochondrial and cellular protection by an Erk1/2-Nrf2-dependent mechanism.

Alpha-lipoic acid alone and combined with clozapine reverses schizophrenia-like symptoms induced by ketamine in mice: Participation of antioxidant, nitrergic and neurotrophic mechanisms.

Oxidative stress has important implications in schizophrenia. Alpha-lipoic acid (ALA) is a natural antioxidant synthesized in human tissues with clinical uses. We studied the effect of ALA or clozapine (CLZ) alone or in combination in the reversal of schizophrenia-like alterations induced by ketamine (KET). Adult male mice received saline or KET for 14 days. From 8th to 14th days mice were additionally administered saline, ALA (100 mg/kg), CLZ 2.5 or 5 mg/kg or the combinations ALA+CLZ2.5 or ALA+CLZ5. Schizophrenia-like symptoms were evaluated by prepulse inhibition of the startle (PPI) and locomotor activity (positive-like), social preference (negative-like) and Y maze (cognitive-like). Oxidative alterations (reduced glutathione - GSH and lipid peroxidation - LP) and nitrite in the prefrontal cortex (PFC), hippocampus (HC) and striatum (ST) and BDNF in the PFC were also determined. KET caused deficits in PPI, working memory, social interaction and hyperlocomotion. Decreased levels of GSH, nitrite (HC) and BDNF and increased LP were also observed in KET-treated mice. ALA and CLZ alone reversed KET-induced behavioral alterations. These drugs also reversed the decreases in GSH (HC) and BDNF and increase in LP (PFC, HC and ST). The combination ALA+CLZ2.5 reversed behavioral and some neurochemical parameters. However, ALA+CLZ5 caused motor impairment. Therefore, ALA presented an antipsychotic-like profile reversing KET-induced positive- and negative-like symptoms. The mechanism partially involves antioxidant, neurotrophic and nitrergic pathways. The combination of ALA+CLZ2.5 improved most of the parameters evaluated in this study without causing motor impairment demonstrating, thus, that possibly when combined with ALA a lower dose of CLZ is required.

Staging and neuroprogression in bipolar disorder: a systematic review of the literature

INTRODUCTION: The use of clinical staging models is emerging as a novel and useful paradigm for diagnosing severe mental disorders. The term "neuroprogression" has been used to define the pathological reorganization of the central nervous system along the course of severe mental disorders. In bipolar disorder (BD), neural substrate reactivity is changed by repeated mood episodes, promoting a brain rewiring that leads to an increased vulnerability to life stress. METHOD: A search in the PubMed database was performed with the following terms: "staging", "neuroprogression", "serum", "plasma", "blood", "neuroimaging", "PET scan", "fMRI", "neurotrophins", "inflammatory markers" and "oxidative stress markers", which were individually crossed with "cognition", "functionality", "response to treatments" and "bipolar disorder". The inclusion criteria comprised original papers in the English language. Abstracts from scientific meetings were not included. RESULTS: We divided the results according to the available evidence of serum biomarkers as potential mediators of neuroprogression, with brain imaging, cognition, functioning and response to treatments considered as consequences. CONCLUSION: The challenge in BD treatment is translating the knowledge of neuronal plasticity and neurobiology into clinical practice. Neuroprogression and staging can have important clinical implications, given that early and late stages of the disorder appear to present different biological features and therefore may require different treatment strategies.

Reduced serum non-enzymatic antioxidant defense and increased lipid peroxidation in schizophrenic patients on a hypocaloric diet.

INTRODUCTION: Growing evidence suggests that oxidative stress (OS) may be associated with the pathophysiology 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. Additionally, 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.

Serum levels of IL-6, IL-10 and TNF-α in patients with bipolar disorder and schizophrenia: differences in pro- and anti-inflammatory balance.

OBJECTIVE: Previous reports suggest that cytokines act as potential mediators of the interaction between the immune and neuroendocrine systems, and that a proinflammatory state may be associated with bipolar disorder and schizophrenia. The aim is to compare cytokine levels in both disorders. METHOD: Twenty euthymic bipolar disorder patients, 53 chronic stabilized schizophrenia patients and 80 healthy controls were recruited. Subjects were all non-smokers and non-obese. Cytokines TNF-α, IL-6, and IL-10 were examined by sandwich ELISA. RESULTS: IL-6 levels were increased in schizophrenia patients when compared to controls (p < 0.0001) and euthymic bipolar disorder patients (p < 0.0001). IL-6 levels were no different in controls compared to euthymic bipolar disorder patients (p = 0.357). IL-10 was lower in controls compared to schizophrenia patients (p = 0.001) or to bipolar disorder patients (p = 0.004). There was no significant difference in TNF-α serum levels among the groups (p = 0.284). Gender-based classification did not significantly alter these findings, and no correlation was found between the antipsychotic dose administered and cytokine levels in patients with schizophrenia. DISCUSSION: These findings evidence a chronic immune activation in schizophrenia. Bipolar disorder seems to present an episode-related inflammatory syndrome. Increased anti-inflammatory factor IL-10 in bipolar disorder and schizophrenia suggests different patterns of inflammatory balance between these two disorders. Results further support the need to investigate cytokines as possible biomarkers of disease activity or treatment response.

Serum levels of IL-6, IL-10 and TNF-α in patients with bipolar disorder and schizophrenia: differences in pro- and anti-inflammatory balance / Níveis séricos de IL-6, IL-10 e TNF-α em pacientes com transtorno bipolar e esquizofrenia: diferenças no equilíbrio pró e antiinflamatório

OBJECTIVE: Previous reports suggest that cytokines act as potential mediators of the interaction between the immune and neuroendocrine systems, and that a proinflammatory state may be associated with bipolar disorder and schizophrenia. The aim is to compare cytokine levels in both disorders. METHOD: Twenty euthymic bipolar disorder patients, 53 chronic stabilized schizophrenia patients and 80 healthy controls were recruited. Subjects were all non-smokers and non-obese. Cytokines TNF-α, IL-6, and IL-10 were examined by sandwich ELISA. RESULTS: IL-6 levels were increased in schizophrenia patients when compared to controls (p < 0.0001) and euthymic bipolar disorder patients (p < 0.0001). IL-6 levels were no different in controls compared to euthymic bipolar disorder patients (p = 0.357). IL-10 was lower in controls compared to schizophrenia patients (p = 0.001) or to bipolar disorder patients (p = 0.004). There was no significant difference in TNF-α serum levels among the groups (p = 0.284). Gender-based classification did not significantly alter these findings, and no correlation was found between the antipsychotic dose administered and cytokine levels in patients with schizophrenia. DISCUSSION: These findings evidence a chronic immune activation in schizophrenia. Bipolar disorder seems to present an episode-related inflammatory syndrome. Increased anti-inflammatory factor IL-10 in bipolar disorder and schizophrenia suggests different patterns of inflammatory balance between these two disorders. Results further support the need to investigate cytokines as possible biomarkers of disease activity or treatment response.

OBJETIVO: Pesquisas sugerem as citocinas como potenciais mediadores da interação entre os sistemas imune e neuroendócrino, e que existe um estado pró-inflamatório associado com transtorno bipolar e esquizofrenia. O objetivo deste estudo é comparar os níveis de citocinas entre os dois distúrbios. MÉTODO: Vinte pacientes com transtorno bipolar eutímicos, 53 pacientes com esquizofrenia crônica estabilizados e 80 controles saudáveis foram recrutados. Todos os indivíduos eram não-fumantes e não-obesos. As citocinas TNF-α, IL-6 e IL-10 foram examinadas por ELISA sanduíche. RESULTADOS: A IL-6 estava aumentada nos pacientes com esquizofrenia quando comparados aos controles (p < 0,0001) e aos pacientes bipolares eutímicos (p < 0,0001). Os níveis de IL-6 não foram diferentes nos controles em comparação com pacientes com transtorno bipolar eutímicos (p = 0,357). Os níveis de IL-10 foram menores nos controles quando comparados aos pacientes com esquizofrenia (p = 0,001) ou aos bipolares (p = 0,004). Não houve diferença significativa nos níveis séricos de TNF-α entre os grupos (p = 0,284). A separação por sexo não mostrou diferenças significativas e não houve correlação entre a dose de antipsicóticos e os níveis de citocinas em pacientes com esquizofrenia. DISCUSSÃO: Estes resultados evidenciam uma ativação imune crônica na esquizofrenia. O transtorno bipolar parece apresentar um aumento da atividade inflamatória relacionado ao episódio de humor. Níveis maiores de IL-10 no transtorno bipolar e esquizofrenia sugerem diferentes padrões de equilíbrio inflamatório entre esses dois transtornos. Resultados fornecem apoio adicional para a investigação de citocinas como possíveis biomarcadores para a atividade da doença ou resposta ao tratamento.

Peripheral biomarkers and illness activity in bipolar disorder.

Recent evidence suggests that peripheral markers related to oxidative stress, inflammation and neurotrophins may be altered during mood episodes in bipolar disorder. These can be seen as proxies of peripheral toxicity or markers of illness activity. Here we report an en bloc assessment of a set of previously described biomarkers in different mood states (n = 60) as well as in healthy subjects (n = 80). To make the point that these are ominous changes, we obtained the same measures from a group of septic patients (n = 15) as a "positive" control group. In this sample, we measured serum levels of brain derived neurotrophic factor, neurotrophin 3, tumor necrosis factor α, interleukin 6, interleukin 10, total reactive antioxidant potential, thiobarbituric acid reactive substances and protein carbonyl content. Several of the markers discriminated between the bipolar and control groups, especially when patients were in acute episodes. In some cases, toxicity was as high in bipolar disorder as that seen in patients with sepsis. We believe these findings highlight the potential of using biomarkers to assess illness activity in bipolar disorder.

Estado nutricional de pacientes com esquizofrenia frequentadores do Centro de Atenção Psicossocial (CAPS) do Hospital de Clínicas de Porto Alegre / Nutritional status of patients with schizophrenia who attend the Psychosocial Care Center (CAPS), Hospital de Clínicas de Porto Alegre

OBJETIVO: Avaliar o estado nutricional de pacientes com esquizofrenia, atendidos por um programa de reabilitação social (CAPS). MÉTODOS: Foi realizado um estudo transversal com 40 pacientes com diagnóstico de esquizofrenia, em uso de antipsicóticos, atendidos no CAPS do Hospital de Clínicas de Porto Alegre. Foram verificados medidas antropométricas (peso, estatura, circunferência abdominal, percentual de gordura corporal), pressão arterial e tabagismo. RESULTADOS: A amostra constitui-se de 65 por cento de homens. A média de peso encontrada foi de 75,39 ± 15,73 kg. O índice de massa corporal médio apresentou-se dentro dos parâmetros de sobrepeso (26,76 ± 4,78 kg/m²), sendo 55 por cento dos pacientes com sobrepeso ou obesidade segundo a classificação da OMS/1998. A circunferência abdominal e o percentual de gordura corporal apresentaram-se elevados na maioria dos pacientes (62,5 por cento e 92,5 por cento, respectivamente). Adicionalmente, não houve associação significativa entre IMC e a classificação de antipsicóticos (típicos, atípicos, clozapina). Encontrou-se uma correlação entre o tempo de doença com o percentual de gordura (r = 0,39, p = 0,033) e escolaridade com o peso (r = 0,362, p = 0,046) e IMC (r = 0,372, p = 0,039). Na regressão linear, 13 por cento da variabilidade do percentual de gordura foi explicada pelo tempo de doença (r² = 0,131, B = 0,233, p = 0,049); 13 por cento da variação do peso foi explicada pela escolaridade (r² = 0,131, B = 1,415, p = 0,046) e 13,8 por cento da variação do IMC foi explicada pela escolaridade (r² = 0,138, B = 0,411, p = 0,039). CONCLUSÃO: Os pacientes apresentaram níveis aumentados de circunferência abdominal, percentual de gordura corporal e peso. Aparentemente, o ganho de peso ocorre em todos os pacientes expostos a antipsicóticos, independentemente do tipo de medicação e de resposta clínica, e a qualquer momento ao longo da evolução da doença. Sugere-se que, adicionalmente, a avaliação dos hábitos alimentare...

OBJECTIVE: To evaluate the nutritional status of patients with schizophrenia attended in a social rehabilitation program (CAPS). METHODS:Cross-sectional study with 40 patients diagnosed with schizophrenia, in antipsychotic use, attended in CAPS of the Hospital de Clínicas de Porto Alegre. Anthropometric measures were verified (weight, height, waist circumference, body fat percentage), blood pressure and cigarette smoking. RESULTS: The sample consisted of 65 percent of men. Mean of weight was 75,39 ± 15,73 kg and mean body mass index was within the parameters of overweight (26,76 ± 4,78 kg/m²), 55 percent of the patients with overweight or obesity according to the OMS/1998 criteria. Waist circumference and body fat percentage were high in most patients (62.5 percent and 92.5 percent, respectively). In addition, there was no significant association between BMI and antipsychotics drugs (typic and atypic, clozapine). We found a correlation between duration of disease with body fat percentage (r = 0.39, p = 0.033) and education correlated with weight (r = 0.362, p = 0.046) and BMI (r = 0.372, p = 0.039). In linear regression 13 percent of the variability in fat percentage was explained by disease duration (r² = 0.131, B = 0.233, p = 0.049), 13 percent of weight variation was explained by education (r² = 0.131, B = 1.415, p = 0.046) and 13.8 percent of the variation in BMI was explained by education level (r² = 0.138, B = 0.411, p = 0.039). CONCLUSION: Patients showed increased levels of waist circumference, body fat percentage and overweight. Apparently, the weight gain occurs in all patients exposed to antipsychotics, independent from type of drug and clinical response, and at any moment along illness evolution. It is suggested that in addition to food habits an nutritional assessment and follow-up, the clinician should take notes about early changes along the course of illness, changes of type and dose of drugs.

Serum levels of brain-derived neurotrophic factor and thiobarbituric acid reactive substances in chronically medicated schizophrenic patients: a positive correlation / Níveis séricos do fator neurotrófico derivado do cérebro e dos produtos de reação com o ácido tiobarbitúrico em pacientes com esquizofrenia cronicamente medicados: correlação positiva

OBJECTIVE: The neurotrophins, antioxidant enzymes and oxidative markers have reciprocal interactions. This report verified in chronically stable medicated schizophrenic patients whether there are correlations between the serum levels of superoxide dismutase, a key enzyme in the antioxidant defense, thiobarbituric acid reactive substances, a direct index of lipid peroxidation, and brain-derived neurotrophic factor, the most widely distributed neurotrophin. METHOD: Sixty DSM-IV schizophrenic patients were included (43 males, 17 females). Mean age was 34.7 ± 10.8 years, mean age at first episode was 19.8 ± 7.9 years, and mean illness duration was 14.9 ± 8.5 years. Each subject had a blood sample collected for the determination of serum levels of brain-derived neurotrophic factor, thiobarbituric acid reactive substances and superoxide dismutase. RESULTS: Brain-derived neurotrophic factor levels showed a positive correlation with thiobarbituric acid reactive substances levels (r = 0.333, p = 0.009). Brain-derived neurotrophic factor levels were not correlated with superoxide dismutase levels (r = - 0.181, p = 0.166), and superoxide dismutase levels were not correlated with thiobarbituric acid reactive substances levels (r = 0.141, p = 0.284). CONCLUSIONS: The positive correlation between brain-derived neurotrophic factor and thiobarbituric acid reactive substances suggests the need of further investigation on intracellular interactions of neurotrophins, antioxidant enzymes and oxidative markers. In addition, this opens a venue for investigation on treatments for the prevention of neurotoxicity along the course of schizophrenia.

OBJETIVO: As neurotrofinas, enzimas antioxidantes e marcadores de oxidação têm interações. Este estudo verificou se existem correlações entre os níveis séricos de superóxido-dismutase, uma enzima chave na defesa antioxidante, os produtos de reação com o ácido tiobarbitúrico, um indicador direto de peroxidação lipídica, e o fator neurotrófico derivado do cérebro, a neurotrofina mais amplamente distribuída. MÉTODO: Sessenta pacientes portadores de Esquizofrenia pelo DSM-IV foram incluídos (43 homens, 17 mulheres), com idade média de 34,7 ± 10,8 anos, idade média no primeiro episódio de 19,8 ± 7,9 anos, e tempo médio de duração da doença de 14,9 ± 8,5 anos. Foi coletado sangue de cada sujeito para a determinação dos níveis séricos de fator neurotrófico derivado do cérebro, superóxido-dismutase e ácido tiobarbitúrico. RESULTADOS: Os níveis de fator neurotrófico derivado do cérebro se correlacionaram positivamente aos de ácido tiobarbitúrico (r = 0,333, p = 0,009) e não mostraram correlação com os de superóxido-dismutase (r = - 0,181, p = 0,166). Este último também não se correlacionou aos níveis de ácido tiobarbitúrico (r = 0,141, p = 0,284). CONCLUSÕES: A correlação positiva entre fator neurotrófico derivado do cérebro e ácido tiobarbitúrico direciona para investigações na interação intracelular entre neurotrofinas, enzimas antioxidantes e marcadores de oxidação, além de abrir perspectives para pesquisa em tratamentos para a prevenção da neurotoxicidade ao longo do curso da esquizofrenia.

Increased dyslipidemia in schizophrenic outpatients using new generation antipsychotics

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 percent) and dyslipidemia (84.7 percent). 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 percentCI = 1.1-9.8) and second generation antipsychotics (p = 0.021; OR = 3.5; 95 percentCI = 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 percentCI = 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.

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 por cento) e dislipidemia (84,7 por cento). 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 por cento = 1,1-9,8) e antipsicóticos de segunda geração (p = 0,021; OR = 3,5; IC95 por cento = 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 por cento = 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.

O impacto dos agentes antipsicóticos na densidade mineral óssea de pacientes esquizofrênicos / Impact of antipsychotic agents in bone mineral density of schizophrenic patients

Estudos têm evidenciado o alto risco de osteoporose em pacientes esquizofrênicos. Alguns estudos têm demonstrado que os neurolépticos típicos e a risperidona podem induzir a osteoporose ou reduzir a densidade mineral óssea. Isso pode ser atribuído ao fato de estas drogas, em uso prolongado, induzirem a hiperprolactinemia a níveis acima do normal, em ambos os sexos, e a baixa dos níveis de estrogênio e de testosterona, aumentando o risco para osteopenia/osteoporose. Neste relato, será apresentado um caso de osteopenia em uma paciente mulher de 53 anos, em uso de antipsicóticos há 30 anos, sendo comentados os procedimentos recomendados para detecção dessa ocorrência e as diretrizes existentes para seu manejo.

Studies have shown a high risk of osteoporosis in schizophrenic patients. Some studies have demonstrated that typical neuroleptics and risperidone may induce osteoporosis or reduce bone mineral density. This can be due to the fact that prolonged use of those drugs induces hyperprolactinemia to levels above normal in both genders, and reduces the levels of estrogen and testosterone, thus increasing the risk of osteopenia/osteoporosis. We report on a case of osteopenia in a 53-year-old female patient using antipsychotics for 30 years. We comment on the recommended procedures to detect osteopenia and on the existing guidelines for its management.

Sobrepeso e obesidade em pacientes esquizofrênicos em uso de clozapina comparado com o uso de outros antipsicóticos / Overweight and obesity in schizophrenic patients taking clozapine compared to the use of other antipsychotics

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 por cento) 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 percent). 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.