Increased uric acid levels in drug-naïve subjects with bipolar disorder during a first manic episode.

Recent evidence suggests that purinergic system dysfunction may play a role in the pathophysiology and therapeutics of bipolar disorder (BPD). Uric acid is a key nitrogenous end product of purine metabolism. In addition to being a potential marker of treatment response, high levels of uric acid may represent a state marker during mania. In this study, we assessed the presence of purinergic dysfunction in 20 treatment-naïve first episode patients with BPD who were experiencing a manic episode. Patients were matched with 24 healthy controls. We found that acutely manic patients had significantly higher levels of plasma uric acid (4.85+/-1.60 mg/dL) compared to healthy controls (2.96+/-0.63 mg/dL, p<0.001; F=28.1). No association between uric acid levels with severity of manic symptoms was observed. These results support the role of purinergic system dysfunction in BPD early in the course of illness, and suggest that this phenomenon is not the result of chronicity or medication exposure. Overall, our findings suggest a novel mechanism in the pathophysiology of BPD.

Oxidative stress parameters in unmedicated and treated bipolar subjects during initial manic episode: a possible role for lithium antioxidant effects.

Studies have proposed the involvement of oxidative stress and neuronal energy dysfunctions in the pathophysiology of bipolar disorder (BD). This study evaluates plasma levels of the oxidative/energy metabolism markers, thiobarbituric acid reactive substances (TBARS), superoxide dismutase (SOD), catalase (CAT), and neuron-specific enolase (NSE) during initial episodes of mania compared to controls in 75 subjects. Two groups of manic subjects (unmedicated n=30, and lithium-treated n=15) were age/gender matched with healthy controls (n=30). TBARS and antioxidant enzymes activity (SOD and CAT) were increased in unmedicated manic patients compared to controls. Conversely, plasma NSE levels were lower during mania than in the controls. In contrast, acute treatment with lithium showed a significant reduction in both SOD/CAT ratio and TBARS levels. These results suggest that initial manic episodes are associated with both increased oxidative stress parameters and activated antioxidant defenses, which may be related to dysfunctions on energy metabolism and neuroplasticity pathways. Antioxidant effects using lithium in mania were shown, and further studies are necessary to evaluate the potential role of these effects in the pathophysiology and therapeutics of BD.

Polypharmacy and suicide attempts in bipolar disorder.

OBJECTIVE: The aim of this study was to assess the association between suicide attempts and the use of multiple drugs in patients with bipolar disorder. METHOD: One hundred sixty-nine bipolar disorder outpatients diagnosed using the DSM-IV Structured Clinical Interview were included. Demographic and socioeconomic data, number of medications currently in use, history of suicide attempts, number of years undiagnosed, age of onset and current psychiatric co-morbidities were assessed using a structured questionnaire and DSM-IV criteria. The main outcome measure was the number of psychotropic drugs currently in use. RESULTS: Approximately half of all patients (48.5%) presented a history of suicide attempt; 84% were using more than one medication, and 19% were using more than three drugs. The most frequent combinations of drugs used by these patients were: lithium + valproate (17%); lithium + antipsychotics (10%); lithium + valproate + antipsychotics (9%); and antidepressants + any drug (6%). The number of suicide attempts was associated with the use of multiple drugs. CONCLUSIONS: Our findings support the notion that the use of combination therapy in bipolar disorder may be related to severity of the BD, such as number of suicide attempts.

Polypharmacy and suicide attempts in bipolar disorder

OBJECTIVE: The aim of this study was to assess the association between suicide attempts and the use of multiple drugs in patients with bipolar disorder. METHOD: One hundred sixty-nine bipolar disorder outpatients diagnosed using the DSM-IV Structured Clinical Interview were included. Demographic and socioeconomic data, number of medications currently in use, history of suicide attempts, number of years undiagnosed, age of onset and current psychiatric co-morbidities were assessed using a structured questionnaire and DSM-IV criteria. The main outcome measure was the number of psychotropic drugs currently in use. RESULTS: Approximately half of all patients (48.5 percent) presented a history of suicide attempt; 84 percent were using more than one medication, and 19 percent were using more than three drugs. The most frequent combinations of drugs used by these patients were: lithium + valproate (17 percent); lithium + antipsychotics (10 percent); lithium + valproate + antipsychotics (9 percent); and antidepressants + any drug (6 percent). The number of suicide attempts was associated with the use of multiple drugs. CONCLUSIONS: Our findings support the notion that the use of combination therapy in bipolar disorder may be related to severity of the BD, such as number of suicide attempts.

OBJETIVO: O objetivo deste trabalho foi verificar associação entre tentativas de suicídio e uso de múltiplas drogas em pacientes com transtorno do humor bipolar. MÉTODO: Cento e sessenta e nove pacientes ambulatoriais com transtorno do humor bipolar, diagnosticados pela entrevista clínica estruturada do DSM-IV, foram incluídos. Dados demográficos e socioeconômicos, número de medicações em uso, história de tentativas de suicídio, número de anos sem diagnóstico, idade de início e comorbidades psiquiátricas foram avaliados através de um questionário estruturado e pelos critérios do DSM-IV. A principal medida de desfecho foi o número de medicamentos psicotrópicos usados correntemente. RESULTADOS: Cerca de metade dos pacientes (48,5 por cento) apresentou uma história de tentativas de suicídio; 84 por cento estavam usando mais do que uma medicação e 19 por cento estavam usando mais do que três medicações. As combinações de fármacos mais utilizadas por estes pacientes foram: lítio + valproato (17 por cento); lítio + antipsicóticos (10 por cento); lítio + valproato + antipsicóticos (9 por cento); e antidepressivos + outros fármacos (6 por cento). O número de tentativas de suicídio mostrou-se associado ao uso de polifarmácia, na análise ajustada. CONCLUSÕES: Nossos resultados sugerem que a polifarmácia em pacientes bipolares pode estar relacionada a indicadores de gravidade, como número de tentativas de suicídio.

Decreased plasma brain derived neurotrophic factor levels in unmedicated bipolar patients during manic episode.

BACKGROUND: Bipolar disorder (BD) has been increasingly associated with abnormalities in neuroplasticity and cellular resilience. Brain Derived Neurotrophic Factor (BDNF) gene has been considered an important candidate marker for the development of bipolar disorder and this neurotrophin seems involved in intracellular pathways modulated by mood stabilizers. Also, previous studies demonstrated a role for BDNF in the pathophysiology and clinical presentation of mood disorders. METHODS: We investigated whether BDNF levels are altered during mania. Sixty subjects (14 M and 46 F) were selected and included in the study. Thirty patients meeting SCID-I criteria for manic episode were age and gender matched with thirty healthy controls. Young Mania Rating Scale (YMRS) evaluated the severity of manic episode and its possible association with the neurotrophin levels. RESULTS: Mean BDNF levels were significantly decreased in drug free/naive (224.8 +/- 76.5 pg/ml) compared to healthy controls (318.5 +/- 114.2), p < .001]. Severity of the manic episode presented a significant negatively correlation to plasma BDNF levels (r= .78; p < .001; Pearson test). CONCLUSIONS: Overall, these results suggest that the decreased plasma BDNF levels may be directly associated with the pathophysiology and severity of manic symptoms in BD. Further studies are necessary to clarify the role of BDNF as a putative biological marker in BD.

Quality of life in a Brazilian sample of patients with Parkinson's disease and their caregivers.

OBJECTIVE: Parkinson's disease is a common neurodegenerative disorder characterized by motor disabilities and increasing dependence on others for daily life activities with consequent impact on patients' and caregivers' quality of life. METHOD: A cross-sectional study was performed in which quality of life was assessed by the WHOQOL-BREF questionnaire in 21 patients with Parkinson's disease and their respective caregivers. RESULTS: Significant differences between patients and caregivers were found in physical (p < 0.001) and psychological (p = 0.002) domains. In the Parkinson's disease group there was a significant inverse correlation between the psychological domain and duration of disease (p = 0.01), as well as between social domain and severity of disease (p = 0.001). There was a positive correlation between physical domain scores and number of people living in the same house (p = 0.02). The only significant finding in the group of caregivers was an inverse correlation between the social domain and the patients' age (p = 0.04). CONCLUSION: Duration, severity of the disease and the number of people living in the same house were the most important predictors of quality of life of Parkinson's disease patients. The age of the patients was the only significant predictor found in the caregivers' quality of life. In order to complement our findings, further short-form questionnaires should be validated for Brazilian samples of Parkinson's disease.

Quality of life in a Brazilian sample of patients with Parkinson's disease and their caregivers / Qualidade de vida de uma amostra de pacientes brasileiros portadores da doença de Parkinson e seus cuidadores

OBJECTIVE: Parkinson's disease is a common neurodegenerative disorder characterized by motor disabilities and increasing dependence on others for daily life activities with consequent impact on patients' and caregivers' quality of life. METHOD: A cross-sectional study was performed in which quality of life was assessed by the WHOQOL-BREF questionnaire in 21 patients with Parkinson's disease and their respective caregivers. RESULTS: Significant differences between patients and caregivers were found in physical (p < 0.001) and psychological (p = 0.002) domains. In the Parkinson's disease group there was a significant inverse correlation between the psychological domain and duration of disease (p = 0.01), as well as between social domain and severity of disease (p = 0.001). There was a positive correlation between physical domain scores and number of people living in the same house (p = 0.02). The only significant finding in the group of caregivers was an inverse correlation between the social domain and the patients´ age (p = 0.04). CONCLUSION: Duration, severity of the disease and the number of people living in the same house were the most important predictors of quality of life of Parkinson's disease patients. The age of the patients was the only significant predictor found in the caregivers' quality of life. In order to complement our findings, further short-form questionnaires should be validated for Brazilian samples of Parkinson's disease.

OBJETIVO: A doença de Parkinson é uma enfermidade neurodegenerativa comum caracterizada por disfunção motora e níveis crescentes de dependência para atividades da vida diária, com conseqüente impacto sobre a qualidade de vida dos pacientes e seus cuidadores. MÉTODO: Foi realizado um estudo transversal avaliando qualidade de vida por meio do questionário WHOQOL-BREF em 21 pacientes com doença de Parkinson e seus respectivos cuidadores. RESULTADOS: Diferenças significativas entre pacientes e cuidadores foram encontradas nos domínios físico (p < 0,001) e psicológico (p = 0,002) do questionário WHOQOL-BREF. No grupo dos pacientes, houve uma significativa correlação inversa entre o domínio psicológico e duração da doença (p = 0,01), assim como entre domínio social e gravidade da doença (p = 0,001). Houve uma correlação positiva entre domínio físico e número de pessoas vivendo na mesma casa (p = 0,02). O único achado significativo no grupo dos cuidadores foi uma correlação inversa entre o domínio social e a idade do paciente (p = 0,04). CONCLUSÃO: Duração, gravidade e número de pessoas vivendo na mesma casa foram os fatores preditores mais importantes sobre a qualidade de vida dos pacientes com doença de Parkinson. A idade dos pacientes foi o único fator preditor encontrado sobre a qualidade de vida dos cuidadores. Outros questionários de aplicação curta devem ser validados para amostras brasileiras de pacientes com doença de Parkinson no sentido de complementar nossos achados.

Changes in S100B cerebrospinal fluid levels of rats subjected to predator stress.

Predator stress is a type of psychogenic stress induced by an innate recognition of threat. S100B, a calcium-binding protein secreted by astrocytes, has been associated with neurotrophic or neurotoxic action in several neuropsychiatric disorders. It has been recently demonstrated that serum S100B levels in rats are increased after stress by immobilization [S. Scaccianoce, P. Del Bianco, G. Pannitteri, F. Passarelli, Relationship between stress and circulating levels of S100B protein, Brain Res. 1004 (2004) 208-11]. This study aimed to measure cerebrospinal fluid (CSF) S100B in rats after an acute stress situation, which is induced by exposure to a predator. S100B was measured in CSF and in hippocampal and cortical slices by ELISA. Forty-three male Wistar rats, aged 70 days, were randomly assigned to handled (control) or stressed groups (exposed to a cat for 5 min). CSF and brain tissue were removed 1 or 24 h after the procedures. Rats exposed to the cat demonstrated a biphasic change in CSF S100B levels. An increase was observed at 1 h after cat exposure, and a decrease was observed 24 h later, although this was not accompanied by changes in S100B content in hippocampus or cerebral cortex. The effectiveness of the stressor used was confirmed by increased freezing response (during cat exposure) and increased anxiety in the plus maze test (1 h after cat exposure). These results indicate that CSF S100B is changed by stress, reinforcing the possibility that this protein is involved in the adaptive response to stress and/or in secondary neuropsychiatric disorders.