Hypericum perforatum chronic treatment affects cognitive parameters and brain neurotrophic factor levels.

OBJECTIVE: To evaluate the effects of Hypericum perforatum (hypericum) on cognitive behavior and neurotrophic factor levels in the brain of male and female rats. METHODS: Male and female Wistar rats were treated with hypericum or water during 28 days by gavage. The animals were then subjected to the open-field test, novel object recognition and step-down inhibitory avoidance test. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-line derived neurotrophic factor (GDNF) levels were evaluated in the hippocampus and frontal cortex. RESULTS: Hypericum impaired the acquisition of short- and long-term aversive memory in male rats, evaluated in the inhibitory avoidance test. Female rats had no immediate memory acquisition and decreased short-term memory acquisition in the inhibitory avoidance test. Hypericum also decreased the recognition index of male rats in the object recognition test. Female rats did not recognize the new object in either the short-term or the long-term memory tasks. Hypericum decreased BDNF in the hippocampus of male and female rats. Hypericum also decreased NGF in the hippocampus of female rats. CONCLUSIONS: The long-term administration of hypericum appears to cause significant cognitive impairment in rats, possibly through a reduction in the levels of neurotrophic factors. This effect was more expressive in females than in males.

Increased oxidative stress in the mitochondria isolated from lymphocytes of bipolar disorder patients during depressive episodes.

The present study aims to investigate the oxidative stress parameters in isolated mitochondria, as well as looking at mitochondrial complex activity in patients with Bipolar Disorder (BD) during depressive or euthymic episodes. This study evaluated the levels of mitochondrial complex (I, II, II-III and IV) activity in lymphocytes from BD patients. We evaluated the following oxidative stress parameters: superoxide, thiobarbituric acid reactive species (TBARS) and carbonyl levels in submitochondrial particles of lymphocytes from bipolar patients. 51 bipolar patients were recruited into this study: 34 in the euthymic phase, and 17 in the depressive phase. Our results indicated that the depressive phase could increase the levels of mitochondrial superoxide, carbonyl and TBARS, and superoxide dismutase, and could decrease the levels of mitochondrial complex II activity in the lymphocytes of bipolar patients. It was also observed that there was a negative correlation between the Hamilton Depression Rating Scale (HDRS) and complex II activity in the lymphocytes of depressive bipolar patients. In addition, there was a positive correlation between HDRS and superoxide, superoxide dismutase, TBARS and carbonyl. Additionally, there was a negative correlation between complex II activity and oxidative stress parameters. In conclusion, our results suggest that mitochondrial oxidative stress and mitochondrial complex II dysfunction play important roles in the depressive phase of BD.

The different effects of lithium and tamoxifen on memory formation and the levels of neurotrophic factors in the brain of male and female rats.

Lithium (Li) is a mood-stabilizing drug used in the treatment of bipolar disorder (BD). Recently, preclinical studies have demonstrated the potential of tamoxifen (TMX) in the treatment of acute episodes of BD. However, the prolonged use of TMX for mood disorders treatment is controversial. In this study, we evaluated the effects of TMX or Li on cognitive behavior, as well as the levels of neurotrophic factors in the brain of male and female rats. Male and female Wistar rats received administrations of water (control group), TMX or Li via gavage for a period of 28days; the rats were then subjected to the open-field test (to evaluate spontaneous locomotion), and the novel object recognition and step-down inhibitory avoidance tests (to evaluate cognition). The levels of NGF, BDNF and GDNF were evaluated in the hippocampus and frontal cortex of the subject rats. No significant differences were observed in the open-field and inhibitory avoidance tests after drug administration in either the male or female rats. The administration of TMX, but not Li, decreased the recognition index of both the male and female rats in the object recognition test. The chronic administration of TMX decreased, whereas Li increased the levels of BDNF in the hippocampus of both the male and female rats. Tamoxifen decreased the levels of NGF in the hippocampus of female rats. In conclusion, it can be suggested that long-term treatments with TMX can lead to significant cognitive impairments by reducing the levels of neurotrophic factors in the brain of rats.

Hypericum perforatum chronic treatment affects cognitive parameters and brain neurotrophic factor levels

Objective: To evaluate the effects of Hypericum perforatum (hypericum) on cognitive behavior and neurotrophic factor levels in the brain of male and female rats. Methods: Male and female Wistar rats were treated with hypericum or water during 28 days by gavage. The animals were then subjected to the open-field test, novel object recognition and step-down inhibitory avoidance test. Nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and glial cell-line derived neurotrophic factor (GDNF) levels were evaluated in the hippocampus and frontal cortex. Results: Hypericum impaired the acquisition of short- and long-term aversive memory in male rats, evaluated in the inhibitory avoidance test. Female rats had no immediate memory acquisition and decreased short-term memory acquisition in the inhibitory avoidance test. Hypericum also decreased the recognition index of male rats in the object recognition test. Female rats did not recognize the new object in either the short-term or the long-term memory tasks. Hypericum decreased BDNF in the hippocampus of male and female rats. Hypericum also decreased NGF in the hippocampus of female rats. Conclusions: The long-term administration of hypericum appears to cause significant cognitive impairment in rats, possibly through a reduction in the levels of neurotrophic factors. This effect was more expressive in females than in males.

A prevalência de comorbidades psiquiátricas em pacientes com transtornoafetivo bipolar atendidos em um ambulatório de pesquisa clínica em psiquiatria / The prevalence of psychiatric comorbidity in patients with bipolar affective disorder seen in the ambulatory clinical research in psychiatry

Introdução: Comorbidades psiquiátricas em pacientescom transtorno bipolar se revelam muito frequentese esta coocorrência está associada com efeitos negativossobre o curso e prognóstico da doença. Objetivos:Conhecer a prevalência de comorbidades psiquiátricase sua relação com as características do transtorno bipolartipo I, em pacientes atendidos no ambulatório depesquisa. Metodologia: Realizamos um estudo exploratório,transversal, observacional e prospectivo, no períodode fevereiro a setembro de 2011. A amostra foicomposta por 24 pacientes diagnosticados com transtornobipolar tipo I avaliados quanto à comorbidadespsiquiátricas através da Entrevista Clínica Estruturadapara Transtornos do Eixo I do DSM-IV, enquanto os outrosdados clínicos dos pacientes foram avaliados porquestionários aplicados, a fim de caracterizar a doença.Resultados: A maioria dos pacientes (62,5%) fechavacritérios diagnósticos para pelo menos uma comorbidade,sendo mais comum a coocorrência de uma ou maiscomorbidades passadas (58,3%) que as atuais (37,5%).Os transtornos de ansiedade se mostraram os mais prevalentes(45,8%), seguidos por transtornos do uso desubstâncias (25,0%), somatoformes (16,7%) e alimentares(4,2%). A associação entre o curso da doença e apresença de comorbidades psiquiátricas não apresentaramrelação significativa. Conclusão: Este estudo mostrouque pacientes bipolares possuem alta prevalênciade comorbidades psiquiátricas do eixo I do DSM-IV,sendo mais comuns os transtornos ansiosos e por usode substâncias, consoante ao encontrado em estudosanteriores. No entanto, diferindo da literatura a relaçãoentre as características da evolução do transtorno bipolare a ocorrência de comorbidades não apresentoudiferença significativa.

Background: Psychiatric comorbidities in patientswith bipolar disorder to reveal a high frequent and thisco-occurrence is associated with negative effects onthe course and prognosis of this pathology. Objective:Know what is the prevalence of psychiatric comorbiditiesand their relation with the characteristics of bipolardisorder type I in patients attended in outpatient clinicof research in the UNESC. Methods: This study was conductedas exploratory, transversal, observational andprospective, in the period from February to September2011. The sample is composed for 24 patients diagnosedwith bipolar disorder I and assessed for psychiatriccomorbidity, through the Structured Clinical Interviewfor Axis I of DSM-IV, as well was applied questionnairesin order to obtain the characteristics of disease. Results:The majority of bipolar patients (62.5%) had diagnosticcriteria closed at least one comorbidity, and the co-occurrenceof one or more longtime comorbidities weremost common (58.3%) than with the current (37.5%).Anxiety disturbances were the most prevalent (45.8%),followed by use of substance disturbance (25.0%), somatoform(16.7%) and eating disorder (4.2%). The relationshipbetween the course of disease and the presenceof psychiatric comorbidities were not significant.Conclusions: Patients with bipolar disorder have a highprevalence of psychiatric comorbid based in Axis I ofDSM-IV, the most common disorders are anxiety andsubstance use. The relationship between the characteristicsof evolution of disease and the occurrence ofcomorbidities did not show different significant.