Graziela Amboni

Mitochondrial Dysfunction and Psychiatric Disorders

Mitochondrial oxidative phosphorylation is the major ATP-producing pathway, which supplies more than 95% of the total energy requirement in the cells. Damage to the mitochondrial electron transport chain has been suggested to be an important factor in the pathogenesis of a range of psychiatric disorders. Tissues with high energy demands, such as the brain, contain a large number of mitochondria, being therefore more susceptible to reduction of the aerobic metabolism. Mitochondrial dysfunction results from alterations in biochemical cascade and the damage to the mitochondrial electron transport chain has been suggested to be an important factor in the pathogenesis of a range of neuropsychiatric disorders, such as bipolar disorder, depression and schizophrenia. Bipolar disorder is a prevalent psychiatric disorder characterized by alternating episodes of mania and depression. Recent studies have demonstrated that important enzymes involved in brain energy are altered in bipolar disorder patients and after amphetamine administration, an animal model of mania. Depressive disorders, including major depression, are serious and disabling. However, the exact pathophysiology of depression is not clearly understood. Several works have demonstrated that metabolism is impaired in some animal models of depression, induced by chronic stress, especially the activities of the complexes of mitochondrial respiratory chain. Schizophrenia is a devastating mental disorder characterized by disturbed thoughts and perception, alongside cognitive and emotional decline associated with a severe reduction in occupational and social functioning, and in coping abilities. Alterations of mitochondrial oxidative phosphorylation in schizophrenia have been reported in several brain regions and also in platelets. Abnormal mitochondrial morphology, size and density have all been reported in the brains of schizophrenic individuals. Considering that several studies link energy impairment to neuronal death, neurodegeneration and disease, this review article discusses energy impairment as a mechanism underlying the pathophysiology of some psychiatric disorders, like bipolar disorder, depression and schizophrenia.

Brain creatine kinase activity in an animal model of mania

There is evidence pointing to dysfunction at the mitochondrial level as an important target for the understanding of the pathophysiology of bipolar disorder (BD). We assessed creatine kinase (CK) activity in rats submitted to an animal model of mania which included the use of lithium and valproate. In the acute treatment, amphetamine (AMPH) or saline was administered to rats for 14 days, and between day 8 and 14, rats were treated with either lithium, valproate or saline. In the maintenance treatment, rats were pretreated with lithium, valproate or saline, and between day 8 and 14, AMPH or saline were administered. In both experiments, locomotor activity was assessed by open-field test and CK activity was evaluated in hippocampus, striatum, cerebellum, whole cortex and prefrontal cortex. Our results showed that mood stabilizers reversed AMPH-induced behavioral effects. Moreover, AMPH (acute treatment) inhibited CK activity in hippocampus, striatum and cortex, but not in cerebellum and prefrontal cortex, and administration of lithium or valproate did not reverse the enzyme inhibition. In the maintenance treatment, AMPH decreased CK activity in saline-pretreated rats in hippocampus, striatum and cortex, but not in cerebellum and prefrontal cortex. AMPH administration in lithium- or valproate-pretreated animals decreased CK activity in hippocampus, striatum and cortex. Our results showed that AMPH inhibited CK activity and that mood stabilizers were not able to reverse and/or prevent the enzyme inhibition. These findings reinforce the hypothesis that mitochondrial dysfunction plays an important role in the pathophysiology of BD.

Características y calidad del sueño de pacientes hipertensos

ObjetivoAnalisar a qualidade do sono de hipertensos registrados no sistema nacional de cadastramento e acompanhamento de hipertensos.MetodoEstudo transversal, quantitativo e descritivo realizado com 280 usuarios hipertensos cadastrados no Programa Nacional de Hipertensao e Diabetes do Governo Federal nos meses de agosto a outubro de 2011. Foram aplicados questionarios que permitiram tracar o perfil sociodemografico, dados sobre hipertensao arterial sistemica e Indice de Qualidade de Sono de Pittsburgh.ResultadosVerificou-se predominio da qualidade de sono ruim entre os entrevistados (156 hipertensos) e altas taxas de uso de medicacoes para dormir (106 hipertensos). Outro dado relevante refere-se a qualidade de sono entre hipertensos que utilizam medicacao para dormir comparados aqueles que nao utilizam (p≤0,01).ConclusaoIndividuos com hipertensao arterial sistemica apresentam associacao negativa com a qualidade do sono.OBJECTIVE Analyzing the quality of sleep of hypertensive patients registered in the national registration system and monitoring of hypertensive patients. METHODS A cross-sectional study of quantitative and descriptive analyses with 280 hypertensive patients registered in the National Program of Hypertension and Diabetes of the Federal Government in the months from August to October 2011. Questionnaires were used which allowed for tracking sociodemographic data on hypertension and Pittsburgh Sleep Quality Index (PSQI). RESULTS The prevalence of poor sleep quality among respondents (156 hypertensive patients) and high rates of using medication for sleeping (106 hypertensive patients) was observed. Other relevant data refers to the quality of sleep among hypertensive patients using sleep medication compared to those who do not use it (p≤0.01). CONCLUSION Individuals with high blood pressure have a negative association with sleep quality.

The quality and characteristics of sleep of hypertensive patients

ObjetivoAnalisar a qualidade do sono de hipertensos registrados no sistema nacional de cadastramento e acompanhamento de hipertensos.MetodoEstudo transversal, quantitativo e descritivo realizado com 280 usuarios hipertensos cadastrados no Programa Nacional de Hipertensao e Diabetes do Governo Federal nos meses de agosto a outubro de 2011. Foram aplicados questionarios que permitiram tracar o perfil sociodemografico, dados sobre hipertensao arterial sistemica e Indice de Qualidade de Sono de Pittsburgh.ResultadosVerificou-se predominio da qualidade de sono ruim entre os entrevistados (156 hipertensos) e altas taxas de uso de medicacoes para dormir (106 hipertensos). Outro dado relevante refere-se a qualidade de sono entre hipertensos que utilizam medicacao para dormir comparados aqueles que nao utilizam (p≤0,01).ConclusaoIndividuos com hipertensao arterial sistemica apresentam associacao negativa com a qualidade do sono.OBJECTIVE Analyzing the quality of sleep of hypertensive patients registered in the national registration system and monitoring of hypertensive patients. METHODS A cross-sectional study of quantitative and descriptive analyses with 280 hypertensive patients registered in the National Program of Hypertension and Diabetes of the Federal Government in the months from August to October 2011. Questionnaires were used which allowed for tracking sociodemographic data on hypertension and Pittsburgh Sleep Quality Index (PSQI). RESULTS The prevalence of poor sleep quality among respondents (156 hypertensive patients) and high rates of using medication for sleeping (106 hypertensive patients) was observed. Other relevant data refers to the quality of sleep among hypertensive patients using sleep medication compared to those who do not use it (p≤0.01). CONCLUSION Individuals with high blood pressure have a negative association with sleep quality.

Associação entre a qualidade de vida e adesão à medicação de indivíduos hipertensos

Objetivo Avaliar a associacao entre a qualidade de vida e a adesao a medicacao de individuos hipertensos. Metodos Estudo transversal, realizado com 432 hipertensos cadastrados em sistema informatizado publico federal. Os dados foram coletados no domicilio por entrevista estruturada com questoes relacionadas a variaveis socioeconomicas, clinicas, avaliacao da adesao ao tratamento e o WHOQOL-BREF para a qualidade de vida. Utilizou-se o teste de H de Kruskal-Wallis para medir a associacao entre as escalas da qualidade de vida e a classificacao da adesao ao tratamento. Resultados Os escores mais baixos estavam presente no dominio autoavaliacao e os mais altos foram encontrados no social. Os individuos que possuiam adesao extrema ao tratamento anti-hipertensivo apresentaram escores mais altos na avaliacao da qualidade de vida em comparacao com individuos classificados como nao adesao extrema ao tratamento anti-hipertensivo. Conclusao A associacao entre a qualidade de vida e adesao a medicacao em individuos hipertensos nao foi preditiva, sendo que os melhores escores estavam presentes nos individuos hipertensos que apresentaram alta adesao a medicacao e os piores escores da qualidade de vida se apresentaram nos individuos de nao adesao extrema e limitrofe a nao adesao total.