Increased levels of plasma IL-1b and BDNF can predict resistant depression patients

SUMMARY BACKGROUND: There is no strong evidence on the link between inflammatory profile and pattern of drug treatment response in depressive patients that could result in Coronary Artery Disease occurrence. OBJECTIVE: This study aimed to compare the subclinical atherosclerosis markers, inflammatory profile, and BDNF production in Resistant Depression (RD) or Bipolar Affective Disorder (BAD) patients under conventional treatment. METHODS: The population evaluated was comprised of 34 RD, 43 BAD, and 41 controls. Subclinical atherosclerosis markers were evaluated using ultrasonography, tomography, and exercise stress test. Plasma concentrations of TNFα, IL-1β, IL-6, and BDNF were measured using Luminex100™. The usCRP concentration was measured using turbidimetric immunoassay. IL1B, IL6, and TNFA expression were determined using TaqMan®. For the statistical analysis, the significance level was established at p<0.05. RESULTS: Concerning subclinical atherosclerosis markers, only O2 consumption was reduced in the BAD group (p = 0.001). Although no differences were found in gene expression, BDNF and IL-1β plasma concentration was increased in the RD group (p = 0.002 and p = 0.005, respectively) even with an antidepressant treatment, which suggests that these drugs have no effect in IL-1β secretion and that the inflammasome may play a role in therapy response. CONCLUSION: Taken together, both BDNF and IL-1β plasma concentrations could be used to the early identification of RD patients.

RESUMO FUNDAMENTAÇÃO: Não há fortes evidências sobre a associação entre o perfil inflamatório e o padrão de resposta ao tratamento medicamentoso em pacientes depressivos que podem resultar em ocorrência de doença coronariana. OBJETIVO: O objetivo deste estudo foi comparar os marcadores de aterosclerose subclínica, o perfil inflamatório e a produção de BDNF em pacientes com Depressão Resistente (DR) ou Transtorno Afetivo Bipolar (BAD) sob tratamento convencional. MÉTODOS: A população avaliada incluiu 34 RD, 43 BAD e 41 controles. Os marcadores de aterosclerose subclínica foram avaliados por ultrassonografia, tomografia e teste de esforço. As concentrações plasmáticas de TNFα, IL-1β, IL-6 e BDNF foram medidas utilizando Luminex100TM. A concentração de usCRP foi medida por imunoensaio turbidimétrico. A expressão de IL1B, IL6 e TNFA foi determinada usando TaqMan®. Para as análises estatísticas, foi estabelecido o nível de significância de p < 0,05. RESULTADOS: Quanto aos marcadores de aterosclerose subclínica, apenas o consumo de O2 foi reduzido no grupo BAD (p = 0,001). Embora não tenham sido encontradas diferenças na expressão gênica, a concentração plasmática de BDNF e IL-1β foi aumentada no grupo RD (p = 0,002 e p = 0,005, respectivamente) mesmo sob tratamento antidepressivo, o que sugere que esses medicamentos não têm efeito na secreção de IL-1β e que o inflamassomo pode desempenhar um papel na resposta terapêutica. CONCLUSÃO: Juntas, as concentrações BDNF e IL-1β poderiam ser usadas para a identificação precoce de pacientes com DR.

Serum BDNF levels in unaffected first-degree relatives of patients with bipolar disorder

Objective: Unaffected relatives of bipolar disorder (BD) patients have been investigated for the identification of endophenotypes in an attempt to further elucidate the pathophysiology of the disease. Brain-derived neurotrophic factor (BDNF) is considered to be implicated in the pathophysiology of BD, but its role as an endophenotype has been poorly studied. We investigated abnormal serum BDNF levels in BD patients, in their unaffected relatives, and in healthy controls. Methods: BDNF levels were obtained from 25 DSM-IV bipolar I disorder patients, 23 unaffected relatives, and 27 healthy controls. All BD patients were in remission. The unaffected subjects were first-degree relatives of the proband who had no lifetime DSM-IV diagnosis of axis I disorder. BDNF serum levels were determined by sandwich ELISA using monoclonal BDNF-specific antibodies. Results: There were no statistical differences in BDNF levels among BD patients, relatives, and healthy controls. Conclusion: Serum BDNF levels may not indicate high genetic risk for BD, possibly acting as state markers rather than trait markers of the disease.

Association of interleukin-10 levels with age of onset and duration of illness in patients with major depressive disorder

Objective: To investigate peripheral levels of interleukin-10 (IL-10) in patients with major depressive disorder (MDD) and bipolar disorder (BD) and evaluate the relationship between IL-10, age of disease onset, and duration of illness. Methods: Case-control study nested in a population-based cohort of 231 individuals (age 18-24 years) living in Pelotas, state of Rio Grande do Sul, Brazil. Participants were screened for psychopathology using the Mini-International Neuropsychiatric Interview (MINI) and the Structured Clinical Interview for DSM-IV (SCID-I). Serum IL-10 was measured using commercially available immunoassay kits. Results: Peripheral levels of IL-10 were not significantly different in individuals with MDD or BD as compared to controls. However, higher IL-10 levels were found in MDD patients with a later disease onset as compared with controls or early-onset patients. In addition, IL-10 levels correlated negatively with illness duration in the MDD group. In the BD group, age of onset and duration of illness did not correlate with IL-10 levels. Conclusion: Higher levels of IL-10 are correlated with late onset of MDD symptoms. Moreover, levels of this cytokine might decrease with disease progression, suggesting that an anti-inflammatory balance may be involved in the onset of depressive symptoms and disease progression in susceptible individuals.

Specific alterations in plasma proteins during depressed, manic, and euthymic states of bipolar disorder

Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2% of the general population of different European countries. Unfortunately, there is no objective laboratory-based test to aid BD diagnosis or monitor its progression, and little is known about the molecular basis of BD. Here, we performed a comparative proteomic study to identify differentially expressed plasma proteins in various BD mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched healthy control subjects were recruited. Seven high-abundance proteins were immunodepleted in plasma samples from the 4 experimental groups, which were then subjected to proteome-wide expression profiling by two-dimensional electrophoresis and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem mass spectrometry. Proteomic results were validated by immunoblotting and bioinformatically analyzed using MetaCore. From a total of 32 proteins identified with 1.5-fold changes in expression compared with healthy controls, 16 proteins were perturbed in BD independent of mood state, while 16 proteins were specifically associated with particular BD mood states. Two mood-independent differential proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be associated with early perturbations in lipid metabolism. Moreover, down-regulation of one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be associated with early perturbations in lipid metabolism that are independent of mood state, while CA-1 may be involved in the pathophysiology of depressive episodes.

Where does her mood come from? An organic approach to a once functional patient / De onde vem seu humor? Uma abordagem orgânica para um paciente previamente funcional

Objective: To report the rare development of manic symptoms in a patient with schizophrenia and discuss its differential diagnosis. Case description: Diagnostic criteria were based on the International Classification of Diseases, 10th edition (ICD-10). A 63-year-old female (diagnosed with schizophrenia since she was 28) was brought to the emergency room with symptoms consistent with manic episode and physical examination suggestive of thyrotoxicosis. Graves' disease was confirmed by subsequent laboratory tests. She was treated successfully with radioiodine ablation, leading to full remission of manic symptoms. Comments: Schizophrenia is a chronic disease that affects about 1% of the population worldwide. The main symptoms of the disorder are altered affection, delusions, and hallucinations. Graves' disease is an autoimmune condition in which antibodies increase the production and release of thyroid hormones. There are reports about the development of mood symptoms in patients with Graves' disease that remit with adequate treatment. .

Objetivo: Relatar um caso raro de desenvolvimento de sintomas maníacos em uma paciente com esquizofrenia e discutir o diagnóstico diferencial desses sintomas. Descrição do caso: Foram utilizados como base os critérios diagnósticos da Classificação Internacional de Doenças, 10ª edição (CID-10). Paciente de 63 anos do sexo feminino e com diagnóstico de esquizofrenia desde os 28 anos foi levada a emergência com sintomas compatíveis com episódio de mania e exame físico sugestivo de tireotoxicose. Doença de Graves foi confirmada por exames subsequentes. A paciente foi tratada com sucesso com ablação por iodo radioativo, levando à remissão dos sintomas maníacos. Comentários: A esquizofrenia é uma doença crônica que afeta cerca de 1% da população mundial. Os principais sintomas do transtorno são o embotamento afetivo, alucinações e delírios. A doença de Graves é uma doença autoimune em que o estímulo humoral aumenta a produção e liberação de hormônios pela tireoide. Há relatos na literatura sobre o desenvolvimento de sintomas maníacos em pacientes com doença de Graves, os quais remitem mediante tratamento adequado. .

Metabolic syndrome and related variables, insulin resistance, leptin levels, and PPAR-γ2 and leptin gene polymorphisms in a pedigree of subjects with bipolar disorder

Objective: Evidence points to a high prevalence of metabolic dysfunction in bipolar disorder (BD), but few studies have evaluated the relatives of subjects with BD. We conducted a cross-sectional study in an extended family of patients with BD type I. Methods: The available relatives of the same family were interviewed (DSM-IV-R) and assessed in fasting conditions for body mass index, constituent variables of the metabolic syndrome (MS), leptin levels, insulin resistance index, and single nucleotide polymorphisms (SNPs) for the leptin receptor and promoter and PPAR-γ2 genes. The frequency of MS was compared with that recorded in the local general population. Results: Ninety-three relatives of three adults with BD were evaluated (30 aged < 18 years, 63 aged > 18 years). The frequency of MS was similar to that of the general population. Significantly higher frequencies of abnormal glucose, total and low density cholesterol (LDL-c) levels (all p < 0.05), waist circumference (p = 0.057), and leptin and insulin resistance values (in adults only) were observed in the family. Adults with the QQ genotype of the leptin receptor displayed higher LDL-c levels than carriers of the R allele. Conclusions: The associations among BD consanguinity, familial hypercholesterolemia, and leptin receptor SNPs reported herein should be replicated and extended in other pedigrees. .

Decreased plasma neurotrophin-4/5 levels in bipolar disorder patients in mania

Objective: To evaluate two poorly explored neurotrophins (NT), NT-3 and NT-4/5, in bipolar disorder (BD). Methods: Forty patients with type I BD (18 in remission and 22 in mania) and 25 healthy controls matched for age, gender, and educational attainment were enrolled in this study. All subjects were assessed by the Mini-International Neuropsychiatric Interview; the Young Mania Rating Scale and the Hamilton Depression Rating Scale were used to evaluate severity of symptoms in BD patients. Plasma levels of NT-3 and NT-4/5 were measured by enzyme-linked immunosorbent assay (ELISA). Results: BD patients in mania presented decreased NT-4/5 plasma levels in comparison with controls (p < 0.05). There were no significant differences in NT-3 plasma levels between BD patients and controls. Conclusion: These findings corroborate the view that neurotrophin dysfunction is associated with mood states in patients with BD. .

Expression of matrix metalloproteinases in patients with bipolar disorder

Objective: High cardiovascular mortality rates have been reported in patients with bipolar disorder (BD). Studies indicate that matrix metalloproteinases (MMPs) are implicated in cardiovascular diseases. We evaluated the expression pattern of MMP-2 and MMP-9 in blood from patients with BD during acute mania and after euthymia, in comparison with healthy controls. Methods: Twenty patients and 20 controls were recruited and matched for sex and age. MMP messenger RNA (mRNA) levels were measured using real-time quantitative polymerase chain reaction (PCR). Body mass index (BMI) was calculated for all subjects. Results: There were no significant differences in MMP-2 and MMP-9 mRNA expression between patients and controls. mRNA levels were not significantly different during mania and euthymia. However, MMP-2 mRNA levels were negatively associated with BMI in BD patients and positively associated with BMI in controls. There was no difference in the pattern of MMP-9 expression between patients and controls. Conclusions: Our results suggest a different pattern of association between MMP-2 and BMI in BD patients as compared with controls. Despite some study limitations, we believe that the role of MMPs in BD should be further investigated to elucidate its relationship with cardiovascular risk. .

Bipolar disorder and medication: adherence, patients' knowledge and serum monitoring of lithium carbonate / Transtorno bipolar e medicamentos: adesão, conhecimento dos pacientes e monitorização sérica do carbonato de lítio / Trastorno bipolar y medicamentos: adhesión, conocimiento de los pacientes y monitorización sérica del carbonato de litio

OBJECTIVES: this study featured patients with affective bipolar disorder who were making use of lithium and received care at an outpatient care center located in a country town in the state of Sao Paulo in 2009; it assessed the adherence and knowledge of these patients in relation to the medication prescribed to them and verified the proportion of blood tests performed per year in the service, for each individual, to measure lithium levels in the blood. METHOD: descriptive study with quantitative approach, involving 36 participants. Structured interviews and review of medical records were used for data collection and descriptive statistics for data analysis. RESULTS: difficulties in reporting the dosage of the medication prescribed and a high rate of non-adherence were identified among the participants. None of the participants in the study was submitted to two tests a year to measure lithium levels in the blood, which is the minimum proportion of tests recommended by the literature for maintenance treatment using lithium carbonate. CONCLUSION: this study highlights the critical factors for the promotion of patients' safety in monitoring lithium drug therapy. .

OBJETIVOS: este estudo teve como objetivo caracterizar pacientes com transtorno afetivo bipolar, em uso de lítio, atendidos no ano 2009 em um serviço ambulatorial do interior de São Paulo, Brasil; avaliar a adesão e conhecimento dos mesmos sobre medicamentos prescritos e verificar a proporção de litemias/ano realizadas, no serviço, para cada indivíduo. MÉTODO: trata-se de estudo descritivo, com abordagem quantitativa, do qual participaram 36 pessoas. Foram utilizadas entrevistas estruturadas e revisão de prontuários para coleta de dados e estatística descritiva para análise dos mesmos. RESULTADOS: entre os participantes, foram identificadas dificuldades em relatar a dose dos fármacos prescritos e alta taxa de não adesão. Em nenhum participante do estudo foi atingida a proporção de duas litemias/ano, que representa a quantidade mínima de litemias preconizada pela literatura para o tratamento de manutenção com carbonato de lítio. CONSIDERAÇÕES FINAIS: este estudo aponta fatores críticos na promoção da segurança do paciente no seguimento da terapêutica medicamentosa com lítio. .

OBJETIVOS: este estudio caracterizó pacientes con trastorno afectivo bipolar, tratadas con litio, atendidos en el año de 2009 en un servicio de ambulatorio del interior del estado de Sao Paulo, en Brasil; evaluó la adhesión y conocimiento de los mismos sobre medicamentos prescritos y verificó la proporción de litemias/año realizadas, en el servicio, para cada individuo. MÉTODO: se trata de estudio descriptivo, con abordaje cuantitativo, del cual participaron 36 personas. Fueron utilizadas entrevistas estructuradas y revisión de fichas para recolección de datos y estadística descriptiva para análisis de los mismos. RESULTADOS: entre los participantes, fueron identificadas dificultades en relatar la dosis de los fármacos prescritos y una alta tasa de no adhesión. En ningún participante del estudio fue alcanzada la proporción de dos litemias/año, que representa la cantidad mínima de litemias preconizada por la literatura para el tratamiento de mantenimiento con carbonato de litio. CONCLUSIÓN: este estudio apunta factores críticos para la promoción de la seguridad del paciente en el seguimiento de la terapéutica medicamentosa con litio. .

Homocysteine and other markers of cardiovascular risk during a manic episode in patients with bipolar disorder

Objective: To evaluate serum levels of different biomarkers associated with cardiovascular disease in patients with bipolar disorder (BD). Patients were prospectively evaluated in two separate instances: during acute mania and after remission of manic symptoms. All measurements were compared with those of healthy controls. Methods: The study included 30 patients with BD and 30 healthy controls, matched for gender and age. Biochemical parameters evaluated included homocysteine (Hcy), folic acid, vitamin B12, ferritin, creatine kinase (CK) and C-reactive protein (CRP). Results: Hcy levels were significantly higher in the BD patients, both during mania and after achieving euthymia. When Hcy was adjusted for body mass index, there was no significant difference between patients and controls. Ferritin was the only marker that showed a significant decrease during mania when compared to both euthymic patients and controls. There were no significant differences for folate, vitamin B12, CK and CRP. Conclusions: These findings do not show an association between alterations of markers of cardiovascular risk during manic episodes. Further studies are necessary to determine factors and mechanisms associated with cardiovascular risk in patients with BD. .

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.

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.

Creatine kinase levels in patients with bipolar disorder: depressive, manic, and euthymic phases / Comparação das fases de depressão, mania e eutimia sobre os níveis de creatina quinase em pacientes bipolares

OBJECTIVE: Bipolar disorder is a severe, recurrent, and often chronic psychiatric illness associated with significant functional impairment, morbidity, and mortality. Creatine kinase is an important enzyme, particularly for cells with high and fluctuating energy requirements, such as neurons, and is a potential marker of brain injury. The aim of the present study was to compare serum creatine kinase levels between bipolar disorder patients, in the various phases (depressive, manic, and euthymic), and healthy volunteers. METHOD: Forty-eight bipolar patients were recruited: 18 in the euthymic phase; 17 in the manic phase; and 13 in the depressive phase. The control group comprised 41 healthy volunteers. The phases of bipolar disorder were defined as follows: euthymic-not meeting the DSM-IV criteria for a mood episode and scoring < 8 on the Hamilton Depression Rating Scale (HDRS) and Young Mania Rating Scale (YMRS); manic-scoring < 7 on the HDRS and > 7 on the YMRS; depressive-scoring > 7 on the HDRS and < 7 on the YMRS. Patients in mixed phases were excluded. Blood samples were collected from all participants. RESULTS: Creatine kinase levels were higher in the manic patients than in the controls. However, we observed no significant difference between euthymic and depressive patients in terms of the creatine kinase level. CONCLUSION: Our results suggest that the clinical differences among the depressive, manic, and euthymic phases of bipolar disorder are paralleled by contrasting levels of creatine kinase. However, further studies are needed in order to understand the state-dependent differences observed in serum creatine kinase activity.

OBJETIVO: O transtorno do humor bipolar é uma doença psiquiátrica grave, recorrente e crônica associada a significativo prejuízo funcional, morbidade e mortalidade. A creatina quinase tem sido proposta como um marcador de dano cerebral. A creatina quinase é uma enzima importante principalmente para células que necessitam de uma grande quantidade de energia, como os neurônios. O objetivo do presente estudo foi comparar os níveis de creatina quinase entre as fases depressiva, maníaca e eutímica de pacientes com transtorno do humor bipolar. MÉTODO: Para avaliação dos níveis de creatina quinase no soro, 48 pacientes bipolares foram recrutados; 18 estavam eutímicos, 17 estavam em mania e 13 em episódio depressivo. Foi feita também uma comparação com um grupo controle que incluiu 41 voluntários saudáveis. Grupo eutimia: foram incluídos os pacientes que não cumpriam os critérios do DSM-IV para episódios de humor e deveriam ter a pontuação inferior a oito nas escalas de avaliação de mania (YMRS) e depressão (HDRS); grupo mania: foram incluídos os pacientes que apresentavam YMRS > 7 e HDRS < 7; grupo depressão: foram incluídos os pacientes que apresentavam HDRS > 7 e YMRS < 7. Os pacientes em episódios mistos não foram incluídos no estudo. Amostras de sangue foram coletadas de todos os participantes. RESULTADOS: Durante a mania, os níveis de creatina quinase foram aumentados em comparação com voluntários saudáveis. Entretanto, não houve diferença significativa nos níveis de creatina quinase em pacientes eutímicos e depressivos, quando comparados com o grupo controle. CONCLUSÃO: Nossos resultados sugerem que as fases maníaca, depressiva e eutímica do transtorno do humor bipolar, além de apresentarem sintomatologia distinta, também podem ser diferenciadas pelo nível de creatina quinase presente no sangue do paciente. Entretanto, mais estudos são necessários para entender as diferenças observadas na atividade da creatina quinase durante as fases do transtorno do humor bipolar.

Staying at the crossroads: assessment of the potential of serum lithium monitoring in predicting an ideal lithium dose / Em uma encruzilhada: potencial do nível plasmático de lítio como preditor da dose ideal

OBJECTIVE: Lithium has been successfully employed to treat bipolar disorder for decades, and recently, was shown to attenuate the symptoms of other pathologies such as Alzheimer's disease, Down's syndrome, ischemic processes, and glutamate-mediated excitotoxicity. However, lithium's narrow therapeutic range limits its broader use. Therefore, the development of methods to better predict its dose becomes essential to an ideal therapy. METHOD: the performance of adult Wistar rats was evaluated at the open field and elevated plus maze after a six weeks treatment with chow supplemented with 0.255 percent, or 0.383 percent of lithium chloride, or normal feed. Thereafter, blood samples were collected to measure the serum lithium concentration. RESULTS: Animals fed with 0.255 percent lithium chloride supplemented chow presented a higher rearing frequency at the open field, and higher frequency of arms entrance at the elevated plus maze than animals fed with a 50 percent higher lithium dose presented. Nevertheless, both groups presented similar lithium plasmatic concentration. DISCUSSION: different behaviors induced by both lithium doses suggest that these animals had different lithium distribution in their brains that was not detected by lithium serum measurement. CONCLUSION: serum lithium concentration measurements do not seem to provide sufficient precision to support its use as predictive of behaviors.

OBJETIVO: Além de ser usado há décadas para tratar distúrbio bipolar, o lítio, mais recentemente, demonstrou-se eficaz para Alzheimer, síndrome de Down, processos isquêmicos e excitotoxicidade mediada por glutamato. Contudo, a estreita janela terapêutica do lítio limita seu uso. Portanto, o estabelecimento de métodos preditivos de dose torna-se importante. MÉTODO: O desempenho de ratos Wistar adultos foi avaliado no campo aberto e labirinto em cruz elevado após seis semanas de tratamento com uma ração suplementada com 0,255 por cento ou 0,383 por cento de cloreto de lítio ou ração normal. Coletou-se amostras de sangue para dosagem plasmática do lítio. RESULTADOS: Os animais alimentados com a ração com 0,255 por cento de cloreto de lítio fizeram mais rearing no campo aberto e tiveram uma maior freqüência de entradas nos braços do labirinto elevado que os animais que ingeriram a dose mais alta. Apesar disso, verificou-se níveis plasmáticos de lítio semelhantes em ambos os grupos. DISCUSSÃO: A variação nos comportamentos destarte a presença de níveis plasmáticos semelhantes sugere que as diferentes doses produziram diferentes concentrações cerebrais não detectadas pela medida plasmática. CONCLUSÃO: Medidas da concentração plasmática de lítio não permitem prever de forma completa seus efeitos comportamentais.

Increased oxidative stress as a mechanism for decreased BDNF levels in acute manic episodes / Aumento do estresse oxidativo como um mecanismo para a diminuição dos níveis de BDNF em episódios maníacos agudos

OBJECTIVE AND METHOD: There is a growing amount of data indicating that alterations in brain-derived neurotrophic factor and increased oxidative stress may play a role in the pathophysiology of bipolar disorder. In light of recent evidence demonstrating that brain-derived neurotrophic factor levels are decreased in situations of increased oxidative stress, we have examined the correlation between serum thiobarbituric acid reactive substances, a measure of lipid peroxidation, and serum brain-derived neurotrophic factor levels in bipolar disorder patients during acute mania and in healthy controls. RESULTS: Serum thiobarbituric acid reactive substances and brain-derived neurotrophic factor levels were negatively correlated in bipolar disorder patients (r = -0.56; p = 0.001), whereas no significant correlation was observed in the control group.. CONCLUSION: These results suggest that alterations in oxidative status may be mechanistically associated with abnormal low levels of brain-derived neurotrophic factor observed in individuals with bipolar disorder.

OBJETIVO E MÉTODO: Existem crescentes evidências indicando que alterações no fator neurotrófico derivado do cérebro e aumento do estresse oxidativo podem estar envolvidos na fisiopatologia do transtorno bipolar. Considerando os achados recentes de que os níveis de fator neurotrófico derivado do cérebro estão diminuídos em situações de aumento de estresse oxidativo, nós testamos a correlação entre os níveis séricos de substâncias reativas do ácido tiobarbitúrico, um índice de peroxidação lipídica, e os níveis séricos de fator neurotrófico derivado do cérebro em pacientes portadores de transtorno bipolar durante mania aguda e em controles saudáveis. RESULTADOS: Os níveis séricos de substâncias reativas do ácido tiobarbitúrico e fator neurotrófico derivado do cérebro apresentaram uma correlação negativa em pacientes bipolares (r = -0,56; p = 0,001), enquanto não houve correlação significativa no grupo controle. CONCLUSÃO: Estes resultados sugerem que alterações de estresse oxidativo podem ser mecanisticamente associadas com níveis reduzidos de BDNF observados em indivíduos com transtorno bipolar.

Endogenous alkaloids in the brain of rats loaded with tyrosine/tryptophan & in the serum of patients of neurodegenerative & psychiatric disorders.

Since binding sites for morphine, nicotine and strychnine exist in the brain, it is possible that they may have some role in neuronal function. The presence/variation in the levels of these alkaloids in the brain of rats fed tryptophan and tyrosine, and in the serum of patients with some neurodegenerative and psychiatric disorders were studied. Brain of rats loaded with tyrosine (500 mg/kg b wt X 14 days) showed increased amounts of morphine, while that from animals loaded with tryptophan (in the same dose) showed presence of strychnine and increased amounts of nicotine. Strychnine is being reported in mammalian brain for the first time. Serum of patients with epilepsy, Parkinson's disease (PD) and manic depressive psychosis (MDP) was also examined for the presence of these alkaloids. Serum of control subjects did not show the presence of any of these alkaloids, while that of all 3 patients groups contained strychnine. Morphine was present only in the serum of patients of MDP. Nicotine was present in trace amounts in the serum of all these patients. Presence of these alkaloids in the serum of patients of neurodegenerative and psychiatric disorders is being reported for the first time, to the best of our knowledge.

Estudio ultraestructural de la sangre de pacientes con esquizofrenia y psicosis maniaco-depresiva / Ultrastructural sudy of the blood in patients with schizophrenic and psychosis depressive-maniac

Muestras de sangre periférica de 6 pacientes psicóticos en estado crítico (2 maníaco-depresivos y 4 esquizofrénicos paranoides) conforme al cirterio DSM-IV y 6 pacientes controles, fueron estudiados mediante técnicas de microscopía electrónica convencional. En el grupo de pacientes psicoticos, en 3 realizó la prueba de aglutinación, uniéndose la capa blanca y el plasma de la muestra de sangre con el líquido cefaloraquídeo del propio paciente, realizándose posteriormente los estudios ultramicroscópicos. Los resultados obtenidos confirman los hallazgos de estudios anteriores con la misma técnica de investigación: la presencia de partículas semejantes a virus y su relación con estructuras con una morfología similar a bacterias que parecen originarse de los hematíes. La ausencia de estos hallazgos en el grupo control permite diferenciar estos de los pacientes. Se analiza el posible signicado que tienen estos resultadoss en relación a la biología molecular de los virus en su interacción con estructuras genéticamente independientementes y la etiología de las psicosis en estudio