Optical coherence tomography findings in bipolar disorder: a preliminary receiver operating characteristic analysis on ganglion cell layer volume for diagnosis

Abstract Background Optical coherence tomography (OCT) has been recently used to investigate neuropsychiatric disorders. Objective The aim of this study was to compare the retinal nerve fiber layer thickness (RNFLT) and the ganglion cell layer (GCL) volume in patients with type 1 bipolar disorder (BPD1, diagnosed according to DSM 5) to the values in healthy controls. Methods Eighty consecutive outpatients with a diagnosis of euthymic BPD1 and 80 healthy controls were enrolled in the study. Following assessment with the Sociodemographic Data Form, Structured Clinical Interview for DSM-IV (SCID-I), Hamilton Depression Scale and Young Mania Evaluation Scale, both groups underwent Optical coherence tomography (OCT). Results The mean RNFL thickness and mean GCL volume were significantly lower in the BPD1 group than in the controls (p < 0.05). The GCL global value had a significant and independent effect in distinguishing the BPD1 patients from the controls. A cut-off value of 101 mm3 for global GCL volume was proposed to distinguish BPD1 patients from controls with a sensitivity of 87.5%. Discussion Lower values of GCL volume and RNFLT in patients suffering from BPD1 suggest that neurodegeneration may occur during the course of BPD and that this degeneration can be characterized in particular by a thinning of the GCL volume.

Cell therapy in the treatment of bipolar mania in an animal model: a proof of concept study / Terapia celular no tratamento do transtorno bipolar: estudo piloto em um modelo animal de mania

Abstract Introduction The rationale of mesenchymal stem cells (MSCs) as a novel therapeutic approach in certain neurodegenerative diseases is based on their ability to promote neurogenesis. Hippocampal atrophy has been related to bipolar disorder (BD) in preclinical, imaging and postmortem studies. Therefore, the development of new strategies to stimulate the neurogenesis process in BD is crucial. Objectives To investigate the behavioral and neurochemical changes induced by transplantation of MSCs in a model of mania-like behavior induced by lisdexamfetamine dimesylate (LDX). Methods Wistar rats (n=65) received one oral daily dose of LDX (10 mg/kg) or saline for 14 days. On the 8th day of treatment, the animals additionally received intrahippocampal saline or MSC (1 µL containing 25,000 cells) or lithium (47.5 mg/kg) as an internal experimental control. Two hours after the last administration, behavioral and neurochemical analyses were performed. Results LDX-treated rats had increased locomotor activity compared to saline-saline rats (p=0.004), and lithium reversed LDX-related hyperactive behavior (p<0.001). In contrast, the administration of MSCs did not change hyperlocomotion, indicating no effects of this treatment on LDX-treated rats (p=0.979). We did not find differences between groups in BDNF levels (p>0.05) in the hippocampus of rats. Conclusion Even though these results suggest that a single intrahippocampal injection of MSCs was not helpful to treat hyperactivity induced by LDX and neither influenced BDNF secretion, we cannot rule out the possible therapeutic effects of MSCs. Further research is required to determine direct effects of LDX on brain structures as well as in other pathophysiological targets related to BD.

Resumo Introdução Células-tronco mesenquimais (CTMs) têm emergido como um promissor tratamento em diversas doenças neurodegenerativas devido a sua plasticidade e capacidade de regenerar tecidos. Estudos pré-clínicos, clínicos e de neuroimagem têm demonstrado a presença de atrofia hipocampal no transtorno bipolar (TB). Portanto, o desenvolvimento de tratamentos capazes de regenerar tecido lesado e estimular a neurogênese poderia ser útil. Objetivos Investigar mudanças comportamentais e neuroquímicas induzidas pelo transplante de CTMs no hipocampo de ratos em um modelo animal de mania induzido por dimesilato de lisdexanfetamina (LDX). Métodos Ratos Wistar (n=65) receberam LDX (10 mg/kg) ou solução salina por via oral durante 14 dias. No oitavo dia, os animais foram transplantados com injeção de CTMs ou solução salina (1 µL contendo 25.000 células) ou lítio (47,5 mg/kg) como controle interno do experimento. Duas horas após a última dose, foram realizadas análises comportamentais e neuroquímicas. Resultados Animais que receberam LDX tiveram um aumento da atividade locomotora comparados ao grupo que recebeu solução salina (p=0,004); já o lítio reverteu a hiperatividade locomotora desses animais (p<0,001). Os animais que receberam CTMs não apresentaram alterações no comportamento, indicando ausência de efeitos sobre hiperatividade locomotora. Os níveis de BDNF hipocampais não diferiram entre os grupos (p>0.05). Conclusão Não foi possível demonstrar efeitos neuroprotetores das CTMs, administradas em dose única, em um modelo animal de mania induzido por LDX. No entanto, não se pode descartar os possíveis efeitos terapêuticos das CTMs. Mais estudos são necessários para determinar os efeitos das CTMs em estruturas cerebrais e outros alvos fisiopatológicos relacionados ao TB.

Conhecimento sobre a luta antimanicomial no interior de Mato Grosso / Community knowledge about anti-asylum movement in Mato Grosso / Conocimiento de la comunidad sobre la lucha antimanicomial en el interior de Mato Grosso

Em 1978, o movimento pela Luta Antimanicomial surgiu para transformar a relação da sociedade e do Estado com a loucura, buscando os direitos das pessoas com sofrimento mental, que nos anos 80, o cenário era de total desassistência. Objetivou-se descrever o conhecimento da comunidade sobre a Luta Antimanicomial. Trata-se de uma pesquisa exploratória, com abordagem quantitativa, realizada com amostragem de conveniência dos participantes da ação realizada no dia 18 de maio de 2015, em alusão a Luta Antimanicomial em Barra do Garças, Mato Grosso. Para coleta de dados, foi utilizado um questionário semiestruturado. As análises foram realizadas no programa Epi Info versão 3.5.2. Os 223 participantes apresentaram idade de 18 a 89 anos, 67% sexo masculino e 40% cursaram o ensino superior. Apenas 42 pessoas reconheceram o dia 18 de maio sendo o dia nacional da Luta Antimanicomial, 49 já ouviram falar sobre a Reforma Psiquiátrica e 96% acreditam que as ações realizadas ajudam a diminuir o preconceito sobre as doenças mentais. Concluiu-se que os participantes, em sua maioria, ainda desconhecem a história da reforma psiquiátrica do Brasil, revelando a necessidade de se desenvolver ações que contribuam para a desmistificação da loucura, para desenvolver indivíduos mais sensíveis à compreensão da dimensão do sofrimento psíquico.

In 1978, the Anti-Asylum Movement emerged to transform the relationship between society and the state with madness, seeking the rights of people with mental suffering, that in the 80s, the scene was a total lack of assistance. This study aimed to describe the community's knowledge about the Anti-Asylum Movement. This is an exploratory research with a quantitative approach, conducted with a convenience sample of participants from the action held on May 18, 2015 in reference to the Anti-Asylum Movement in Barra do Garças, Mato Grosso. For data collection, a semi-structured questionnaire was used. Analyses were performed using the program Epi Info version 3.5.2. The 223 participants were aged 18 to 89 years, 67% male and 40% have higher education. Only 42 people recognized May 18 as the National Day for the Anti-Asylum Movement, 49 heard about the Psychiatric Reform and 96% believe that the actions taken help reducing prejudice regarding mental illness. In conclusion, most of the participants are still unaware of the history of psychiatric reform in Brazil, revealing the need for the development of actions that contribute to the demystification of madness, in order to develop individuals more sensitive to the understanding of psychological distress dimension.

En 1978, el movimiento de por la Lucha Antimanicomial surgió para transformar la relación entre la sociedad y el estado con la locura, buscando los derechos de las personas con sufrimiento mental, que en los años 80, la escena era la falta total de asistencia. Este estudio tuvo como objetivo describir el conocimiento de la comunidad sobre la Lucha Antimanicomial. Tratase de un estudio exploratorio con enfoque cuantitativo, realizado con una muestra de conveniencia de los participantes de la acción realizada el 18 de mayo de 2015, en referencia a la Lucha Antimanicomial en Barra do Garças, Mato Grosso. Para la recolección de datos fue utilizado un cuestionario semiestructurado. Los análisis realizaronse utilizando la versión 3.5.2 del programa Epi Info. Los 223 participantes mostraron edad de 18 a 89 años, 67% hombres y el 40% ha cursado la educación superior. Sólo 42 personas han reconocido que el 18 de mayo es el Día Nacional de la Lucha Antimanicomial, 49 han oído hablar de la Reforma Psiquiátrica y el 96% cree que las acciones realizadas ayudan a reducir los prejuicios sobre la enfermedad mental. Concluyóse que la mayoría de los participantes aún no conoce la historia de la reforma psiquiátrica en Brasil, revelando la necesidad de desarrollar acciones que contribuyan para la desmitificación de la locura, para desarrollar los individuos más sensibles a la comprensión de la dimensión de los sufrimientos psicológicos.

Antipsychotic Prescribing Patterns in First-episode Schizophrenia: A Five-year Comparison

OBJECTIVE: Early treatment choice is critical in first-episode schizophrenia-spectrum disorders. The purpose of this study was to describe prescribing trends of antipsychotics use in patients with first-episode schizophrenia in 2005 and 2010, respectively. METHODS: We reviewed the medical records of newly treated patients with schizophrenia from a university psychiatric hospital in 2005 (n=47) and 2010 (n=52). We defined patients as receiving a high antipsychotic dose if their ratio of prescribed daily dose (PDD) to defined daily dose (DDD) was greater than 1.5. RESULTS: The rates of high-dose antipsychotic prescription were 61.7% and 53.8% in 2005 and 2010, respectively. The rates of antipsychotic polypharmacy were 34.6% in 2005 and 34.0% in 2010. The most common first-prescribed antipsychotics were (in descending order of prescription frequency) olanzapine, risperidone, aripiprazole, and haloperidol in 2005 and risperidone, quetiapine, paliperidone, and olanzapine in 2010. High-dose antipsychotics were significantly associated with antipsychotic poly-pharmacy (odds ratio=23.97; p<0.01). More individuals were treated with mood stabilizers in 2010 than in 2005 (p=0.003). CONCLUSION: The practice of prescribing high-dose antipsychotics and associated antipsychotic polypharmacy were common even for initial treatment of first-episode schizophrenia in 2005 and 2010. In 2010, the list of the most common first-prescribed antipsychotics changed, and the use of mood stabilizers increased in non-affective schizophrenia.

Histone deacetylase activity and brain-derived neurotrophic factor (BDNF) levels in a pharmacological model of mania

Objective: In the present study, we aimed to examine the effects of repeated D-amphetamine (AMPH) exposure, a well-accepted animal model of acute mania in bipolar disorder (BD), and histone deacetylase (HDAC) inhibitors on locomotor behavior and HDAC activity in the prefrontal cortex (PFC) and peripheral blood mononuclear cells (PBMCs) of rats. Moreover, we aimed to assess brain-derived neurotrophic factor (BDNF) protein and mRNA levels in these samples. Methods: We treated adult male Wistar rats with 2 mg/kg AMPH or saline intraperitoneally for 14 days. Between the 8th and 14th days, rats also received 47.5 mg/kg lithium (Li), 200 mg/kg sodium valproate (VPT), 2 mg/kg sodium butyrate (SB), or saline. We evaluated locomotor activity in the open-field task and assessed HDAC activity in the PFC and PBMCs, and BDNF levels in the PFC and plasma. Results: AMPH significantly increased locomotor activity, which was reversed by all drugs. This hyperactivity was associated with increased HDAC activity in the PFC, which was partially reversed by Li, VPT, and SB. No differences were found in BDNF levels. Conclusion: Repeated AMPH administration increases HDAC activity in the PFC without altering BDNF levels. The partial reversal of HDAC increase by Li, VPT, and SB may account for their ability to reverse AMPH-induced hyperactivity. .

El litio y su relación con la acuaporina-2 y el canal de sodio ENaC / Lithium and its relation with the epithelial sodium channel and aquaporin-2

Desde hace más de cuarenta años que el litio es usado para el tratamiento de la enfermedad bipolar; recientes estudios sugieren también su utilidad en el trastorno cognitivo mínimo tipo amnésico. El litio es filtrado en el glomérulo y un 65-75% del mismo es reabsorbido en el túbulo contorneado proximal y en el asa ascendente de Henle por el transportador Na+, K+, 2Cl- y vía paracelular. Una pequeña fracción del litio entra en las células principales del túbulo colector por medio del canal epitelial de sodio sensible al amiloride (ENaC) localizado en la membrana apical de la célula. Luego de 10- 20 años de tratamiento con litio los enfermos pueden desarrollar poliuria, acidosis tubular e insuficiencia renal crónica que puede terminar en una forma de diabetes que no responde a la arginina vasopresina llamada diabetes insípida nefrogénica. Se cree que estas fallas renales son consecuencias de una reducción en el número de moléculas de acuaporina 2 en la membrana apical. Las causas para esto son complejas. El litio es un poderoso inhibidor de la isoforma beta de la enzima glicógeno sintetasa quinasa y esto está asociado a una menor actividad de la adenilato ciclasa que lleva a una disminución en la concentración intracelular de cAMP. Esto finalmente interferiría con la síntesis de nuevas moléculas de acuaporina 2 y con el tráfico de ellas desde la zona subapical de la célula hacia la membrana celular, causando la disminución en la reabsorción de agua en la parte distal del nefrón.

For more than 40 years lithium has been used to treat bipolar disorder and recent trials suggest a potential efficacy also in the treatment of the amnestic mild cognitive impairment. Lithium is filtered by the glomerulus and 65% - 75% of the filtered amount is reabsorbed along the proximal tubule and in the thick ascending limb of Henle's loop by the Na+, K+, 2Cl- transporter and via paracellular. A small fraction of lithium is reabsorbed in the collecting duct's principal cells through the epithelial Na channel (ENaC) located on the apical side of the cells. Polyuria, renal tubular acidosis and chronic renal failure are the most frequent adverse effects of lithium after 10-20 years of treatment and these alterations can reach to a vasopressin nonresponding form of diabetes insipidus entity called nephrogenic diabetes insipidus. It is believed that the molecular mechanisms of these renal changes are related to a reduction in the number of aquaporin-2 inserted in the apical membrane of the cells. The causes of this are complex. Lithium is a powerful inhibitor of the enzyme glycogen synthase kinase 3β and this is associated with a lower activity of adenylate cyclase with a reduction in the cAMP levels inside of the cells. The latter may interfere with the synthesis of aquaporin-2 and also with the traffic of these molecules from the subapical site to membrane promoting the impairment of water reabsorption in the distal part of the kidney.

Lithium-induced sinus node dysfunction at therapeutic serum levels.

Lithium-induced cardiotoxicity, though rare at therapeutic levels, has been reported frequently in overdoses. We report a patient who developed sinus bradycardia while being treated with lithium carbonate even though the serum lithium levels were within the therapeutic range. It reversed following withdrawal of lithium and did not reappear with subsequent treatment with valproate.

O tratamento farmacológico do transtorno bipolar: uma revisão sistemática e crítica dos aspectos metodológicos dos estudos clínicos modernos / The pharmacological treatment of bipolar disorder: a systematic and critical review of the methodological aspects of modern clinical trials

OBJETIVO: Revisar sistematicamente os principais estudos clínicos sobre o tratamento farmacológico do transtorno bipolar e fazer uma análise crítica de seus aspectos metodológicos. MÉTODO: Realizou-se uma busca nas bases de dados Medline, ISI e PsycINFO, utilizando-se os seguintes termos de busca: "bipolar", "randomized", "placebo" e "controlled". Foram selecionados estudos clínicos randomizados, duplo-cegos e controlados por placebo sobre o tratamento farmacológico do transtorno bipolar. Além disso, de acordo com os nossos critérios, as amostras deveriam ser de no mínimo 100 pacientes e a substância testada deveria ser usada como monoterapia. RESULTADOS: 34 artigos se adequaram aos critérios de seleção. Todas as substâncias atualmente indicadas para mania, depressão bipolar e para o tratamento de manutenção foram mais eficazes que o placebo em pelo menos um estudo. Todavia, esses estudos tiveram amostras altamente selecionadas, altas taxas de abandono e baixas taxas de resposta clínica. CONCLUSÃO: Os modernos estudos clínicos sobre o tratamento farmacológico do transtorno bipolar apresentam algumas importantes limitações metodológicas. Assim, seus resultados devem ser considerados com cautela.

OBJECTIVE: To review systematically the main clinical trials on the pharmacological treatment of bipolar disorder and to make a critical analysis of their methodological aspects. METHOD: A search in Medline, ISI and PsycINFO databases was conducted, using the following search terms: "bipolar", "randomized", "placebo" e "controlled". Randomized, double-blind, placebo-controlled clinical trials on the pharmacological treatment of bipolar disorder were selected. Besides, according to our criteria, samples had to consist of at least 100 patients and experimental drug had to be used as monotherapy. RESULTS: 34 articles met our selection criteria. All drugs currently indicated for mania, bipolar depression and maintenance treatment of bipolar disorder were more effective than placebo in at least one clinical trial. However, these studies had highly selected samples, high dropout rates and low response rates. CONCLUSION: Modern clinical trials on pharmacological treatment of bipolar disorder have important methodological limitations. So, their results should be taken with caution.

Encefalopatía inducida por ácido valproico: serie de siete casos / Valproic acid-induced encephalopathy: series of seven cases

Introducción: La encefalopatía inducida por ácido valproico (AV) es una complicación infrecuente caracterizada por disminución del nivel de conciencia, déficits neurológicos focales, enlentecimiento cognitivo, vómitos, somnolencia y letargia, con o sin hiperamonemia. El electroencefalograma (EEG) muestra enlentecimiento difuso. Los hallazgos EEG, las manifestaciones clínicas y la hiperamonemia tienden a normalizarse con la suspensión del AV. Pacientes y Métodos: Se presenta una serie de 7 pacientes que desarrollaron encefalopatía por AV, en el Servicio de Neurología del Hospital del Salvador, entre 2003 y 2010. Se detallan dos casos clínicos ilustrativos. Resultados: La serie está compuesta por 5 mujeres y 2 hombres. Cinco pacientes desarrollaron hiperamonemia (amonemia sobre 50 ug/dl). El promedio de edad fue de 55 años (37 a 82 años). Las dosis de AV fueron de 375 a 2.000 mg (promedio = 903). La latencia entre el inicio o ajuste significativo del AVfue de 3 días hasta 16 años y un mes. Todos los pacientes presentaban daño orgánico cerebral. La politerapia con fenobarbital, fenitoína y carbamazepina fue significativa. El patrón de EEG más frecuente fue el enlentecimiento difuso. Una paciente de 82 años desarrolló actividad pseudoperiódica sugerente de un status epilepticus no convulsivo. En todos los pacientes hubo normalización clínica, de laboratorio y del EEG con la suspensión del AV. Conclusiones: La encefalopatía inducida por ácido valproico es una reacción adversa reversible pero potencialmente fatal que requiere un alto índice de sospecha. El daño orgánico cerebral y la politerapia parecen ser importantes factores de riesgo para su producción.

Introduction: Valproic acid (VA) induced encephalopathy is an unusual complication characterized by decreasing level of consciousness, focal neurological deficits, cognitive slowing, vomiting, drowsiness, and lethargy, with or without hyperammonemia. Electroencephalography (EEG) is characterized by continuous generalized slowing. The EEG findings, as well as clinical manifestations and hyperammonemia, tend to normalize after VA withdrawal. Patients and Methods: We present a series of seven patients who developed VA-induced encephalopathy at the Neurology Department of Hospital Salvador between 2003 and 2010. We report two illustrative cases in extenso. Results: Our series is composed by five women and two men. Five patients developed hyperammonemia (ammonemia above 50 ug/dl). 55years was the average of patients (range: 37 to 82 years). VA dose was between 375 and 2.000 mg (average 903 mg). Latency between start or important change in VA dose was 3 days to 16 years and a month. All patients had brain damage. Polytherapy with phenobarbital, phenytoin and carbamazepine was significant. The most frequent EEG pattern was diffuse slowing. A 82-year-old female developed a seudo-periodic activity suggesting a non-convulsive status epilepticus. The clinical manifestations, EEG findings and laboratory normalized after VA withdrawal. Conclusions: Acid valproic-induced encephalopathy is a reversible but potentially fatal adverse reaction that requires a high index of suspicion. Brain damage and polytherapy seem to be important risk factors.

Differential Expression of Activating Transcription Factor-2 and c-Jun in the Immature and Adult Rat Hippocampus Following Lithium-Pilocarpine Induced Status Epilepticus

PURPOSE: Lithium-pilocarpine induced status epilepticus (LPSE) causes selective and age-dependent neuronal death, although the mechanism of maturation-related injury has not yet been clarified. The activating transcription factor-2 (ATF-2) protein is essential for the normal development of mammalian brain and is activated by c-Jun N-terminal kinase (JNK). It induces the expression of the c-jun gene and modulates the function of the c-Jun protein, a mediator of neuronal death and survival. Therefore, we investigated the expression of c-Jun and ATF-2 protein in the immature and adult rat hippocampus to understand their roles in LPSE-induced neuronal death. MATERIALS AND METHODS: Lithium chloride was administrated to P10 and adult rats followed by pilocarpine. Neuronal injury was assessed by silver and cresyl violet staining, performed 72 hours after status epilepticus. For evaluation of the expression of ATF-2 and c-Jun by immunohistochemical method and Western blot, animals were sacrificed at 0, 4, 24, and 72 hours after the initiation of seizure. RESULTS: Neuronal injury and expression of c-Jun were maturation-dependently increased by LPSE, whereas ATF-2 immunoreactivity decreased in the mature brain. Since both c-Jun and ATF-2 are activated by JNK, and targets and competitors in the same signal transduction cascade, we could speculate that ATF-2 may compete with c-Jun for JNK phosphorylation. CONCLUSION: The results suggested a neuroprotective role of ATF-2 in this maturation-related evolution of neuronal cell death from status epilepticus.

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.

Health-related quality of life in Thai bipolar disorder.

BACKGROUND: Bipolar disorder (BPD) affects both patients 'functioning and well-being. Quality of life (QoL) has gained increasing attention as an important functional outcome in BPD. The present study was conducted to assess QoL of Thai BPD patients. MATERIAL AND METHOD: The authors obtained cross-sectional demographic, clinical, and functional ratings from 285 BPD outpatients. SF-36 and Thai Mania Rating Scale (TMRS) were used to assess QoL and severity of symptoms respectively. RESULTS: The mean TMRS was 4.42 +/- 5.87. Compared with the Thai general population, SF-36 scores of study population were significantly lower, except for bodily pain and social functioning domains. Sodium valproate treated group's SF-36 scores was better than lithium carbonate treated group' (p = 0.02). CONCLUSION: The present study is one of the pioneers in assessing the impact of co-morbidity on health-related QoL in Thai BPD patients. Even in the stable phase, patients were less functioning than the normal Thai population.

Tratamiento del trastorno afectivo bipolar en el embarazo / Treatment of bipolar disorder during pregnancy

A number offactors must be evaluated in order to determine the safety ofany medication that is being considered for use during pregnancy All psychotropic medications diffuse readily across the placenta. No psychotropic medication has been approved by the Food and Drug Administration (FDA) for use during the pregnancy and pregnant women have traditionally been excluded from pharmacologic research. Numerous studies have shown a high relapse rate in psychiatrk patient during the pregnancy whose medications were discontinued. When deciding whether or not to treat a psychiatrk patient during the pregnancy the guiding principie is to weigh the risks of fetal exposure to a psychotropic medication against the risks to both the mother and fetus of not treating a psychiatrk illness. Patients with bipolar disorder are at significant risk of relapse ifuntreated, particularly following abrupt discontinuation of lithium. Untreated bipolar illness with recurrence of mania may result in progression of the disorder. Another risk is disease chronkity and treatment resistance.

Una serie de factores deben ser evaluados a fin de determinar la seguridad de la medicación que se está considerando para su uso durante el embarazo. Todos los medicamentos psicotrópicos difunden fácilmente a través de la placenta. Ninguna medicación psicotrópica ha sido aprobada por la Food and Drug Administration (FDA) para su uso durante el embarazo, y las mujeres embarazadas han sido tradicionalmente excluidas de la investigación farmacológica. Numerosos estudios han demostrado una alta tasa de recaídas en pacientes psiquiátricos cuyos medicamentos fueron descontinuados. Al decidir si se debe o no tratar a una paciente psiquiátrica durante el embarazo, el principio rector es sopesar los riesgos de la exposición del feto a una medicación psicotrópica contra los riesgos para la madre y el feto de no tratar una enfermedad psiquiátrica. Los pacientes con trastorno bipolar se encuentran en gran riesgo de recaída si no se tratan, en particular después de la interrupción abrupta de litio. Si no se trata la enfermedad bipolar, con la recurrencia de la manía puede darse lugar a la progresión del trastorno. Otro riesgo es la cronicidad de la enfermedad y la resistencia al tratamiento.

Effect of the Dysbindin Gene on Antimanic Agents in Patients with Bipolar I Disorder

OBJECTIVE: We previously reported an association between dysbindin gene (DTNBP1) variants and bipolar I disorder (BID). This paper expands upon previous findings suggesting that DTNBP1 variants may play a role in the response to acute mood stabilizer treatment. METHODS: A total of 45 BID patients were treated with antimanic agents (lithium, valproate, or carbamazepine) for an average of 36.52 (+/-19.87) days. After treatment, the patients were evaluated using the Clinical Global Impression (CGI) scale and the Young Mania Rating Scale (YMRS) and genotyped for their DTNBP1 variants (rs3213207 A/G, rs1011313 C/T, rs2005976 G/A, rs760761 C/T and rs2619522 A/C). RESULTS: There was no association between the variants investigated and response to mood stabilizer treatment, even after considering possible stratification factors. CONCLUSION: Although the small number of subjects is an important limitation in our study, DTNBP1 does not seem to be involved in acute antimanic efficacy.