Adaptation and validation of the Mood Rhythm Instrument for use in Brazilian adolescents

Objective: Adapt and validate the Mood Rhythm Instrument (MRhI), a self-reported questionnaire that assesses self-perceived rhythmicity of mood-related symptoms in adults, into a version that assesses and evaluates perceived mood-related symptoms in adolescents (MRhI-Y). Methods: Adaptation of the Brazilian Portuguese version of the MRhI for an adolescent population followed three steps: review by consultants, analysis by experts, and pilot testing through a visual analogue scale (VAS). The final questionnaire (MRhI-Y) was applied to 171 adolescents aged 12-17 years. Internal consistency was calculated using Cronbach's alpha and McDonald's omega. The psychometric properties of the MRhI-Y were evaluated using exploratory factor analysis (EFA). Results: The MRhI-Y was designed to use wording more appropriate for adolescents than that of the MRhI. Expert agreement about item quality ranged between 82 and 100%. Adolescents' VAS ratings indicated good comprehension of the items. Cronbach's alpha and McDonalds' omega coefficients were 0.71 and 0.74. The EFA resulted in a three-factor solution (affective, cognitive, and somatic). Younger adolescents (ages 12 to 13) reported lower rhythmicity scores than older groups (ages 14 to 15 and 16 to 17), even controlling for chronotype. Conclusions: The Brazilian Portuguese version of the MRhI-Y presented adequate comprehension by adolescents and good internal consistency. The MRhI-Y is a promising tool to improve our understanding of the underlying characteristics of mood fluctuation in adolescence.

Melatonin use during pregnancy and lactation: A scoping review of human studies

Objective: The prevalence of sleep disorders during the perinatal period is high and large health administrative database surveys have shown that the use of exogenous melatonin in pregnant populations is quite common, about 4%. Much of the concern about using melatonin during pregnancy and breastfeeding stems from animal research. Thus, the objective of this article is to provide a critical review of human studies related to exogenous melatonin use during pregnancy and breastfeeding. Methods: The electronic databases Ovid, MEDLINE, Embase, and the Cochrane Library were searched using terms and keywords related to melatonin, pregnancy, and breastfeeding. Results: Fifteen studies were included in this review. Eight focused on melatonin use during pregnancy and seven focused on melatonin use during breastfeeding. There was a variety of study designs, including case reports, cohort studies, and clinical trials. There is a lack of randomized, controlled trials examining the efficacy and safety of melatonin as a treatment for sleep disorders during pregnancy or breastfeeding and, notably, insomnia was not the primary outcome measure in any of the studies included in this review. Clinical trials that used exogenous melatonin during pregnancy and breastfeeding for other clinical conditions have not suggested major safety concerns or adverse events. Conclusion: Contrary to what animal studies have suggested, evidence from clinical studies to date suggests that melatonin use during pregnancy and breastfeeding is probably safe in humans. This review further emphasizes the need for clinical studies on sleep disorders, including exogenous melatonin, during pregnancy and lactation.

Effective recommendations towards healthy routines to preserve mental health during the COVID-19 pandemic

Objective: To assess the adherence to a set of evidence-based recommendations to support mental health during the coronavirus disease 2019 (COVID-19) pandemic and its association with depressive and anxiety symptoms. Methods: A team of health workers and researchers prepared the recommendations, formatted into three volumes (1: COVID-19 prevention; 2: Healthy habits; 3: Biological clock and sleep). Participants were randomized to receive only Volume 1 (control), Volumes 1 and 2, Volumes 1 and 3, or all volumes. We used a convenience sample of Portuguese-speaking participants over age 18 years. An online survey consisting of sociodemographic and behavioral questionnaires and mental health instruments (Patient Health Questionnaire-9 [PHQ-9] and Generalized Anxiety Disorder-7 [GAD-7]) was administered. At 14 and 28 days later, participants were invited to complete follow-up surveys, which also included questions regarding adherence to the recommendations. A total of 409 participants completed the study - mostly young adult women holding university degrees. Results: The set of recommendations contained in Volumes 2 and 3 was effective in protecting mental health, as suggested by significant associations of adherence with PHQ-9 and GAD-7 scores (reflecting anxiety and depression symptoms, respectively). Conclusion: The recommendations developed in this study could be useful to prevent negative mental health effects in the context of the pandemic and beyond.

Physician suicide demographics and the COVID-19 pandemic

Objective: To identify suicide rates and how they relate to demographic factors (sex, race and ethnicity, age, location) among physicians compared to the general population when aggravated by the coronavirus disease 2019 (COVID-19) pandemic. Methods: We searched U.S. databases to report global suicide rates and proportionate mortality ratios (PMRs) among U.S. physicians (and non-physicians in health occupations) using National Occupational Mortality Surveillance (NOMS) data and using Wide-ranging Online Data for Epidemiologic Research (WONDER) in the general population. We also reviewed the effects of age, suicide methods and locations, COVID-19 considerations, and potential solutions to current challenges. Results: Between NOMS1 (1985-1998) and NOMS2 (1999-2013), the PMRs for suicide increased in White male physicians (1.77 to 2.03) and Black male physicians (2.50 to 4.24) but decreased in White female physicians (2.66 to 2.42). Conclusions: The interaction of non-modifiable risk factors, such as sex, race and ethnicity, age, education level/healthcare career, and location, require further investigation. Addressing systemic and organizational problems and personal resilience training are highly recommended, particularly during the additional strain from the COVID-19 pandemic.

Lifestyle predictors of depression and anxiety during COVID-19: a machine learning approach

Abstract Introduction Recent research has suggested an increase in the global prevalence of psychiatric symptoms during the COVID-19 pandemic. This study aimed to assess whether lifestyle behaviors can predict the presence of depression and anxiety in the Brazilian general population, using a model developed in Spain. Methods A web survey was conducted during April-May 2020, which included the Short Multidimensional Inventory Lifestyle Evaluation (SMILE) scale, assessing lifestyle behaviors during the COVID-19 pandemic. Depression and anxiety were examined using the PHQ-2 and the GAD-7, respectively. Elastic net, random forest, and gradient tree boosting were used to develop predictive models. Each technique used a subset of the Spanish sample to train the models, which were then tested internally (vs. the remainder of the Spanish sample) and externally (vs. the full Brazilian sample), evaluating their effectiveness. Results The study sample included 22,562 individuals (19,069 from Brazil, and 3,493 from Spain). The models developed performed similarly and were equally effective in predicting depression and anxiety in both tests, with internal test AUC-ROC values of 0.85 (depression) and 0.86 (anxiety), and external test AUC-ROC values of 0.85 (depression) and 0.84 (anxiety). Meaning of life was the strongest predictor of depression, while sleep quality was the strongest predictor of anxiety during the COVID-19 epidemic. Conclusions Specific lifestyle behaviors during the early COVID-19 epidemic successfully predicted the presence of depression and anxiety in a large Brazilian sample using machine learning models developed on a Spanish sample. Targeted interventions focused on promoting healthier lifestyles are encouraged.

From anatomy to function: the role of the somatosensory cortex in emotional regulation

Since the pioneering work of Penfield and his colleagues in the 1930s, the somatosensory cortex, which is located on the postcentral gyrus, has been known for its central role in processing sensory information from various parts of the body. More recently, a converging body of literature has shown that the somatosensory cortex also plays an important role in each stage of emotional processing, including identification of emotional significance in a stimulus, generation of emotional states, and regulation of emotion. Importantly, studies conducted in individuals suffering from mental disorders associated with abnormal emotional regulation, such as major depression, bipolar disorder, schizophrenia, post-traumatic stress disorder, anxiety and panic disorders, specific phobia, obesity, and obsessive-compulsive disorder, have found structural and functional changes in the somatosensory cortex. Common observations in the somatosensory cortices of individuals with mood disorders include alterations in gray matter volume, cortical thickness, abnormal functional connectivity with other brain regions, and changes in metabolic rates. These findings support the hypothesis that the somatosensory cortex may be a treatment target for certain mental disorders. In this review, we discuss the anatomy, connectivity, and functions of the somatosensory cortex, with a focus on its role in emotional regulation.

Salivary cortisol during memory encoding in pregnancy predicts postpartum depressive symptoms: a longitudinal study / Cortisol salivar durante aquisição de memória na gravidez prediz sintomas depressivos no período pós-parto: um estudo longitudinal

Abstract Introduction Postpartum depression (PPD) is a common disorder that substantially decreases quality of life for both mother and child. In this longitudinal study, we investigated whether emotional memory, salivary cortisol (sCORT) or alpha-amylase during pregnancy predict postpartum depressive symptoms. Methods Forty-four pregnant women (14 euthymic women with a diagnosis of major depressive disorder [MDD] and 30 healthy women) between the ages of 19 and 37 years (mean age = 29.5±4.1 years) were longitudinally assessed in the 2nd trimester of pregnancy (12-22 weeks of gestational age) and again at 14-17 weeks postpartum. Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS). Results Follow-ups were completed for 41 women (7% attrition). Postpartum EPDS scores were predicted by sCORT collected immediately after an incidental encoding memory task during pregnancy (b=-0.78, t -2.14, p=0.04). Postpartum EPDS scores were not predicted by positive (p=0.27) or negative (p=0.85) emotional memory. Conclusions The results of this study indicate that higher levels of sCORT during a memory encoding task in the 2nd trimester of pregnancy are associated with lower postpartum EPDS scores. While the hypothalamus-pituitary-adrenal (HPA) axis has long been associated with the neurobiology of MDD, the role of the HPA axis in perinatal depression deserves more attention.

Resumo Introdução A depressão pós-parto é um transtorno prevalente que afeta negativamente a qualidade de vida da mãe e da criança. Neste estudo longitudinal, nós investigamos se a memória emocional, o cortisol salivar (salivary cortisol, sCORT) ou alfa-amilase durante a gravidez predizem sintomas depressivos no período pós-parto. Métodos Um total de 44 mulheres grávidas [14 eutímicas com diagnóstico de transtorno depressivo maior (TDM) e 30 voluntárias sadias] entre 19 e 37 anos de idade (idade média = 29.5±4.1 anos) foram avaliadas longitudinalmente no 2° trimestre da gravidez (12-22 semanas de gestação) e na 1417ª semana pós-parto. Sintomas depressivos foram avaliados com a Escala de Depressão Pós-Natal de Edimburgo (Edinburgh Postnatal Depression Scale, EPDS). Resultados Quarenta e uma mulheres completaram o seguimento (7% de perda). sCORT coletado imediatamente antes de um teste de aquisição memória durante a gravidez foi preditor dos escores da escala EPDS no período pós-parto (b=-0.78, t -2.14, p=0.04). Memória emocional positiva (p=0.27) ou negativa (p=0.85) não foram preditores dos escores da escala EPDS no período pós-parto. Conclusão Os resultados deste estudo indicam que altos níveis de sCORT durante um teste de aquisição de memória no 2° trimestre da gravidez foram associados com baixos escores na escala EPDS no período pós-parto. Uma vez que o eixo hipotálamo-hipófise-adrenal (HHA) tenha sido envolvido na neurobiologia do TDM, o papel do eixo HHA na depressão perinatal merece mais atenção.

Validation of the Brazilian Portuguese version of the Premenstrual Symptoms Screening Tool (PSST) and association of PSST scores with health-related quality of life

Objective: To develop and validate a Brazilian Portuguese version of the Premenstrual Symptoms Screening Tool (PSST), a questionnaire used for the screening of premenstrual syndrome (PMS) and of the most severe form of PMS, premenstrual dysphoric disorder (PMDD). The PSST also rates the impact of premenstrual symptoms on daily activities. Methods: A consecutive sample of 801 women aged ≥ 18 years completed the study protocol. The internal consistency, test-retest reliability, and content validity of the Brazilian PSST were determined. The independent association of a positive screen for PMS or PMDD and quality of life determined by the World Health Organization Quality of Life instrument-Abbreviated version (WHOQOL-Bref) was also assessed. Results: Of 801 participants, 132 (16.5%) had a positive screening for PMDD. The Brazilian PSST had adequate internal consistency (Cronbach’s alpha = 0.91) and test-retest reliability. The PSST also had adequate convergent/discriminant validity, without redundancy. Content validity ratio and content validity index were 0.61 and 0.94 respectively. Finally, a positive screen for PMS/PMDD was associated with worse WHOQOL-Bref scores. Conclusions: These findings suggest that PSST is a reliable and valid instrument to screen for PMS/PMDD in Brazilian women.

Relationship between inflammatory biomarkers and depressive symptoms during late pregnancy and the early postpartum period: a longitudinal study

Objective: Perinatal depressive symptoms often co-occur with other inflammatory morbidities of pregnancy. The goals of our study were 1) to examine whether changes in inflammatory markers from the third trimester of pregnancy to 12 weeks postpartum were associated with changes in depressive symptoms; 2) to examine whether third trimester inflammatory markers alone were predictive of postpartum depressive symptoms; and 3) to examine the relationship between inflammatory markers and depressive symptoms during the third trimester of pregnancy and at 12 weeks postpartum. Methods: Thirty-three healthy pregnant women were recruited from the Women’s Health Concerns Clinic at St. Joseph’s Healthcare in Hamilton, Canada. The impact of depressive symptoms on the levels of interleukin (IL)-6, IL-10, tumor necrosis factor alpha (TNF-α), and C-reactive protein (CRP) at the third trimester of pregnancy, at 12 weeks postpartum, and across time was assessed using linear and mixed-model regression. Results: Regression analysis revealed no significant association between depressive symptoms and any of the candidate biomarkers during pregnancy, at 12 weeks postpartum, or over time. Pregnancy depressive symptoms (p > 0.001), IL-6 (p = 0.025), and IL-10 (p = 0.006) were significant predictors of postpartum Edinburgh Perinatal Depression Scale (EPDS) score. Conclusions: Our study supports previous reports from the literature showing no relationship between inflammatory biomarkers and depressive symptoms during late pregnancy, early postpartum, or across time. Our study is the first to observe an association between late pregnancy levels of IL-6 and IL-10 and postpartum depressive symptoms. Further studies with larger samples are required to confirm these findings.

The Mood Rhythm Instrument: development and preliminary report

Objective: To describe the initial steps in the development and validation of a new self-reported instrument designed to assess daily rhythms of mood symptoms, namely, the Mood Rhythm Instrument. Methods: A multidisciplinary group of experts took part in systematic meetings to plan the construction of the instrument. Clarity of items, their relevance to evaluation of mood states, and the consistency of findings in relation to the available evidence on the biological basis of mood disorders were investigated. The internal consistency of the questionnaire was evaluated through Cronbach’s alpha. Results: All of the items proposed in a first version were well rated in terms of clarity. The items more frequently rated as “rhythmic” were related to the somatic symptoms of mood. Their peaks in 24 hours were more frequent in the morning. The items associated with affective symptoms of mood were rated as less rhythmic, and their peak in 24 hours occurred more frequently in the afternoon and evening. Males and females behaved more similarly with respect to somatic than behavioral-affective items. The second version of the Mood Rhythm Instrument had a Cronbach’s alpha of 0.73. Conclusion: The proposed Mood Rhythm Instrument may be able to detect individual rhythms of cognitive and behavioral measures associated with mood states. Validation in larger samples and against objective measures of rhythms, such as actigraphy, is warranted.

Mitochondrial Dysfunction in Bipolar Disorder: Lessons from Brain Imaging and Molecular Markers / Disfunción mitocondrial en el trastorno bipolar: lecciones de las imágenes cerebrales y los marcadores moleculares

Bipolar disorder (BD) is a chronic major mental illness characterized by extreme mood episodes, cognitive impairment, and high rates of disability. Several lines of evidence suggest that BD may be associated with abnormalities in mitochondrial function. Here we critically review findings from brain imaging and from preclinical studies that investigated markers of energy metabolism in BD. Research with postmortem brain and peripheral tissue revealed changes in size and distribution of mitochondria, as well as decreased mitochondrial electron transport chain function, increased oxidative stress, and increased lipid and protein damage. PET imaging studies revealed decreased glucose metabolism in sub-areas of the prefrontal cortex, amygdala, and hippocampus structures in BD. On the other hand, increased lactate levels in BD have been found in cerebrospinal fluid and in gray matter by magnetic resonance spectroscopy, which suggest that distinct pathophysiological processes may be region-specific. Resting state fMRI studies have demonstrated decreased functional connectivity between fronto-limbic circuits. In conclusion, these results support the hypothesis of mitochondrial dysfunction in BD and suggest that BD is associated with decreased energy production and a shift towards anaerobic glycolysis. Such changes in energy metabolism can potentially decrease cell plasticity and ultimately disrupt brain circuits associated with mood and cognitive control.

El trastorno bipolar (TB) es una enfermedad mental crónica grave caracterizada por episodios de ánimo extremo, trastornos cognitivos y altas tasas de discapacidad. Varias líneas de evidencia sugieren que el TB puede estar asociado con anormalidades en la función mitocondrial. Aquí analizamos críticamente los hallazgos de las imágenes cerebrales y de los estudios preclínicos que han investigado los marcadores del metabolismo de energía en TB. Las investigaciones post mórtem basadas en tejidos cerebrales y tejidos periféricos revelaron cambios en el tamaño y en la distribución de las mitocondrias, además de una disminución en la funcionalidad de la cadena de transporte de electrones de las mitocondrias, un mayor estrés oxidativo y mayores daños lipídicos y proteínicos. Estudios con imágenes TEP revelan un metabolismo de glucosa disminuido en las subáreas de la corteza prefrontal, la amígdala y el hipocampo en TB. Por otro lado, se han hallado concentraciones mayores de lactato en TB en el líquido cefalorraquídeo cerebral y en la materia gris utilizando la espectroscopia con resonancia magnética, lo cual sugiere que los procesos fisiopatológicos individuales pueden ser específicos de las distintas regiones. Los estudios con resonancias magnéticas funcionales han demostrado una menor conectividad funcional entre los circuitos frontolímbicos. En conclusión, estos resultados apoyan la hipótesis de una disfunción mitocondrial en el TB y sugieren que el TB está asociado con una menor producción de energía y un cambio hacia la glicólisis anaeróbica. Estos cambios en el metabolismo energético pueden disminuir potencialmente la plasticidad celular y, en últimas, perturbar los circuitos cerebrales asociados con el estado de ánimo y el control cognitivo.

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.

Fluvoxamina no transtorno depressivo maior: um estudo multicêntrico aberto / Fluvoxamine in the treatment of major depressive disorder: an open multicentric study

OBJETIVO: Este trabalho estudou a eficácia e a tolerabilidade da fluvoxamina no tratamento, de forma aberta, sem comparação com placebo ou outros agentes, por 6 semanas, de pacientes com o diagnóstico de transtorno depressivo maior (TDM). Constitui-se em objetivo secundário do estudo avaliar os efeitos da fluvoxamina sobre o sono dos pacientes. MÉTODOS: Foram incluídos 104 pacientes, maiores de 18 anos, com o diagnóstico de TDM, de acordo com os critérios do Manual Diagnóstico e Estatístico de Transtornos Mentais, 4ª edição (DSM-IV), e com escores, na Escala de Hamilton para Depressão, versão de 17 itens (HAM-D 17), de 17 pontos ou mais. Avaliou-se a eficácia da fluvoxamina por meio das Escalas HAM-D 17 e da CGI (Impressão Clínica Global). A análise dos itens 4, 5 e 6 da HAM-D 17 foi utilizada para a avaliação do sono dos pacientes. Avaliaram-se a segurança e a tolerabilidade da fluvoxamina ao longo das 6 semanas, registrando-se quaisquer eventos adversos. A fluvoxamina foi inicialmente ministrada em doses de 50 ou 100 mg/dia, podendo haver aumentos progressivos até 300 mg/dia. RESULTADOS: Dos 104 pacientes incluídos, 81 (78 por cento) concluíram o estudo. Obtiveram resposta favorável (diminuição de 50 por cento ou mais na HAM-D 17) 69 por cento dos pacientes, e a taxa de remissão (HAM-D 17 < 7) foi de 52 por cento. A análise da CGI indicou ter havido melhora significante (p < 0,001) em relação aos escores de base. A análise específica dos itens relativos ao sono, na HAM-D 17, revelou melhora significativa já na segunda visita, mantendo-se ao longo das 6 semanas. Os eventos adversos foram os esperados para inibidores seletivos de recaptação da serotonina, predominando as queixas gastrointestinais, em sua maioria transitórias e de pequena intensidade. CONCLUSÃO: O estudo vem confirmar a eficácia e a tolerabilidade da fluvoxamina no tratamento do transtorno depressivo maior, assim como sua eficácia no tratamento das alterações do sono encontradas...

OBJECTIVE: This research studied the efficacy and tolerability of fluvoxamine in the treatment of major depressive disorder (MDD), during 6 weeks, in an open trial, without placebo or active comparator. A secondary objective was the evaluation of the effects of fluvoxamine on the sleep of the pacients. METHODS: 104 patients were inicially included, with the diagnosis of MDD in accordance to the criteria of the Diagnostic and Statistical Manual for Mental Disorders, 4th edition (DSM-IV). Patients should have scores > 17 in the Hamilton Depression Scale for Depression 17 itens (HAM-D 17). The efficacy of fluvoxamine was studied through the HAM-D 17 and CGI (Clinical Global Impression). The analysis of the HAM-D 17 itens 4, 5, and 6 was used for the evaluation of the quality of sleep of the patients. Security and tolerability of fluvoxamine was assessed throughout the six weeks, being registered any adverse event. Fluvoxamine was inicially administered at the doses of 50 or 100 mg/day; the doses could be progressively increased until 300 mg/day. RESULTS: From the 104 included patients, 81 (78 percent) concluded the study. Sixty nine percent (69 percent) of the patients obtained favorable response (defined as 50 percent improvement in the HAM-D 17) and the remission rate (HAM-D 17 < 7) was 52 percent. The specific analysis of CGI showed significant improvement (p < 0.001) comparing to the baseline scores. The speficic analysis of the sleep itens of the HAM-D 17 showed significant improvement from the 2nd week; the improvement was sustained until the end of the 6 weeks study. The adverse events were those expected for the serotonin selective reuptake inhibitors (SSRI), predominantly gastrointestinal complaints, transitory and of low intensity in most of the cases. CONCLUSION: This study confirms the efficacy and tolerability of fluvoxamine in the treatment of MDD, and also its efficacy in the treatment of sleep disturbs among depressed patients. The...

As bases neurobiológicas do transtorno bipolar / Neurobiological basis of bipolar disorder

Neste artigo, os autores revisam importantes aspectos associados às bases biológicas do transtorno de humor bipolar (THB). O THB está relacionado com o surgimento de diversas alterações bioquímicas e moleculares em sistemas de neurotransmissão e vias de segundos-mensageiros geradores de sinais intracelulares. Essas modificações em neurônios e glia parecem estar associadas com o surgimento de sintomas maníacos e depressivos. Ainda neste contexto, disfunções na homeostasia e no metabolismo energético cerebral tem sido associado com alterações comportamentais, na modulação do humor e ritmo circadiano em humanos e em modelos animais da doença. Assim, alterações metabólicas em neurônios e células gliais têm sido associadas com quadros depressivos e maníacos. Nos últimos anos, avanços nas técnicas de neuroimagem, genéticos e de biologia moleculares têm gerado novos conhecimentos acerca das bases biológicas da bipolaridade. Os autores destacam que a doença parece estar relacionada diretamente com disfunções em diferentes mecanismos adaptativos a estresse em células neurais, gerando perda na capacidade celular de induzir neuroplasticidade e neurotrofismo, facilitando assim o surgimento da doença.

Tratamento farmacológico do transtorno bipolar: as evidências de ensaios clínicos randomizados / Pharmacological treatment of bipolar disorder: evidence from randomized clinical trials

O presente artigo é uma síntese das evidências provenientes de ensaios clínicos randomizados sobre o tratamento do transtorno bipolar. A metodologia para a busca do material disponível é descrita, e os resultados são apresentados. Com o melhor nível de evidência disponível, ou seja, revisões sistemáticas de mais de um ensaio clínico randomizado ou pelo menos um ensaio clínico randomizado, temos as seguintes recomendações: 1) a mania aguda pode ser tratada com Lítio, Valproato, Carbamazepina, e antipsicóticos; 2) a depressão bipolar pode ser tratada com antidepressivos (com risco aumentado de virada para mania), com lamotrigina e a associação fluoxetina/olanzapina e 3) a manutenção do transtorno bipolar pode ser realizada com o lítio, valproato, carbamazepina, olanzapina e lamotrigina (quando o objetivo for a profilaxia da depressão bipolar). A não existência de ensaios clínicos publicados não significa que determinadas intervenções não sejam úteis.

Fisiopatologia do transtorno afetivo bipolar: o que mudou nos últimos 10 anos? / Physiopathology of bipolar disorders: what have changed in the last 10 years?

Apesar dos crescentes esforços para o entendimento da neurobiologia do transtorno afetivo bipolar (TAB), sua exata fisiopatologia permanece indeterminada. Inicialmente, a pesquisa estava voltada para o estudo das aminas biogênicas, devido aos efeitos dos diversos agentes psicofarmacológicos. Mais recentemente, evidências apontam que disfunções nos sistemas de sinalização intracelular e de expressão gênica podem estar associadas ao TAB. Estas alterações podem estar associadas a interrupções nos circuitos reguladores do humor, como sistema límbico, estriado e córtex pré-frontal, sendo que os efeitos neuroprotetores do uso crônico dos estabilizadores de humor podem reverter este processo patológico. Este artigo tem como objetivo trazer uma atualização dos achados recentes sobre a neuroquímica do TAB.

Anormalidades neuropatológicas e neuroquímicas no transtorno afetivo bipolar / Neuropatological and neurochemical abnormalities in bipolar disorder

OBJETIVOS: Estudos pós-mortem, farmacológicos, de neuroimagem e em modelos animais têm demonstrado uma possível associação de mecanismos de sinalização intracelular na fisiopatologia do transtorno afetivo bipolar (TAB). Esse trabalho tem como objetivo revisar os achados em neuropatologia e bioquímica celular. MÉTODOS: Foi realizada uma pesquisa ao MEDLINE, entre 1980 e 2003, tendo sido utilizados os unitermos: bipolar disorder, signaling, second messengers e postmortem, além de referências cruzadas dos artigos selecionados. RESULTADOS: uropatológicos demonstraram uma diminuição do número de células neuronais e gliais, principalmente no córtex pré-frontal de pacientes bipolares. Estudos neuroquímicos demonstraram alterações nas vias do AMPc, fosfatidilinositol, Wnt/GSK-3beta e Ca++ intracelular nesses pacientes. CONCLUSÃO: Os achados de alterações neuropatológicas e neuroquímicas no TAB podem estar relacionados com a fisiopatologia deste transtorno e com os efeitos dos estabilizadores de humor. No entanto, mais estudos são necessários para esclarecer o papel das cascatas de sinalização intracelular na patogênese deste transtorno.

A integração da psicofarmacoterapia e psicoterapia de orientação analítica: uma revisão crítica / The integration of psychopharmacotherapy and psychoanalytical psychotherapy: a critical review

OBJETIVO: A integração entre a psicoterapia e a psicofarmacoterapia tem sido uma questão conflitante na história da psiquiatria. Ainda hoje, observa-se uma dicotomia entre as correntes "biológica" e "psicológica", embora estudos mais recentes venham demonstrando a importância da associação dessas modalidades na prática psiquiátrica atual. O objetivo deste trabalho é revisar os aspectos psicodinâmicos e técnicos, entre outros, que envolvem a integração entre o tratamento medicamentoso e psicoterápico. MÉTODOS: A revisão da literatura foi realizada através da busca on-line das bases de dados MEDLINE, PsychoINFO e Lilacs, no período entre 1966 e setembro de 2002. RESULTADOS: Os estudos revisados demonstraram que a aplicação do tratamento combinado parece ser uma associação positiva. CONCLUSÕES: A eficácia do tratamento combinado depende da capacidade de integração das diferentes formas de tratamento. São necessárias mais pesquisas nesta área.