Variations in seasonal solar insolation are associated with a history of suicide attempts in bipolar I disorder

Background: Bipolar disorder is associated with circadian disruption and a high risk of suicidal behavior. In a previous exploratory study of patients with bipolar I disorder, we found that a history of suicide attempts was associated with differences between winter and summer levels of solar insolation. The purpose of this study was to confirm this finding using international data from 42% more collection sites and 25% more countries. Methods: Data analyzed were from 71 prior and new collection sites in 40 countries at a wide range of latitudes. The analysis included 4876 patients with bipolar I disorder, 45% more data than previously analyzed. Of the patients, 1496 (30.7%) had a history of suicide attempt. Solar insolation data, the amount of the sun’s electromagnetic energy striking the surface of the earth, was obtained for each onset location (479 locations in 64 countries). Results: This analysis confirmed the results of the exploratory study with the same best model and slightly better statistical significance. There was a significant inverse association between a history of suicide attempts and the ratio of mean winter insolation to mean summer insolation (mean winter insolation/mean summer insolation). This ratio is largest near the equator which has little change in solar insolation over the year, and smallest near the poles where the winter insolation is very small compared to the summer insolation. Other variables in the model associated with an increased risk of suicide attempts were a history of alcohol or substance abuse, female gender, and younger birth cohort. The winter/summer insolation ratio was also replaced with the ratio of minimum mean monthly insolation to the maximum mean monthly insolation to accommodate insolation patterns in the tropics, and nearly identical results were found. All estimated coefficients were significant at p < 0.01. Conclusion: A large change in solar insolation, both between winter and summer and between the minimum and maximum monthly values, may increase the risk of suicide attempts in bipolar I disorder. With frequent circadian rhythm dysfunction and suicidal behavior in bipolar disorder, greater understanding of the optimal roles of daylight and electric lighting in circadian entrainment is needed

Biological pathways associated with neuroprogression in bipolar disorder

There is evidence suggesting clinical progression in a subset of patients with bipolar disorder (BD). This progression is associated with worse clinical outcomes and biological changes. Molecular pathways and biological markers of clinical progression have been identified and may explain the progressive changes associated with this disorder. The biological basis for clinical progression in BD is called neuroprogression. We propose that the following intertwined pathways provide the biological basis of neuroprogression: inflammation, oxidative stress, impaired calcium signaling, endoplasmic reticulum and mitochondrial dysfunction, and impaired neuroplasticity and cellular resilience. The nonlinear interaction of these pathways may worsen clinical outcomes, cognition, and functioning. Understanding neuroprogression in BD is crucial for identifying novel therapeutic targets, preventing illness progression, and ultimately promoting better outcomes

Patogênese da encefalopatia hepática: um papel para os receptores de benzodiazepínicos?

A encefalopatia hepática (EH) é uma síndrome multifatorial, na qual a função do sistema nervoso central está alterada devido às conseqüências metabólicas da disfunção hepática. Os dois principais componentes das doenças hepáticas que levam à EH são a diminuição no número de hepatócitos funcionantes e o rearranjo vascular, que leva à diminuição na fração de sangue, efetivamente detoxificado pelo fígado. Os sintomas da EH podem variar de déficits cognitivos leves até o coma profundo. Algum grau de morte neuronal pode ser observado em pacientes com EH, como conseqüência da cirrose hepática, ou, na EH avançada, da presença de edema cerebral. No entanto, a maior parte da síndrome neurológica é reversível com a compensação da doença hepática. A etiologia da EH não é totalmente conhecida e trata-se, provavelmente, de um processo multifatorial. Inicialmente, as teorias apontavam para o acúmulo de neurotoxinas que prejudicariam a função neuronal. Mais recentemente, anormalidades em vários sistemas de neurotransmissão foram propostos como causas potencias da EH como, por exemplo, o aumento observado na neurotransmissão GABAérgica. Existe evidência de que este aumento esteja relacionado com o aumento da potenciação GABAérgica por substâncias de ação similar aos benzodiazepínicos, as quais se encontram aumentadas na EH. Com esta evidência em mente, foi tentada a terapia desta síndrome com flumazenil, um antagonista benzodiazepínico, o qual tem mostrado eficácia clínica em uma porcentagem variável de pacientes em estudos recentes. No entanto, ainda não há evidências conclusivas para sustentar uma relação causal entre o aumento de ligantes ao receptor de benzodiazepínicos e os sintomas da EH. É possível que esta relação exista em alguns, mas não em todos os pacientes com esta síndrome.Hepatic encephalopathy (HE) is a multifactorial syndrome in which the function of the central nervous system is impaired due to the metabolic consequences of liver disease. The two main components of liver pathology which lead to HE are the decrease in the number of functioning hepatocytes and the vascular rearrangement causing blood from the portal vein to bypass the liver. The symptoms of HE range from mild cognitive impairment to deep coma. Some degree of neuronal loss may be found in HE patients as a consequence of chronic cirrhosis and, in advanced HE, of brain edema; however, most of the HE syndrome is reversible with compensation of the liver disease. The pathogenesis of HE is not fully understood and &nbsp;is likely to be multifactorial. The initial theories implicated accumulation of neurotoxins leading to an impairment of neuronal function. With better understanding of the physiology of neuroreceptors, abnormalities in several neurotransmission systems have been put forward as potential causes of HE, such as a reported increase in GABAergic neurotransmission. There is evidence that this enhancement is related to an increase in the potentiation of GABAergic action by ligands to the benzodiazepine receptor (BZR), which are known to be increased in liver disease. With this evidence in mind, therapy with the benzodiazepine antagonist flumazenil has been attempted in HE, yielding clinical benefit in a variable percentage of patients in recent studies. However, there is still a lack of evidence to support a causal relationship between increased levels of benzodiazepine agonist ligands and HE symptoms. It is feasible to think that this relationship exists in some but not all HE patients

Pilot-project of implantation of pharmaceutical care close to the program of bipolar mood disorder of the Hospital of Clinics of Porto Alegre

The Bipolar Mood Disorder is characterized by the alternation of depressive crises with episodes of mania or euphoria, having these patients 15 to 35 times more chances of suicide, as compared with people without this disorder. The pharmacotherapy is fundamental for this disease, aiming to decrease the frequency of episodes and disease severity. In these patients, the polypharmacy has recently increased and one of the main difficulties is the adherence to treatment. The objective of this study was to contribute for the improvement of bipolar patients health conditions, developing their respective pharmacotherapeutic follow-up. Twenty eight adult bipolar patients who were participants of a specialized clinic within a tertiary hospital in Porto Alegre have been randomly selected, and the Dader Method of pharmacotherapeutic follow-up has been applied. The more common clinical comorbidities were: hypertension (50%), obesity (46.43%), and hypothyroidism (36.29%). The bipolar patients are more susceptible to clinical comorbidities, and many of them could be due to pharmacotherapy. Only 1.43% of patients presented Drug Related Problems, being all of them resolved along the study. It was also observed that 32.14% of evaluated patients presented low adherence to treatment, and between these patients, 55.56% passed to have good adherence after pharmacotherapeutic follow-up. The pharmacotherapeutic follow-up is fundamental for the improvement of patient's health. New studies, with higher number of patients and longer duration, are necessary to evaluate the percentage of patients that could be beneficiary of Pharmaceutical Care.O Transtorno do Humor Bipolar é caracterizando pela alternância de crises depressivas com episódios de mania ou euforia, tendo estes pacientes 15-35 vezes mais chances de suicídio em comparação com pessoas sem este transtorno. A farmacoterapia é fundamental, visando diminuir a freqüência dos episódios e a gravidade da doença. Nestes pacientes, a polifarmácia tem aumentado ultimamente e uma das maiores dificuldades é a adesão ao tratamento. O objetivo do estudo foi contribuir para a melhoria das condições de saúde de pacientes bipolares, realizando o acompanhamento farmacoterapêutico dos mesmos. Foram selecionados aleatoriamente 28 pacientes bipolares adultos, participantes de um ambulatório especializado de um hospital terciário em Porto Alegre e aplicado o Método Dáder de acompanhamento farmacoterapêutico. As co-morbidades clínicas mais comuns foram: hipertensão (50%), obesidade (46,43%) e hipotiroidismo (39,29%). Os pacientes bipolares são mais suscetíveis a co-morbidades clínicas e muitas destas podem ser devidas a farmacoterapia. Apenas 1,43% dos pacientes apresentavam Problemas Relacionados a Medicamentos, sendo todos solucionados no decorrer do estudo. Também se observou que 32,14% dos pacientes avaliados apresentavam baixa adesão ao tratamento e entre estes, 55,56% passaram a ter boa adesão após o acompanhamento farmacoterapêutico. É fundamental para a melhoria da saúde do paciente o acompanhamento farmacoterapêutico. Novos estudos, com maior número de pacientes e maior duração, são necessários para avaliar o percentual de pacientes que poderão ser beneficiados pela Atenção Farmacêutica

Mild depression levels alter self-perceptions of future but not the recall of verbal information in elderly inpatients

In order to determine the correlation of levels of symptoms of depression and rate of forgetting and perception of the future, a total of 68 elderly inpatients without Major Depression admitted to a general hospital were evaluated by: 1) the Montgomery-Asberg Depression Rating Scale (MADRS), 2) the Mini-Mental State Examination (MMSE), 3) a questionnaire on future self-perceptions (FSPQ), and 4) a test on the recall of verbal information to estimate the rate of forgetting. They were grouped according to the clinical prognosis of their disease (good, N = 48, 25 women, 23 men, age mean ± SD, 68 ± 6.64; poor, N = 20, 10 women, 10 men, age mean± SD, 69 ± 6.68) which correlates with morbidity-mortality rates (low/high). There was no relationship between mild levels of signs and symptoms of depression and increased forgetting. However, levels of depression were negatively correlated to the score of future perceptions (B = -0.18, beta = -0.29, P = 0.032). Patients with diseases with good prognosis did not present different levels of depression, rates of forgetting or future expectations from those of patients with poor prognosis (high mortality rates). However, individuals with negative FSPQ scores showed significantly higher MADRS scores, independent of the type of disease. These data suggest that the modifications in the processing of information related to the future are present in clinical patients without Major Depression but they occur within a small range of very mild signs and symptoms of depression