Objectives: Ketamine has a fast onset of action that may offer a paradigm change for depression management at the end of life. We aimed to synthesize evidence regarding the safety and efficacy of ketamine in depression treatment within a broad palliative care concept. Methods: We searched seven databases and included studies on the safety and efficacy of ketamine for depression treatment in patients diagnosed with any life-threatening disease. We also conducted a narrative review of the evidence. Results: Among 2,252 screened titles and abstracts, we included 32 studies in our final synthesis: 14 case reports, two case series, two quasi-experimental studies, and seven randomized clinical trials (RCTs), as well as data from three unpublished clinical trials and seven cases from four larger case series. Most case reports reported a robust effect; however, the larger studies reported conflicting findings. Five RCTs reported positive outcomes; however, four of them were focused on a perioperative setting. Two negative studies did not primarily focus on depression and did not apply severity cutoffs. Conclusion: Although ketamine is generally safe and potentially useful, its efficacy in palliative care settings remains unclear. It may be a reasonable alternative for perioperative depression in oncological patients.

ABSTRACT Background: Patients with Bipolar Disorder (BD) have the highest lifetime risk for suicidal behavior (SB) compared to other psychiatric disorders. Neuroimaging research provides evidence of some structural and functional abnormalities in the brain of BD suicide attempters (SA), but interpretation of these findings may represent a number of features. Objective: The purpose of this study was to evaluate the volume of the prefrontal cortex in euthymic BD type I outpatients, with and without history of SA. Methods: 36 euthymic BD I outpatients (18 with and 18 without suicide attempt history) were underwent structural MRI and total and regional gray matter volumes were assessed and compared with 22 healthy controls (HC). Results: We did not found any differences in all areas between suicidal and non-suicidal BD I patients and BD patients as a group compared to HC as well. Discussion: our findings suggest that can be a different subgroups of patients in relation to prefrontal cortex volumes according to some clinical and socio-demographic caractheristics, such as number of previous episodes and continuous use of medical psychotropic drugs that may induce neuroplasticity phenomena, which restore cerebral volume and possibly can lead to long-term euthymia state.

Abstract Background Brain-imaging studies in post-traumatic stress disorder (PTSD) have consistently revealed alterations in brain structure and function and this is correlated to symptomatology. However, few studies have investigated the role of biomarkers in PTSD some specific groups, as police officers. Objective To evaluate prefrontal and limbic volumes, and cortical thickness of police officers exposed to trauma during work who developed post-traumatic stress disorder, resilient matched controls (without PTSD), and compared to healthy civilians. Methods Prefrontal and limbic volumes, and cortical thickness of 12 police officers with PTSD, 12 resilient police officers, and 12 healthy civilians who underwent brain MRI were analyzed. Results Differences in limbic structures volume were not significative after Bonferroni correction. A significant reduction in cortical thickness on right rostral cingulate, right and left middle frontal gyrus, left superior frontal, left lingual, calcarine and cuneus were observed in PTSD group in comparison to controls was observed. Discussion Although preliminary, our results suggested not only the association between cortical thickness and PTSD, but also indicated that patients and controls have anatomical differences.

OBJECTIVE: To establish whether alterations of brain structures in Alzheimer's disease are associated with executive dysfunction. METHODS: Nineteen patients with Alzheimer's disease and 22 older control subjects underwent a comprehensive evaluation. The clock drawing test, digit span test, executive motor function test, Behavioral Assessment of the Dysexecutive Syndrome battery (Rule Shift Cards test), and Stroop test were used to evaluate executive dysfunction. A multiparametric approach using the FreeSurfer image analysis suite provided a description of volumetric and geometric features of the gray matter structures. RESULTS: The cortical thickness maps showed a negative correlation between the Behavioral Assessment of the Dysexecutive Syndrome battery (Rule Shift Cards test) and the right middle frontal gyrus; a positive correlation between the executive motor function test and the left superior parietal gyrus, left middle temporal gyrus, bilateral supramarginal gyri, right middle frontal gyrus, and right precuneus; a negative correlation between the Stroop test (part III) and the right superior parietal gyrus; and a negative correlation between the Stroop test (part III) and the right middle temporal gyrus. CONCLUSION: Executive dysfunction in Alzheimer's disease is correlated with alterations not only in the frontal areas but also within many temporal and parietal regions.

Objective: Functional neuroimaging techniques represent fundamental tools in the context of translational research integrating neurobiology, psychopathology, neuropsychology, and therapeutics. In addition, cognitive-behavioral therapy (CBT) has proven its efficacy in the treatment of anxiety disorders and may be useful in phobias. The literature has shown that feelings and behaviors are mediated by specific brain circuits, and changes in patterns of interaction should be associated with cerebral alterations. Based on these concepts, a systematic review was conducted aiming to evaluate the impact of CBT on phobic disorders measured by functional neuroimaging techniques. Methods: A systematic review of the literature was conducted including studies published between January 1980 and April 2012. Studies written in English, Spanish or Portuguese evaluating changes in the pattern of functional neuroimaging before and after CBT in patients with phobic disorders were included. Results: The initial search strategy retrieved 45 studies. Six of these studies met all inclusion criteria. Significant deactivations in the amygdala, insula, thalamus and hippocampus, as well as activation of the medial orbitofrontal cortex, were observed after CBT in phobic patients when compared with controls. Conclusion: In spite of their technical limitations, neuroimaging techniques provide neurobiological support for the efficacy of CBT in the treatment of phobic disorders. Further studies are needed to confirm this conclusion.

RESUMO Novas evidências sugerem que o cerebelo apresenta alterações estruturais e funcionais nos transtornos psiquiátricos. Objetivo: Medir o volume do cerebelo e de suas sub-regiões em indivíduos portadores de transtornos psiquiátricos e relacionar tais achados aos sintomas. Métodos: Foi realizada a identificação de pacientes com diferentes graus de prejuízo cognitivo proveniente de um estudo populacional (Epidemiologia do Idoso - UNIFESP), pacientes com transtorno do estresse pós-traumático proveniente de outro estudo populacional e portadores de transtorno bipolar proveniente de um ambulatório especializado (Universidade Federal da Bahia). Todos os sujeitos foram submetidos à ressonância magnética estrutural de 1.5T. As medidas de volume, assim como os sintomas medidos por escalas psicométricas foram comparadas entre pacientes e controles. Resultados: Foi observado que o volume do cerebelo está reduzido nos portadores de prejuízo cognitivo sem demência e com demência, no transtorno do estresse pós-traumático e no transtorno bipolar quando comparados aos controles. Na demência e no transtorno do estresse pós-traumático o volume do hemisfério cerebelar esquerdo e do vérmis estão reduzidos. No transtorno bipolar os volumes de ambos os hemisférios e do vérmis estão reduzidos. Nos dois primeiros estudos estas reduções correlacionaram com os sintomas. Conclusão: A natureza exata do envolvimento do cerebelo nos processos mentais ainda não é compreendida. Entretanto, anormalidades na estrutura cerebelar e em suas funções têm sido relatadas em algumas dessas doenças. Pesquisas futuras, com amostras maiores, ainda são necessárias para esclarecer tais achados e investigar se são importantes para o tratamento e prognóstico.

ABSTRACT. New evidence suggests that the cerebellum has structural and functional abnormalities in psychiatric disorders. Objective: In this research, the goal was to measure the volume of the cerebellum and its subregions in individuals with psychiatric disorders and to relate these findings to their symptoms. Methods: Patients with different degrees of cognitive impairment (Epidemiology of the Elderly - UNIFESP) and patients with post-traumatic stress disorder (PTSD) from population studies were analyzed. Also, patients with bipolar disorder from an outpatient clinic (Center for the Study of Mood and Anxiety Disorders, Universidade Federal da Bahia) were recruited for this study. All subjects underwent a 1.5T structural magnetic resonance scan. Volumetric measures and symptom measurements, by psychometric scales, were performed and compared between patients and controls. Results: The cerebellum volume was reduced in patients with cognitive impairment without dementia and with dementia, in patients with PTSD, and in patients with bipolar disorder compared to controls. In dementia and PTSD, the left cerebellar hemisphere and vermis volume were reduced. In bipolar disorder, volumes of both hemispheres and the vermis were reduced. In the first two studies, these cerebellar volumetric reductions correlated with symptoms of the disease. Conclusion: The exact nature of cerebellar involvement in mental processes is still not fully understood. However, abnormalities in cerebellar structure and its functions have been reported in some of these diseases. Future studies with larger samples are needed to clarify these findings and investigate whether they are important for treatment and prognosis.

OBJETIVO: Avaliar a combinação de dois fatores: clinical dementia rating sum of boxes scores (CDR-SB) e volume hipocampal (VH) como preditores de conversão de ditúrbio cognitivo leve (DCL) em demência. MÉTODO: Vinte e oito indivíduos (9 normais e 19 com DCL) foram classificados de acordo com a soma dos escores CDR-SB em 3 grupos. RESULTADOS: O volume do hipocampo foi significativamente menor no grupo de alto risco e naqueles que desenvolveram demência depois de dois anos. A taxa de conversão foi crescente entre os três grupos. CONCLUSÃO: Propusemos uma medição adicional do volume do hipocampo que pode ser útil no prognóstico. No entanto, notou-se que a CDR-SB é um método tão eficiente quanto neuroimagem para prever demência com a vantagem de ser um processo de baixo custo e de fácil implementação, mais consistente com a política pública.

OBJECTIVE: To evaluate the combination of two factors: clinical dementia rating sum of boxes scores (CDR-SB) and hippocampal volume (HV) as predictors of conversion from mild cognitive impairment (MCI) to dementia. METHODS: Twenty-eight individuals (9 normal and 19 with MCI) were classified according to their CDR sum of boxes scores into 3 groups. RESULTS: The hippocampal volume was significantly lower in the high-risk group and in those who developed dementia after two years. The rate of conversion was crescent among the three groups. CONCLUSION: We were proposed an additional measurement of the hippocampal volume which may be helpful in the prognosis. However, we noted that the CDR-SB is a method as efficient as neuroimaging to predict dementia with the advantage of being a procedure for low cost and easy implementation, more consistent with public policy.

OBJETIVO: Relatar estudos de neuroimagens estruturais e funcionais explorando o papel potencial do córtex orbitofrontal (COF) na fisiopatologia dos transtornos psiquiátricos (TP) mais prevalentes. MÉTODO: Foi realizada uma revisão não sistemática da literatura no MEDLINE, usando como parâmetros os seguintes termos: "córtex orbitofrontal", "esquizofrenia", "transtorno bipolar", "depressão maior", "transtornos ansiosos", "transtornos de personalidade" e "dependência a drogas". A pesquisa eletrônica foi feita até julho de 2011. DISCUSSÃO: Foram relatadas anormalidades estruturais e funcionais do COF em muitos TP, particularmente esquizofrenia, transtornos afetivos, transtornos ansiosos, transtornos de personalidade e dependência a drogas. Estudos de aquisição de imagens estruturais por ressonância magnética relataram a redução do volume do COF em pacientes portadores de esquizofrenia, transtornos afetivos, TEPT, transtorno do pânico, transtornos de personalidade do grupo B e dependência a drogas. Além disso, estudos de aquisição de imagens funcionais por ressonância magnética empregando paradigmas cognitivos demonstraram alterações na atividade do COF em todos os TP anteriormente relacionados. CONCLUSÃO: Estudos de neuroimagens observaram um envolvimento importante do COF em vários TP. Entretanto, estudos futuros são claramente necessários para caracterizar o papel específico do COF em cada TP, assim como para a compreensão de seu papel tanto no comportamento normal como no patológico, na regulação do humor e no funcionamento cognitivo.

OBJECTIVE: To report structural and functional neuroimaging studies exploring the potential role of the orbitofrontal cortex (OFC) in the pathophysiology of the most prevalent psychiatric disorders (PD). METHOD: A non-systematic literature review was conducted by means of MEDLINE using the following terms as parameters: "orbitofrontal cortex", "schizophrenia", "bipolar disorder", "major depression", "anxiety disorders", "personality disorders" and "drug addiction". The electronic search was done up to July 2011. DISCUSSION: Structural and functional OFC abnormalities have been reported in many PD, namely schizophrenia, mood disorders, anxiety disorders, personality disorders and drug addiction. Structural magnetic resonance imaging studies have reported reduced OFC volume in patients with schizophrenia, mood disorders, PTSD, panic disorder, cluster B personality disorders and drug addiction. Furthermore, functional magnetic resonance imaging studies using cognitive paradigms have shown impaired OFC activity in all PD listed above. CONCLUSION: Neuroimaging studies have observed an important OFC involvement in a number of PD. However, future studies are clearly needed to characterize the specific role of OFC on each PD as well as understanding its role in both normal and pathological behavior, mood regulation and cognitive functioning.

OBJETIVO: O objetivo deste estudo foi examinar o volume cerebelar em indivíduos em diferentes fases da doença de Alzheimer e investigar se sua redução estaria relacionada com o declínio cognitivo. MÉTODO: Noventa e seis indivíduos de um estudo epidemiológico foram submetidos à ressonância magnética e avaliados por meio do Mini Exame do Estado Mental e do Questionário de Atividades Funcionais. Os sujeitos foram divididos em cinco grupos de acordo com a Escala de Gravidade da Demência. Vinte e seis indivíduos do grupo original que não tinham o diagnóstico de demência no início do estudo foram reavaliados após dois anos para detectar o desenvolvimento da doença. RESULTADOS: Os volumes dos hemisférios cerebelares, lobo cerebelar posterior, vermis e lobo temporal estavam diminuídos proporcionalmente à gravidade da doença. Houve correlações positivas e significativas entre o Questionário de Atividades Funcionais, Mini Exame do Estado Mental e seus respectivos subtestes para linguagem e atenção com os volumes do lobo temporal e cerebelar. A análise de regressão logística demonstrou que o volume reduzido do lobo temporal, lobo cerebelar posterior e vermis pode ser um fator de risco para o futuro desenvolvimento de demência. CONCLUSÃO: Este é o primeiro estudo que demonstrou que o volume do cerebelo pode estar reduzido na fase pré-demência e reforça o papel dessa estrutura na progressão da doença de Alzheimer. Considerando que o cerebelo pode não estar diretamente associado com a origem da doença de Alzheimer, este achado tem valor para o prognóstico.

OBJECTIVE: The aim of this study was to examine the cerebellar volume of subjects at different stages of Alzheimer's disease and to investigate whether volume reductions in this structure are related to cognitive decline. METHOD: Ninety-six subjects from an epidemiological study were submitted to a magnetic resonance imaging scan and evaluated using the Mini-Mental State Examination and the Functional Activities Questionnaire. Subjects were divided into five groups according to the Clinical Dementia Rating scale. Twenty-six subjects from the original group who had no dementia diagnosis at baseline were re-evaluated for the onset of dementia after two years. RESULTS: The volumes of the cerebellar hemispheres, posterior cerebellar lobe, vermis and temporal lobe were found to be reduced as a function of the severity of the disease. There were significant positive correlations between the volume of the temporal lobe and cerebellum and the language, attention, and total scores in the Mini-Mental State Examination and the Functional Activities Questionnaire. A logistic regression analysis demonstrated that reduced temporal lobe, posterior cerebellar lobe and vermal volume at baseline is a risk factor for the onset of dementia. CONCLUSION: This is the first study demonstrating that reduced cerebellar volume is already apparent at the predementia stage. The results of this study support the involvement of the cerebellum in the progression of dementia. Whereas the cerebellum might not be directly associated with the origin of Alzheimer's disease, it may provide useful information related to its prognosis.

OBJETIVO: Comparar a eficácia da olanzapina, ziprasidona, haloperidol associado ao midazolam, haloperidol associado à prometazina e haloperidol isoladamente por via intramuscular como primeira escolha no tratamento de pacientes em agitação e agressividade. MÉTODO: Cento e cinquenta pacientes com agitação psicomotora por transtorno psicótico ou transtorno bipolar foram recrutados para estudo duplo-cego e receberam olanzapina, ziprasidona, haloperidol associado a midazolam, haloperidol associado a prometazina ou haloperidol isoladamente. Foram aplicadas as escalas Overt Agitation Severity Scale, Overt Aggression Scale e Ramsay Sedation Scale no período de 12 horas após a primeira aplicação. RESULTADOS: Todas as medicações foram capazes de acalmar os pacientes após uma hora da administração. Apenas a olanzapina e o haloperidol reduziram a agitação para menos de 10 pontos e apenas a olanzapina reduziu a agressividade para menos de quatro pontos nesse período. Doze horas depois, apenas o haloperidol com midazolam apresentou valores altos para a agitação e agressividade, e também esteve relacionado com maior proporção de efeitos colaterais. A ziprasidona, a olanzapina e o haloperidol apresentaram resultados mais estáveis para o controle da agitação e a ziprasidona, haloperidol associado a prometazina e olanzapina para o controle da agressividade. CONCLUSÃO: A olanzapina, a ziprasidona, o haloperidol associado a prometazina, o haloperidol associado ao midazolam e o haloperidol isoladamente foram efetivos no controle da agitação e da agressividade secundária a transtornos mentais dentro de 12 horas. Todas as drogas apresentaram vantagens e desvantagens, exceto pela associação haloperidol e midazolam que demonstrou os piores resultados em todos os parâmetros.

OBJECTIVE: To compare the effectiveness of intramuscular olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone as the first medication(s) used to treat patients with agitation and aggressive behavior. METHOD: One hundred fifty patients with agitation caused by psychotic or bipolar disorder were randomly assigned under double-blind conditions to receive olanzapine, ziprasidone, haloperidol plus midazolam, haloperidol plus promethazine or haloperidol alone. The Overt Agitation Severity Scale, Overt Aggression Scale and Ramsay Sedation Scale were applied within 12 hours after the first dosage. RESULTS: All medications produced a calming effect within one hour of administration, but only olanzapine and haloperidol reduced agitation by less than 10 points, and only olanzapine reduced aggression by less than four points in the first hour. After twelve hours, only patients treated with haloperidol plus midazolam had high levels of agitation and aggression and also more side effects. Ziprasidone, olanzapine and haloperidol alone had more stable results for agitation control, while ziprasidone, haloperidol plus promethazine and olanzapine had stable results for aggression control. CONCLUSION: Olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol were effective in controlling agitation and aggression caused by mental illness over 12 hours. Although all the drugs had advantages and disadvantages, haloperidol plus midazolam was associated with the worst results in all the observed parameters.

INTRODUCTION: The role of structural brain changes and their correlations with neuropsychiatric symptoms and disability in Alzheimer's disease are still poorly understood. OBJECTIVE: To establish whether structural changes in grey matter volume in patients with mild Alzheimer's disease are associated with neuropsychiatric symptoms and disability METHODS: Nineteen Alzheimer's disease patients (9 females; total mean age =75.2 y old +4.7; total mean education level =8.5 y +4.9) underwent a magnetic resonance imaging (MRI) examination and voxel-based morphometry analysis. T1-weighted images were spatially normalized and segmented. Grey matter images were smoothed and analyzed using a multiple regression design. The results were corrected for multiple comparisons. The Neuropsychiatric Inventory was used to evaluate the neuropsychiatric symptoms, and the Functional Activities Questionnaire and Disability Assessment for Dementia were used for functional evaluation RESULTS: A significant negative correlation was found between the bilateral middle frontal gyri, left inferior temporal gyrus, right orbitofrontal gyrus, and Neuropsychiatric Inventory scores. A negative correlation was found between bilateral middle temporal gyri, left hippocampus, bilateral fusiform gyri, and the Functional Activities Questionnaire. There was a positive correlation between the right amygdala, bilateral fusiform gyri, right anterior insula, left inferior and middle temporal gyri, right superior temporal gyrus, and Disability Assessment for Dementia scores CONCLUSIONS: The results suggest that the neuropsychiatric symptoms observed in Alzheimer's disease patients could be mainly due to frontal structural abnormalities, whereas disability could be associated with reductions in temporal structures.

OBJETIVO: Este artigo de atualização tem como objetivo avaliar estudos em neuroimagem estrutural e funcional a fim de explorar o papel do cerebelo na patofisiologia dos transtornos psiquiátricos. MÉTODO: Uma revisão não sistemática foi realizada através do Medline utilizando-se como parâmetro os seguintes termos: "cerebellum", "cerebellar vermis", "schizophrenia", "bipolar disorder", "depression", "anxiety disorders", "dementia" e "attention deficit hyperactivity disorder". A busca eletrônica foi feita até abril de 2008. DISCUSSÃO: Anormalidades cerebelares estruturais e funcionais têm sido relatadas em muitos transtornos psiquiátricos, entre eles a esquizofrenia, transtorno bipolar, transtorno depressivo, transtornos ansiosos, demências e transtorno de déficit de atenção e hiperatividade. Estudos utilizando imagem por ressonância magnética estrutural relataram a diminuição do volume total do cerebelo e do vermis cerebelar na esquizofrenia, transtornos do humor e transtorno de falta de atenção com hiperatividade. Estudos utilizando ressonância magnética funcional e paradigmas cognitivos têm demonstrado alterações na atividade cerebelar na esquizofrenia, transtornos ansiosos e transtorno de falta de atenção com hiperatividade. Nas demências, o cerebelo é afetado nos estágios mais avançados dessas doenças. CONCLUSÃO: Contrastando com as primeiras teorias, o cerebelo parece apresentar um papel mais importante em diferentes funções cerebrais além do controle motor e do equilíbrio, incluindo a regulação emocional e cognição. Futuros estudos são necessários para melhor elucidar o papel do cerebelo em ambos os comportamentos, normal e patológico, na regulação do humor e nas funções cognitivas.

OBJECTIVE: The objective of this update article is to report structural and functional neuroimaging studies exploring the potential role of cerebellum in the pathophysiology of psychiatric disorders. METHOD: A non-systematic literature review was conducted by means of Medline using the following terms as a parameter: "cerebellum", "cerebellar vermis", "schizophrenia", "bipolar disorder", "depression", "anxiety disorders", "dementia" and "attention deficit hyperactivity disorder". The electronic search was done up to April 2008. DISCUSSION: Structural and functional cerebellar abnormalities have been reported in many psychiatric disorders, namely schizophrenia, bipolar disorder, major depressive disorder, anxiety disorders, dementia and attention deficit hyperactivity disorder. Structural magnetic resonance imaging studies have reported smaller total cerebellar and vermal volumes in schizophrenia, mood disorders and attention deficit hyperactivity disorder. Functional magnetic resonance imaging studies using cognitive paradigms have shown alterations in cerebellar activity in schizophrenia, anxiety disorders and attention deficit hyperactivity disorder. In dementia, the cerebellum is affected in later stages of the disease. CONCLUSION: Contrasting with early theories, cerebellum appears to play a major role in different brain functions other than balance and motor control, including emotional regulation and cognition. Future studies are clearly needed to further elucidate the role of cerebellum in both normal and pathological behavior, mood regulation, and cognitive functioning.