Evaluation of 10-minute post-injection 11C-PiB PET and its correlation with 18F-FDG PET in older adults who are cognitively healthy, mildly impaired, or with probable Alzheimer's disease

Objective: Positron emission tomography (PET) allows in vivo evaluation of molecular targets in neurodegenerative diseases, such as Alzheimer's disease. Mild cognitive impairment is an intermediate stage between normal cognition and Alzheimer-type dementia. In vivo fibrillar amyloid-beta can be detected in PET using [11C]-labeled Pittsburgh compound B (11C-PiB). In contrast, [18F]fluoro-2-deoxy-d-glucose (18F-FDG) is a neurodegeneration biomarker used to evaluate cerebral glucose metabolism, indicating neuronal injury and synaptic dysfunction. In addition, early cerebral uptake of amyloid-PET tracers can determine regional cerebral blood flow. The present study compared early-phase 11C-PiB and 18F-FDG in older adults without cognitive impairment, amnestic mild cognitive impairment, and clinical diagnosis of probable Alzheimer's disease. Methods: We selected 90 older adults, clinically classified as healthy controls, with amnestic mild cognitive impairment, or with probable Alzheimer's disease, who underwent an 18F-FDG PET, early-phase 11C-PiB PET and magnetic resonance imaging. All participants were also classified as amyloid-positive or -negative in late-phase 11C-PiB. The data were analyzed using statistical parametric mapping. Results: We found that the probable Alzheimer's disease and amnestic mild cognitive impairment group had lower early-phase 11C-PiB uptake in limbic structures than 18F-FDG uptake. The images showed significant interactions between amyloid-beta status (negative or positive). However, early-phase 11C-PiB appears to provide different information from 18F-FDG about neurodegeneration. Conclusions: Our study suggests that early-phase 11C-PiB uptake correlates with 18F-FDG, irrespective of the particular amyloid-beta status. In addition, we observed distinct regional distribution patterns between both biomarkers, reinforcing the need for more robust studies to investigate the real clinical value of early-phase amyloid-PET imaging.

Frequency and factors associated with hospital readmission after COVID-19 hospitalization: the importance of post-COVID diarrhea

Abstract Purpose: The aim of this study was to describe the incidence and risk factors for hospital readmission and infection during the months after COVID-19 hospital admission. Methods: This prospective study included adult patients who were hospitalized due to COVID-19 and had been discharged from April 2020 to August 2020. All patients had a medical evaluation with a structured questionnaire 6 to 11 months after hospital admission. The authors included only patients with confirmed COVID-19 by RT-PCR. Patients with pregnant/postpartum women, with a proven COVID-19 reinfection or incapable of answering the questionnaire were excluded. Results: A total of 822 patients completed the follow-up assessment, and 68% reportedat least one recurrent symptom related to COVID-19. The most frequent symptom was myalgia (42%). Thirty-two percent of patients visited an emergency room after COVID-19 hospitalization, and 80 (10%) patients required re-hospitalization. Risk factors for hospital readmission were orotracheal intubation during COVID-19 hospitalization (p = 0.003, OR = 2.14), Charlson score (p = 0.002, OR = 1.21), congestive heart failure (p = 0.005, OR = 2.34), peripheral artery disease (p = 0.06, OR= 2.06) and persistent diarrhea after COVID-19 hospitalization discharge (p= 0.02, OR = 1.91). The main cause of hospital readmission was an infection, 43 (54%). Pneumonia was the most frequent infection (29%). Conclusions: The presence of symptoms after six months of COVID-19 diagnosis was frequent, and hospital readmission was relatively high. HIGHLIGHTS 32% of the patients visited an emergency room after COVID-19 hospitalization. The rate of hospital readmission after COVID-19 hospitalization is high, in the present sample 10% of patients needed a second hospitalization in 6-months Patients with persistent diarrhea after COVID-19 discharge had two times more chance to have another hospitalization in the next 6-months.

Subjective sleep parameters in prodromal Alzheimer's disease: a case-control study

Objective: People with Alzheimer's disease (AD) dementia have impaired sleep. However, the characteristics of sleep in the early stages of AD are not well known, and studies with the aid of biomarkers are lacking. We assessed the subjective sleep characteristics of non-demented older adults and compared their amyloid profiles. Methods: We enrolled 30 participants aged ≥ 60 years, with no dementia or major clinical and psychiatric diseases. They underwent [11C]PiB-PET-CT, neuropsychological evaluations, and completed two standardized sleep assessments (Pittsburgh Sleep Quality Inventory and Epworth Sleep Scale). Results: Comparative analysis of subjective sleep parameters across the two groups showed longer times in bed (p = 0.024) and reduced sleep efficiency (p = 0.05) in individuals with positive amyloid. No differences in other subjective sleep parameters were observed. We also found that people with multiple-domain mild cognitive impairment (MCI) had shorter self-reported total sleep times (p = 0.034) and worse overall sleep quality (p = 0.027) compared to those with single-domain MCI. Conclusions: Older adults testing positive for amyloid had a longer time in bed and lower sleep efficiency, regardless of cognitive status. In parallel, individuals with multiple-domain MCI reported shorter sleep duration and lower overall sleep quality.

Psychiatric neuroimaging research in Brazil: historical overview, current challenges, and future opportunities

The last four decades have witnessed tremendous growth in research studies applying neuroimaging methods to evaluate pathophysiological and treatment aspects of psychiatric disorders around the world. This article provides a brief history of psychiatric neuroimaging research in Brazil, including quantitative information about the growth of this field in the country over the past 20 years. Also described are the various methodologies used, the wealth of scientific questions investigated, and the strength of international collaborations established. Finally, examples of the many methodological advances that have emerged in the field of in vivo neuroimaging are provided, with discussion of the challenges faced by psychiatric research groups in Brazil, a country of limited resources, to continue incorporating such innovations to generate novel scientific data of local and global relevance.

Topography of 11C-Pittsburgh compound B uptake in Alzheimer's disease: a voxel-based investigation of cortical and white matter regions

Objective: To compare results of positron emission tomography (PET) with carbon-11-labeled Pittsburgh compound B (11C-PIB) obtained with cerebellar or global brain uptake for voxel intensity normalization, describe the cortical sites with highest tracer uptake in subjects with mild Alzheimer's disease (AD), and explore possible group differences in 11C-PIB binding to white matter. Methods: 11C-PIB PET scans were acquired from subjects with AD (n=17) and healthy elderly controls (n=19). Voxel-based analysis was performed with statistical parametric mapping (SPM). Results: Cerebellar normalization showed higher 11C-PIB uptake in the AD group relative to controls throughout the cerebral cortex, involving the lateral temporal, orbitofrontal, and superior parietal cortices. With global uptake normalization, greatest cortical binding was detected in the orbitofrontal cortex; decreased 11C-PIB uptake in white matter was found in the posterior hippocampal region, corpus callosum, pons, and internal capsule. Conclusion: The present case-control voxelwise 11C-PIB PET comparison highlighted the regional distribution of amyloid deposition in the cerebral cortex of mildly demented AD patients. Tracer uptake was highest in the orbitofrontal cortex. Decreased 11C-PIB uptake in white-matter regions in this patient population may be a marker of white-matter damage in AD.

Voxel-based morphometry in Alzheimers disease and mild cognitive impairment: Systematic review of studies addressing the frontal lobe / Morfometria baseada em Voxel em Doença de Alzheimer e comprometimento cognitivo leve: revisão sistemática de estudos abordando o lobo frontal

ABSTRACT Voxel-based morphometry (VBM) is a useful approach for investigating neurostructural brain changes in dementia. We systematically reviewed VBM studies of Alzheimer's disease (AD) and mild cognitive impairment (MCI), specifically focusing on grey matter (GM) atrophy in the frontal lobe. Methods: Two searches were performed on the Pubmed database. A set of exclusion criteria was applied to ensure the selection of only VBM studies that directly investigated GM volume abnormalities in AD and/or MCI patients compared to cognitively normal controls. Results: From a total of 46 selected articles, 35 VBM studies reported GM volume reductions in the frontal lobe. The frontal subregions, where most of the volume reductions were reported, included the inferior, superior and middle frontal gyri, as well as the anterior cingulate gyrus. We also found studies in which reduced frontal GM was detected in MCI patients who converted to AD. In a minority of studies, correlations between frontal GM volumes and behavioural changes or cognitive deficits in AD patients were investigated, with variable findings. Conclusion: Results of VBM studies indicate that the frontal lobe should be regarded as an important brain area when investigating GM volume deficits in association with AD. Frontal GM loss might not be a feature specific to late AD only. Future VBM studies involving large AD samples are warranted to further investigate correlations between frontal volume deficits and both cognitive impairment and neuropsychiatric symptoms.

RESUMO Morfometria baseada em voxel (MBV) é uma abordagem útil para investigar mudanças neuroestruturais no cérebro em demência. Revisamos sistematicamente estudos de MBV de doença de Alzheimer (DA) e comprometimento cognitivo leve (CCL), focando especificamente na atrofia de matéria cinzenta (MC) no lobo frontal. Métodos: Duas pesquisas foram realizadas na base de dados do Pubmed. Critérios de exclusão foram utilizados para assegurar a seleção somente de estudos de MBV que investigassem diretamente anormalidades de volume de MC em pacientes com DA e/ou CCL comparados com controles de cognição normal. Resultados: De um total de 46 artigos selecionados, 35 estudos de MBV reportaram reduções de volume de MC no lobo frontal. As sub-regiões frontais em que a maioria das reduções de volume foram encontradas incluem os giros frontais inferior, superior e médio, bem como o giro do cíngulo anterior. Também acharam-se perdas de MC em pacientes com CCL que desenvolveram DA. Uma menor parte dos estudos investigou correlações entre volumes de MC frontal e mudanças comportamentais ou déficits cognitivos em DA, com achados variáveis. Conclusão: Os resultados de estudos de MBV indicam que o lobo frontal deve ser visto como uma importante área cerebral quando da investigação de déficits de volume de MC em associação com DA. Perda de MC frontal pode não ser uma característica apenas de DA tardia. Estudos de MBV futuros com grandes amostras de pacientes com DA são necessários para investigar mais a fundo a relação entre déficits de volume frontal e sintomas de comprometimento cognitivo e neuropsiquiátricos.

Psychopathic traits in young offenders vs. non-offenders in similar socioeconomic condition

Objective: To analyze the differences in psychopathic traits between offender and non-offender youths with similar socioeconomic backgrounds. Method: The Psychopathy Checklist Revised (PCL-R) scale was used to identify whether 39 young offenders with no history of mental disorders or criteria for psychopathy exhibited differences in its total score, and specifically for factor 1 or factor 2 of this scale, when compared with 32 other young people, living in similar socioeconomic conditions, who had not committed offenses. Results: We observed statistically significant between-group differences (p < 0.01) in mean PCL-R scores, with a mean score of 13.4 in the offender group vs. 2.1 in the non-offender group. We also detected significant between-group differences when we analyzed mean factor 1 (p < 0.01) and factor 2 (p < 0.01) scores separately. Although the groups exhibited statistically significant difference in educational attainment, between-group comparison of mean PCL-R scores controlling for educational attainment by analysis of covariance (ANCOVA) showed that the difference in PCL-R scores remained statistically significant (p < 0.01). Conclusions: We conclude that, in this sample, the presence of both primary (interpersonal/affective characteristics) and secondary (lifestyle/antisocial behavior) psychopathic traits differed between offender and non-offender youths, even when excluding psychopathy and other mental disorders from the assessments. These results suggest a need for wide-ranging interventions, not restricted to socioeconomic aspects, for the management of juvenile delinquency. .

Depression and temporal lobe epilepsy represent an epiphenomenon sharing similar neural networks: clinical and brain structural evidences / Depressão e epilepsia de lobo temporal representam um epifenômeno compartilhando redes neurais similares: evidências clínicas e de neuroimagem estrutural

The relationship between depression and epilepsy has been known since ancient times, however, to date, it is not fully understood. The prevalence of psychiatric disorders in persons with epilepsy is high compared to general population. It is assumed that the rate of depression ranges from 20 to 55% in patients with refractory epilepsy, especially considering those with temporal lobe epilepsy caused by mesial temporal sclerosis. Temporal lobe epilepsy is a good biological model to understand the common structural basis between depression and epilepsy. Interestingly, mesial temporal lobe epilepsy and depression share a similar neurocircuitry involving: temporal lobes with hippocampus, amygdala and entorhinal and neocortical cortex; the frontal lobes with cingulate gyrus; subcortical structures, such as basal ganglia and thalamus; and the connecting pathways. We provide clinical and brain structural evidences that depression and epilepsy represent an epiphenomenon sharing similar neural networks.

A relação entre depressão e epilepsia é conhecida desde a antiguidade; entretanto, até o momento, não é completamente compreendida. A prevalência de transtornos psiquiátricos nas pessoas com epilepsia é elevada quando comparada à população em geral. A taxa de depressão varia de 20 a 55% nos pacientes com epilepsia refratária, especialmente considerando-se aqueles com epilepsia do lobo temporal causada por esclerose mesial temporal. A epilepsia do lobo temporal é um bom modelo biológico para compreender as bases estruturais comuns entre a epilepsia e a depressão. É relevante ressaltar que a epilepsia do lobo mesial e a depressão apresentam circuitos similares envolvendo: os lobos temporais com o hipocampo, a amigdala, o córtex entorrinal e o neocortex; os lobos frontais com o giro cíngulo; estruturas subcorticais, como os núcleos da base e o tálamo, e suas vias de conexão. Postulamos por meio de evidências clínicas e estruturais que a depressão e a epilepsia representam um epifenômeno com redes neuronais similares.

New molecular targets for PET and SPECT imaging in neurodegenerative diseases / Novos alvos moleculares para tomografia por emissão de pósitrons (PET) e tomografia computadorizada por emissão de fóton único (SPECT) em doenças neurodegenerativas

The pathophysiology of neurodegenerative diseases (ND) such as Alzheimer's disease (AD) and Parkinson's disease (PD) has not yet been completely elucidated. However, in the past few years, there have been great knowledge advances about intra-and extracellular proteins that may display impaired function or expression in AD, PD and other ND, such as amyloid beta (Aβ), α-synuclein, tau protein and neuroinflammatory markers. Recent developments in the imaging techniques of positron emission tomography (PET) and single photon emission computed tomography (SPECT) now allow the non-invasive tracking of such molecular targets of known relevance to ND in vivo. This article summarizes recent findings of PET and SPECT studies using these novel methods, and discusses their potential role in the field of drug development for ND as well as future clinical applications in regard to differential diagnosis of ND and monitoring of disease progression.

A fisiopatologia das doenças neurodegenerativas (DN), tais como a doença de Alzheimer (DA) e a doença de Parkinson (DP), ainda não é completamente compreendida. No entanto, nos últimos anos, houve grandes avanços em termos do conhecimento sobre proteínas intra e extracelulares, tais como beta-amiloide (Aβ), α-sinucleína, proteína tau e marcadores neuroinflamatórios, que podem ter sua função ou expressão prejudicada na DA, DP ou em outras DN. Progressos recentes nas técnicas de tomografia por emissão de pósitrons (PET) e tomografia computadorizada por emissão de fóton único (SPECT) permitem hoje em dia a identificação não invasiva de tais alvos moleculares in vivo. Este artigo resume descobertas recentes de estudos de PET e SPECT cerebral usando esses alvos moleculares inovadores e discute o papel potencial dessas técnicas no campo do desenvolvimento de novos medicamentos para as DN, bem como futuras aplicações clínicas em relação ao diagnóstico diferencial e monitoramento da progressão dessas doenças.

BDNF gene polymorphism, cognition and symptom severity in a Brazilian population-based sample of first-episode psychosis subjects / Polimorfismo do gene do BDNF, cognição e gravidade dos sintomas em uma amostra de base populacional brasileira de indivíduos apresentando o primeiro episódio psicótico

OBJECTIVE: To investigate the influence of brain-derived neurotrophic factor (BDNF) gene variations on cognitive performance and clinical symptomatology in first-episode psychosis (FEP). METHODS: We performed BDNF val66met variant genotyping, cognitive testing (verbal fluency and digit spans) and assessments of symptom severity (as assessed with the PANSS) in a population-based sample of FEP patients (77 with schizophreniform psychosis and 53 with affective psychoses) and 191 neighboring healthy controls. RESULTS: There was no difference in the proportion of Met allele carriers between FEP patients and controls, and no significant influence of BDNF genotype on cognitive test scores in either of the psychosis groups. A decreased severity of negative symptoms was found in FEP subjects that carried a Met allele, and this finding reached significance for the subgroup with affective psychoses (p < 0.01, ANOVA). CONCLUSIONS: These results suggest that, in FEP, the BDNF gene Val66Met polymorphism does not exert a pervasive influence on cognitive functioning but may modulate the severity of negative symptoms.

OBJETIVO: Investigar a influência da variação do gene do fator neurotrófico derivado do cérebro (BDNF) no desempenho cognitivo e na sintomatologia clínica durante o primeiro episódio psicótico (PEP). MÉTODOS: Foram realizados a genotipificação das variantes Val66met do BDNF, o teste cognitivo (fluência verbal e repetição de dígitos) e as avaliações da gravidade dos sintomas (conforme avaliado pela Positive and Negative Syndrome Scale [PANSS]) em uma amostra de pacientes com PEP de base populacional (77 com psicose esquizofreniforme e 53 com psicose afetiva) e 191 vizinhos controle saudáveis. RESULTADOS: Não houve diferença na proporção de portadores do alelo Met entre pacientes com PEP e o grupo controle. Não houve influência significativa do genótipo do BDNF sobre a pontuação de cada um dos grupos psicóticos. Foi encontrada uma diminuição da gravidade dos sintomas negativos em sujeitos com PEP portadores do alelo Met, e essa descoberta mostrou-se significativa para o subgrupo com psicose afetiva (p < 0,01, ANOVA). CONCLUSÕES: Os resultados sugerem que, no PEP, o polimorfismo Val66Met do gene do BDNF não exerce uma influência importante sobre o funcionamento cognitivo, mas pode modular a gravidade dos sintomas negativos.

Cerebral perfusion and automated individual analysis using SPECT among an obsessive-compulsive population / Perfusão cerebral e análise individual automatizada utilizando SPECT em uma população com transtorno obsessivo-compulsivo

OBJECTIVE: To make individual assessments using automated quantification methodology in order to screen for perfusion abnormalities in cerebral SPECT examinations among a sample of subjects with OCD. METHODS: Statistical parametric mapping (SPM) was used to compare 26 brain SPECT images from patients with OCD individually with an image bank of 32 normal subjects, using the statistical threshold of p < 0.05 (corrected for multiple comparisons at the level of individual voxels or clusters). The maps were analyzed, and regions presenting voxels that remained above this threshold were sought. RESULTS: Six patients from a sample of 26 OCD images showed abnormalities at cluster or voxel level, considering the criteria described above, which represented 23.07 percent. However, seven images from the normal group of 32 were also indicated as cases of perfusional abnormality, representing 21.8 percent of the sample. CONCLUSION: The automated quantification method was not considered to be a useful tool for clinical practice, for analyses complementary to visual inspection.

OBJETIVO: Avaliar uma amostra de pacientes com transtorno obsessivo-compulsivo (TOC), individualmente, empregando uma metodologia de quantificação automatizada para rastrear anormalidades de perfusão em exames de SPECT cerebral. MÉTODOS: Foi utilizado o Statistical Parametric Mapping (SPM) para comparar 26 imagens de SPECT cerebral de pacientes com TOC, individualmente, com um banco de 32 imagens de voluntários normais, usando o limiar estatístico de p < 0,05 (corrigido para comparações múltiplas ao nível do voxel individual ou clusters). Os mapas foram analisados procurando por regiões que apresentassem voxels acima desse limiar. RESULTADOS: Seis pacientes da amostra de 26 imagens com TOC mostraram anormalidades ao nível do cluster ou voxel, considerando os critérios descritos acima, os quais representaram 23,07 por cento. Contudo, sete imagens do grupo de 32 voluntários normais também foram apontadas com anormalidades de perfusão, que representou 21,8 por cento da amostra. CONCLUSÃO: O método de quantificação automatizada não foi considerado como uma ferramenta útil na prática clínica, como forma de análise complementar à inspeção visual.

Diagnosis of regional cerebral blood flow abnormalities using SPECT: agreement between individualized statistical parametric maps and visual inspection by nuclear medicine physicians with different levels of expertise in nuclear neurology

INTRODUCTION: Visual analysis is widely used to interpret regional cerebral blood flow (rCBF) SPECT images in clinical practice despite its limitations. Automated methods are employed to investigate between-group rCBF differences in research studies but have rarely been explored in individual analyses. OBJECTIVES: To compare visual inspection by nuclear physicians with the automated statistical parametric mapping program using a SPECT dataset of patients with neurological disorders and normal control images. METHODS: Using statistical parametric mapping, 14 SPECT images from patients with various neurological disorders were compared individually with a databank of 32 normal images using a statistical threshold of p<0.05 (corrected for multiple comparisons at the level of individual voxels or clusters). Statistical parametric mapping results were compared with visual analyses by a nuclear physician highly experienced in neurology (A) as well as a nuclear physician with a general background of experience (B) who independently classified images as normal or altered, and determined the location of changes and the severity. RESULTS: Of the 32 images of the normal databank, 4 generated maps showing rCBF abnormalities (p<0.05, corrected). Among the 14 images from patients with neurological disorders, 13 showed rCBF alterations. Statistical parametric mapping and physician A completely agreed on 84.37 percent and 64.28 percent of cases from the normal databank and neurological disorders, respectively. The agreement between statistical parametric mapping and ratings of physician B were lower (71.18 percent and 35.71 percent, respectively). CONCLUSION: Statistical parametric mapping replicated the findings described by the more experienced nuclear physician. This finding suggests that automated methods for individually analyzing rCBF SPECT images may be a valuable resource to complement visual inspection in clinical practice.

Correlation between voxel based morphometry and manual volumetry in magnetic resonance images of the human brain

This is a comparative study between manual volumetry (MV) and voxel based morphometry (VBM) as methods of evaluating the volume of brain structures in magnetic resonance images. The volumes of the hippocampus and the amygdala of 16 panic disorder patients and 16 healthy controls measured through MV were correlated with the volumes of gray matter estimated by optimized modulated VBM. The chosen structures are composed almost exclusively of gray matter. Using a 4 mm Gaussian filter, statistically significant clusters were found bilaterally in the hippocampus and in the right amygdala in the statistical parametric map correlating with the respective manual volume. With the conventional 12 mm filter,a significant correlation was found only for the right hippocampus. Therefore,narrowfilters increase the sensitivity of the correlation procedure, especially when small brain structures are analyzed. The two techniques seem to consistently measure structural volume.

Trata-se de estudo comparativo entre a volumetria manual(VM) e a morfometria baseada no vóxel (MBV), como métodos de avaliação do volume de estruturas cerebrais. Os volumes do hipocampo e da amídala de 16 pacientes de pânico e 16 controles sadios medidos através da VM foram correlacionados com os volumes de matéria cinzenta estimados pela MBV.As estruturas escolhidas são constituídas quase exclusivamente de matéria cinzenta. Utilizando um filtro Gaussiano de 4 mm, encontram-se, bilateralmente, aglomerados significativos de correlação nas duas estruturas no mapa estatístico paramétrico, correspondendo ao respectivo volume manual. Com o filtro convencional de 12 mm, apenas uma correlação significativa foi encontrada no hipocampo direito. Portanto, filtros estreitos aumentam a sensibilidade do procedimento de correlação,especialmente quando estruturas pequenas são analisadas. Ambas as técnicas parecem medir consistentemente o volume estrutural.

Fisiopatologia da esquizofrenia: aspectos atuais / Physiopathology of schizophrenia: current aspects

CONTEXTO: A esquizofrenia é uma das mais intrigantes doenças psiquiátricas e, talvez por isso, a mais pesquisada, com grandes avanços sobre sua fisiopatologia no último século. OBJETIVO: Revisar os principais avanços na compreensão fisiopatológica da esquizofrenia. MÉTODO: Revisão da literatura para cada tópico proposto a partir de artigos levantados no Medline e/ou considerados importantes a partir da experiência dos autores. RESULTADOS: A hipótese dopaminérgica representa uma das primeiras teorias etiológicas e permanece até os dias atuais como uma das que apresenta evidências mais consistentes. No entanto, essa teoria falha em explicar a história natural, os prejuízos cognitivos e as alterações estruturais encontradas na esquizofrenia. A demonstração de estudos epidemiológicos de fatores de risco genéticos e ambientais, somados aos estudos neuropatológicos e de neuroimagem, sugerem um modelo interativo em que inúmeros fatores atuam conjuntamente para alterações mais globais do desenvolvimento cerebral. CONCLUSÃO: A compreensão fisiopatológica da esquizofrenia avançou bastante no último século, evoluindo de teorias etiológicas unicausais para modelos mais complexos que consideram a interação de inúmeros fatores genéticos e ambientais.

BACKGROUND: Schizophrenia is one of the most intriguing and studied psychiatric diseases and its physiopathology has advanced a lot in the last century. OBJECTIVE: To review the most important advances in the physiopathology of schizophrenia. METHOD: Review of the literature of each proposed topic by articles searched in Medline and/or chosen accordingly the authors’ experience. RESULTS: The dopaminergic hypothesis was one of the first ethiological theories and until today is among the ones that presents the most consistent evidences. However, it fails to explain important features found in schizophrenia, such as the natural history, the cognitive impairments and the structural abnormalities. Evidences provided by epidemiological studies of genetic and environmental risk factors, associated with the findings of neuropathological and neuroimaging studies, suggest an interactive model with several factors acting together to create a global alteration of the brain development. CONCLUSION: The physiophatology of schizophrenia has advanced a lot in the last century, evolving from unicausal theories towards more complex models that consider the interaction among several genetic and environmental factors.

Fatores de risco cardiovascular, declínio cognitivo e alterações cerebrais detectadas através de técnicas de neuroimagem / Cognitive decline, cardiovascular risk factors, and neuroimaging abnormalities

Diversos estudos têm demonstrado associação entre fatores de risco cardiovascular e desenvolvimento de declínio cognitivo. Também há evidências do aumento das taxas de morbimortalidade em pacientes com doenças cardiovasculares e déficit cognitivo. Dentre os fatores de risco cardiovascular, hipertensão arterial e insuficiência cardíaca apresentaram forte associação com a presença de déficit cognitivo, entretanto os mecanismos cerebrais subjacentes não foram totalmente esclarecidos. Nos pacientes cardiopatas, o prejuízo cognitivo se dá principalmente nos aspectos de memória (fixação e aprendizado) e processamento das informações. Nesse artigo, revisa-se os achados de neuroimagem observados em amostras de pacientes com fatores de risco cardiovascular com declínio cognitivo, incluindo achados regionais de anormalidades volumétricas, hiperintensidade de substância branca, acidentes vasculares silenciosos, infartos lacunares e déficits funcionais na perfusão cerebral global (associada à redução do débito cardíaco) e perfusão cerebral regional. Discute-se, também, as implicações destes achados para a fisiopatologia do declínio cognitivo e suas aplicações clínicas. Finalmente, aborda-se o potencial de utilização de novas técnicas de imagem em estudos futuros na avaliação das alterações estruturais e funcionais associadas a fatores de riscos vasculares em amostras de base populacional.

Efeitos cerebrais da maconha: resultados dos estudos de neuroimagem / Brain effects of cannabis: neuroimaging findings

A maconha é a droga ilícita mais utilizada. Apesar disto, apenas um pequeno número de estudos investigaram as conseqüências neurotóxicas de longo prazo do uso de cannabis. As técnicas de neuroimagem se constituem em poderosos instrumentos para investigar alterações neuroanatômicas e neurofuncionais e suas correlações clínicas e neuropsicológicas. Uma revisão computadorizada da literatura foi conduzida nos indexadores MEDLINE e PsycLIT entre 1966 e novembro de 2004 com os termos 'cannabis', 'marijuana', 'neuroimaging', 'magnetic resonance', 'computed tomography', 'positron emission tomography', 'single photon emission computed tomography", 'SPET', 'MRI' e 'CT'. Estudos de neuroimagem estrutural apresentam resultados conflitantes, com a maioria dos estudos não relatando atrofia cerebral ou alterações volumétricas regionais. Contudo, há uma pequena evidência de que usuários de longo prazo que iniciaram um uso regular no início da adolescência apresentam atrofia cerebral assim como redução na substância cinzenta. Estudos de neuroimagem funcional relatam aumento na atividade neural em regiões que podem estar relacionadas com intoxicação por cannabis e alteração do humor (lobos frontais mesial e orbital) e redução na atividade de regiões relacionadas com funções cognitivas prejudicadas durante a intoxicação aguda. A questão crucial se efeitos neurotóxicos residuais ocorrem após o uso prolongado e regular de maconha permanece obscura, não existindo até então estudo endereçando esta questão diretamente. Estudos de neuroimagem com melhores desenhos, combinados com avaliação cognitiva, podem ser elucidativos neste aspecto.