Geraldo Busatto Filho

Depression and temporal lobe epilepsy represent an epiphenomenon sharing similar neural networks: clinical and brain structural evidences

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.

Fisiopatologia da esquizofrenia: aspectos atuais

CONTEXTO: A esquizofrenia e uma das mais intrigantes doencas psiquiatricas e, talvez por isso, a mais pesquisada, com grandes avancos sobre sua fisiopatologia no ultimo seculo. OBJETIVO: Revisar os principais avancos na compreensao fisiopatologica da esquizofrenia. METODO: Revisao da literatura para cada topico proposto a partir de artigos levantados no Medline e/ou considerados importantes a partir da experiencia dos autores. RESULTADOS: A hipotese dopaminergica representa uma das primeiras teorias etiologicas e permanece ate os dias atuais como uma das que apresenta evidencias mais consistentes. No entanto, essa teoria falha em explicar a historia natural, os prejuizos cognitivos e as alteracoes estruturais encontradas na esquizofrenia. A demonstracao de estudos epidemiologicos de fatores de risco geneticos e ambientais, somados aos estudos neuropatologicos e de neuroimagem, sugerem um modelo interativo em que inumeros fatores atuam conjuntamente para alteracoes mais globais do desenvolvimento cerebral. CONCLUSAO: A compreensao fisiopatologica da esquizofrenia avancou bastante no ultimo seculo, evoluindo de teorias etiologicas unicausais para modelos mais complexos que consideram a interacao de inumeros fatores geneticos e ambientais.

Structural brain changes as biomarkers and outcome predictors in patients with late-life depression: a cross-sectional and prospective study.

The relationship between structural changes in grey matter and treatment response in patients with late-life depression remains an intriguing area of research. This magnetic resonance imaging (MRI) study compares the baseline grey matter volume of elderly people with and without major depression (according to the DSM-IV-TR criteria) and assesses its association with antidepressant treatment response. Brain MRI scans were processed using statistical parametric mapping and voxel-based morphometry. The sample consisted of 30 patients with depression and 22 healthy controls. We found a significant volumetric reduction in the orbitofrontal cortex bilaterally in patients in comparison with controls. According to their remission status after antidepressant treatment, patients were classified as remitted or not remitted. Compared with controls, remitted patients showed a volumetric reduction in the orbitofrontal cortex bilaterally and in another cluster in the right middle temporal pole. Non-remitted patients showed an even greater volumetric reduction in the orbitofrontal cortex bilaterally compared with controls. To investigate predictive factors of remission after antidepressant treatment, we used a logistic regression. Both baseline Mini Mental State Examination score and baseline left superior lateral orbitofrontal cortex volume (standardized to the total grey matter volume) were associated with remission status. Our findings support the use of regional brain atrophy as a potential biomarker for depression. In addition, baseline cognitive impairment and regional grey matter abnormalities predict antidepressant response in patients with late-life depression.

Fatores de risco cardiovascular, declínio cognitivo e alterações cerebrais detectadas através de técnicas de neuroimagem

Diversos estudos tem demonstrado associacao entre fatores de risco cardiovascular e desenvolvimento de declinio cognitivo. Tambem ha evidencias do aumento das taxas de morbimortalidade em pacientes com doencas cardiovasculares e deficit cognitivo. Dentre os fatores de risco cardiovascular, hipertensao arterial e insuficiencia cardiaca apresentaram forte associacao com a presenca de deficit cognitivo, entretanto os mecanismos cerebrais subjacentes nao foram totalmente esclarecidos. Nos pacientes cardiopatas, o prejuizo cognitivo se da principalmente nos aspectos de memoria (fixacao e aprendizado) e processamento das informacoes. Nesse artigo, revisa-se os achados de neuroimagem observados em amostras de pacientes com fatores de risco cardiovascular com declinio cognitivo, incluindo achados regionais de anormalidades volumetricas, hiperintensidade de substância branca, acidentes vasculares silenciosos, infartos lacunares e deficits funcionais na perfusao cerebral global (associada a reducao do debito cardiaco) e perfusao cerebral regional. Discute-se, tambem, as implicacoes destes achados para a fisiopatologia do declinio cognitivo e suas aplicacoes clinicas. Finalmente, aborda-se o potencial de utilizacao de novas tecnicas de imagem em estudos futuros na avaliacao das alteracoes estruturais e funcionais associadas a fatores de riscos vasculares em amostras de base populacional.

Novas técnicas de neuroimagem em psiquiatria: qual o potencial de aplicações na prática clínica?

Introdução Desde o surgimento das novas técnicas de neuroimagem, inúmeros estudos de pesquisa têm contribuído para o entendimento sobre as estruturas e o funcionamento cerebral relacionados à fisiopatologia dos transtornos neuropsiquiátricos. Esses desenvolvimentos mantêm viva a expectativa de que a neuroimagem possa ter utilidade também na prática clínica psiquiátrica, para auxiliar no diagnóstico e no seguimento de um paciente, assim como na avaliação de prognóstico etc. No campo das doenças cerebrais orgânicas, a utilidade das técnicas de neuroimagem na rotina clínica é amplamente aceita. Os métodos mais acessíveis, como a tomografia computadorizada (TC), a ressonância magnética (RM) e a tomografia computadorizada por emissão de fóton único (single photon emission computed tomography – SPECT) são recursos importantes para o diagnóstico diferencial de demências; para o diagnóstico e manejo de doenças neurológicas que comumente cursam com sintomas psiquiátricos, como as epilepsias e acidentes vasculares cerebrais; e para a investigação do possível acometimento central em condições médicas, como o lupus eritematoso sistêmico e a síndrome de imunodeficiência adquirida. Além disso, visto que sinais e sintomas característicos dos transtornos mentais podem ocasionalmente representar a primeira manifestação de doenças cerebrais orgânicas, como tumores e doenças cerebrovasculares, solicita-se, na prática clínica, um exame de neuroimagem como TC ou RM na vigência do primeiro surto psicótico; de outros quadros psiquiátricos iniciados fora da faixa etária usual com apresentação clínica e curso atípicos e/ou má resposta a tratamento; de déficits cognitivos intensos e não-compatíveis com os demais dados de apresentação clínica; de síndromes catatônicas ou delirium; e de sinais focais neurológicos ao exame clínico e história de trauma encefálico grave. Se há aplicações práticas para a neuroimagem no diagnóstico diferencial de doenças que cursam com patologia cerebral bem definida, o mesmo não se pode dizer com relação aos transtornos psiquiátricos outrora classificados como “funcionais”, como a esquizofrenia, o transtorno depressivo maior, o transtorno obsessivo compulsivo (TOC) dentre outros. Apesar do imNovas técnicas de neuroimagem em psiquiatria: qual o potencial de aplicações na prática clínica?

A anatomia estrutural e funcional da esquizofrenia: achados de neuropatologia e neuroimagem

A existencia de alteracoes cerebrais subjacentes aos sinto-mas da esquizofrenia ja era admitida desde as propostas declassificacao classicas para esse transtorno. Entre as variasestrategias de pesquisa biologica utilizadas nas ultimas deca-das, as tecnicas neuropatologicas e de neuroimagem estao en-tre as que mais tem contribuido para o conhecimento dos meca-nismos cerebrais alterados na esquizofrenia.NeuropatologiaDesde a decada de 80, estudos morfometicos quantitativospost mortem tem mostrado anormalidades nos cerebros de al-guns pacientes esquizofrenicos, incluindo diminuicoes globaisde volume/peso e reducoes localizadas em areas temporais efrontais.

Padrões de ativação cerebral em idosos sadios durante tarefa de memória verbal de reconhecimento: a single-photon emission computerized tomography study

INTRODUCTION: PET, SPECT and functional magnetic resonance imaging studies have allowed the delineation of brain circuits activated during several types of cognitive tasks. The field of declarative memory has been one of the most extensively investigated. In the present study, the regional cerebral blood flow (rCBF) SPECT technique was used to investigate changes in brain activity during a verbal memory task in a group of elderly healthy volunteers (n=15). METHODS:Two SPECT acquisitions were performed in the same session, using the split-dose 99mTc-HMPAO technique. Measures of rCBF were taken during a recognition memory task and a simpler control task. Between-task comparisons were performed automatically using the Statistical Parametric Mapping (SPM) program. RESULTS: Increased rCBF during the memory task was seen in several brain regions, including: the lateral prefrontal cortex on both hemispheres (more intensely on the left side); posterior and medial portions of the left occipital and parietal cortices; the right and left cerebellar hemispheres; and the right and left lateral temporal cortex (p<0.001, uncorrected for multiple comparisons). Unexpected foci of decreased rCBF were seen in the right posterior cingulate cortex, left orbitofrontal cortex, right inferior temporal cortex and left cerebellar vermis (p<0.05, corrected for multiple comparisons). CONCLUSION:These results suggest that multifocal neural circuits are engaged during recognition memory, and replicate locations seen in previous studies in the literature. The use of the protocols described here in patients with neuropsychiatric disorders may allow investigation of brain abnormalities underlying the memory deficits seen in these disorders.

Aspectos neurorradiológicos do transtorno obsessivo-compulsivo: o papel dos gânglios da base

Contemporary neuroanatomical models for obsessive-compulsive disorder (OCD) propose that abnormalities of specific cortico-subcortical circuits mediate the disorders symptoms. This paper focuses on the basal ganglia, believed to play a critical role in the functioning of those brain circuits. Clinical and experimental studies investigating the presence of abnormalities of basal ganglia structures in OCD are reviewed, with particular emphasis on the neuroimaging literature. Despite controversies in the area, a considerable amount of data has accumulated suggesting that abnormalities of the caudate and putamen nuclei can be associated with OCD. These abnormalities may be particularly relevant to specific subtypes of the disorder, such as early-onset OCD. With the continuing sophistication of neuroimaging technologies, future studies may be able to further clarify the role of each basal ganglia component in the pathophysiology of the various clinical features of OCD.

Distinct domains of impulsivity are impaired in juvenile myoclonic epilepsy but not in temporal lobe epilepsy

OBJECTIVE The Barratt Impulsiveness Scale (BIS-11) is the most widely used questionnaire to study impulsivity in persons with psychiatric disorders, but it has rarely been applied to persons with epilepsy. The present study aimed to evaluate the usefulness of BIS-11 as a tool to explore impulsivity in two distinct epilepsy syndromes. METHOD The BIS-11 was applied to 20 patients with juvenile myoclonic epilepsy (JME) (32.5±8.95years old), 20 patients with temporal lobe epilepsy (TLE) (37.7±13.25years old), and 26 healthy controls (31.86±11.25years old). The scores in motor, attentional, and lack of planning impulsivity were compared between groups. RESULTS Patients with JME showed higher scores than patients with TLE and controls in all domains: motor (JME vs TLE: 28.60 vs 13.25 (mean score), p<0.001 and JME vs controls: 28.60 vs 14.12, p<0.001), attentional (JME vs TLE: 21.55 vs 13.45, p<0.001 and JME vs controls: 21.55 vs 14.88, p<0.001) and nonplanning (JME vs TLE: 28.05 vs 13.10, p<0.001 and JME vs controls: 28.05 vs 16.15, p<0.001). CONCLUSION Higher BIS-11 scores in all domains of impulsivity [i.e., motor, attentional, and lack of planning] corroborated previous findings described in patients with JME. On the other hand, BIS-11 could not demonstrate problem solving and inhibitory control deficits related to impulsive behavior, which were described in patients with TLE. Other behavioral measures may be more sensitive to some aspects of impulsivity in TLE. Our results reinforce the concept that distinct epileptic syndromes require different neuropsychological approaches, especially considering a complex construct such as impulsivity.

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.