Layer-specific reduced neuronal density in the orbitofrontal cortex of older adults with obsessive-compulsive disorder.

Neurobiological models have provided consistent evidence of the involvement of cortical-subcortical circuitry in obsessive-compulsive disorder (OCD). The orbitofrontal cortex (OFC), involved in motivation and emotional responses, is an important regulatory node within this circuitry. However, OFC abnormalities at the cellular level have so far not been studied. To address this question, we have recruited a total of seven senior individuals from the Sao Paulo Autopsy Services who were diagnosed with OCD after an extensive post-mortem clinical evaluation with their next of kin. Patients with cognitive impairment were excluded. The OCD cases were age- and sex-matched with 7 control cases and a total of 14 formalin-fixed, serially cut, and gallocyanin-stained hemispheres (7 subjects with OCD and 7 controls) were analyzed stereologically. We estimated laminar neuronal density, volume of the anteromedial (AM), medial orbitofrontal (MO), and anterolateral (AL) areas of the OFC. We found statistically significant layer- and region-specific lower neuron densities in our OCD cases that added to a deficit of 25% in AM and AL and to a deficit of 21% in MO, respectively. The volumes of the OFC areas were similar between the OCD and control groups. These results provide evidence of complex layer and region-specific neuronal deficits/loss in old OCD cases which could have a considerable impact on information processing within orbitofrontal regions and with afferent and efferent targets.

Facial emotion recognition in euthymic patients with bipolar disorder and their unaffected first-degree relatives.

BACKGROUND: Facial emotion recognition (FER) is an important task associated with social cognition because facial expression is a significant source of non-verbal information that guides interpersonal relationships. Increasing evidence suggests that bipolar disorder (BD) patients present deficits in FER and these deficits may be present in individuals at high genetic risk for BD. The aim of this study was to evaluate the occurrence of FER deficits in euthymic BD patients, their first-degree relatives, and healthy controls (HC) and to consider if these deficits might be regarded as an endophenotype candidate for BD. METHODS: We studied 23 patients with DSM-IV BD type I, 22 first-degree relatives of these patients, and 27 HC. We used the Penn Emotion Recognition Tests to evaluate tasks of FER, emotion discrimination, and emotional acuity. Patients were recruited from outpatient facilities at the Institute of Psychiatry of the University of Sao Paulo Medical School, or from the community through media advertisements, had to be euthymic, with age above 18years old and a diagnosis of DSM-IV BD type I. RESULTS: Euthymic BD patients presented significantly fewer correct responses for fear, and significantly increased time to response to recognize happy faces when compared with HC, but not when compared with first-degree relatives. First-degree relatives did not significantly differ from HC on any of the emotion recognition tasks. CONCLUSION: Our results suggest that deficits in FER are present in euthymic patients, but not in subjects at high genetic risk for BD. Thus, we have not found evidence to consider FER as an endophenotype candidate for BD.

A sib-pair analysis of impulsivity in bipolar disorder type I.

OBJECTIVE: The aim of this study was to compare impulsivity among patients with bipolar disorder, their siblings, and healthy controls in order to examine whether impulsivity in bipolar disorder is related to genetic liability for the illness. METHODS: Using the Barratt Impulsiveness Scale, we assessed 204 subjects: 67 euthymic outpatients with bipolar disorder type I, 67 siblings without bipolar disorder, and 70 healthy controls. RESULTS: Impulsivity scores were higher among patients with bipolar disorder than among healthy controls. Siblings showed higher motor impulsivity scores than did healthy controls. CONCLUSIONS: Our results suggest that motor impulsivity may be a vulnerability marker for bipolar disorder. Our data may contribute to further improve preventive strategies in subjects at high risk for bipolar disorder.

Impact of comorbid migraine on the clinical course of bipolar disorder.

BACKGROUND: Recent evidence suggests an association between migraine and bipolar disorder (BD), although the impact of this association in the clinical course of BD is relatively unknown. OBJECTIVE: This study aimed to compare 2 groups of individuals with BD (with vs without comorbid migraine) and evaluate differences in severity of clinical course. METHODS: Three hundred thirty-nine adults with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition-defined bipolar I or II disorder were enrolled and divided into 2 groups: with and without comorbid migraine. Demographic and clinical data were obtained using standardized interviews. RESULTS: Patients with comorbid migraines had more mood episodes, especially those with depressive polarity. In addition, comorbid migraine was associated with a higher prevalence of psychiatric and general medical comorbidities. Differences between the 2 groups in number of lifetime hospitalizations for depression/mania, rates of rapid cycling, and history of suicide attempts were not observed after Bonferroni correction. CONCLUSIONS: Comorbid migraine seems to be associated with poor outcomes in BD. Additional studies should be conducted to investigate shared vulnerabilities and pathophysiologic mechanisms as well as treatment optimization of both illnesses.

Morphometric post-mortem studies in bipolar disorder: possible association with oxidative stress and apoptosis.

Despite extensive research in the last decades, the pathophysiology of bipolar disorder (BD) remains unclear. Access to post-mortem brain tissue of subjects who had BD offers an opportunity to investigate neurobiology and this approach has led to some progress, particularly, due to the availability of more sophisticated molecular and cellular biological methodologies and well characterized brain collections over the past decade. Here we review the findings of morphometric post-mortem studies in BD and interpret them in the context of a potential physiopathological mechanism involving oxidative stress and apoptosis. A review of the literature was conducted to identify post-mortem studies that investigated cellular changes such as number, density and size of neurons and glia, in brains of subjects with BD. We found decreased density of neurons and glia and decreased size of neurons in frontal and subcortical areas of the brain. Based on recent studies that found evidence of increased apoptosis and oxidative stress in BD, we hypothesize that the cell abnormalities described are due to an increase in the apoptotic process that can be triggered, through its intrinsic pathway, by the existence of an exacerbated production of reactive oxygen species and oxidative damage in the disease.

A preliminary controlled trial of cognitive behavioral therapy in clozapine-resistant schizophrenia.

The use of cognitive-behavior therapy (CBT) in addition to antipsychotic regimen to treat persistent psychotic symptoms of schizophrenia is growing. The aim of this study was to compare the efficacy of CBT to a befriending (BF) control group in patients with schizophrenia who are refractory to clozapine. Twenty-one patients completed the 21-week trial. In comparison with the control group, the CBT group showed a significant improvement in the General Psychopathology and total score of the Positive and Negative Syndrome Scale, as well as an improvement of Quality of Life scale. The improvement in psychopathology persisted at 6-month follow-up assessment.

Estudo do córtex pré-frontal dorsolateral esquerdo de pacientes portadores de transtorno afetivo bipolar em comorbidade com alcoolismo através do uso de espectroscopia por ressonância magnética de hidrogênio / Study of the left dorsolateral prefrontal cortex of bipolar disorder patients with comorbid alcoholism using proton magnetic resonance spectroscopy

Cerca de 50% dos pacientes portadores de transtorno afetivo bipolar (TAB) apresentam comorbidade com abuso ou dependência de álcool. A presença de alcoolismo nos pacientes com TAB está associada a manifestações clínicas mais graves e a uma pior resposta ao tratamento do transtorno de humor. Entretanto, as anormalidades neurobiológicas subjacentes à co-ocorrência de TAB e alcoolismo são desconhecidas. Neste estudo, nosso objetivo foi o de comparar o perfil neuroquímico do córtex pré-frontal dorsolateral esquerdo de pacientes portadores de TAB e diagnóstico prévio de alcoolismo ao de pacientes portadores de TAB não-alcoolistas e ao de indivíduos saudáveis, usando espectroscopia por ressonância magnética de hidrogênio. Para isso, obtivemos uma aquisição de espectroscopia de hidrogênio de voxel único e tempo de eco curto em campo magnético de 1,5 Tesla do córtex préfrontal dorsolateral esquerdo em 23 pacientes bipolares alcoolistas, 27 pacientes bipolares não-alcoolistas e 57 indivíduos saudáveis. Níveis absolutos de N-acetilaspartato (NAA), compostos de colina, creatina mais fosfocreatina, mio-inositol, glutamato mais glutamina (Glu+Gln), e glutamato foram determinados e comparados entre os três grupos. Pacientes bipolares alcoolistas apresentaram níveis menores de Glu+Gln (p = 0,06) e de glutamato (p = 0,03) do que pacientes bipolares nãoalcoolistas. Pacientes bipolares alcoolistas apresentaram níveis menores de NAA do que controles saudáveis (p = 0,06). Esses achados sugerem que anormalidades do sistema glutamatérgico, e, possivelmente, da integridade neuronal, estão presentes no córtex pré-frontal dorsolateral esquerdo de pacientes portadores de TAB em comorbidade com alcoolismo. Tais anormalidades podem caracterizar processos fisiopatológicos que seriam específicos da comorbidade entre TAB e alcoolismo.

About 50% of bipolar disorder (BD) patients present comorbidity with alcohol abuse or dependence. The presence of alcoholism in BD is associated with worse clínical manifestations and refractoriness to treatment of the mood disorder. Nevertheless, the neurochemical underpinnings that underlie the co-occurrence of bipolar disorder and alcoholism are unknown. In this study, we sought to compare the neurochemical profile of the left dorsolateral pre-frontal cortex of BD patients with a prior diagnosis of alcoholism to non-alcoholic BD patients and healthy controls (HC), using proton (1H) magnetic resonance spectroscopy. We obtained a short-TE, single-voxel 1H spectroscopy acquisition at 1.5 Tesla from the left dorsolateral pré-frontal córtex (DLFPC) of 23 alcoholic BD patients, 27 non-alcoholic BD patients and 57 HC. Absolute levels of N-acetyl-aspartate (NAA), choline-containing compounds, phosphocreatine plus creatine, myo-inositol, glutamato plus glutamina (Glu+Gln) and glutamato were determined and compared among the three groups. Alcoholic BD patients showed lower Glu+Gln (p = 0.06) and glutamate levels (p = 0.03) than non-alcoholic BD patients. Alcoholic BD patients tended to have lower NAA levels than HC (p = 0.06). These findings suggest that glutamatergic abnormalities, and possibly, neuronal integrity abnormalities, are present in the left DLPFC of BD patients with comorbid alcoholism. Such abnormalities may characterize pathophysiological processes that are specific for the comorbidity between BD and alcoholism.

Influência do estresse psicossocial no lúpus eritematoso sistêmcio / Influence of the psychosocial stress on systemic lupus erythematosus

Vários estudos mostram que doenças clínicas podem piorar sob a influência de fatores psicologicamente estressantes. Entretanto, poucos estudos foram feitos para estabelecer esta correlação no lúpus eritematoso sistêmico (LES). No presente artigo, revisamos estudos sobre a associação ou influência de estresse psicológico ou social em pacientes com LES. Os estudos foram identificados por uma busca no Medline, através dos termos stress, lupus, disease activity e flare. Foram selecionados 14 artigos que apresentaram uma grande variação na metodologia empregada. A maioria falhou em encontrar associações entre a presença de estresse e a piora da atividade laboratorial ou clínica do LES. Apesar disso, foi identificada uma associação positiva entre presença de estresse e pior percepção da saúde física pelo paciente, através de medidas subjetivas. Três estudos de modelo laboratorial de estresse psicológico mostraram que a resposta biológica ao estresse em pacientes com LES difere de controles normais e pacientes com artrite reumatóide. Apenas um estudo mostrou que estresse diário em relações ou obrigações sociais no mês prévio precedia a exacerbação do LES.

Anorexia nervosa e gravidez: relato de caso / Anorexia nervosa and pregnancy: a case report

Relata-se o caso de uma adolescente de 18 anos que desenvolveu quadro de hiperemese gravídica seguida de anorexia nervosa durante sua primeira gravidez, chegando a índice de massa corporal (IMC) de 14,3 Kg/m². Os sintomas apresentados remitiram após o término prematuro da gestaçäo. Apesar de a anorexia nervosa ser incomum na gravidez, seu diagnóstico é importante em virtude dos riscos para a saúde materna e fetal

Pancreatite aguda: etiopatogenia, fisiopatologia e tratamento / Acute pancreatitis: etiopathogeny, pathophysiology and treatment

Com o objetivo de verificar os progressos na etiopatogenia e fisiopatologia da pancreatite aguda e as tendências atuais em seu tratamento, apresentamos uma revisäo de trabalhos publicados recentemente sobre esses temas. Em 60 a 80 por cento dos casos, a pancreatite aguda está associada à litíase biliar ou ao consumo de etanol. Entretanto, a cada dia novos fatores säo associados a essa doença. Os mecanismos fisiopatológicos responsáveis pelo seu desencadeamento näo estäo bem determinados. Várias teorias säo propostas. A mais recente associa as lesöes pancreáticas à liberaçäo de radicais livres de oxigênio provenientes do metabolismo celular. Näo há um tratamento específico para a pancreatite aguda. Nos casos leves, as primeiras medidas terapeuticas säo a suspensäo da ingesta oral, analgesia e, se necessário, hidrataçäo venosa. Nos pacientes mais graves säo necessários cuidados intensivos. O tratamento cirúrgico precoce está indicado apenas em situaçöes de urgência. Tardiamente, a decisäo para tratamento cirúrgico deve ser baseada em dados clínicos, morfológicos e bacteriológicos.