Débora Pastore Bassitt

Insight and regional brain volumes in schizophrenia

We have investigated the relationship between insight impairment and regional brain volumes (gray and white matter) in schizophrenia using voxel-based morphometry (VBM). Fifty patients with schizophrenia were evaluated using the Scale for Unawareness of Mental Disorders. Magnetic resonance images were acquired, segmented and spatially normalized using optimized VBM routines. No significant inverse correlations were detected between insight impairment and gray or white matter volumes in the prefrontal region (where significant findings had been predicted a priori), or in any other brain areas. Our results do not support previous hypotheses suggesting a relationship between frontal lobe atrophy and impaired insight in patients with schizophrenia.

Cholinesterase inhibitors as adjunctive therapy in patients with schizophrenia and schizoaffective disorder: a review and meta-analysis of the literature

AbstractBackground: Cognitive deficits have been described in patients with schizophrenia from the first descriptions of dementia praecox to current concepts of cognitive dysmetria. Nevertheless, little is known about how to deal with them. In Alzheimer disease, cholinergic deficit is found and cholinesterase inhibitors have been used to delay the progression of memory and cognitive dysfunction. Several lines of evidence suggest that the cholinergic system may be disrupted in schizophrenia. Objective: To evaluate cognitive and clinical effects of adjunctive cholinesterase inhibitors in patients with schizophrenia and schizoaffective disorder. Method: We conducted a literature search on PubMed and EMBASE (up to December 2008) for articles that investigated adjunctive cholinesterase inhibitors in patients with schizophrenia. The terms ‘schizophrenia’, ‘acetylcholinesterase inhibitors’, ‘rivastigmine’, ‘donepezil’, ‘galantamine’ and ‘cognitive deficit’ were searched with restriction for English language and without a year limit. All articles that presented original data from randomized, double-blind, placebo-controlled trials with donepezil, rivastigmine or galantamine in patients with schizophrenia or schizoaffective disorder were included in the meta-analysis. Studies were excluded for the following reasons: (i) case study/letter/correspondence/review; (ii) animal study; (iii) molecular/genetic investigation; and (iv) inclusion of patients with schizophrenia and co-morbid dementia. Few appropriate data for meta-analysis were found because of the large heterogeneity of the assessment instruments used. Nevertheless, effects of cholinesterase inhibitors in some cognitive domains (executive function, memory and language), psychopathology (using the Positive and Negative Syndrome Scale) and extrapyramidal symptoms could be analysed. Results: Six open-label and 24 double-blind studies were found. In five open-label studies there was an improvement in memory, attention and executive functions. Thirteen double-blind studies (four with rivastigmine, six with donepezil and three with galantamine) contributed to the meta-analysis. Significant improvement was found in this analysis for memory and the Trail Making test part A. Conclusions: The reviewed studies suggest that specific cognitive deficits (memory, and the motor speed and attention part of executive function) of patients with schizophrenia and schizoaffective disorder are responsive to rivastigmine, donepezil and galantamine as adjunctive therapy. Confirmatory studies are needed to determine the clinical utility of this treatment strategy.

Clozapine efficacy in tardive dyskinesia in schizophrenic patients

Abstract Tardive dyskinesia (TD) is a long-term severe complication of antipsychotic treatment, with mean prevalence of 20–35%. The aim of this study was to evaluate effects of clozapine in severe TD. In an open trial seven patients with schizophrenia and severe TD were given clozapine for 6 months. Tardive dyskinesia severity was evaluated with AIMS and ESRS and schizophrenic psychopathology with PANSS. Clozapine mean dose at the end of the study was 392.86 mg/day. A mean reduction of 52% was observed in ESRS scores for TD. Two patients also had dystonic movements, and there was 50% reduction in one of them and complete remission in the other. There was also a 27% mean reduction in PANSS scores. Clozapine seems to be an alternative in the treatment of schizophrenic patients with severe TD.

Conjugated estrogens as adjuvant therapy in the treatment of acute schizophrenia: a double-blind study

In a double-blind, placebo controlled study, conjugated estrogens (CE) (0.625 mg/day) were added to a fixed dosage of haloperidol (5 mg daily). Forty-four female inpatients with acute schizophrenia were included in the study and randomized to one of the groups; 40 patients completed the trial. They were followed for 28 days and evaluated periodically with the BPRS, Negative Symptoms Rating Scale, Simpson Angus Extrapyramidal Rating Scale and UKU rating scale. Hormonal concentrations (estradiol, estrone, progesterone, FSH, LH and prolactine) were measured at baseline and weekly throughout the trial. Both groups showed similar clinical improvement during the evaluation, although there was a trend for the CE group to show a better improvement than the placebo group (p < 0.10). Side effects and the use of anticholinergics were similar in both groups. Conjugated estrogens caused elevation only of estrone levels in the CE group; estradiol and prolactin showed a similar profile for both groups. Our negative findings regarding the antipsychotic effect of conjugated estrogens does not preclude, however, a possible efficacy of other estrogens, such as 17-beta-estradiol, in schizophrenia.

Maintenance treatment of severe tardive dyskinesia with clozapine: 5 years' follow-up.

Abstract: Drug-induced tardive dyskinesia (TD) affects approximately 20% to 30% of schizophrenic patients. Although it is usually mild, from 1% to 8% of patients may develop severe TD. Second-generation antipsychotics have demonstrated a lower risk of inducing TD. However, despite the advances brought by second-generation antipsychotics, the treatment strategies for TD remain problematic, given both the lack of an established therapeutic choice and the need for long-term use of antipsychotics in the treatment of schizophrenia. Clozapine is an atypical antipsychotic with minimal risk of inducing TD. Furthermore, it has been suggested that clozapine might actually improve the symptoms of TD. Accordingly, we evaluated the effects of clozapine on severe TD over 5 years. Seven patients meeting Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria for chronic exacerbated schizophrenia (mean age 28.5 ± 10.2 years) and presenting severe TD, defined as Abnormal Involuntary Movements Scale score above 13, were treated with clozapine and followed up for 5 years. Extrapyramidal Symptoms Rating Scale assessment was performed in all patients at baseline, after 6 months and 3 and 5 years. Mean Extrapyramidal Symptoms Rating Scale scores decreased 83% after 3 years and 87.5% after 5 years. Mean dose for all patients was 428 ± 269 mg/d after 5 years. Results from this open-label study suggest that clozapine may be a further option for the treatment of TD over long term.

Patterns of regional gray matter loss at different stages of schizophrenia: A multisite, cross-sectional VBM study in first-episode and chronic illness

Background: Structural brain abnormalities in schizophrenia have been repeatedly demonstrated in magnetic resonance imaging (MRI) studies, but it remains unclear whether these are static or progressive in nature. While longitudinal MRI studies have been traditionally used to assess the issue of progression of brain abnormalities in schizophrenia, information from cross-sectional neuroimaging studies directly comparing first-episode and chronic schizophrenia patients to healthy controls may also be useful to further clarify this issue. With the recent interest in multisite mega-analyses combining structural MRI data from multiple centers aiming at increased statistical power, the present multisite voxel-based morphometry (VBM) study was carried out to examine patterns of brain structural changes according to the different stages of illness and to ascertain which (if any) of such structural abnormalities would be specifically correlated to potential clinical moderators, including cumulative exposure to antipsychotics, age of onset, illness duration and overall illness severity. Methods: We gathered a large sample of schizophrenia patients (161, being 99 chronic and 62 first-episode) and controls (151) from four previous morphometric MRI studies (1.5 T) carried out in the same geographical region of Brazil. Image processing and analyses were conducted using Statistical Parametric Mapping (SPM8) software with the diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) algorithm. Group effects on regional gray matter (GM) volumes were investigated through whole-brain voxel-wise comparisons using General Linear Model Analysis of Co-variance (ANCOVA), always including total GM volume, scan protocol, age and gender as nuisance variables. Finally, correlation analyses were performed between the aforementioned clinical moderators and regional and global brain volumes. Results: First-episode schizophrenia subjects displayed subtle volumetric deficits relative to controls in a circumscribed brain regional network identified only in small volume-corrected (SVC) analyses (p < 0.05, FWE-corrected), including the insula, temporolimbic structures and striatum. Chronic schizophrenia patients, on the other hand, demonstrated an extensive pattern of regional GM volume decreases relative to controls, involving bilateral superior, inferior and orbital frontal cortices, right middle frontal cortex, bilateral anterior cingulate cortices, bilateral insulae and right superior and middle temporal cortices (p < 0.05, FWE-corrected over the whole brain). GM volumes in several of those brain regions were directly correlated with age of disease onset on SVC analyses for conjoined (first-episode and chronic) schizophrenia groups. There were also widespread foci of significant negative correlation between duration of illness and relative GM volumes, but such findings remained significant only for the right dorsolateral prefrontal cortex after accounting for the influence of age of disease onset. Finally, significant negative correlations were detected between life-time cumulative exposure to antipsychotics and total GM and white matter volumes in schizophrenia patients, but no significant relationship was found between indices of antipsychotic usage and relative GM volume in any specific brain region. Conclusion: The above data indicate that brain changes associated with the diagnosis of schizophrenia are more widespread in chronic schizophrenia compared to first-episode patients. Our findings also suggest that relative GM volume deficits may be greater in (presumably more severe) cases with earlier age of onset, as well as varying as a function of illness duration in specific frontal brain regions. Finally, our results highlight the potentially complex effects of the continued use of antipsychotic drugs on structural brain abnormalities in schizophrenia, as we found that cumulative doses of antipsychotics affected brain volumes globally rather than selectively on frontal-temporal regions.

Psychotic symptoms in older people without dementia from a Brazilian community‐based sample

The international prevalence of psychotic symptoms in older subjects without dementia varies from 0.9% to 8.0%. However, an analysis of these symptoms in developing countries has not been undertaken.

Transtorno de personalidade na terceira idade

CONTEXT: Interpersonal difficulties, affective instability, distortions of the clinician-patient relationship, and unpredictable responses to clinical interventions, are characteristics found in older adults as well as in younger patients with personality disorders. CASE REPORT: We report the case of a 68 years old patient with histrionic personality disorder and other psychiatric comorbidities. CONCLUSION: Personality disorders are frequently overlooked in the diagnostic workout of complex psychogeriatric syndromes, and require a comprehensive assessment of personality traits. The correct identification of personality disorders and their subtypes is critical for planning the therapeutic approach, including pharmacotherapy and psychological management.

Variation of plasma cortisol levels in patients with depression after treatment with bilateral electroconvulsive therapy

INTRODUCTION More than 60 years after the introduction of modern psychopharmacology, electroconvulsive therapy (ECT) continues to be an essential therapeutic modality in the treatment of mental disorders, but its mechanism of action remains unclear. Hormones play an essential role in the development and expression of a series of behavioral changes. One aspect of the influence of hormones on behavior is their potential contribution to the pathophysiology of psychiatric disorders and the mechanism of action of psychotropic drugs and ECT. OBJECTIVE We measured blood levels of the hormone cortisol in patients with unipolar depression according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) and compared results with levels found in healthy adults. METHOD Blood cortisol levels were measured before the beginning of treatment with ECT, at the seventh session, and at the last session, at treatment completion. Depression symptoms were assessed using the Beck Depression Inventory (BDI). RESULTS Cortisol levels remained stable in both men and women between the seventh and the last sessions of ECT; values ranged from 0.686±9.6330 g/dL for women, and there was a mean decrease of 5.825±6.0780 g/dL (p = 0.024). Mean number of ECT sessions was 12. After the seventh and the last ECT sessions, patients with depression and individuals in the control group had similar cortisol levels, whereas BDI scores remained different. CONCLUSION Cortisol levels decreased during ECT treatment. ECT seems to act as a regulator of the hypothalamic-pituitaryadrenal axis.

Interface entre pensamento obsessivo e delírio: relato de dois casos

In psychopathology, the difficulties in distinguishing between delusion and obsessive thought require some reflection. There is a significant degree of uncertainty and complexity surrounding these categories, the symptoms of which seem to overlap each other. Two cases are presented in which both diagnoses are plausible using criteria of the Diagnostic and Statistical Manual of Mental Disorders. The Positive and Negative Syndrome Scale and Yale-Brown Obsessive Compulsive Scale were applied, but did not help clarify the differences. In search for the best diagnosis, a dialogue with the studies of Carol Sonenreich is herein proposed in a counterpoint to code classifications, guides and the state-of-the-art literature.