Randomized, double-blind, sham-controlled trial to evaluate the efficacy and tolerability of electroconvulsive therapy in patients with clozapine-resistant schizophrenia.

There is no established treatment for patients with clozapine-resistant schizophrenia (CRS). Clozapine augmentation strategies with antipsychotics or others substances are effective in comparison with placebo while and Electroconvulsive therapy (ECT) showed to be effective in comparison with treatment as usual (TAU) but not with placebo (sham-ECT). In the present double- blind randomized controlled trial, we compared 40 outpatients who received 20 sessions of ECT (n = 21) or sham-ECT (n = 19) (age = 37.40 ± 9.62, males = 77.5 %, illness duration = 14.95 ± 8.32 years, mean total Positive and Negative Syndrome Scale (PANSS) = 101.10 ± 24.91) who fulfilled well-defined CRS criteria including baseline clozapine plasma levels ≥350 ng/mL. The primary outcome was the ≥50 % PANSS Total Score reduction; secondary outcomes were the scores of the PANSS subscales, PANSS five-factor dimensions, PANSS-6 and the Calgary Depression Rating Scale (CDRS). Treatment response was analyzed by percentage reduction, Linear Mixed Models and effect sizes. At baseline both groups showed no differences except for years of school education (included as a covariate). At endpoint, only 1/19 of the completers (5.26 %) in the ECT group and 0/17 in the sham-ECT group showed a ≥50 % total PANSS score reduction. Both groups showed no significant differences of the total PANSS score (F = 0.12; p = 0.73), Positive (F = 0.27, p = 0.61), Negative (F = 0.25, p = 0.62), and General Psychopathology scores (F = 0.01, p = 0.94) as well for all PANSS five factors, the PANSS-6 and CDRS. Thus, the present study found no evidence that ECT is better than Sham-ECT in patients with CRS. Future sham-ECT controlled studies with larger sample sizes are warranted to test the efficacy of ECT for patients with CRS.

Decreased S100-beta protein in schizophrenia: preliminary evidence.

The S100 proteins are a family of calcium-binding proteins found in the central and peripheral nervous systems of vertebrates. S100beta, the most abundant member of this family in the CNS, mediates calcium signal transduction, and shows neurotrophic, gliotrophic and mitogenic actions that influence the development and maintenance of the nervous system. Another member of the S100 family (S100A10) was found to modulate phospholipid turnover by inhibiting the activity of enzyme phospholipase A2 (PLA2). We determined the concentration of S100beta protein in the plasma of 23 medicated schizophrenic patients and 23 healthy controls. S100beta protein accounts for 96% of the total S100 in the brain. Schizophrenic patients showed reduced S100beta concentrations (p=0.003), and this finding was not related to clinical variables or to intake of antipsychotic medication. Decreased S100beta could be related to the findings of increased PLA2 activity and to brain maldevelopment in schizophrenia. These results are discussed further with respect to the role of adenosine in S100beta release.

Analysis of a novel functional polymorphism within the promoter region of the serotonin transporter gene (5-HTT) in Brazilian patients affected by bipolar disorder and schizophrenia.

It has been suggested that the serotonin transporter (5-hydroxytryptamine-transporter or 5-HTT) may be involved in the pathogenesis of affective disorders. Recently, Collier et al. (1996) found that the frequency of the low-activity short variant (s) of the 5-HTT-linked polymorphic region (5-HTTLPR) was higher among patients with affective disorders than in normal controls. However, since the observed level of significance was not high, they suggest that these findings should be replicated in independent samples. We have analyzed 86 unrelated patients (47 with bipolar disorder and 39 with schizophrenia) and 98 normal controls from the Brazilian population for the 5-HTTLPR. Statistical analysis revealed that the genotypes (LL, Ls, ss) as well as the estimated allele frequencies (L,s) did not differ significantly among the three studied groups or between bipolar and normal controls. In addition, although not statistically significant, the genotype ss in our sample was less frequent among our bipolar patients than in our normal controls (12.8% versus 16.3%) which is the opposite of what was found by Collier et al. (24% versus 18%) in the European study. Although it will be important to extend the present analysis in a larger sample, our preliminary results suggest that the 5-HTTLPR does not seem to play a major role in the genetics of bipolar and schizophrenic disorders at least in this group of Brazilian psychiatric patients.

Meta-analysis about efficacy of anti-resorptive drugs in post-menopausal osteoporosis.

OBJECTIVE: The purpose of this study was to compare the effect of three groups of anti-resorptive drugs in post-menopausal osteoporosis. DATA SOURCES: We collected data covering the period between 1983 and 1995, by first using MEDLINE. References retrieved were scanned further to identify additional papers. STUDY SELECTION: Only randomized studies evaluating bone mass by means of dual-photon or dual energy densitometry over a period of 1 year were accepted. DATA EXTRACTION: Studies were arranged into three drug groups. We used densitometry results after 1 year in all treatment or control groups. Factors which might interfere with the results were recorded for subsequent separate analysis. DATA SYNTHESIS: The MEDLINE search identified almost 25,000 studies. On reading the abstracts, 275 trials appeared to be controlled trials and original copies were retrieved for detailed analysis. A total of 31 articles which satisfied the inclusion criteria were identified. The first meta-analysis included studies which compared oestrogens and placebo, and the global effect-size was 0.54 (95% CI 0.34, 0.73). The second meta-analysis compared calcitonins with placebo and produced an effect-size of 0.41 (95% CI 0.21, 0.61) The third analysis compared bisphosphonates and placebo and showed an effect-size of 0.87 (95% CI 0.68, 1.07). Only oestrogen dose affected the results found. CONCLUSIONS: Bisphosphonates had the greatest effect on bone mass in post-menopausal osteoporosis.

Increased prefrontal sulcal prominence in relatively young patients with unipolar major depression.

Although several studies have reported ventricular enlargement and sulcal prominence in mixed samples of patients with affective disorders (unipolar and bipolar subtypes), it is not established if these findings extend to a homogeneous sample of relatively young patients with unipolar major depression ventricular:brain ratio (VBR) and prefrontal sulcal prominence (PSP). In the present study, measures of ventricle-brain ratio (VBR) and prefrontal sulcal prominence (PSP) were compared in patients with affective disorders (n = 24, mean age = 39), medical control subjects (n = 40), patients with schizophrenia (n = 101) on ventricular : brain ratio (VBR) and prefrontal sulcal prominence (PSP). No statistically significant differences were noted in VBR in the three groups. Both patient groups had significantly greater PSP than the medical control subjects but did not differ significantly from each other. The results of the present study extend the finding of prefrontal sulcal prominence, but not ventricular enlargement, to relatively young patients with unipolar depression. Furthermore, the results of the present study suggest that patients with schizophrenia and patients with affective disorders differ only slightly or not at all in brain morphology, at the level of resolution studied.

Meta-analyses of studies of ventricular enlargement and cortical sulcal prominence in mood disorders. Comparisons with controls or patients with schizophrenia.

BACKGROUND: The findings of ventricular enlargement and increased sulcal prominence are well documented in schizophrenia, but the consistency of similar findings in mood disorders is less well appreciated. Reliable documentation of the presence of these structural abnormalities in mood disorders would require a reassessment of their significance for both schizophrenia and mood disorders. In this article, we meta-analytically review the literature on ventricular enlargement and cortical sulcal prominence in patients with mood disorders compared with controls and patients with schizophrenia. METHODS: Four meta-analytic reviews were conducted, two comparing patients with mood disorders with normal controls on ventricular enlargement (meta-analysis 1) or sulcal prominence (meta-analysis 2) and two comparing patients with mood disorders with schizophrenic patients on these same measures (meta-analyses 3 and 4). RESULTS: Meta-analyses 1 and 2 revealed statistically significant (P < .001) moderate composite effect sizes (d) for the comparisons of patients with mood disorders with controls on both ventricular enlargement (d = 0.44) and sulcal prominence (d = 0.42). Meta-analysis 3 further revealed that patients with schizophrenia have significantly greater ventricular enlargement than patients with mood disorders (P = .002), but the effect size was small (d = -0.20). There were too few studies comparing these patient groups on sulcal prominence to support a quantitative meta-analysis. CONCLUSIONS: This review documents the presence of ventricular enlargement and increased sulcal prominence in mood disorders. Patients with mood disorders have less ventricular enlargement than patients with schizophrenia, but this effect is small. These results reinforce previous suggestions of the nonspecificity of structural brain changes in schizophrenia and mood disorders.