Multicenter randomized controlled trial of bifrontal, bitemporal, and right unilateral electroconvulsive therapy in major depressive disorder.

AIM: Electroconvulsive therapy (ECT) has been shown to be the most effective and rapid treatment for severe depression. Electrode placement is one of the most important factors that affect ECT's efficacy and side-effects profile. Bifrontal, bitemporal, and unilateral are the three most used electrode placements. Very few studies have directly compared the efficacy and cognitive side-effects of the three placements. The aim of this study was to compare the efficacy and cognitive side-effects associated with bifrontal, bitemporal, and unilateral electrode placements. METHODS: This multicenter randomized, blinded, controlled trial included 40 patients in each of the three groups. Most of the patients (94.8%) completed six ECT treatments. We used mixed-model analyses to compare differences in 17-item Hamilton Depression Rating Scale (HAMD-17) and Clinical Global Impression (CGI) scores among the three groups and the five times series (baseline, Week 1, Week 2, Week 3, and Week 4). The cognitive outcome was Mini-Mental State Examination (MMSE) score. RESULTS: HAMD-17 and CGI scores did not differ significantly across the groups (HAMD-17 scores: z = -1.13, P = 0.259; CGI scores: z = -0.35, P = 0.729). MMSE scores at pre- and post-ECT were similar across the three groups (F = 2.06, P = 0.133). However, subgroup analysis using paired t-tests showed that MMSE scores improved in the right unilateral and bifrontal groups (t = 2.745, P = 0.0098; t = 2.464, P = 0.0204), but did not change in the bitemporal group (t = 1.188, P = 0.2461). CONCLUSION: The efficacy of right unilateral and bifrontal ECT placement was similar to that of bitemporal ECT. The physical side-effects were also similar across the three groups. Right unilateral and bifrontal ECT placement were associated with improved cognitive outcomes, but bitemporal ECT placement was not.

Association between SCAP and SREBF1 gene polymorphisms and metabolic syndrome in schizophrenia patients treated with atypical antipsychotics.

OBJECTIVES: The use of atypical antipsychotics (AAPs) in the treatment of schizophrenia has been relevant because of the high prevalence of metabolic syndrome (MetS). The sterol-regulatory element-binding protein (SREBP) pathway may contribute to the underlying pathophysiology of AAP-induced metabolic adverse effects. We explored the association between the variants of the sterol-regulatory element-binding transcription factor-1 (SREBF1) gene and the SREBP cleavage-activation protein (SCAP) gene with AAP-induced MetS in a genetic case-control study. METHODS: Eleven single nucleotide polymorphisms (SNPs) of SREBF1 and five of SCAP were genotyped in a Han Chinese population in Beijing, China: a sample of 722 schizophrenia patients on monotherapy with AAPs (clozapine, olanzapine or risperidone). Metabolic parameters were collected and evaluated for MetS criteria. RESULTS: The rs11654081 T-allele of the SREBF1 gene was significantly associated with an increased risk for MetS after correction (P = 0.019, odds ratio, OR =2.56, 95% confidence interval, CI: 1.4 4-4.54). The rs11654081-TT genotype appeared more frequently in MetS than in non-MetS after correction (P = 0.026, OR =2.37, 95% CI: 1.3 6-4.12). SCAP polymorphisms with drug-induced MetS were negative in this study. CONCLUSIONS: The genetic polymorphisms of SREBF1 could play a role in the mechanism for interindividual variation of AAP-induced MetS.

Association between SREBF2 gene polymorphisms and metabolic syndrome in clozapine-treated patients with schizophrenia.

BACKGROUND: Patients with schizophrenia using antipsychotics often develop metabolic side effects, especially with clozapine. Previous studies indicated that antipsychotics could activate the pathway of the sterol regulatory element-binding protein (SREBP). The sterol regulatory element binding transcription factor 2 (SREBF2) gene mainly regulates the cholesterol biosynthetic gene. Therefore, we hypothesized that the SREBF2 gene would be a candidate gene for interindividual variation in drug-induced metabolic syndrome (MetS). In this genetic case-control study, we examined the SREBF2 gene polymorphisms in the risk of MetS patients treated with clozapine. METHODS: Ten single nucleotide polymorphisms (SNPs) of SREBF2 were genotyped in a CHB (Han Chinese in Beijing, China) population, a sample of 621 schizophrenia patients treated with clozapine. Patients were evaluated for metabolic parameters and screened for the MetS criteria. RESULTS: The incidence of MetS among all subjects was 41.8% (260/621). Two markers of SREBF2 were associated with MetS induced by clozapine after False Discovery Rate (FDR) correction (rs1052717, corrected Pallele=0.010, corrected Pgenotype=0.022; and rs2267443, corrected Pgenotype=0.015). Patients who received clozapine and carried the A-allele of rs2267443 or rs1052717 had an increased risk of MetS (rs2267443, odds ratio (OR)=1.67, 95% confidence interval (CI): 1.20-2.34; and rs1052717, OR=1.81, 95% CI: 1.15-1.98), adjusted by logistic regression for clinical characteristics. CONCLUSION: The results suggest that the genetic polymorphisms of SREBF2 gene may be associated with MetS in patients treated with clozapine.