Effects of transcranial direct current stimulation on working memory and negative symptoms in schizophrenia: a phase II randomized sham-controlled trial.

BACKGROUND: The lack of efficacy of pharmacological treatments for cognitive and negative symptoms in schizophrenia highlights the need for new interventions. We investigated the effects of tDCS on working memory and negative symptoms in patients with schizophrenia. METHOD: Double-blinded, randomized, sham-controlled clinical trial, investigating the effects of 10 sessions of tDCS in schizophrenia subjects. Stimulation used 2 mA, for 20 min, with electrodes of 25 cm2 wrapped in cotton material soaked in saline solution. Anode was positioned over the left DLPFC and the cathode in the contralateral area. Twenty-four participants were assessed at baseline, after intervention and in a three-months follow-up. The primary outcome was the working memory score from MATRICS and the secondary outcome the negative score from PANSS. Data were analyzed using generalized estimating equations. RESULTS: We did not find group ∗ time interaction for the working memory (p = 0.720) score or any other cognitive variable (p > 0.05). We found a significant group ∗ time interaction for PANSS negative (p < 0.001, d = 0.23, CI.95 = -0.59-1.02), general (p = 0.011) and total scores (p < 0.001). Exploratory analysis of PANSS 5 factors suggests tDCS effect on PANSS negative (p = 0.012), cognitive (p = 0.016) and depression factors (p = 0.029). CONCLUSION: The results from this trial highlight the therapeutic effects of tDCS for treatment of persistent symptoms in schizophrenia, with reduction of negative symptoms. We were not able to confirm the superiority of active tDCS over sham to improve working memory performance. Larger sample size studies are needed to confirm these findings.

Hemoencephalography self-regulation training and its impact on cognition: A study with schizophrenia and healthy participants.

BACKGROUND: Cognitive impairments in schizophrenia are strongly correlated to functional outcome and recovery rates, with no pharmacological agent approved for its treatment. Neurofeedback has emerged as a non-pharmacological approach to enhance neuroplasticity, which consists in inducing voluntary control of brain responses through operant conditioning. METHOD: The effects of hemoencephalography neurofeedback (HEG-NFBK) in 4 brain sites (F7, Fp1, Fp2 and F8) was studied in 8 patients with schizophrenia (SCH, mean age 36.5±9.98) and 12 health controls (mean age 32.17±5.6). We analyzed groups' performance (10 sessions) and cognitive differences in 3 time points (baseline, after training and follow-up) with generalized estimated equations. For SCH we also evaluate the impact on psychopathology. RESULTS: We found a group∗time interaction for HEG-NFBK performance in the left hemisphere sites (F7 an Fp1) and a near-to-significant in the right frontotemporal region (F8), with no group differences and a significant time effect. Most of cognitive domains improved after intervention, including information processing speed, attention processing, working memory, executive functioning, verbal and visual learning. No group∗time interaction was found. Results suggest that both groups benefit from HEG-NFBK training regardless of cognitive differences at baseline. No significant time effects were found for Calgary and PANSS total scale and subscales (positive, negative neither general). CONCLUSION: To our knowledge, this is the first controlled trial showing effects of NFBK on cognitive performance improvement in schizophrenia. Further research investigating the effects of HEG-NFBK training in schizophrenia should be performed.

Intestinal and multivisceral retransplantation results: literature review.

BACKGROUND: Intestinal/multivisceral transplantation (IT/MVT) is the gold standard treatment for patients with intestinal failure and complications related to total parenteral nutrition, gastrointestinal inoperable indolent tumors, or diffuse portal trombosis. Currently, the reported 1-year patient survival rate is around 80%, similar to other solid organ abdominal transplantations. Unfortunately, the patient survival decreases after the first year with the 5-year rate not close to 70% yet. Acute cellular rejection is the main cause of graft loss. Its early diagnosis may make it possible to improve survival of retransplantations. OBJECTIVE: To analyze the reported results published in the last 5 years by leading transplant centers to evaluate IT/MVT retransplantation results. METHODS: We performed a literature review using PubMed focusing on multivisceral and intestinal retransplantation in articles published between 2006 and 2012. In relation to the first transplantation, we analyzed demographics, imunosuppression, rejection, infection as well as graft and patient survival rates. RESULTS: Two centers reported results on intestinal and multivisceral retransplantations. Mazariegos et al reported their experience with 15 intestinal retransplantations in 14 pediatric recipients. Four patients died from posttransplant lymphoperliferative disease, severe acute cellular rejection, fungal sepsis, or bleeding from a pseudoaneurysm at a mean time of 5.7 months post-transplantation. Total parenteral nutrition was weaned at a median time of 32 days. Abu-Elmaged et al reported 47 cases with a 5-year survival of 47% for all retransplant modalities. Retransplantation with liver-contained visceral allograft achieved a 5-year survival rate of 61% compared with 16% for liver-free visceral grafts. CONCLUSION: Despite those huge improvements, some transplanted patients develop severe acute cellular rejection, culminating in graft loss and retransplantation. Repots on multivisceral and intestinal retransplantation outcomes suggest that it is a viable procedure with appropriate patient survival after primary graft loss.

Intestinal and multivisceral transplantation immunosuppression protocols--literature review.

INTRODUCTION: Currently the most used techniques for small bowel transplant are isolated intestinal transplantation, multivisceral transplantation (MVT), and modified multivisceral transplantation. One important factor is early diagnosis of acute cellular rejection (ACR). In addition, improvements in immunosuppression have recently reduced the number and enhanced treatment of ACR episodes, enabling graft recovery. OBJECTIVE: We analyzed immunosuppression protocols of leading transplantation centers in the last 5 years. METHOD: We reviewed papers published in PubMed from major multivisceral and intestinal transplantation centers from 2006 to 2010 in adult recipients. The 211 adults transplanted in seven centers were divided into three groups according to the immunosuppression protocol used: protocol 1: daclizumab induction with tacrolimus and steroid maintenance; protocol 2: alemtuzumab and tacrolimus; and protocol 3: thymoglobulin and rituximab and tacrolimus. RESULTS: Protocol 2 showed the lowest rate of ACR (34%). Protocols 1 and 3 displayed 54% and 48% ACR rates; respectively. However, protocol 1 patients developed only mild ACR, whereas those in protocols 2 and 3 developed moderate ACR in 26.3% and 11.7%, and severe ACR in 7.9% and 47% of cases, respectively. The infection rate was considerably lower in protocol 3 (7.4%). Protocols 1 and 2 showed infection rates of 62.5% and 52%, respectively. One-year patient survival rates were 70%, 79% and 81%, respectively. Three-year patient survival rates were 62%, 56%, and 78% for protocols 1, 2 and 3, respectively. CONCLUSION: Protocol 2 was the strongest immunosuppressive regimen capable of reducing ACR rates when compared with the other protocols, but the strong effect resulted in high infection rate that impacts 1-year patient survival. Protocol 3 seems to be the best available one balancing ACR and infection rates.