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.

Association between HLA-DR4 haplotypes and tuberculin skin test response in the Aché population.

The human leukocyte antigen (HLA) system has a major role in the regulation of the immune response as it is involved in the defense against pathogens. Evidence for association with tuberculosis (TB) is more consistent for class II than for class I HLA genes. TB is important among indigenous peoples in South America, not only because of its historical role in regional depopulation, but also because it is still widespread. The aim of this study was to evaluate the association of HLA class II alleles, haplotypes and genotypes and tuberculin skin test response (TST) in 76 individuals of the Aché population. Poisson Regression was employed to assess risk genotypes. DRB1*04, DQA1*03 and DQB1*03:02 were associated with TST response in this population.

Cytokine gene polymorphisms are associated with susceptibility to tuberculosis in an Amerindian population.

SETTING: Cytokines play an important role in anti-tuberculosis immune response, combined with antigen-presenting cells and lymphocytes. Immune response gene polymorphisms have been reported to be associated with tuberculosis (TB) susceptibility in some but not all studies. OBJECTIVE: To evaluate the association of immune response genes with susceptibility to tuberculin skin test (TST) reactivity and/or TB. DESIGN: Fourteen single nucleotide polymorphisms were genotyped in 96 individuals of the Aché, a native Paraguayan population, by allelic discrimination using real-time polymerase chain reaction. Univariate and multivariate Poisson regression were employed to assess risk genotypes. RESULTS: A higher prevalence of purified protein derivative reactivity was associated with the TNF-α CCA/TCG haplotype (PR 1.298, 95%CI 1.059-1.589) and with the IL-10 AT/CC diplotype (PR 1.181, 95% CI 1.024-1.362), and the presence of the IL-8 rs4073 T allele was associated with protection against TB (PR 0.482, 95%CI 0.273-0.851). CONCLUSIONS: These results suggest that polymorphisms in genes associated with immune response are involved in TST reactivity and susceptibility to TB in the Aché population.

Distribution patterns of variability for 18 immune system genes in Amerindians--relationship with history and epidemiology.

Native American populations generally have a higher prevalence of infectious diseases than non-Native populations and this fact can induce different pressures in their immune system. We investigated the patterns of population differentiation (FST ) of 32 polymorphisms related to adaptive immune response in four Native American populations (Aché, Guarani-Kaiowá, Guarani-Ñandeva and Kaingang), and the results were compared with the three major world population data [Yoruba of Ibadan, Nigeria (YRI), Utah residents with northern and Western Europe ancestry (CEU) and Han Chinese of Beijing, China (CHB)] available in the HapMap database. The Aché clearly differentiated from the other Amerindians, but when all Native Americans were compared with the samples of other ethnic groups the lowest difference (0.08) was found with CHB (Asians), the second lowest (0.15) with YRI (Africans) and the most marked with CEU (European-derived). The considerable intra and interethnic differences found can be explained both in terms of diverse evolutionary distances and more recent environmental pathogen exposures; and they should be appropriately considered prior to any specific public health action.