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Research Interests: Bipolar Disorder, Medicine, Hippocampus, Brain, Bdnf, and 15 moreHumans, Medicina, Animals, Male, Ketamine, Animal Model, Dietary Supplements, Interpersonal Relations, Analysis of Variance, Neurosciences, Enzyme Linked Immunosorbent Assay, Cognition disorders, Motor activity, Avoidance Learning, and Medical and Health Sciences
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Research Interests: Psychology, Cognitive Science, Psychiatry, Bipolar Disorder, Medicine, and 15 moreElectroconvulsive therapy, Bdnf, Humans, Female, Male, Memantine, Clinical Neurology, Clinical Sciences, Adult, Pilot Projects, Double Blind, Placebo Controlled Trial, Neurotrophic Factors, Neurosciences, and Clozapine
Research Interests: Psychology, Pathogenesis, Medicine, Gender Identity, Neuroplasticity, and 15 moreBdnf, Humans, Internal Medicine, Female, Male, Young Adult, Gender Identity Disorder, Transsexualism, Clinical Sciences, Adult, Psychiatric, Neurotrophic Factors, Psychiatric Status Rating Scales, Psychology and Cognitive Sciences, and Medical and Health Sciences
Research Interests: Psychology, Psychiatry, Schizophrenia, Bipolar Disorder, Biomarkers, and 15 moreMedicine, Episodic Memory, Brain, Psychiatric Disorders, Mental Disorders, Metaanalysis, Cognitive Performance, Hypothesis, Science Technology, Gray Matter Volume, Inflammatory Cytokines, Pathological, Life Sciences & Biomedicine, Psychology and Cognitive Sciences, and Medical and Health Sciences
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ABSTRACT Bipolar disorder (BD) is commonly comorbid with many medical disorders including atopy, and appears characterized by progressive social, neurobiological, and functional impairment associated with increasing number of episodes and... more
ABSTRACT Bipolar disorder (BD) is commonly comorbid with many medical disorders including atopy, and appears characterized by progressive social, neurobiological, and functional impairment associated with increasing number of episodes and illness duration. Early and late stages of BD may present different biological features and may therefore require different treatment strategies. Consequently, the aim of this study was to evaluate serum levels of eotaxin/CCL11, eotaxin-2/CCL24, IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α, IFNγ, BDNF, TBARS, carbonyl, and GPx in a sample of euthymic patients with BD at early and late stages compared to controls. Early-stage BD patients, 12 late-stage patients, and 25 controls matched for sex and age were selected. 10mL of peripheral blood was drawn from all subjects by venipuncture. Serum levels of BDNF, TBARS, carbonyl content, glutathione-peroxidase activity (GPx), cytokines (IL-2, IL-4, IL-6, IL-10, IL-17, TNF-α and IFNγ), and chemokines (eotaxin/CCL11 and eotaxin-2/CCL24) were measured. There were no demographic differences between patients and controls. No significant differences were found for any of the biomarkers, except chemokine eotaxin/CCL11, whose serum levels were higher in late-stage patients with BD when compared to controls (p=0.022; Mann-Whitney U test). Small number of subjects and use of medication may have influenced in our results. The present study suggests a link between biomarkers of atopy and eosinophil function and bipolar disorder. These findings are also in line with progressive biological changes partially mediated by inflammatory imbalance, a process referred to as neuroprogression. Copyright © 2014 Elsevier B.V. All rights reserved.
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Research Interests: Neuroscience, Psychology, Cognitive Science, Schizophrenia, Medicine, and 15 moreHumans, Internal Medicine, Female, Blood sampling, Male, Adult, Cognitive Function, Atypical Antipsychotics, Antipsychotic, Neurotrophic Factors, Neurosciences, Clozapine, Brain-derived neurotrophic factor (BDNF), Antipsychotic agents, and Cognitive Deficit
Research Interests: Endocrinology, Psychiatry, Bipolar Disorder, Biology, Oxidative Stress, and 15 moreMitochondria, Medicine, Pathophysiology, Humans, Internal Medicine, Female, Male, Lipid peroxidation, Middle Aged, Adult, Psychiatric, Mitochondrion, Psychology and Cognitive Sciences, Protein carbonylation, and Medical and Health Sciences
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There is strong evidence that oxygen free radicals may play an important role in the pathophysiology of schizophrenia. Impaired antioxidant defense and increased lipid peroxidation have been previously reported in drug-naïve, first... more
There is strong evidence that oxygen free radicals may play an important role in the pathophysiology of schizophrenia. Impaired antioxidant defense and increased lipid peroxidation have been previously reported in drug-naïve, first episode and chronically medicated schizophrenic patients using typical neuroleptics. We measured serum SOD and TBARS in two groups of chronic medicated DSM-IV schizophrenic patients, under haloperidol (n = 10) or clozapine (n = 7) and a group of healthy controls (n = 15). Serum SOD and TBARS were significantly higher (p = 0.001) in schizophrenic patients (7.1 +/- 3.0 and 3.8 +/- 0.8) than in controls (4.0 +/- 1.6 and 2.5 +/- 0.7). Among patients, serum TBARS was significantly higher (p = 0.008) in those under clozapine (4.4 +/- 0.7) than in those under haloperidol treatment (3.4 +/- 0.7). For SOD levels the difference between groups was not found. It is reasonable to argue that the difference found in TBARS levels might be due to the course of the disease, instead of medication. Further investigation on the role of oxidative tonus and lipid peroxidation in different schizophrenia subtypes and different outcome patterns in this disorder is warranted. Additionally it could also address questions concerning a possible oxidant/antioxidant imbalance in schizophrenia.
Research Interests: Schizophrenia, Oxidative Stress, Medicine, Humans, Internal Medicine, and 15 moreFemale, Male, Superoxide Dismutase, Lipid peroxidation, Haloperidol, Middle Aged, Antioxidant enzyme, TBARS, Adult, Thiobarbituric Acid Reactive Substance, Clozapine, Antipsychotic agents, Psychology and Cognitive Sciences, Medical and Health Sciences, and Thiobarbituric acid
Research Interests: Psychology, Schizophrenia, Nonparametric Statistics, Cytokines, Oxidative Stress, and 15 moreMedicine, Humans, Internal Medicine, Chronic Disease, Female, Male, Middle Aged, Adult, Psychiatric, Inflammatory Cytokines, Age of Onset, Mediator complex, Psychology and Cognitive Sciences, Protein carbonylation, and Medical and Health Sciences
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Research Interests: Bipolar Disorder, Evidence Based Practice, Brazil, Medicine, Humans, and 15 moreFemale, Male, Clinical Sciences, Antipsychotics, Antidepressants, Middle Aged, Adult, Disease Progression, Clinical Protocols, Clozapine, Antipsicóticos, Antidepressivos, Neuropsychological Tests, Antipsychotic agents, and Antidepressive agents
Research Interests: Clinical Psychology, Child abuse and neglect, Mental Health, Health Education, Brazil, and 15 moreMedicine, Humans, Child, Child Sexual Abuse, Child Abuse, Evaluation methods, Female, Male, Incidence, Adult, Cross Sectional Studies, Child Neglect, Disability Evaluation, mass Screening, and functional outcome
Research Interests: Psychology, Applied Psychology, Schizophrenia, Cognition, Medicine, and 9 morePsychological Medicine, Population, Socioeconomic Status, Public health systems and services research, Social Factors, Low and Middle Income Countries, Mental Health and Psychiatry Nursing, Neurosciences, and Latin Americans
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Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse... more
Gender inequality across the world has been associated with a higher risk to mental health problems and lower academic achievement in women compared to men. We also know that the brain is shaped by nurturing and adverse socio-environmental experiences. Therefore, unequal exposure to harsher conditions for women compared to men in gender-unequal countries might be reflected in differences in their brain structure, and this could be the neural mechanism partly explaining women’s worse outcomes in gender-unequal countries. We examined this through a random-effects meta-analysis on cortical thickness and surface area differences between adult healthy men and women, including a meta-regression in which country-level gender inequality acted as an explanatory variable for the observed differences. A total of 139 samples from 29 different countries, totaling 7,876 MRI scans, were included. Thickness of the right hemisphere, and particularly the right caudal anterior cingulate, right medial orbitofrontal, and left lateral occipital cortex, presented no differences or even thicker regional cortices in women compared to men in gender-equal countries, reversing to thinner cortices in countries with greater gender inequality. These results point to the potentially hazardous effect of gender inequality on women’s brains and provide initial evidence for neuroscience-informed policies for gender equality.
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BackgroundCognition heavily relies on social determinants and genetic background. Latin America comprises approximately 8% of the global population and faces unique challenges, many derived from specific demographic and socioeconomic... more
BackgroundCognition heavily relies on social determinants and genetic background. Latin America comprises approximately 8% of the global population and faces unique challenges, many derived from specific demographic and socioeconomic variables, such as violence and inequality. While such factors have been described to influence mental health outcomes, no large-scale studies with Latin American population have been carried out. Therefore, we aim to describe the cognitive performance of a representative sample of Latin American individuals with schizophrenia and its relationship to clinical factors. Additionally, we aim to investigate how socioeconomic status (SES) relates to cognitive performance in patients and controls.MethodsWe included 1175 participants from five Latin American countries (Argentina, Brazil, Chile, Colombia, and Mexico): 864 individuals with schizophrenia and 311 unaffected subjects. All participants were part of projects that included cognitive evaluation with MATRICS Consensus Cognitive Battery and clinical assessments.ResultsPatients showed worse cognitive performance than controls across all domains. Age and diagnosis were independent predictors, indicating similar trajectories of cognitive aging for both patients and controls. The SES factors of education, parental education, and income were more related to cognition in patients than in controls. Cognition was also influenced by symptomatology.ConclusionsPatients did not show evidence of accelerated cognitive aging; however, they were most impacted by a lower SES suggestive of deprived environment than controls. These findings highlight the vulnerability of cognitive capacity in individuals with psychosis in face of demographic and socioeconomic factors in low- and middle-income countries.
Research Interests: Psychology, Applied Psychology, Schizophrenia, Cognition, Medicine, and 9 morePsychological Medicine, Population, Socioeconomic Status, Public health systems and services research, Social Factors, Low and Middle Income Countries, Mental Health and Psychiatry Nursing, Neurosciences, and Latin Americans
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Aims: Clozapine treatment of schizophrenia is effective only in 30–60% of individuals. Since genetic factors are believed to play a significant role in the variation of response to antipsychotics, the aim of the present study was to... more
Aims: Clozapine treatment of schizophrenia is effective only in 30–60% of individuals. Since genetic factors are believed to play a significant role in the variation of response to antipsychotics, the aim of the present study was to verify the effect of a G-protein gene polymorphism on clozapine response and clozapine-induced generalized seizures in Brazilian patients with schizophrenia. Patients & methods: In total, 121 schizophrenic patients in treatment with clozapine were genotyped for the 825C>T polymorphism it the GNB3 gene using PCR. Results: Homozygosity for the T825 allele was more frequent among nonresponders (χ2 = 7.708; p = 0.021), and carriers of this allele had a higher risk to present a convulsion episode (χ2 = 7.279; p = 0.007). These results were confirmed after controlling for covariates by logistic regression. Conclusion: Our data suggest an influence of the 825C>T polymorphism on clozapine response in persons with schizophrenia and also on a specific neurological side effect (generalized seizures) under clozapine treatment.
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Research Interests: Psychology, Schizophrenia, Adolescent, Medicine, Neurodegenerative Diseases, and 15 moreBrain, Humans, Internal Medicine, Female, Male, Astrocyte, Glial Cell, Middle Aged, Adult, Psychiatric, Calcium Binding Protein, Brain Damage, Psychology and Cognitive Sciences, Medical and Health Sciences, and S proteins
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Melhora dos sintomas positivos e negativos da esquizofrenia com memantina como terapia adjuvante à clozapina não está relacionada com níveis séricos de BDNF : resultados de um estudo duplo-cego randomizado controlado com placebo. ...
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Background Social and environmental factors such as poverty or violence, modulate the risk and course of schizophrenia, but how they affect the brain in patients with psychosis remains unclear. We here studied how they are related to... more
Background Social and environmental factors such as poverty or violence, modulate the risk and course of schizophrenia, but how they affect the brain in patients with psychosis remains unclear. We here studied how they are related to brain structure in schizophrenia and healthy controls in Latin America, where these factors are large and unequally distributed. Methods This is an MRI multi-center study in patients with schizophrenia and healthy controls from six Latin American cities: Buenos Aires, Medellin, Mexico City, Santiago, Sao Paulo and Porto Alegre. Total and voxel-level gray matter volumes obtained from T1-weighted MRI images and their relationship with income and homicide rates were analyzed using a general linear model. Results 334 patients with schizophrenia and 262 controls were included. Income was differentially related to total gray matter volume in the two groups (P=0.006). Controls showed a positive correlation between total gray matter volume and income (R=0.14, P...
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For years, the management of schizophrenia has represented a challenge for clinicians, with antipsychotic treatments usually resulting in relapses and new hospitalizations. Clozapine has been shown to be an effective medication for... more
For years, the management of schizophrenia has represented a challenge for clinicians, with antipsychotic treatments usually resulting in relapses and new hospitalizations. Clozapine has been shown to be an effective medication for treatment-resistant schizophrenia (TRS), but is currently underused due to its potential side effects. Nevertheless, research has suggested that clozapine reduces future hospitalizations in patients with TRS. This study aims to verify the rates of hospitalizations in patients with TRS under long-term use of clozapine. We retrospectively analyzed clinical data from 52 individuals with TRS before and after the use of clozapine. The mean duration of treatment with and without clozapine was 6.6 (± 3.9) and 8.5 years (± 6.6), respectively. Patients had a median of 0.5 (0.74) hospitalizations per year before the use of clozapine and 0 (0.74) hospitalizations after it (p = 0.001). Therefore, the use of clozapine resulted in an expected reduction in the number of...
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Previous studies have suggested that subjects participating in schizophrenia research are not representative of the demographics of the global population of people with schizophrenia, particularly in terms of gender and geographical... more
Previous studies have suggested that subjects participating in schizophrenia research are not representative of the demographics of the global population of people with schizophrenia, particularly in terms of gender and geographical location. We here explored if this has evolved throughout the decades, examining changes in geographical location, gender and age of participants in studies of schizophrenia published in the last 50 years. We examined this using a meta-analytical approach on an existing database including over 3,000 studies collated for another project. We found that the proportion of studies and participants from low-and-middle income countries has significantly increased over time, with considerable input from studies from China. However, it is still low when compared to the global population they represent. Women have been historically under-represented in studies, and still are in high-income countries. However, a significantly higher proportion of female participants have been included in studies over time. The age of participants included has not changed significantly over time. Overall, there have been improvements in the geographical and gender representation of people with schizophrenia. However, there is still a long way to go so research can be representative of the global population of people with schizophrenia, particularly in geographical terms.
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Abstract Schizophrenia (SZ) is associated with increased somatic morbidity and mortality, in addition to cognitive impairments similar to those seen in normal aging, which may suggest that pathological accelerated aging occurs in SZ.... more
Abstract Schizophrenia (SZ) is associated with increased somatic morbidity and mortality, in addition to cognitive impairments similar to those seen in normal aging, which may suggest that pathological accelerated aging occurs in SZ. Therefore, we aim to evaluate the relationships of age, telomere length (TL) and CCL11 (aging and inflammatory biomarkers), and gray matter volumes (GM) to episodic memory performance in individuals with SZ compared to healthy controls (HC). 112 participants (48 SZ and 64 HC) underwent clinical and memory assessments, structural MRI, and had their peripheral blood drawn for biomarkers analysis. Comparisons of group means and correlations were performed. Participants with SZ had decreased TL and GM residual volume, increased CCL11, and worse memory performance compared to HC. In SZ, shorter TL was related to increased CCL11, and they were both related to reduced GM residual volume, all of which were related to worse memory performance. Older age was only associated with reduced GM, but longer duration of illness was related with all the aforementioned variables. Younger age of disease onset was related with increased CCL11 levels and worse memory performance. In HC, there were no significant correlations except for between memory and GM. Our results are consistent with accelerated aging in SZ. These results may indicate that it is not age itself, but the impact of the disease associated with a pathological accelerated aging that leads to impaired outcomes in SZ.Akira Sawa, johns Hopkins University, Johns Hopkins Hospital and Medical Institutions
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Research Interests: Psychology, Neuroimaging, Bipolar Disorder, Treatment Outcome, Medicine, and 14 moreBrain, Humans, Staging, Clinical Sciences, Bipolar Disorders, Biological markers, Disease Progression, Physiological Stress Markers, Allostasis, Transtorno Bipolar, Neurosciences, Neuroprogression, Clinical response, and Serum biomarkers
OBJECTIVE: Previous reports suggest that cytokines act as potential mediators of the interaction between the immune and neuroendocrine systems, and that a proinflammatory state may be associated with bipolar disorder and schizophrenia.... more
OBJECTIVE: Previous reports suggest that cytokines act as potential mediators of the interaction between the immune and neuroendocrine systems, and that a proinflammatory state may be associated with bipolar disorder and schizophrenia. The aim is to compare cytokine levels in both disorders. METHOD: Twenty euthymic bipolar disorder patients, 53 chronic stabilized schizophrenia patients and 80 healthy controls were recruited. Subjects were all non-smokers and non-obese. Cytokines TNF-α, IL-6, and IL-10 were examined by sandwich ELISA. RESULTS: IL-6 levels were increased in schizophrenia patients when compared to controls (p < 0.0001) and euthymic bipolar disorder patients (p < 0.0001). IL-6 levels were no different in controls compared to euthymic bipolar disorder patients (p = 0.357). IL-10 was lower in controls compared to schizophrenia patients (p = 0.001) or to bipolar disorder patients (p = 0.004). There was no significant difference in TNF-α serum levels among the groups ...
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Research Interests: Neuroscience, Psychology, Cognitive Science, Bipolar Disorder, Medicine, and 15 moreElectroconvulsive therapy, Humans, Female, Drug Resistance, Male, Depressive Disorder, Middle Aged, Pilot study, Biological markers, Mechanism of action, Pilot Projects, Neurotrophic Factors, Neurosciences, Drug treatment, and Medical and Health Sciences
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The notion that schizophrenia is a neuroprogressive disorder is based on clinical perception of cumulative impairments over time and is supported by neuroimaging and biomarker research. Nevertheless, increasing evidence has indicated that... more
The notion that schizophrenia is a neuroprogressive disorder is based on clinical perception of cumulative impairments over time and is supported by neuroimaging and biomarker research. Nevertheless, increasing evidence has indicated that schizophrenia first emerges as a neurodevelopmental disorder that could follow various pathways, some of them neuroprogressive. The objective of this review is to revisit basic research on cognitive processes and neuroimaging findings in a search for candidate keys to the intricate connections between neurodevelopment and neuroprogression in schizophrenia. In the complete panorama, schizophrenia is a neurodevelopmental disorder, possibly associated with an additional burden over the course of the disease through pathologically accelerated aging, and cognitive heterogeneity may explain the different trajectories of each patient.
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Background Sexual function is highly neglected in individuals with schizophrenia (SZ). Clinicians usually underestimate the rates of sexual dysfunctions in these patients, and this group does not spontaneously complain about it. Sexual... more
Background Sexual function is highly neglected in individuals with schizophrenia (SZ). Clinicians usually underestimate the rates of sexual dysfunctions in these patients, and this group does not spontaneously complain about it. Sexual dysfunction in this population could reach up to 80% and its known to affect all domains of sexual function. Moreover, it may be linked to stigma and discrimination factors. Medication side effects on sexuality concern more than any other side effects, and it is known to be a major cause of poor quality of life and non-adherence to medication. Furthermore, the relationship between sexual dysfunction and other psychiatric symptoms in SZ is still unclear. Our aim was to describe the sexual dysfunction in chronic patients with SZ and its relation to negative, positive and depressive symptoms. Methods A convenience and exploratory sample of 57 patients (age 43.75±10.38, 69% men, 86,2% single) were recruited from an university outpatient schizophrenia clin...