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Bipolar Disorder: HELP
Articles from Miscellaneous institutions in Sao Paulo
Based on 32 articles published since 2010
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These are the 32 published articles about Bipolar Disorder that originated from Miscellaneous institutions in Sao Paulo during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2
1 Review A critical review of trials of transcranial direct current stimulation and trigeminal nerve stimulation for depression: the issue of treatment-emergent mania. 2017

Shiozawa, Pedro / Cordeiro, Quirino / Cho, Hyong Jin / Trevizol, Alisson Paulino / Brietzke, Elisa. ·Centro Interdisciplinar de Neuromodulação Clínica, Faculdade de Ciências Médicas, Santa Casa de São Paulo, São Paulo, SP, Brazil. · University of California (UCLA), San Diego, USA. · Laboratório Interdisciplinar de Neurociências Clínicas (LiNC), Departamento de Psiquiatria, Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil. ·Trends Psychiatry Psychother · Pubmed #28403323.

ABSTRACT: Objective:: This study is a critical review analyzing occurrence of treatment-emergent mania (TEM) related to transcranial direct current stimulation (tDCS) and trigeminal nerve stimulation (TNS). Method:: We present a systematic review of the literature on TEM related to tDCS and TNS treatment for major depressive disorder (MDD), conducted in accordance with the recommendations from Cochrane Group and the PRISMA guidelines. Results:: Our search identified few reported episodes of TEM in the literature. In fact, we found 11 trials focused on treatment of MDD (seven controlled trials of tDCS and four trials of TNS, three open label and one controlled). We highlight the need for safety assessment in clinical research settings to establish with precision and in larger samples the risks inherent to the technique under investigation. Conclusion:: Safety assessment is of fundamental importance in clinical research. TEM is a very important safety issue in MDD trials. Further and larger controlled trials will help to clarify both the safety and the clinical effects of combinations of pharmacotherapy and tDCS or TNS in daily clinical practice.

2 Review Selfish brain and selfish immune system interplay: A theoretical framework for metabolic comorbidities of mood disorders. 2017

Yamagata, Ana Sayuri / Mansur, Rodrigo Barbachan / Rizzo, Lucas Bortolotto / Rosenstock, Tatiana / McIntyre, Roger S / Brietzke, Elisa. ·Institute of Biosciences University of São Paulo (USP). R. do Matão, 14, 321 - Butantã, São Paulo, SP, 05508-090, Brazil,; Research Group of Behavioral and Molecular Neuroscience of Bipolar Disorder, Department of Psychiatry, Federal University of São Paulo (Unifesp). R. Pedro de Toledo, 669-3rd Floor, Vila Clementino, São Paulo, SP, CEP 04039-032, Brazil. Electronic address: ana.yamagata@usp.br. · Research Group of Behavioral and Molecular Neuroscience of Bipolar Disorder, Department of Psychiatry, Federal University of São Paulo (Unifesp). R. Pedro de Toledo, 669-3rd Floor, Vila Clementino, São Paulo, SP, CEP 04039-032, Brazil; Mood Disorders Psychopharmachology Unit (MDPU), University of Toronto. 399 Bathurst Street, MP 9-325, Toronto, Ontario, M5T 2S8, Canada. · Research Group of Behavioral and Molecular Neuroscience of Bipolar Disorder, Department of Psychiatry, Federal University of São Paulo (Unifesp). R. Pedro de Toledo, 669-3rd Floor, Vila Clementino, São Paulo, SP, CEP 04039-032, Brazil. · Department of Physiological Science, Santa Casa de São Paulo Medical School. R. Doutor Cesário Motta Júnior, 61 - Vila Buarque, São Paulo - SP, 01221-020 Brazil. · Mood Disorders Psychopharmachology Unit (MDPU), University of Toronto. 399 Bathurst Street, MP 9-325, Toronto, Ontario, M5T 2S8, Canada. ·Neurosci Biobehav Rev · Pubmed #27871787.

ABSTRACT: According to the "selfish brain" theory, the brain regulates its own energy supply influencing the peripheral metabolism and food intake according to its needs. The immune system has been likewise "selfish" due to independent energy consumption; and it may compete with the brain (another high energy-consumer) for glucose. In mood disorders, stress in mood episodes or physiological stress activate homeostasis mechanisms from the brain and the immune system to solve the imbalance. The interaction between the selfish brain and the selfish immune system may explain various conditions of medical impairment in mood disorders, such as Metabolic Syndrome (MetS), obesity, type 2 diabetes mellitus (T2DM) and immune dysregulation. The objective of this study is to comprehensively review the literature regarding the competition between the brain and the immune system for energy substrate. Targeting the energetic regulation of the brain and the immune system and their cross-talk open alternative treatments and a different approach in the study of general medical comorbidities in mood disorders, although more investigation is needed.

3 Review [Cannabis abuse in patients with psychiatric disorders: an update to old evidence]. 2010

Diehl, Alessandra / Cordeiro, Daniel Cruz / Laranjeira, Ronaldo. ·Unidad de Pesquisa em Alcool e Drogas, Instituto Nacional de Políticas do Alcool e Drogas, Departamento Psiquiatria, Escola Paulista de Medicina, Universidad Federal de São Paulo, SP, Brasil. alediehl@terra.com.br ·Braz J Psychiatry · Pubmed #20512269.

ABSTRACT: OBJECTIVE: To perform an update on cannabis abuse by patients with psychiatric disorders. METHOD: A search was performed in the electronic databases Medline, The Cochrane Library Database, Lilacs, PubMed, and SciELO, using the keywords 'marijuana abuse', 'cannabis abuse', 'psychiatric disorders', and 'mental disorders'. Articles published until December 2009, dealing with cannabis abuse and dependence in association with other psychiatric disorders were included. RESULTS: Cannabis abuse was found to be associated with increased risk for the onset of schizophrenia and chronic psychotic symptoms, although these findings require confirmation from additional research. Cannabis seems to be one of the drugs of choice of individuals with bipolar disorder, despite evidence that manic states can be induced by its use. Cannabis abuse also occurs frequently in individuals with anxiety disorders, but the relationship between the chronic nature of these conditions and the use of marijuana remains uncertain. In respect to depression, there is no clear evidence to date that depressive patients use cannabis as a form of self-medication. In individuals with psychiatric disorders, the use of cannabis has been associated with increased positive symptoms, additional negative symptoms in the course of illness, impaired treatment compliance, and more hospitalizations. CONCLUSION: The abuse of cannabis by patients with psychiatric disorders such as schizophrenia and mood and anxious disorders has a negative impact both in the acute and advanced stages of these conditions, although further investigation on this association is still necessary.

4 Article Peripheral biomarkers allow differential diagnosis between schizophrenia and bipolar disorder. 2019

Tasic, Ljubica / Larcerda, Acioly L T / Pontes, João G M / da Costa, Tássia B B C / Nani, João V / Martins, Lucas Gelain / Santos, Leonardo A / Nunes, Marielle F Q / Adelino, Marcelo P M / Pedrini, Mariana / Cordeiro, Quirino / Bachion de Santana, Felipe / Poppi, Ronei J / Brietzke, Elisa / Hayashi, Mirian Akemi Furuie. ·Chemical Biology Laboratory, Department of Organic Chemistry, Institute of Chemistry, Universidade Estadual de Campinas (Unicamp), Campinas, SP, Brazil. Electronic address: ljubica@unicamp.br. · Department of Psychiatry, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, SP, Brazil; Center for Research and Clinical Trials Sinapse-Bairral, Instituto Bairral de Psiquiatria, Brazil. · Chemical Biology Laboratory, Department of Organic Chemistry, Institute of Chemistry, Universidade Estadual de Campinas (Unicamp), Campinas, SP, Brazil. · Department of Pharmacology, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil; National Institute for Translational Medicine (INCT-TM, CNPq), Brazil. · Center for Research and Clinical Trials Sinapse-Bairral, Instituto Bairral de Psiquiatria, Brazil. · Department of Psychiatry, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP/EPM), São Paulo, SP, Brazil. · Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), São Paulo, SP, Brazil. · Department of Analytical Chemistry, Laboratório de Quimiometria em Química Analítica, Institute of Chemistry, Unicamp, Campinas, SP, Brazil. · Department of Pharmacology, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, SP, Brazil; National Institute for Translational Medicine (INCT-TM, CNPq), Brazil. Electronic address: mhayashi@unifesp.br. ·J Psychiatr Res · Pubmed #31568986.

ABSTRACT: Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental disorders that pose important challenges for diagnosis by sharing common symptoms, such as delusions and hallucinations. The underlying pathophysiology of both disorders remains largely unknown, and the identification of biomarkers with potential to support diagnosis is highly desirable. In a previous study, we successfully discriminated SCZ and BD patients from healthy control (HC) individuals by employing proton magnetic resonance spectroscopy (

5 Article Reduced Annexin A3 in schizophrenia. 2019

Joaquim, Helena P G / Costa, Alana Caroline / Serpa, Maurício Henriques / Talib, Leda L / Gattaz, Wagner F. ·Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, University of Sao Paulo, Rua Dr. Ovídio Pires de Campos, 785, 3º andar, São Paulo, SP, 05403-010, Brazil. · Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBioN), Conselho Nacional de Desenvolvimento Cientifico e Tecnológico, São Paulo, Brazil. · Laboratory of Psychiatric Neuroimaging (LIM-21), Department and Institute of Psychiatry, University of Sao Paulo Medical School, São Paulo, Brazil. · Laboratory of Neuroscience (LIM-27), Department and Institute of Psychiatry, University of Sao Paulo, Rua Dr. Ovídio Pires de Campos, 785, 3º andar, São Paulo, SP, 05403-010, Brazil. gattaz@usp.br. · Instituto Nacional de Biomarcadores em Neuropsiquiatria (INBioN), Conselho Nacional de Desenvolvimento Cientifico e Tecnológico, São Paulo, Brazil. gattaz@usp.br. ·Eur Arch Psychiatry Clin Neurosci · Pubmed #31372726.

ABSTRACT: The cellular and molecular mechanisms underlying onset and development of schizophrenia have not yet been completely elucidated, but the association of disturbed neuroplasticity and inflammation has gained particular relevance recently. These mechanisms are linked to annexins functions. ANXA3, particularly, is associated to inflammation and membrane metabolism cascades. The aim was to determine the ANXA3 levels in first-onset drug-naïve psychotic patients. We investigated by western blot the protein expression of annexin A3 in platelets of first-onset, drug-naïve psychotic patients (diagnoses according to DSM-IV: 28 schizophrenia, 27 bipolar disorder) as compared to 30 age- and gender-matched healthy controls. Annexin A3 level was lower in schizophrenia patients as compared to healthy controls (p < 0.001) and to bipolar patients (p < 0.001). Twenty out of 28 schizophrenic patients had undetectable annexin A3 levels, as compared to none from the bipolar and none from the control subjects. ANXA3 was reduced in drug-naïve patients with schizophrenia. ANXA3 affects neuroplasticity, inflammation and apoptosis, as well as it modulates membrane phospholipid metabolism. All these processes have been discussed in regard to the biology of schizophrenia. In face of these data, we feel that further studies with larger samples are warranted to investigate the possible role of reduced ANXA3 as a possible risk marker for schizophrenia.

6 Article Increased levels of plasma IL-1b and BDNF can predict resistant depression patients. 2019

Uint, Luciana / Bastos, Gisele Medeiros / Thurow, Helena Strelow / Borges, Jessica Bassani / Hirata, Thiago Dominguez Crespo / França, João Italo Dias / Hirata, Mario Hiroyuki / Sousa, Amanda Guerra de Moraes Rego. ·Dante Pazzanese Institute of Cardiology, São Paulo, SP, Brasil. · School of Pharmaceutical Science, University of São Paulo, São Paulo, SP, Brasil. ·Rev Assoc Med Bras (1992) · Pubmed #30994834.

ABSTRACT: BACKGROUND: There is no strong evidence on the link between inflammatory profile and pattern of drug treatment response in depressive patients that could result in Coronary Artery Disease occurrence. OBJECTIVE: This study aimed to compare the subclinical atherosclerosis markers, inflammatory profile, and BDNF production in Resistant Depression (RD) or Bipolar Affective Disorder (BAD) patients under conventional treatment. METHODS: The population evaluated was comprised of 34 RD, 43 BAD, and 41 controls. Subclinical atherosclerosis markers were evaluated using ultrasonography, tomography, and exercise stress test. Plasma concentrations of TNFα, IL-1β, IL-6, and BDNF were measured using Luminex100™. The usCRP concentration was measured using turbidimetric immunoassay. IL1B, IL6, and TNFA expression were determined using TaqMan®. For the statistical analysis, the significance level was established at p<0.05. RESULTS: Concerning subclinical atherosclerosis markers, only O2 consumption was reduced in the BAD group (p = 0.001). Although no differences were found in gene expression, BDNF and IL-1β plasma concentration was increased in the RD group (p = 0.002 and p = 0.005, respectively) even with an antidepressant treatment, which suggests that these drugs have no effect in IL-1β secretion and that the inflammasome may play a role in therapy response. CONCLUSION: Taken together, both BDNF and IL-1β plasma concentrations could be used to the early identification of RD patients.

7 Article Oligopeptidases activity in bipolar disorder: Ndel1 and angiotensin I converting enzyme. 2019

Dal Mas, Caroline / Carvalho, Michelle S / Marins, Lucas A / Yonamine, Camila M / Cordeiro, Quirino / McIntyre, Roger S / Mansur, Rodrigo B / Brietzke, Elisa / Hayashi, Mirian A F. ·Department of Pharmacology, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), Rua 3 de maio 100, Ed. INFAR, 3rd floor, CEP 04044-020 São Paulo, Brazil. · Department of Psychiatry, Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), São Paulo, Brazil. · Mood Disorders Psychopharmacology Unit, Toronto Western Hospital, University Health Network, Toronto, ON, Canada. · Department of Psychiatry, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), Rua Pedro de Toledo, 669, 3rd floor, Vila Clementino, CEP 04039-032 São Paulo, Brazil. Electronic address: elisa.brietzke@unifesp.br. · Department of Pharmacology, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), Rua 3 de maio 100, Ed. INFAR, 3rd floor, CEP 04044-020 São Paulo, Brazil. Electronic address: mhayashi@unifesp.br. ·J Affect Disord · Pubmed #30321766.

ABSTRACT: BACKGROUND: Abnormal activity of two enzymes relevant to neurodevelopment, namely nuclear-distribution element-like 1 (Ndel1) and angiotensin I-converting enzyme (ACE), was reported in individuals with schizophrenia; to our knowledge, these oligopeptidases were never measured in bipolar disorder (BD). AIMS: Evaluate the enzyme activity of Ndel1 and ACE in euthymic individuals with BD type 1 which was compare to healthy control (HC) group. METHODS: Ndel1 and ACE activities were assessed in the serum of individuals with BD type 1 according to DSM-IV criteria (n = 70) and a HC group (n = 34). The possible differences between BD type 1 and HC groups were evaluated using Analysis of Covariance (ANCOVA), and the results were adjusted for age, gender and body mass index. RESULTS: We observed a positive correlation between Ndel1 activity and the total YMRS score in BD group (p = 0.030) and a positive correlation between ACE activity and Ham-D score (p = 0.047). ANCOVA analysis showed lower Ndel1 activity in BDs compared to HCs. Interestingly, we did not observe between-groups differences in ACE activity, despite the recognized correlation of ACE activity levels with cognitive functions, also described to be worsened in psychiatric patients. CONCLUSION: Oligopeptidases, especially Ndel1, which has been strongly correlated with neurodevelopment and brain formation, are potentially a good new target in the study of the neurobiology of BD. LIMITATIONS: The relatively small sample size did not permit to examine the cause-effect relationship of clinical dimensions of BD and the enzymatic activity.

8 Article Periodontal condition and levels of bacteria associated with periodontitis in individuals with bipolar affective disorders: A case-control study. 2019

Cunha, Fabiano A / Cota, Luís O M / Cortelli, Sheila C / Miranda, Tais B / Neves, Fernando S / Cortelli, José R / Costa, Fernando O. ·Federal University of Minas Gerais, Belo Horizonte, Brazil. · University of Taubaté, Taubaté, São Paulo, Brazil. ·J Periodontal Res · Pubmed #30207388.

ABSTRACT: OBJECTIVE: To evaluate the epidemiological and microbiological aspects of the potential association between bipolar affective disorder (BAPD) and periodontitis. METHODOLOGY: The present case-control study comprised 176 individuals with BAPD and 176 controls. All individuals underwent a complete full-mouth periodontal examination and microbiological sampling. Data on bleeding on probing, probing depth, and clinical attachment level in all present teeth were recorded. Quantification of total bacterial load and Aggregatibacter actinomycetemcomitans, Treponema denticola, and Porphyromonas gingivalis counts were performed through qPCR. Data were analyzed using univariate analysis, Spearman correlation and multivariate logistic regression. RESULTS: The prevalence of periodontitis was 39.7% among controls and 58.5% among individuals with BAPD (OR = 2.13; 95% CI 1.39-3.27). A. actinomycetemcomitans and P. gingivalis counts were significantly higher in individuals with BPAD and periodontitis. The final multivariate logistic regression revealed that periodontitis was strongly associated with the total bacterial load (OR = 1.91; 95% IC = 1.0-1.99; P < 0.001) and the depressive phase of BPAD (OR = 28.94; 95% IC = 4.44-177.27; P < 0.001). CONCLUSION: BAPD was associated with increased risk for periodontitis. Individuals with BPAD presented higher levels of A. actinomycetemcomitans and P. gingivalis, suggesting that periodontitis could be a co-morbidity frequently found in individuals with BAPD.

9 Article Differential Impact of Obesity on CD69 Expression in Individuals with Bipolar Disorder and Healthy Controls. 2018

Yamagata, Ana S / Rizzo, Lucas B / Cerqueira, Raphael O / Scott, Janine / Cordeiro, Quirino / McIntyre, Roger S / Mansur, Rodrigo B / Brietzke, Elisa. ·Research Group in Molecular and Behavioral Neuroscience of Bipolar Disorder, Department of Psychiatry, Federal University of São Paulo, São Paulo, Brazil. · Institute of Neuroscience, Newcastle University, Newcastle upon Tyne, UK. · Centre for Affective Disorders, IoPPN, Kings College, London, UK. · Psychiatry Department, Santa Casa School of Medical Sciences, São Paulo, Brazil. · Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, Toronto, Ontario, Canada. ·Mol Neuropsychiatry · Pubmed #29888230.

ABSTRACT: Preliminary evidence suggests that premature immunosenescence is involved in bipolar disorder (BD) pathophysiology. The cellular marker CD69 is expressed in T lymphocyte surface during their activation and its expression is negatively correlated with age. The objective of this study was to assess the moderating effects of obesity on the reduction of expression of CD69, a marker of immunosenescence. Forty euthymic patients with BD type I, aged 18-65 years, were included in this study. The healthy comparison group consisted of 39 volunteers who had no current or lifetime history of mental disorders, no use of psychotropic medications, and no known family history of mood disorders or psychosis. Peripheral blood mononuclear cells from BD patients and healthy controls were collected and isolated. The cells were allowed to grow in culture and stimulated for 3 days. CD69 was marked and read in flow cytometry. We found that the lower expression of CD69 in BD patients was moderated by body mass index (BMI) in both CD4+ (RR = 0.977, 95% CI 0.960-0.995,

10 Article Stimulation of the Nigrotectal Pathway at the Level of the Superior Colliculus Reduces Threat Recognition and Causes a Shift From Avoidance to Approach Behavior. 2018

Almada, Rafael C / Genewsky, Andreas J / Heinz, Daniel E / Kaplick, Paul M / Coimbra, Norberto C / Wotjak, Carsten T. ·Department of Stress Neurobiology and Neurogenetics, Neuronal Plasticity, Max Planck Institute of Psychiatry, Munich, Germany. · Laboratory of Neuroanatomy and Neuropsychobiology, Department of Pharmacology, Ribeirão Preto Medical School (FMRP), University of São Paulo (USP), São Paulo, Brazil. · Behavioral Neurosciences Institute (INeC), São Paulo, Brazil. · Neuroscience Master's Program, Interdisciplinary Center for Neurosciences (IZN), Heidelberg University, Heidelberg, Germany. · NAP-USP-Neurobiology of Emotions Research Center (NuPNE), Ribeirão Preto Medical School (FMRP), University of São Paulo (USP), São Paulo, Brazil. ·Front Neural Circuits · Pubmed #29867370.

ABSTRACT: Defensive behavioral responses are essential for survival in threating situations. The superior colliculus (SC) has been implicated in the generation of defensive behaviors elicited by visual, tactile and auditory stimuli. Furthermore, substantia nigra pars reticulata (SNr) neurons are known to exert a modulatory effect on midbrain tectum neural substrates. However, the functional role of this nigrotectal pathway in threating situations is still poorly understood. Using optogenetics in freely behaving mice, we activated SNr projections at the level of the SC, and assessed consequences on behavioral performance in an open field test (OFT) and the beetle mania task (BMT). The latter confronts a mouse with an erratic moving robo-beetle and allows to measure active and passive defensive responses upon frequent encounter of the threatening object. Channelrhodopsin-2 (ChR2)-mediated activation of the inhibitory nigrotectal pathway did not affect anxiety-like and exploratory behavior in the OFT, but increased the number of contacts between robo-beetle and test mouse in the BMT. Depending on the size of the arena, active avoidance responses were reduced, whereas tolerance and close following of the robo-beetle were significantly increased. We conclude from the data that the nigrotectal pathway plays holds the potential to modulate innate fear by attenuating threat recognition and causing a shift from defensive to approach behavior.

11 Article An immunological age index in bipolar disorder: A confirmatory factor analysis of putative immunosenescence markers and associations with clinical characteristics. 2018

Rizzo, Lucas B / Swardfager, Walter / Maurya, Pawan Kumar / Graiff, Maiara Zeni / Pedrini, Mariana / Asevedo, Elson / Cassinelli, Ana Cláudia / Bauer, Moisés E / Cordeiro, Quirino / Scott, Jan / Brietzke, Elisa / Cogo-Moreira, Hugo. ·Interdisciplinary Laboratory of Clinical Neuroscience (LINC), Federal University of Sao Paulo (Unifesp), Sao Paulo, Brazil. · Department of Psychiatry, University of Tuebingen, Tuebingen, Germany. · Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, Ontario, Canada. · Department of Pharmcology and Toxicology, University of Toronto, Toronto, Ontario, Canada. · Amity Institute of Biotechnology, Amity University Uttar Pradesh, New Delhi, India. · Centro Interdisciplinar de Neuromodulação Clínica, Faculdade de Ciências Médicas, Santa Casa de São Paulo, Brazil. · Faculty of Biosciences, Pontifical Catholic University of Porto Alegre, Porto Alegre, Brazil. · Department of Academic Psychiatry, Wolfson Unit, Institute of Neuroscience, Newcastle University, Newcastle, UK. · Research Group in Molecular and Behavioral Neuroscience in Bipolar Disorder, Federal University of Sao Paulo (Unifesp), São Paulo, Brazil. · Department of Psychiatry (Psychiatry and Medical Psychology Graduate Program), Federal University of Sao Paulo (Unifesp), São Paulo, Brazil. ·Int J Methods Psychiatr Res · Pubmed #29691917.

ABSTRACT: OBJECTIVES: The study aims to generate an immunological age (IA) trait on the basis of immune cell differentiation parameters, and to test whether the IA is related to age and disease characteristics. METHODS: Forty-four euthymic type I bipolar disorder patients were included in this study. Five immunosenescence-related parameters were assessed: proportions of late-differentiated cells (e.g., CD3+CD8+CD28-CD27- and CD3-CD19+IgD-CD27-), and the expression of CD69, CD71, and CD152 after stimulation. Confirmatory factor analysis was applied to generate an IA trait underling the 5 measures. RESULTS: The best-fit model was constituted by 4 parameters that were each related to an underlying IA trait, with 1 cell population positively correlated (CD3+CD8+CD28-CD27- [λ = 0.544, where λ represents the loading of the parameter onto the IA trait] and 3 markers negatively correlated (CD69 [λ = -0.488], CD71 [λ = -0.833], and CD152 [λ = -0.674]). The IA trait was associated with chronological age (β = 0.360, p = .013) and the number of previous mood episodes (β = 0.426, p = .006). In a mediation model, 84% of the effect between manic episodes, and IA was mediated by body mass index. CONCLUSION: In bipolar disorder type I, premature aging of the immune system could be reliably measured using an index that validated against chronological age, which was related to adverse metabolic effects of the disease course.

12 Article Heart rate variability in patients with bipolar disorder: From mania to euthymia. 2018

Wazen, Guilherme Luiz Lopes / Gregório, Michele Lima / Kemp, Andrew Haddon / Godoy, Moacir Fernandes de. ·Department of Psychiatry and Medical Psychology of São José do Rio Preto Medical School, Famerp, São José do Rio Preto, São Paulo, Brazil. Electronic address: wazenguilherme@yahoo.com.br. · Transdisciplinary Nucleus for Chaos and Complexity Studies (NUTECC), São José do Rio Preto Medical School, Famerp, São José do Rio Preto, São Paulo, Brazil. · Department of Psychology, College of Human and Health Sciences, Swansea University, Swansea, Wales, United Kingdom; Department of Psychiatry, University of Sao Paulo, Sao Paulo, Brazil; School of Psychology, University of Sydney, Sydney, Australia. · Transdisciplinary Nucleus for Chaos and Complexity Studies (NUTECC), São José do Rio Preto Medical School, Famerp, São José do Rio Preto, São Paulo, Brazil; Department of Cardiology and Cardiovascular Surgery of São José do Rio Preto Medical School, Famerp, São Paulo, Brazil. Electronic address: mfgodoy@famerp.br. ·J Psychiatr Res · Pubmed #29407285.

ABSTRACT: Bipolar Disorder (BD) is characterized by the occurrence of mania alternating with euthymia. The aim of the present study was to investigate the impact of BD on the autonomic nervous system, as indicated by heart rate variability (HRV). The study was registered in the Clinical Trials Registration (NCT01272518). Nineteen hospitalized, male patients (age: 34.0 ± 12.3 years) with type I BD were assessed during mania and at discharge on euthymia. HRV data were collected during 20- minutes in supine position at rest, on spontaneous breathing, using the Polar RS 800 CX frequencymeter. HRV measures included variables in time, frequency and non-linear domains. Psychiatric conditions were evaluated by the Mini International Neuropsychiatric Interview (MINI) and the Bech-Rafaelsen mania scale (BRMS). Time domain measures of RMSSD (Cohen's d = 0.668) and pNN50 (Cohen's d = 0.688) increased from first to second assessments. The high-frequency component (HFms2) also increased (Cohen's d = 0.586), while the LF/HF ratio decreased (Cohen's d = 0.785). Non-linear domain measures including the SD1 component (Cohen's d = 0.668), and the SD1/SD2 ratio (Cohen's d = 1.2934) extracted from the Poincare plot analysis increased from first to second assessment. The variables Lmean (Cohen's d = 0.9627), Lmax (Cohen's d = 1.2164), REC% (Cohen's d = 1.0595) and EntShannon (Cohen's d = 1.0607) were higher in mania. By contrast, ApEn (Cohen's d = 0.995) and EntSample (Cohen's d = 1.189) were less during mania, all reflecting ANS improvement. Findings are interpreted in the context of recently published models relating to neurovisceral integration across the continuum of time, and the implications for the future health and wellbeing of patients are considered.

13 Article The differential association between history of childhood sexual abuse and body mass index in early and late stages of bipolar disorder. 2018

Leclerc, Emilie / Mansur, Rodrigo B / Grassi-Oliveira, Rodrigo / Cordeiro, Quirino / Kapczinski, Flavio / McIntyre, Roger S / Brietzke, Elisa. ·Research Group of Molecular and Behavioral Neuroscience of Bipolar Disorder, Department of Psychiatry, Federal University of São Paulo (Unifesp), São Paulo, SP, Brazil; Post-Graduation Program in Psychiatry and Medical Psychology, Federal University of São Paulo (Unifesp), São Paulo, SP, Brazil. · Mood Disorders Psychopharmacology Unit (MDPU), University Health Network (UHN), Toronto, ON, Canada. · Developmental Cognitive Neuroscience Laboratory (DCNL), Brain Institute (InsCer), Pontifical Catholic University of Rio Grande do Sul (PUCRS), Porto Alegre, RS, Brazil. · Santa Casa School of Medical Sciences of São Paulo, São Paulo, Brazil. · Brain and Cognition Discovery Foundation (BCDF), Toronto, ON, Canada. · Mood Disorders Psychopharmacology Unit (MDPU), University Health Network (UHN), Toronto, ON, Canada; Brain and Cognition Discovery Foundation (BCDF), Toronto, ON, Canada. · Research Group of Molecular and Behavioral Neuroscience of Bipolar Disorder, Department of Psychiatry, Federal University of São Paulo (Unifesp), São Paulo, SP, Brazil; Post-Graduation Program in Psychiatry and Medical Psychology, Federal University of São Paulo (Unifesp), São Paulo, SP, Brazil; Mood Disorders Psychopharmacology Unit (MDPU), University Health Network (UHN), Toronto, ON, Canada. Electronic address: elisabrietzke@hotmail.com. ·J Affect Disord · Pubmed #29102835.

ABSTRACT: BACKGROUND: History of distal stressors such as childhood trauma is a well-established, non-specific vulnerability factor for multiple mental illnesses. The objective of this study was to investigate the possible association between history of childhood trauma and body mass index (BMI) in individuals in early and late stages of bipolar disorder (BD) and to verify is there was any difference in the association of sexual abuse history and obesity in early versus late stages of BD. METHODS: Seventy-one euthymic BD-type I patients and eighty-one healthy controls were evaluated using the Childhood Trauma Questionnaire (CTQ) and body mass index (BMI). The association between BMI and CTQ total and subscores were evaluated dividing BD population in early-stage BD-I (less than 10 years since onset of disease) or late-stage BD (more than 10 years). RESULTS: BD individuals had higher rates of history of childhood trauma than HC, especially sexual and emotional abuse, after adjusting for confounders. We observed a moderating effect of group on the association between BMI and sexual abuse (SA), but not on other modalities of childhood trauma, after adjustments for age, gender, ethnicity, education, alcohol and tobacco use. LIMITATIONS: Our sample included a predominance of female individuals. The study cross-sectional design does not allow concluding a cause-effect relationship. In dividing the BD subgroups in relation with the time since the onset, we supposed that the natural course of BD is linear. The CTQ is subject to recall bias. CONCLUSION: There is a relationship between childhood sexual abuse and BMI, but the direction of the association varies across the different stages of BD-I.

14 Article A preliminary study of bipolar disorder type I by mass spectrometry-based serum lipidomics. 2017

Ribeiro, Henrique C / Klassen, Aline / Pedrini, Mariana / Carvalho, Michelle S / Rizzo, Lucas B / Noto, Mariane N / Zeni-Graiff, Maiara / Sethi, Sumit / Fonseca, Francisco A H / Tasic, Ljubica / Hayashi, Mirian A F / Cordeiro, Quirino / Brietzke, Elisa / Sussulini, Alessandra. ·Laboratory of Bioanalytics and Integrated Omics (LaBIOmics), Department of Analytical Chemistry, Institute of Chemistry, University of Campinas (UNICAMP), P.O. Box 6154, 13083-970 Campinas, SP, Brazil. · Department of Chemistry, Federal University of São Paulo (UNIFESP), Diadema, SP, Brazil. · Research Group in Behavioral and Molecular Neuroscience of Bipolar Disorder, Department of Psychiatry, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil. · Department of Pharmacology, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil. · Cardiology Division, Department of Medicine, Federal University of São Paulo(UNIFESP), São Paulo, SP, Brazil. · Chemical Biology Laboratory, Department of Organic Chemistry, Institute of Chemistry, University of Campinas (UNICAMP), P.O. Box 6154, 13083-970 Campinas, SP, Brazil. · Department of Psychiatry, Santa Casa de São Paulo, School of Medical Sciences, São Paulo, SP, Brazil. · Research Group in Behavioral and Molecular Neuroscience of Bipolar Disorder, Department of Psychiatry, Federal University of São Paulo (UNIFESP), São Paulo, SP, Brazil. Electronic address: elisabrietzke@hotmail.com. · Laboratory of Bioanalytics and Integrated Omics (LaBIOmics), Department of Analytical Chemistry, Institute of Chemistry, University of Campinas (UNICAMP), P.O. Box 6154, 13083-970 Campinas, SP, Brazil. Electronic address: sussulini@iqm.unicamp.br. ·Psychiatry Res · Pubmed #28918859.

ABSTRACT: The present study aimed at investigating possible alterations in the serum lipid profile of euthymic patients with bipolar disorder type I (BD) compared to healthy controls (HC). Thirty-five individuals from both genders were recruited, with 14 diagnosed and treated as BD patients (BD group) and 21 healthy subjects (HC group). Clinical assessment was based on the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Young Mania Rating Scale (YMRS), and 17-items of Hamilton Depression Rating Scale (HDRS-17) data, which were used to confirm diagnosis, to verify psychiatric comorbidities, and to estimate the severity of manic and depressive symptoms. Ultra-high performance liquid chromatography (UHPLC) coupled to high resolution mass spectrometry (HRMS) was applied to analyze the lipids extracted from all serum samples from both studied groups. In this pioneer and exploratory study, we observed different serum lipid profiles for BD and HC groups, especially regarding glycerophospholipid, glycerolipid, and sphingolipid distribution. Multivariate statistical analyses indicated that 121 lipids were significantly different between BD and HC. Phosphatidylinositols were identified as the most altered lipids in BD patient sera. The results of this preliminary study reinforce the role of lipid abnormalities in BD and offer additional methodological possibilities for investigation in the field.

15 Article Plasma copeptin and metabolic dysfunction in individuals with bipolar disorder. 2017

Mansur, Rodrigo B / Rizzo, Lucas B / Santos, Camila M / Asevedo, Elson / Cunha, Graccielle R / Noto, Mariane N / Pedrini, Mariana / Zeni-Graiff, Maiara / Cordeiro, Quirino / McIntyre, Roger S / Brietzke, Elisa. ·Reserach Group in Behavioral and Molecular Neuroscience of Bipolar Disorder, Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. · Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada. · Department of Psychiatry, Clinic for Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany. · Vila Maria Outpatient Clinic, São Paulo, Brazil. · Department of Psychiatry, Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), São Paulo, Brazil. ·Psychiatry Clin Neurosci · Pubmed #28457001.

ABSTRACT: AIM: This study aimed to compare plasma copeptin levels, the c-terminal of provasopressin, between individuals with bipolar disorder (BD) and healthy controls and to assess the relation between copeptin and metabolic parameters. METHODS: We measured plasma levels of copeptin in individuals with BD (n = 55) and healthy controls (n = 21). Information related to psychiatric/medical history, as well as to metabolic comorbidities and laboratorial parameters was also captured. Insulin resistance and β-cell function in basal state were calculated from fasting plasma glucose and C-peptide using the HOMA2 calculator. Impaired glucose metabolism was defined as pre-diabetes or type 2 diabetes mellitus. Copeptin, adiponectin, and leptin plasma levels were determined by enzyme-linked immunosorbent assay. RESULTS: Plasma copeptin levels were lower in individuals with BD, relative to healthy controls (P < 0.001). There were significant interactions between BD and plasma copeptin on β-cell function (rate ratio [RR] = 1.048; P = 0.030) and on leptin levels (RR = 1.087; P = 0.012), indicating that there was a positive correlation between these markers in the BD group, but a negative one in healthy controls. Finally, in individuals with BD only, the association between β-cell function, body mass index (RR = 1.007; P < 0.001), and insulin resistance (RR = 1.001; P = 0.037) was moderated by copeptin levels. CONCLUSION: Copeptin levels were lower in individuals with BD than in healthy controls. There were differential associations between copeptin and metabolic parameters within the BD and healthy control subgroups, suggesting an association between abnormal copeptin and metabolic dysregulation only in the BD population.

16 Article None 2017

Sethi, Sumit / Pedrini, Mariana / Rizzo, Lucas B / Zeni-Graiff, Maiara / Mas, Caroline Dal / Cassinelli, Ana Cláudia / Noto, Mariane N / Asevedo, Elson / Cordeiro, Quirino / Pontes, João G M / Brasil, Antonio J M / Lacerda, Acioly / Hayashi, Mirian A F / Poppi, Ronei / Tasic, Ljubica / Brietzke, Elisa. ·Department of Psychiatry, Universidade Federal de São Paulo-UNIFESP, Rua Borges Lagoa, 570. Vila Clementino, São Paulo, CEP 04038-020, Brazil. · Department of Pharmacology, Universidade Federal de São Paulo-UNIFESP, Rua Três de Maio, 100. Vila Clementino, São Paulo, CEP 04044-020, Brazil. · Department of Psychiatry, Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), Rua Major Maragliano, 287. Vila Mariana, São Paulo, CEP 04017-030, Brazil. · Laboratório de Química Biológica, Department of Organic Chemistry, Institute of Chemistry, Universidade Estadual de Campinas-UNICAMP, Caixa Postal 6154, Campinas, São Paulo, CEP 13083-970, Brazil. · Department of Analytical Chemistry, Institute of Chemistry, Universidade Estadual de Campinas-UNICAMP, Caixa Postal 6154, Campinas, São Paulo, CEP 13083-970, Brazil. · Laboratório de Química Biológica, Department of Organic Chemistry, Institute of Chemistry, Universidade Estadual de Campinas-UNICAMP, Caixa Postal 6154, Campinas, São Paulo, CEP 13083-970, Brazil. ljubica@iqm.unicamp.br. · Department of Psychiatry, Universidade Federal de São Paulo-UNIFESP, Rua Borges Lagoa, 570. Vila Clementino, São Paulo, CEP 04038-020, Brazil. elisabrietzke@hotmail.com. ·Int J Bipolar Disord · Pubmed #28447334.

ABSTRACT: BACKGROUND: The objective of this study was to identify molecular alterations in the human blood serum related to bipolar disorder, using nuclear magnetic resonance (NMR) spectroscopy and chemometrics. METHODS: Metabolomic profiling, employing RESULTS: The investigated groups presented distinct metabolic profiles, in which the main differential metabolites found in the serum sample of bipolar disorder patients compared with those from controls were lipids, lipid metabolism-related molecules (choline, myo-inositol), and some amino acids (N-acetyl-L-phenyl alanine, N-acetyl-L-aspartyl-L-glutamic acid, L-glutamine). In addition, amygdalin, α-ketoglutaric acid, and lipoamide, among other compounds, were also present or were significantly altered in the serum of bipolar disorder patients. The data presented herein suggest that some of these metabolites differentially distributed between the groups studied may be directly related to the bipolar disorder pathophysiology. CONCLUSIONS: The strategy employed here showed significant potential for exploring pathophysiological features and molecular pathways involved in bipolar disorder. Thus, our findings may contribute to pave the way for future studies aiming at identifying important potential biomarkers for bipolar disorder diagnosis or progression follow-up.

17 Article Gene expression alterations related to mania and psychosis in peripheral blood of patients with a first episode of psychosis. 2016

Gouvea, E S / Ota, V K / Noto, C / Santoro, M L / Spindola, L M / Moretti, P N / Carvalho, C M / Xavier, G / Rios, A C / Sato, J R / Hayashi, M A F / Brietzke, E / Gadelha, A / Bressan, R A / Cordeiro, Q / Belangero, S I. ·Department of Psychiatry, Universidade Federal de São Paulo, São Paulo, Brazil. · Department of Psychiatry, Irmandade da Santa Casa de Misericórdia de São Paulo, São Paulo, Brazil. · Genetics Division, Department of Morphology and Genetics, UNIFESP, São Paulo, Brazil. · LiNC-Interdisciplinary Laboratory of Clinical Neurosciences, UNIFESP, São Paulo, Brazil. · Center of Mathematics, Computation and Cognition, Universidade Federal do ABC, São Paulo, Brazil. · Department of Pharmacology, UNIFESP, São Paulo, Brazil. · Research Group in Behavioral and Molecular Neuroscience of Bipolar Disorder, UNIFESP, São Paulo, Brazil. ·Transl Psychiatry · Pubmed #27701407.

ABSTRACT: Psychotic disorders affect ~3% of the general population and are among the most severe forms of mental diseases. In early stages of psychosis, clinical aspects may be difficult to distinguish from one another. Undifferentiated psychopathology at the first-episode of psychosis (FEP) highlights the need for biomarkers that can improve and refine differential diagnosis. We investigated gene expression differences between patients with FEP-schizophrenia spectrum (SCZ; N=53) or FEP-Mania (BD; N=16) and healthy controls (N=73). We also verified whether gene expression was correlated to severity of psychotic, manic, depressive symptoms and/or functional impairment. All participants were antipsychotic-naive. After the psychiatric interview, blood samples were collected and the expression of 12 psychotic-disorder-related genes was evaluated by quantitative PCR. AKT1 and DICER1 expression levels were higher in BD patients compared with that in SCZ patients and healthy controls, suggesting that expression of these genes is associated more specifically to manic features. Furthermore, MBP and NDEL1 expression levels were higher in SCZ and BD patients than in healthy controls, indicating that these genes are psychosis related (independent of diagnosis). No correlation was found between gene expression and severity of symptoms or functional impairment. Our findings suggest that genes related to neurodevelopment are altered in psychotic disorders, and some might support the differential diagnosis between schizophrenia and bipolar disorder, with a potential impact on the treatment of these disorders.

18 Article Inter-relation between brain-derived neurotrophic factor and antioxidant enzymes in bipolar disorder. 2016

Mansur, Rodrigo B / Santos, Camila M / Rizzo, Lucas B / Cunha, Graccielle R / Asevedo, Elson / Noto, Mariane N / Pedrini, Mariana / Zeni, Maiara / Cordeiro, Quirino / McIntyre, Roger S / Brietzke, Elisa. ·Research Group in Behavioral Neuroscience of Bipolar Disorder (GP-TB), Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. · Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada. · Department of Psychiatry, Clinic for Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany. · Vila Maria Outpatient Clinic, São Paulo, Brazil. · Department of Psychiatry, Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), São Paulo, Brazil. ·Bipolar Disord · Pubmed #27488494.

ABSTRACT: OBJECTIVES: Accumulating evidence indicates that oxidative stress and neurotrophins have a bidirectional relationship. In this post hoc, exploratory analysis, we investigated the association between plasma brain-derived neurotrophic factor (BDNF) levels and activities of the antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD) in individuals with bipolar disorder (BD) and healthy controls. METHODS: We measured plasma levels of BDNF and activities of GPx and SOD in individuals with BD (n=59) and healthy controls (n=26). Information related to current and past psychiatric/medical history, as well as to metabolic comorbidities, was also reported. RESULTS: There were negative correlations between BDNF, GPx (r=-.449, P≤.001) and GPx/SOD ratio (r=-.503, P<.001), and a positive correlation between BDNF and SOD (r=.254, P=.020). There was a moderating effect of body mass index (BMI) on the association between BDNF and GPx/SOD rate ratio [(RR)=1.002, P=.034]; interactions between impaired glucose metabolism (IGM), GPx (RR=1.016, P=.033), and GPx/SOD ratio (RR=1.026, P=.002) were also observed. These results were significant in models that included age, gender, alcohol, tobacco and medication use. CONCLUSIONS: There was a robust and independent correlation between peripheral BDNF and antioxidant enzyme activities in individuals with BD, which was moderated by metabolic comorbidities. These results reinforce the concept that these systems are associated and further extend knowledge of the putative effect of metabolic comorbidities in the pathophysiological substrates of BD.

19 Article Brain-derived neurotrophic factor, impaired glucose metabolism, and bipolar disorder course. 2016

Mansur, Rodrigo B / Santos, Camila M / Rizzo, Lucas B / Asevedo, Elson / Cunha, Graccielle R / Noto, Mariane N / Pedrini, Mariana / Zeni-Graiff, Maiara / Cordeiro, Quirino / Vinberg, Maj / Kapczinski, Flavio / McIntyre, Roger S / Brietzke, Elisa. ·Department of Psychiatry, Research Group in Behavioral Neuroscience of Bipolar Disorder (GP-TB), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. · Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada. · Department of Psychiatry, Clinic for Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany. · Vila Maria Outpatient Clinic, São Paulo, Brazil. · Department of Psychiatry, Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), São Paulo, Brazil. · Psychiatric Center Copenhagen, University of Copenhagen, Copenhagen, Denmark. · Bipolar Disorder Program and Laboratory of Molecular Psychiatry, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil. ·Bipolar Disord · Pubmed #27324989.

ABSTRACT: OBJECTIVES: The neurotrophin brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker in bipolar disorder (BD). However, current evidence is limited and results have been highly heterogeneous. This study aimed to assess the moderating effect of impaired glucose metabolism (IGM) on plasma levels of BDNF in individuals with BD, and on the relationship between BDNF and variables of illness course. METHODS: We measured and compared the plasma levels of BDNF in individuals with BD (n=57) and healthy controls (n=26). IGM was operationalized as pre-diabetes or type 2 diabetes mellitus. Information related to current and past psychiatric/medical history, as well as prescription of pharmacological treatments was also captured. RESULTS: Individuals with BD had lower levels of BDNF, relative to healthy controls, after adjustment for age, gender, current medications, smoking, alcohol use, and IGM (P=.046). There was no effect of IGM (P=.860) and no interaction between BD diagnosis and IGM (P=.893). Peripheral BDNF levels were positively correlated with lifetime depressive episodes (P<.001), psychiatric hospitalizations (P=.001) and suicide attempts (P=.021). IGM moderated the association between BDNF and the number of previous mood episodes (P<.001), wherein there was a positive correlation in euglycemic participants and a negative correlation in individuals with IGM. CONCLUSIONS: BD is independently associated with lower levels of BDNF; IGM may modify the relationship between BDNF and BD course, suggesting an interactive effect of BDNF with metabolic status on illness progression.

20 Article Psychiatric and clinical correlates of rapid cycling bipolar disorder: a cross-sectional study. 2016

Gigante, Alexandre D / Barenboim, Ivan Y / Dias, Rodrigo da S / Toniolo, Ricardo A / Mendonça, Tiago / Miranda-Scippa, Ângela / Kapczinski, Flávio / Lafer, Beny. ·Programa de Transtorno Bipolar (PROMAN), Departamento de Psiquiatria, Faculdade de Medicina, Universidade de São Paulo (USP), São Paulo, SP, Brazil. · Insper Instituto de Ensino e Pesquisa, São Paulo, SP, Brazil. · Centro de Estudos de Transtornos de Humor e Ansiedade (CETHA), Departamento de Psiquiatria, Universidade Federal da Bahia (UFBA), Salvador, BA, Brazil. · Programa de Atendimento do Transtorno de Humor Bipolar (PROTAHBI), Departamento de Psiquiatria, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. ·Braz J Psychiatry · Pubmed #27304255.

ABSTRACT: Objective:: Rapid cycling (RC) is a feature of bipolar disorder (BD) that has been associated with worse outcome and more severe disability. Our goal was to investigate the association of demographic and clinical factors with RC. Methods:: We compared RC and non-rapid cycling (NRC) BD patients from the Brazilian Research Network in Bipolar Disorder (BRN-BD) regarding age at onset of BD; total number of episodes; previous number of manic, depressive, mixed, and hypomanic episodes; polarity of the first episode; gender; number of suicide attempts; number of lifetime hospitalizations and lifetime history of at least one hospitalization; family history of mood disorder; clinical comorbidities such as hypothyroidism, hyperthyroidism, seizures; and current use of medications such as lithium, anticonvulsants, antipsychotics, and antidepressants. Results:: We studied 577 patients and found that 100 (17.3%) met the criteria for RC in the year before the investigation. RC patients had earlier age at onset, longer duration of disease, more lifetime depressive and manic episodes, higher number of suicide attempts, and higher rate antidepressant use. Conclusion:: The presence of RC in the previous year was associated with specific clinical characteristics closely related to worse outcome in the course of BD.

21 Article Bipolar disorder course, impaired glucose metabolism and antioxidant enzymes activities: A preliminary report. 2016

Mansur, Rodrigo B / Rizzo, Lucas B / Santos, Camila M / Asevedo, Elson / Cunha, Graccielle R / Noto, Mariane N / Pedrini, Mariana / Zeni-Graiff, Maiara / Gouvea, Eduardo S / Cordeiro, Quirino / Reininghaus, Eva Z / McIntyre, Roger S / Brietzke, Elisa. ·Interdisciplinary Laboratory of Clinical Neurosciences (LINC), Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil; Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada. Electronic address: rodrigomansur71@uol.com.br. · Interdisciplinary Laboratory of Clinical Neurosciences (LINC), Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil; Department of Psychiatry, Clinic for Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany. · Interdisciplinary Laboratory of Clinical Neurosciences (LINC), Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. · Interdisciplinary Laboratory of Clinical Neurosciences (LINC), Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil; Vila Maria Outpatient Clinic, São Paulo, Brazil. · Department of Psychiatry, Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), Brazil. · Medical University of Graz, Department of Psychiatry, Graz, Austria. · Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada. ·J Psychiatr Res · Pubmed #27281261.

ABSTRACT: This study aimed to examine the role of oxidative stress in bipolar disorder (BD) by evaluating the relationship among antioxidant enzymes activities, impaired glucose metabolism (IGM) and illness course. We measured the activities of plasma superoxide dismutase (SOD) and glutathione peroxidase (GPx) in individuals with BD (N = 55) and healthy controls (N = 28). Information related to current and past psychiatric/medical history, as well as prescription of any pharmacological treatments was captured. Impaired glucose metabolism was operationalized as pre-diabetes or type 2 diabetes mellitus. Our results showed that, after adjustment for age, gender, alcohol use, smoking and current medication, both BD (p < 0.001) and IGM (p = 0.019) were associated with increased GPx activity, whereas only BD was associated with decreased SOD activity (p = 0.008). We also observed an interaction between BD and IGM on SOD activity (p = 0.017), whereas the difference between BD and controls was only significant in individuals with IGM (p = 0.009). IGM, GPx and SOD activity were independently associated with variables of illness course. Moreover, IGM moderated the association between SOD activity and number of mood episodes (p < 0.001), as a positive correlation between SOD activity and mood episodes was observed only in participants with IGM. In conclusion, BD and IGM are associated with independent and synergistic effects on markers of oxidative stress. The foregoing observations suggest that the heterogeneity observed in previous studies evaluating antioxidant enzymes in BD may be a function of concurrent IGM; and that imbalances in the oxidative system may subserve the association between BD and IGM, as well as its relationship with illness course.

22 Article Antioxidant effect of simvastatin throught oxidative imbalance caused by lisdexamfetamine dimesylate. 2016

Eger, Guilherme A / Ferreira, Vinícius V / Batista, Camila R / Bonde, Henrique / de Lima, Daniela D / Wyse, Angela T S / da Cruz, Júlia N / Rodrigues, André F / Magro, Débora D Dal / da Cruz, José G P. ·Departamento de Medicina, Universidade Regional de Blumenau, Blumenau, SC, Brasil. · Departamento de Medicina, Universidade da Região de Joinville, Joinville, SC, Brasil. · Departamento de Bioquímica, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brasil. · Instituto Dante Pazzanese de Cardiologia, São Paulo, SP, Brasil. · Departamento de Ciências Naturais, Universidade Regional de Blumenau, Blumenau, SC, Brasil. ·An Acad Bras Cienc · Pubmed #26871491.

ABSTRACT: The present study aims to directly investigate the behavioral and antioxidant effects of simvastatin in a model of bipolar mania induced by lisdexamfetamine dimesylate. Wistar rats were treated for 30 days with simvastatin. On the 24th day after the start of treatment, each rat was administered lisdexamfetamine dimesylate for 7 days. The results suggest that simvastatin combined with lisdexamfetamine dimesylate induced a significant increased locomotion and lisdexamfetamine dimesylate administration causes an oxidative imbalance determined by an increment in lipid peroxidation, protein oxidation and alterations in the activities of antioxidant enzymes in brain areas; moreover, in the presence of simvastatin, most of these effects were prevented. These findings contribute to a better understanding of the critical roles of lisdexamfetamine dimesylate in the treatment of neuropsychiatric disorders, associated with increased oxidative stress and changes in antioxidant enzymatic defense. In view of the central role played by lisdexamfetamine dimesylate, the established antioxidant effect of simvastatin therapy is of major interest.

23 Article Impaired glucose metabolism moderates the course of illness in bipolar disorder. 2016

Mansur, Rodrigo B / Rizzo, Lucas B / Santos, Camila M / Asevedo, Elson / Cunha, Graccielle R / Noto, Mariane N / Pedrini, Mariana / Zeni, Maiara / Cordeiro, Quirino / McIntyre, Roger S / Brietzke, Elisa. ·Interdisciplinary Laboratory of Clinical Neurosciences (LINC), Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil; Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada. Electronic address: rodrigomansur71@uol.com.br. · Interdisciplinary Laboratory of Clinical Neurosciences (LINC), Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil; Department of Psychiatry, Clinic for Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany. · Interdisciplinary Laboratory of Clinical Neurosciences (LINC), Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil. · Interdisciplinary Laboratory of Clinical Neurosciences (LINC), Department of Psychiatry, Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil; Vila Maria Outpatient Clinic in São Paulo, Brazil. · Department of Psychiatry, Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), Brazil. · Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada. ·J Affect Disord · Pubmed #26866976.

ABSTRACT: BACKGROUND: The longitudinal course of bipolar disorder (BD) is highly heterogeneous, and is moderated by the presence of general medical comorbidities. This study aimed to investigate the moderating effects of impaired glucose metabolism (IGM) on variables of illness course and severity in a BD population. METHODS: Fifty-five patients with BD were evaluated. All subjects were evaluated with respect to current and past psychiatric and medical disorders, as well as lifetime use of any medication. Body mass index (BMI) and metabolic parameters were obtained. IGM was operationalized as pre-diabetes or type 2 diabetes mellitus. RESULTS: Thirty (54.5%) individuals had IGM. After adjustment for age, gender, ethnicity, alcohol use, smoking, BMI and past and current exposure to psychotropic medications, individuals with IGM, when compared to euglycemic participants, had an earlier age of onset (RR: 0.835, p=0.024), longer illness duration (RR: 1.754, p=0.007), a higher number of previous manic/hypomanic episodes (RR: 1.483, p=0.002) and a higher ratio of manic/hypomanic to depressive episodes (RR: 1.753, p=0.028). Moreover, we observed a moderating effect of IGM on the association between number of mood episodes and other variables of illness course, with the correlation between lifetime mood episodes and frequency of episodes being significantly greater in the IGM subgroup (RR: 1.027, p=0.029). All associations observed herein remained significant after adjusting for relevant confounding factors (e.g. age, alcohol and tobacco use, exposure to psychotropic agents, BMI). LIMITATIONS: Cross-sectional design, small sample size. CONCLUSIONS: Comorbid IGM may be a key moderator of illness progression in BD.

24 Article Adipokines, metabolic dysfunction and illness course in bipolar disorder. 2016

Mansur, Rodrigo B / Rizzo, Lucas B / Santos, Camila M / Asevedo, Elson / Cunha, Graccielle R / Noto, Mariane N / Pedrini, Mariana / Zeni, Maiara / Cordeiro, Quirino / McIntyre, Roger S / Brietzke, Elisa. ·Interdisciplinary Laboratory of Clinical Neurosciences (LINC), Department of Psychiatry, Federal University of São Paulo (UNIFESP), São Paulo, Brazil; Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada. Electronic address: rodrigomansur71@uol.com.br. · Interdisciplinary Laboratory of Clinical Neurosciences (LINC), Department of Psychiatry, Federal University of São Paulo (UNIFESP), São Paulo, Brazil; Department of Psychiatry, Clinic for Psychiatry and Psychotherapy, University of Tübingen, Tübingen, Germany. · Interdisciplinary Laboratory of Clinical Neurosciences (LINC), Department of Psychiatry, Federal University of São Paulo (UNIFESP), São Paulo, Brazil. · Interdisciplinary Laboratory of Clinical Neurosciences (LINC), Department of Psychiatry, Federal University of São Paulo (UNIFESP), São Paulo, Brazil; Vila Maria Outpatient Clinic in São Paulo, Brazil. · Department of Psychiatry, Irmandade da Santa Casa de Misericórdia de São Paulo (ISCMSP), Brazil. · Mood Disorders Psychopharmacology Unit (MDPU), University Health Network, University of Toronto, Toronto, Canada. ·J Psychiatr Res · Pubmed #26748249.

ABSTRACT: Replicated evidence indicates that individuals with BD are differentially affected by metabolic comorbidities and that its occurrence is a critical mediator and/or moderator of BD outcomes. This study aimed to explore the role of adipokines on bipolar disorder (BD) course and its relationship with metabolic comorbidities (i.e. type 2 diabetes mellitus, obesity). We measured plasma levels of adiponectin and leptin, as well as anthropometric and metabolic parameters of 59 patients with BD and 28 healthy volunteers. Our results showed that, in female participants, adiponectin was lower in individuals with BD, relative to healthy controls (p = 0.017). In the BD population, adiponectin levels were correlated with fasting glucose (r = -0.291, p = 0.047), fasting insulin (r = -0.332, p = 0.023), C-peptide (r = 0.040, p = 0.040), homeostatic model assessment-insulin resistance (r = -0.411, p = 0.004), HDL (r = 0.508, p < 0.001), VLDL (r = -0.395, p = 0.005) and triglycerides (r = -0.310, p = 0.030). After adjustment for age, gender and BMI, individuals with BD and low adiponectin levels (i.e. < 7.5 μg/ml), had a higher number of mood episodes (p < 0.001), lower number of psychiatric hospitalizations (p = 0.007), higher depressive symptoms (p < 0.001) and lower levels of functioning (p = 0.020). In conclusion, adiponectin levels, either directly or as a proxy of metabolic dysfunction, is independently associated with an unfavorable course of illness in BD.

25 Article Development of a level A in vitro-in vivo correlation for extended release dosage forms of quetiapine fumarate. 2016

Gonçalves de Lima, L / Rossi de Campos, D. ·Universidade São Francisco, Bragança Paulista - São Paulo - Brazil. ·Drug Res (Stuttg) · Pubmed #26697891.

ABSTRACT: Quetiapine is an atypical antipsychotic recommended as first-line treatment for acute bipolar depression. The extended-release quetiapine formulation is intended to be administered as an once-daily dosing. The development of an in vitro-in vivo correlation (IVIVC) and the use of in vitro data to predict in vivo bioavailability parameters has been of great interest for the rational development and evaluation process for extended release dosage forms. The aim of this study was to develop an IVIVC for quetiapine extended release formulation. In vitro dissolution rate data were obtained using USP apparatus 2 at 50 rpm, in 3 bio-relevant dissolution media with different pH values (1.2, 4.5 and 6.8). The drug release profiles of the 2 extended release dosage forms were compared using the similarity factor (f 2). The relative bioavailability of quetiapine was evaluated by a single-dose, randomized-sequence, open-label, 2 period cross over study with 16 healthy volunteers. A linear level A IVIVC model was established using percentage of absorbed and dissolved data obtained at pH 1.2. The developed IVIVC model was employed to predict quetiapine concentration-time profiles, as well as the bioequivalence parameters for test formulation. Percent prediction errors were estimated for Cmax and AUC to evaluate the validity of the correlation. The values did not exceed 15%, proving the predictability of the correlation model. In conclusion, the established level A IVIVC model proved to be an excellent tool for predicting the rate and extent of quetiapine absorption as characterized by Cmax and AUC for test formulation.

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