Papers by Sandra Odebrecht Vargas Nunes
Molecular neurobiology, Jan 21, 2018
Accumulating evidence indicates that oxidative and nitrosative stress (O&NS) pathways play a key ... more Accumulating evidence indicates that oxidative and nitrosative stress (O&NS) pathways play a key role in the pathophysiology of bipolar disorder (BD) and major depressive disorder (MDD). However, only a handful of studies have directly compared alterations in O&NS pathways among patients with MDD and BD types I (BPI) and BPII. Thus, the current study compared superoxide dismutase (SOD1), lipid hydroperoxides (LOOH), catalase, nitric oxide metabolites (NOx), malondialdehyde (MDA), and advanced oxidation protein products (AOPP) between mood disorder patients in a clinically remitted state. To this end 45, 23, and 37 participants with BPI, BPII, and MDD, respectively, as well as 54 healthy controls (HCs) were recruited. Z-unit weighted composite scores were computed as indices of reactive oxygen species (ROS) production and nitro-oxidative stress driving lipid or protein oxidation. SOD1, NOx, and MDA were significantly higher in MDD than in the other three groups. AOPP was significantl...
Although, staging models gained momentum to stage define affective disorders, no attempts were ma... more Although, staging models gained momentum to stage define affective disorders, no attempts were made to construct mathematical staging models using clinical and biomarker data in patients with major depression and bipolar disorder.The aims of this study were to use clinical and biomarker data to construct statistically-derived staging models, which are associated with early lifetime traumata (ELTs), affective phenomenology and biomarkers.In the current study, 172 subjects participated, 105 with affective disorders (both bipolar and unipolar) and 67 controls. Staging scores were computed by extracting latent vectors (LVs) from clinical data including ELTs, recurring flare ups and suicidal behaviors, outcome data such as disabilities and health-related quality of life (HR-QoL), and paraoxonase (PON)1 actvities and nitro-oxidative stress biomarkers.Recurrence of episodes and suicidal behaviors could reliably be combined into a LV with adequate composite reliability (the “recurrenc...
Biomolecular Concepts, 2018
BackgroundEarly life trauma (ELT) may drive mood disorder phenomenology, nitro-oxidative pathways... more BackgroundEarly life trauma (ELT) may drive mood disorder phenomenology, nitro-oxidative pathways and impairments in semantic memory. There are no data regarding the impact of ELT on affective phenomenology and whether these pathways are mediated by staging or lowered lipid-associated antioxidant defences.MethodsThis study examined healthy controls (n=54) and patients with affective disorders including major depression, bipolar disorder and anxiety disorders (n=118). ELT was assessed using the Child Trauma Questionnaire. In addition, we measured affective phenomenology and assayed advanced oxidation protein products; malondialdehyde, paraoxonase 1 (CMPAase) activity, high-sensitivity C-reactive protein (hsCRP), and high-density lipoprotein (HDL) cholesterol.ResultsELT was associated into with increased risk for mood and comorbid anxiety disorders and a more severe phenomenology, including staging characteristics, depression and anxiety severity, suicidal behaviours, type of treatmen...
Revista Brasileira de Psiquiatria, 2015
Objectives: To describe the onset pattern, frequency, and severity of the signs and symptoms of t... more Objectives: To describe the onset pattern, frequency, and severity of the signs and symptoms of the prodrome of the first hypomanic/manic episode and first depressive episode of bipolar disorder (BD) and to investigate the influence of a history of childhood maltreatment on the expression of prodromal symptoms. Methods: Using a semi-structured interview, the Bipolar Prodrome Symptom Scale-Retrospective (BPSS-R), information regarding prodromal symptoms was assessed from patients with a DSM-IV diagnosis of BD. History of childhood maltreatment was evaluated using the Childhood Trauma Questionnaire (CTQ). Results: Forty-three individuals with stable BD were included. On average, the prodrome of mania lasted 35.8668.7 months and was predominantly subacute or insidious, with rare acute presentations. The prodrome of depression lasted 16.6623.3 months and was also predominantly subacute or insidious, with few acute presentations. The prodromal symptoms most frequently reported prior to the first hypomanic or manic episode were mood lability, depressive mood, and impatience. A history of childhood abuse and neglect was reported by 81.4% of participants. Presence of childhood maltreatment was positively associated with prodromal symptoms, including social withdrawal, decreased functioning, and anhedonia. Conclusions: This study provides evidence of a long-lasting, symptomatic prodrome prior to first hypomanic/manic and depressive episode in BD and suggests that a history of childhood maltreatment influences the manifestations of this prodrome.
Journal of Affective Disorders, 2021
Background: There is a strong comorbidity between mood disorders and metabolic syndrome (MetS). I... more Background: There is a strong comorbidity between mood disorders and metabolic syndrome (MetS). Increased levels of reactive oxygen and nitrogen species (RONS) and nitro-oxidative stress toxicity (NOSTOX) partially underpin this comorbidity. Aims: To examine the associations of RONS/NOSTOX biomarkers with MetS after adjusting for the significant effects of mood disorders (major depression, and bipolar type 1 and 2), generalized anxiety disorder (GAD), tobacco use disorder (TUD), and male sex. Methods: The study included subjects with (n=65) and without (n=107) MetS and measured levels of superoxide dismutase 1 (SOD1), lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), malondialdehyde (MDA), and advanced oxidation protein products (AOPP) and computed z unit-weighted composite scores which reflect RONS/NOSTOX. The study included 105 patients with mood disorders, 46 with GAD, and 95 with TUD. Results: MetS was associated with increased levels of MDA and AOPP, independently from mood disorders, TUD, sex and GAD. Atherogenicity and insulin resistance (IR) were significantly associated with a NOSTOX composite score. Mood disorders, TUD, GAD, male sex and MetS independently contribute to increased RONS/NOSTOX. The RONS/NOSTOX profile of MetS was different from that of GAD, which showed increased SOD1 and NOx levels. TUD was accompanied by increased SOD1, LOOH and MDA, and male sex by increased LOOH and AOPP. Conclusions: MetS is characterized by increased lipid peroxidation with aldehyde formation and chlorinative stress, and atherogenicity and IR are strongly mediated by RONS/NOSTOX. Partially shared RONS/NOSTOX pathways underpin the comorbidity of MetS with mood disorders, GAD, and TUD.
Tabagismo abordagem prevenção e tratamento, 2010
Avaliaram-se as caracteristicas clinicas, historia tabagistica, comorbidades, idade de inicio, a ... more Avaliaram-se as caracteristicas clinicas, historia tabagistica, comorbidades, idade de inicio, a severidade da dependencia a nicotina, familiares fumantes a qualidade de vida de fumantes. Foram 171 fumantes provenientes de centros de atencao primaria. Os pacientes apresentaram as seguintes caracteristicas socio demograficas: predominio do sexo feminino, cor branca, idade media de 45 anos, capazes para atividades domesticas e trabalho. A media de idade do inicio do tabaco foi de 15 anos. O teste de Fagerstrom de dependencia a nicotina foi = 4 (37% e 29%); > 4 (62.3% e 71.0%). As comorbidades medicas foram doencas cardiovasculares e hipertensao arterial (23.9% e 32.3%), câncer (1.4% e 8.3%), doenca pulmonar (34.7% e 22.9%), diabetes (9.7% e 4.2%), depressao (58.3% e 63.5%), abuso de alcool (9.2% e 11. 7%). A cessacao de tabaco em quatro semanas foi 39% e 46.5%. Os resultados sugerem que o tratamento de cessar de fumar devera avaliar o contexto clinico e a comorbidades dos fumantes
Background: Hypertension, atherogenicity and insulin resistance are major risk factors of cardiov... more Background: Hypertension, atherogenicity and insulin resistance are major risk factors of cardiovascular disorder (CVD), which shows a strong comorbidity with major depression (MDD) and bipolar disorder (BD). Activated oxidative and nitrosative stress (O&NS), inflammatory pathways, and increased atherogenicity are shared pathways underpinning CVD and mood disorders. Methods: The current study examined the effects of lipid hydroperoxides (LOOH), superoxide dismutase (SOD), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), and malondialdehyde (MDA) on systolic (SBP) and diastolic (DBP) blood pressure in 96 mood disordered patients and 60 healthy controls. Results: A large part of the variance in SBP (31.6%) was explained by the regression on a z unit-weighted composite score (based on LOOH, AOPP, SOD, NOx) reflecting nitro-oxidative stress toxicity (NOSTOX), coupled with highly sensitive C-reactive protein, body weight and use of antihypertensives. Increased ...
European Neuropsychopharmacology, 2018
Background: First episode psychosis (FEP), schizophrenia and affective disorders are accompanied ... more Background: First episode psychosis (FEP), schizophrenia and affective disorders are accompanied by activation of the immune inflammatory response system (IRS). The compensatory immune-regulatory reflex system (CIRS) is a regulatory immune response that is induced by the IRS but exerts negative feedback through, for example, increased levels of anti-inflammatory cytokines such as IL-4, IL-13 and IL-10. Different phenotypes of schizophrenia may exhibit distinct IRS and CIRS immune profiles. Aims: This study aims to examine the IRS and CIRS components, including macrophagic M1, T-helper (Th)-1, Th-2, Th-17 and T-regulatory (Treg) phenotypes, in antipsychotic-naïve FEP patients before and after risperidone treatment. Methods: We included 31 antipsychotic-naïve FEP patients who had measurements of IRS and CIRS biomarkers before and after treatment with risperidone for 10 weeks, and 22 healthy controls. Results: Antipsychotic-naive FEP patients showed interrelated increments in M1, Th-1, Th-2, Th-17 and Treg phenotypes and a relatively greater IRS response (especially granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-6 and IL-12) as compared with the CIRS response (IL-4, IL-13, IL-5 and IL-10). Inflammatory markers, especially IL-6 and IL-8, were significantly correlated with negative, psychotic, affective and excitation symptom dimensions. Treatment with risperidone significantly suppressed the IRS and CIRS. Baseline levels of CIRS biomarkers, especially higher soluble tumor necrosis factor receptor-1 and IL-10 predicted clinical improvement during treatment. Discussion: Our findings indicate that FEP is characterized by robust IRS (M1 + Th-1 + Th-17) and CIRS responses, suggesting that monocytes, macrophages, Th-1, Th-2,
Neurotoxicity research, Jan 7, 2018
Accumulating evidence shows that nitro-oxidative pathways play an important role in the pathophys... more Accumulating evidence shows that nitro-oxidative pathways play an important role in the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD) and maybe anxiety disorders. The current study aims to examine superoxide dismutase (SOD1), catalase, lipid hydroperoxides (LOOH), nitric oxide metabolites (NOx), advanced oxidation protein products (AOPP), malondialdehyde (MDA), glutathione (GSH), paraoxonase 1 (PON1), high-density lipoprotein cholesterol (HDL), and uric acid (UA) in participants with and without generalized anxiety disorder (GAD) co-occurring or not with BD, MDD, or tobacco use disorder. Z unit-weighted composite scores were computed as indices of nitro-oxidative stress driving lipid and protein oxidation. SOD1, LOOH, NOx, and uric acid were significantly higher and HDL and PON1 significantly lower in participants with GAD than in those without GAD. GAD was more adequately predicted by increased SOD + LOOH + NOx and lowered HDL + PON1 composite scores....
Journal of affective disorders, Nov 1, 2017
Insulin resistance (IR) is a key factor in diabetes mellitus, metabolic syndrome (MetS) and obesi... more Insulin resistance (IR) is a key factor in diabetes mellitus, metabolic syndrome (MetS) and obesity and may occur in mood disorders and tobacco use disorder (TUD), where disturbances of immune-inflammatory, oxidative and nitrosative stress (IO&NS) pathways are important shared pathophysiological pathways. This study aimed to a) examine IR and β-cell function as measured by the homeostasis model assessment of insulin resistance (HOMA-IR) and insulin sensitivity and β cell function (HOMA-B) and glucotoxicity (conceptualized as increased glucose levels versus lowered HOMA-B values) in 74 participants with major depressive disorder (MDD) and bipolar disorder, with and or without MetS and TUD, versus 46 healthy controls, and b) whether IR is associated with IO&NS biomarkers, including nitric oxide metabolites (NOx), lipid hydroperoxides (LOOH), plasma advanced oxidation protein products (AOPP), C-reactive protein (CRP), haptoglobin (Hp) and uric acid. Mood disorders are not associated wi...
The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry, Jan 30, 2017
Mood disorders (MDs) frequently co-exist with cardiovascular disease (CVD) and immune-inflammator... more Mood disorders (MDs) frequently co-exist with cardiovascular disease (CVD) and immune-inflammatory and oxidative stress are important shared pathophysiological pathways. Even though there has been an extensive investigation of the enzyme paraoxonase 1 (PON1) as a biomarker of susceptibility for CVD, there are few reports studying PON1 in MDs. The aim of this study was to determine the association between PON1 activities as well as functional genotypes and MD diagnosis, clinical characteristics and outcomes. PON1 activities and functional genotypes were assayed in 58 bipolar disorder (BD) and 32 major depressed patients (MDD) and compared with 59 controls. Our findings show significantly lower PON1 total and CMPAase activities in MDs, which are partly related to the number of previous depressive and manic episodes. Lowered CMPAase activity is associated with a worse outcome of MDs as indicated by lowered quality of life (WHOQoL-BREF scale) and increased disability in the Sheeham scal...
Progress in neuro-psychopharmacology & biological psychiatry, Aug 21, 2017
This review examines the shared immune-inflammatory, oxidative and nitrosative stress (IO&NS) and... more This review examines the shared immune-inflammatory, oxidative and nitrosative stress (IO&NS) and metabolic pathways underpinning metabolic syndrome (MetS), bipolar disorder (BD) and major depressive disorder (MDD). Shared pathways in both MetS and mood disorders are low grade inflammation, including increased levels of pro-inflammatory cytokines and acute phase proteins, increased lipid peroxidation with formation of malondialdehyde and oxidized low density lipoprotein cholesterol (LDL-c), hypernitrosylation, lowered levels of antioxidants, most importantly zinc and paraoxonase (PON1), increased bacterial translocation (leaky gut), increased atherogenic index of plasma and Castelli risk indices; and reduced levels of high-density lipoprotein (HDL-c) cholesterol. Insulin resistance is probably not a major factor associated with comorbid MetS and mood disorders. Given the high levels of IO&NS and metabolic dysregulation in BD and MDD and the high comorbidity with the atherogenic comp...
Molecular Neurobiology, 2017
Evidence indicates that major depression is accompanied by increased translocation of gut commens... more Evidence indicates that major depression is accompanied by increased translocation of gut commensal Gramnegative bacteria (leaky gut) and consequent activation of oxidative and nitrosative (O&NS) pathways. This present study examined the associations among chronic apical periodontitis (CAP), root canal endotoxin levels (lipopolysaccharides, LPS), O&NS pathways, depressive symptoms, and quality of life. Measurements included advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), lipid peroxides (LOOH), −sulfhydryl (SH) groups, total radical trapping antioxidant parameter (TRAP), and paraoxonase (PON)1 activity in participants with CAP, with and without depression, as well as healthy controls (no depression, no CAP). Root canal LPS levels were positively associated with CAP, clinical depression, severity of depression (as measured with the Hamilton Depression Rating Scale (HDRS) and the Beck Depression Inventory) and O&NS biomarkers, especially NOx and TRAP. CAP-related depression was accompanied by increased levels of NOx, LOOH, AOPP, and TRAP. In CAP participants, there was a strong correlation (r = 0.734, p < 0.001) between root canal LPS and the HDRS score. There were significant and positive associations between CAP or root canal endotoxin with the vegetative and physiosomatic symptoms of the HDRS as well as a significant inverse association between root canal endotoxin and quality of life with strong effects on psychological, environmental, and social domains. It is concluded that increased root canal LPS accompanying CAP may cause depression and a lowered quality of life, which may be partly explained by activated O&NS pathways, especially NOx thereby enhancing
Schizophrenia Research, 2006
An autoimmune or an inflammatory process in patients with schizophrenia, schizoaffective disorder... more An autoimmune or an inflammatory process in patients with schizophrenia, schizoaffective disorder, and in their biological relatives Dear Editors, Elevated serum levels of the potent stimulant of antibody production interleukin-6 (IL-6) were described especially in patients with schizophrenia with predominant negative symptoms and/or poor therapy outcome (Schwarz et al., 2001). An increased antibody production led to the discussion of an autoimmune origin of schizophrenia. Antibodies against brain structures such as hippocampus, septum, cingulated gyrus, amygdala, and frontal cortex, or non-specific autoantibodies have been observed in schizophrenia (Rothermundt et al., 2001). The goals of the present study were to determine possible inflammatory or autoimmune processes in patients with schizophrenia, schizoaffective disorder, and in their biological relatives, by means of the assessment of serum levels of interleukin-6 (IL-6), and antibodies against hippocampus. The subjects were 50 patients with schizophrenia, schizoaffective disorder, outpatients, and were in remission, in chronic treatment with typical antipsychotic and atypical antipsychotic agents. 50
Revista Dor, 2012
BACKGROUND AND OBJECTIVES: The association between depression, fibromyalgia and child abuse sugge... more BACKGROUND AND OBJECTIVES: The association between depression, fibromyalgia and child abuse suggests that they divide the model of developmental traumatology. This study aimed at presenting a case of depressive disorder and fibromyalgia, associated to child abuse, as well as at discussing causes and consequences of both diagnoses. CASE REPORT: Female patient, 54 years old, with fibromyalgia and recurrent depressive disorder, current severe episode, without psychotic symptoms, with somatic symptoms for approximately six months. With history of negative childhood events with loss of affective relationship, problems related to alleged child abuse and frightening childhood experience. CONCLUSION: Early life stress may be the causal factor of painful symptoms in depression and fibromyalgia.
Revista Brasileira de Educação Médica, 2008
Este artigo relata uma experiência de ensino de psiquiatria, habilidades de comunicação e atitude... more Este artigo relata uma experiência de ensino de psiquiatria, habilidades de comunicação e atitudes no currículo integrado do curso de Medicina da Universidade Estadual de Londrina. O mapa conceitual do módulo temático de problemas mentais e do comportamento foi proposto para facilitar uma aprendizagem interdisciplinar significativa de psiquiatria. O conhecimento de psiquiatria é adquirido utilizando-se a metodologia de Aprendizagem Baseada em Problemas. O treinamento de habilidades de comunicação e atitudes é realizado de diferentes formas, com pacientes verdadeiros, pacientes simulados, vídeos, relatos de casos, dramatizações e trabalhos em pequenos grupos. Os métodos de avaliação do conhecimento de psiquiatria, habilidades de comunicação e atitudes incluem avaliação somativa eformativa, que fornecem feedback ao estudante acerca de seu progresso, o exame clínico estruturado por objetivo (Osce), portfolios e relatórios de casos. As competências de conhecimento de psiquiatria, habili...
Neuroscience Letters, 2015
h i g h l i g h t s • We examine the biological underpinnings of comorbid mood and tobacco use di... more h i g h l i g h t s • We examine the biological underpinnings of comorbid mood and tobacco use disorder (TUD). • Comorbid TUD and mood disorders are associated with lower paraoxonase 1 activity. • This comorbidity is associated with the STin2.10/10 genotype and STin2.12 allele. • This comorbidity is associated with the glutathione-S-transferase T1/M1 null genotype. • The comorbidity is associated with oxidative and serotonin signaling pathways.
Neuroscience Letters, 2014
h i g h l i g h t s • TRAP and PON1, 197 healthy, 91 with unipolar depression and 45 with bipolar... more h i g h l i g h t s • TRAP and PON1, 197 healthy, 91 with unipolar depression and 45 with bipolar disorder. • PON1, male gender, RR genotype and body mass index are inversely correlated with TRAP. • PON1 activity, interactions between PON1 Q192R genotypes and smoking influence TRAP.
Redox Report, 2014
Background: The metabolic syndrome (MetS) is a complex of multiple risk factors that contribute t... more Background: The metabolic syndrome (MetS) is a complex of multiple risk factors that contribute to the onset of cardiovascular disorder, including lowered levels of high-density lipoprotein (HDL) and abdominal obesity. Smoking, mood disorders, and oxidative stress are associated with the MetS. Paraoxonase (PON)1 is an antioxidant bound to HDL, that is under genetic control by functional polymorphisms in the PON1 Q192R coding sequence. Aims and methods: This study aimed to delineate the associations of the MetS with plasma PON1 activity, PON1 Q192R genotypes, smoking, and mood disorders (major depression and bipolar disorder), while adjusting for HDL cholesterol, body mass index, age, gender, and sociodemographic data. We measured plasma PON1 activity and serum HDL cholesterol and determined PON1 Q192R genotypes through functional analysis in 335 subjects, consisting of 97 with and 238 without MetS. The severity of nicotine dependence was measured using the Fagerström Nicotine Dependence Scale. Results: PON1 Q192R functional genotypes and PON1 Q192R genotypes by smoking interactions were associated with the MetS. The QQ and QR genotypes were protective against MetS while smoking increased metabolic risk in QQ carriers only. There were no significant associations between PON1 Q192R genotypes and smoking by genotype interactions and obesity or overweight, while body mass index significantly increased MetS risk. Smoking and especially severe nicotine dependence are significantly associated with the MetS although these effects were no longer significant after considering the effects of the smoking by PON1 Q192R genotype interaction. The MetS was not associated with mood disorders, major depression or bipolar disorder. Discussion: PON1 Q192R genotypes and genotypes by smoking interactions are risk factors for the MetS that together with lowered HDL and increased body mass and age contribute to the MetS.
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Papers by Sandra Odebrecht Vargas Nunes