Minocycline as Treatment for Psychiatric and Neurological Conditions: A Systematic Review and Meta-Analysis.

Minocycline has anti-inflammatory, antioxidant, and anti-apoptotic properties that explain the renewed interest in its use as an adjunctive treatment for psychiatric and neurological conditions. Following the completion of several new clinical trials using minocycline, we proposed an up-to-date systematic review and meta-analysis of the data available. The PICO (patient/population, intervention, comparison and outcomes) framework was used to search 5 databases aiming to identify randomized controlled trials that used minocycline as an adjunctive treatment for psychiatric and neurological conditions. Search results, data extraction, and risk of bias were performed by two independent authors for each publication. Quantitative meta-analysis was performed using RevMan software. Literature search and review resulted in 32 studies being included in this review: 10 in schizophrenia, 3 studies in depression, and 7 in stroke, with the benefit of minocycline being used in some of the core symptoms evaluated; 2 in bipolar disorder and 2 in substance use, without demonstrating a benefit for using minocycline; 1 in obsessive-compulsive disorder, 2 in brain and spinal injuries, 2 in amyotrophic lateral sclerosis, 1 in Alzheimer's disease, 1 in multiple systems atrophy, and 1 in pain, with mixes results. For most of the conditions included in this review the data is still limited and difficult to interpret, warranting more well-designed and powered studies. On the other hand, the studies available for schizophrenia seem to suggest an overall benefit favoring the use of minocycline as an adjunctive treatment.

A review of the neurobiological underpinning of comorbid substance use and mood disorders.

BACKGROUND: There is evidence that substance use disorders and other mental disorders may have shared biological mechanisms. However, the neurobiological basis of this comorbidity remains only partially explained. This review describes the historical evolution of the dual disorders concept and approach, and reviews the existing literature on neurobiological findings specifically regarding comorbid substance use and mood disorders. METHODS: Searches were conducted using PubMed and Scopus in December 2017. A Boolean search was performed using combinations of "dual diagnosis" or "dual disorder" or "depression" or "bipolar" or "affective disorder" or "mood disorder" and "substance use" or "substance abuse" and "neurobiology" or "functional neuroimaging" or "genetics" or "neurotransmitters" or "neuroendocrinology" in the title or abstract, or as keywords, using no language restriction. RESULTS: 32 studies met the inclusion criteria. We found robust evidence for involvement of the neurotransmitters dopamine, GABA and glutamate and their receptors, as well as by the central corticotrophin-releasing hormone, hypothalamic-pituitary-adrenal axis activation, oxidative stress and inflammation. Recent studies focusing on neuroimaging and genetics have not shown consistent results. LIMITATIONS: Only two search tools were used; most identified studies excluded the population of interest (comorbid mood and substance abuse disorders). CONCLUSIONS: The neurobiological relevance for the occurrence of comorbid mood and substance abuse disorders has not been fully elucidated. Considering the high levels of individuals who experience comorbidity in these areas as well as the negative associated outcomes, this is clearly an area that requires further in-depth investigation. Furthermore, findings from this area can help to inform drug abuse prevention and intervention efforts, and especially how they relate to populations with psychiatric symptoms.

Oxidative and nitrosative stress biomarkers in chronic schizophrenia.

There is evidence that the acute phase of schizophrenia (SCZ) is accompanied by specific changes in oxidative and nitrosative stress (O&NS) biomarkers. There are, however, no firm data regarding these biomarkers in chronic SCZ. Therefore, this study aimed to delineate O&NS biomarkers in patients with chronic SCZ. 125 outpatients with SCZ and 118 controls were enrolled. The markers included lipid hydroperoxides (LOOH), advanced oxidation protein products (AOPP), nitric oxide metabolites (NOx), total radical-trapping antioxidant parameter (TRAP) and paraoxonase 1 (PON-1) activity. Immune-inflammatory markers known to be altered in SCZ were also measured: leptin, IL-6, soluble TNF receptors (sTNF-Rs) and the chemokines CCL-11 and CCL-3. There were no significant associations between chronic SCZ and the O&NS markers (AOPP, NOx, LOOH) and the anti-oxidants PON-1 and TRAP. Leptin, sTNF-R, CCL-3 and CCL-11 were significantly higher in SCZ. There were significant associations between pro-inflammatory and O&NS biomarkers (leptin/CCL-8 and AOPP; IL-6 and NOx; CCL-3 and LOOH; CCL-3/IL-6/NOx and TRAP). In conclusion, there were significant intercorrelations between inflammatory and O&NS pathways, which play a role in the pathophysiology of chronic SCZ. O&NS markers and the enzyme PON-1 are not useful as biomarkers in chronic stable polymedicated SCZ patients.

Parkinson's Disease is Accompanied by Intertwined Alterations in Iron Metabolism and Activated Immune-inflammatory and Oxidative Stress Pathways.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder characterized by a complex interplay between peripheral and central inflammatory and oxidative stress pathways. OBJECTIVE: To investigate immune-inflammatory and oxidative stress pathways in relation to iron metabolism in peripheral blood of PD patients and healthy controls. METHOD: We recruited 56 healthy individuals and 56 PD patients in stages 1-3 of Hoehn and Yahr Scale. Plasma haptoglobin (Hp), homocysteine, interleukin 6, soluble interleukin 6 receptor, iron (Fe), ferritin, total iron binding capacity, transferrin (Tf), soluble transferrin receptor (sTfR), malondialdehyde (MDA) and paraoxonase 1 (PON1) were measured. RESULTS: PD was associated with significant changes in Tf (lowered), sTfR, ferritin, Hp, interleukin 6 and MDA (all increased) levels, while there was a trend towards a negative association with PON1. Logistic regression showed that the most significant biomarkers of PD were MDA, sTfR, Hp and ferritin. Moreover, Fe levels were negatively associated with Hp and positively with PON1, total iron binding capacity and Tf, while ferritin and sTfR were positively associated with MDA levels. CONCLUSION: Our study indicates a state of systemic inflammation and oxidative stress in PD patients coupled with alterations in Fe metabolism. Chronic inflammation and oxidative pathways in PD may in part determine changes in iron metabolism. New drug treatments for PD should target inflammatory and oxidative stress pathways and iron metabolism as well.

Are PTH levels related to oxidative stress and inflammation in chronic kidney disease patients on hemodialysis?

INTRODUCTION:: Patients at end stage renal disease have higher levels of inflammation and oxidative stress than the general population. Many factors contribute to these issues, and the parathyroid hormone (PTH) is also implicated. OBJECTIVE:: The study was conducted in order to assess the relationship between PTH levels and inflammation and oxidative stress in hemodialysis patients. METHODS:: Cross-sectional study with patients of two hemodialysis facilities in Londrina, Brazil. Patients with other conditions known to generate oxidative stress and inflammation were excluded. Blood levels of PTH and biochemical parameters of inflammation (interleukins 1 and 6, tumor necrosis factor-alpha) and oxidative stress (total plasma antioxidant capacity, malonic dialdehyde, lipid hydroperoxidation, advanced oxidation protein products, quantification of nitric oxide metabolites, and 8-isoprostane) were measured before a dialysis session. Then, we made correlation analyses between PTH levels - either as the continuous variable or categorized into tertiles-, and inflammatory and oxidative stress biomarkers. RESULTS:: PTH did not show any correlation with the tested inflammation and oxidative stress parameters, nor as continuous variable neither as categorical variable. CONCLUSION:: In this descriptive study, the results suggest that the inflammation and oxidative stress of hemodialysis patients probably arise from mechanisms other than secondary hyperparathyroidism. INTRODUÇÃO:: Pacientes com doença renal em estágio terminal têm níveis de inflamação e estresse oxidativo maiores do que a população geral. Muitos fatores contribuem para isso, e o hormônio paratireoidiano (PTH) é um deles. OBJETIVO:: Estudo foi realizado para avaliar a relação entre os níveis de PTH e níveis de inflamação e estresse oxidativo em pacientes em hemodiálise. MÉTODOS:: estudo transversal com pacientes de duas unidades de hemodiálise de Londrina, Brasil. Pacientes com condições causadoras de inflamação e estresse oxidativo foram exclusos. Níveis plasmáticos de PTH e parâmetros bioquímicos de inflamação (interleucina 1 e 6, fator de necrose tumoral alfa) e estresse oxidativo (capacidade antioxidante plasmática total, dialdeído malônico, hidroperoxidação lipídica, produtos avançados da degradação proteica, quantificação de metabólitos de óxido nítrico e 8-isoprostano) foram dosados antes da sessão de hemodiálise. Realizou-se análise de correlação entre os níveis de PTH - tanto como variável continua como variável categórica em tercis - e os parâmetros de inflamação e estresse oxidativo. RESULTADOS:: Não houve correlação do PTH com nenhum dos parâmetros testados, nem como variável contínua, nem como categórica. CONCLUSÃO:: Neste estudo descritivo, os resultados sugerem que a inflamação e o estresse oxidativo em pacientes em hemodiálise provavelmente tem origem em mecanismos que não incluem o hiperparatireoidismo secundário.

Are PTH levels related to oxidative stress and inflammation in chronic kidney disease patients on hemodialysis? / Os níveis de PTH estão relacionados com estresse oxidativo e inflamação em pacientes renais crônicos em hemodiálise?

Abstract Introduction: Patients at end stage renal disease have higher levels of inflammation and oxidative stress than the general population. Many factors contribute to these issues, and the parathyroid hormone (PTH) is also implicated. Objective: The study was conducted in order to assess the relationship between PTH levels and inflammation and oxidative stress in hemodialysis patients. Methods: Cross-sectional study with patients of two hemodialysis facilities in Londrina, Brazil. Patients with other conditions known to generate oxidative stress and inflammation were excluded. Blood levels of PTH and biochemical parameters of inflammation (interleukins 1 and 6, tumor necrosis factor-alpha) and oxidative stress (total plasma antioxidant capacity, malonic dialdehyde, lipid hydroperoxidation, advanced oxidation protein products, quantification of nitric oxide metabolites, and 8-isoprostane) were measured before a dialysis session. Then, we made correlation analyses between PTH levels - either as the continuous variable or categorized into tertiles-, and inflammatory and oxidative stress biomarkers. Results: PTH did not show any correlation with the tested inflammation and oxidative stress parameters, nor as continuous variable neither as categorical variable. Conclusion: In this descriptive study, the results suggest that the inflammation and oxidative stress of hemodialysis patients probably arise from mechanisms other than secondary hyperparathyroidism.

Resumo Introdução: Pacientes com doença renal em estágio terminal têm níveis de inflamação e estresse oxidativo maiores do que a população geral. Muitos fatores contribuem para isso, e o hormônio paratireoidiano (PTH) é um deles. Objetivo: Estudo foi realizado para avaliar a relação entre os níveis de PTH e níveis de inflamação e estresse oxidativo em pacientes em hemodiálise. Métodos: estudo transversal com pacientes de duas unidades de hemodiálise de Londrina, Brasil. Pacientes com condições causadoras de inflamação e estresse oxidativo foram exclusos. Níveis plasmáticos de PTH e parâmetros bioquímicos de inflamação (interleucina 1 e 6, fator de necrose tumoral alfa) e estresse oxidativo (capacidade antioxidante plasmática total, dialdeído malônico, hidroperoxidação lipídica, produtos avançados da degradação proteica, quantificação de metabólitos de óxido nítrico e 8-isoprostano) foram dosados antes da sessão de hemodiálise. Realizou-se análise de correlação entre os níveis de PTH - tanto como variável continua como variável categórica em tercis - e os parâmetros de inflamação e estresse oxidativo. Resultados: Não houve correlação do PTH com nenhum dos parâmetros testados, nem como variável contínua, nem como categórica. Conclusão: Neste estudo descritivo, os resultados sugerem que a inflamação e o estresse oxidativo em pacientes em hemodiálise provavelmente tem origem em mecanismos que não incluem o hiperparatireoidismo secundário.

Highly specific changes in antioxidant levels and lipid peroxidation in Parkinson's disease and its progression: Disease and staging biomarkers and new drug targets.

There is evidence that immune-inflammatory, stress of reactive oxygen and nitrogen species (IO&NS) processes play a role in the neurodegenerative processes observed in Parkinson's disease (PD). The aim of the present study was to investigate peripheral IO&NS biomarkers in PD. We included 56 healthy individuals and 56 PD patients divided in two groups: early PD stage and late PD stage. Plasma lipid hydroperoxides (LOOH), malondialdehyde (MDA), nitric oxide metabolites (NOx), sulfhydryl (SH) groups, catalase (CAT) activity, superoxide dismutase (SOD) activity, paraoxonase (PON)1 activity, total radical trapping antioxidant parameter (TRAP) and C-reactive protein (CRP) were measured. PD is characterized by increased LOOH, MDA and SOD activity and lowered CAT activity. A combination of five O&NS biomarkers highly significantly predicts PD with a sensitivity of 94.5% and a specificity of 86.8% (i.e., MDA, SOD activity, TRAP, SH-groups and CAT activity). The single best biomarker of PD is MDA, while LOOH and SOD activity are significantly associated with late PD stage, but not early PD stage. Antiparkinson drugs did not affect O&NS biomarkers, but levodopa+carbidopa significantly increased CRP. It is suggested that MDA may serve as a disease biomarker, while LOOH and SOD activity are associated with late PD stage characteristic. New treatments for PD should not only target dopamine but also lipid peroxidation.

Factors influencing insulin resistance in relation to atherogenicity in mood disorders, the metabolic syndrome and tobacco use disorder.

OBJECTIVE: This study examines the effects of malondialdehyde (MDA) and uric acid on insulin resistance and atherogenicity in subjects with and without mood disorders, the metabolic syndrome (MetS) and tobacco use disorder (TUD). METHODS: We included 314 subjects with depression and bipolar depression, with and without the MetS and TUD and computed insulin resistance using the updated homeostasis model assessment (HOMA2IR) and atherogenicity using the atherogenic index of plasma (AIP), that is log10 (triglycerides/high density lipoprotein (HDL) cholesterol. RESULTS: HOMA2IR is correlated with body mass index (BMI) and uric acid levels, but not with mood disorders and TUD, while the AIP is positively associated with BMI, mood disorders, TUD, uric acid, MDA and male sex. Uric acid is positively associated with insulin and triglycerides and negatively with HDL cholesterol. MDA is positively associated with triglyceride levels. Comorbid mood disorders and TUD further increase AIP but not insulin resistance. Glucose is positively associated with increasing age, male gender and BMI. DISCUSSION: The results show that mood disorders, TUD and BMI together with elevated levels of uric acid and MDA independently contribute to increased atherogenic potential, while BMI and uric acid are risk factors for insulin resistance. The findings show that mood disorders and TUD are closely related to an increased atherogenic potential but not to insulin resistance or the MetS. Increased uric acid is a highly significant risk factor for insulin resistance and increased atherogenic potential. MDA, a marker of lipid peroxidation, further contributes to different aspects of the atherogenic potential. Mood disorders and TUD increase triglyceride levels, lower HDL cholesterol and are strongly associated with the atherogenic, but not insulin resistance, component of the MetS.

Association of paraoxonase (PON)1 activity, glutathione S-transferase GST T1/M1 and STin.2 polymorphisms with comorbidity of tobacco use disorder and mood disorders.

There is evidence that genetic factors influence the probability of comorbidity of tobacco use disorder (TUD) with mood disorders. This study was carried out to examine whether both TUD and mood disorders are associated with genetic biomarkers particularly paraoxonase 1 (PON1) status, polymorphisms of glutathione S-transferases (GSTs), such as GSTM1 and GSTT1, and the STIn 2 polymorphism of the serotonin transporter. PON1 status (Q192R polymorphism and PON1 plasmatic activity), GSTM1, GSTT1, and STin.2 genotypes and alleles were assayed in 4 mutually exclusive study groups, i.e., comorbid mood disorder and TUD (n=95); TUD without mood disorders (n=90); mood disorders but no TUD (n=62); and controls (never-smokers without mood disorders; n=113). Logistic regression analyses showed that comorbid mood disorders and TUD were associated with significantly lower PON1 activity, the STin2.10/10 genotype (protective) or the Stin2.12 allele (risk factor) and the GSTM1 and GSTT1 null genotypes (protective). These results show that comorbid mood disorders and TUD are associated with specific biomarkers related to oxidative stress and serotonin pathways.

Paraoxonase 1 status and interactions between Q192R functional genotypes by smoking contribute significantly to total plasma radical trapping antioxidant potential.

The measurement of the total radical trapping antioxidant potential (TRAP) is a general marker of peripheral blood antioxidant defenses. Paraoxonase 1 (PON1) is a potent antioxidant, which protects against lipid peroxidation. The study aimed to examine the relation between TRAP levels and PON1 activity, PON1 Q192R functional genotypes, smoking, interactions between PON1 genotypes and smoking, and mood disorders, while adjusting for effects of ethnicity, marital status, body mass index (BMI) and gender. The analyses were performed in 197 controls and 136 subjects with mood disorders. TRAP levels were significantly associated with higher plasma PON1 activity, the RR functional genotype, non smoking by RR carriers, male gender and a higher BMI. TRAP levels were significantly lower in patients with mood disorders than in controls, but this association was no longer significant after considering the effects of the above predictors. The risk in the subgroup with low TRAP levels is increased by a smoking X RR genotype interaction and decreased by male gender, the RR genotype, and higher BMI and PON1 activity. Plasma PON1 activity, the PON1 Q192R functional genotypes and specific interactions between this genotype and smoking contribute significantly to TRAP levels. Gender and BMI also appear to influence TRAP levels.

Paraoxonase (PON)1 Q192R functional genotypes and PON1 Q192R genotype by smoking interactions are risk factors for the metabolic syndrome, but not overweight or obesity.

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.

Lowered plasma paraoxonase (PON)1 activity is a trait marker of major depression and PON1 Q192R gene polymorphism-smoking interactions differentially predict the odds of major depression and bipolar disorder.

BACKGROUND: Major depression and bipolar disorder are accompanied by the activation of immune-inflammatory and Oxidative and Nitrosative Stress (O&NS) pathways and lowered levels of antioxidants. Paraoxonase (PON)1 (EC 3.1.8.1) is an antioxidant bound to High Density Lipoprotein (HDL). Polymorphisms in the PON1 Q192R coding sequence determine three functional genotypes, i.e. 192QQ, 192QR and 192RR. AIMS: This study was carried out to delineate the associations of plasma PON1 activity and functional PON1 Q192R genotypes in major depression and bipolar disorder. METHODS: PON1 status that is plasma PON1 abundance and three functional PON1 Q192R genotypes were assayed in 91 major depressed and 45 bipolar patients and compared to 199 normal controls. RESULTS: Major depression, but not bipolar disorder, was accompanied by lowered PON1 activity. PON1 activity was decreased by smoking and a diagnosis by genotype interaction (i.e. lower PON1 in major depression with the QQ genotype). Logistic regression showed that smoking by QQ genotype significantly increased the odds of bipolar disorder and that major depression was predicted by plasma PON1 activity, serum HDL cholesterol and interactions between genotype×smoking. DISCUSSION: The results suggest that lowered plasma PON1 activity is a trait marker of major depression and that PONQ192R gene-environment (smoking) interactions differentially predict the odds of depression and bipolar disorder. LIMITATIONS: Association studies are prone to a risk of false positive findings and replication is essential. CONCLUSIONS: The findings suggest that there are differential PON1 Q192R functional genotype×environment interactions in major depression and bipolar disorder. The effects of lowered PON1 activity may contribute to increased O&NS and immune-inflammatory burden in depression. PON1 status may contribute to the comorbidity between depression and other immune- and O&NS-related disorders, e.g. cardiovascular disorder.

Passiflora incarnata treatment during gestation and lactation: toxicological and antioxidant evaluation in wistar dams

Passiflora incarnata is marketed in many countries as a phytomedicine. Even though the directions of most marketed phytomedicines recommend them to be used under medical supervision, reproductive and developmental studies are sparse and not mandatory for regulatory purposes. In this study, a reproductive toxicity evaluation of P. incarnata was conducted in Wistar rats gavaged (30 or 300 mg/kg) during pregnancy and lactation. Moreover, considering that antioxidant properties have been attributed to flavonoids present in the genus Passiflora, it was also evaluated the antioxidant/pro-oxidant balance in the plasma of these dams and the antioxidant potential in an in vitro test. P. incarnata treatment did not influence dams´ body weight as well as reproductive (gestation length, post-implantation loss, litter size, litter weight) and hepatic (albumin, AST, ALT, GGT) parameters. The antioxidant property of P. incarnata was evidenced both in vivo (increase in the total antioxidant plasmatic potential) and in vitro (decrease in neutrophil-induced respiratory burst). The results from the present study indicate that under the experimental conditions evaluated, P. incarnata treatment during gestation and lactation presented antioxidant activity in the absence of maternal reproductive toxicity.

Passiflora incarnata é comercializada em muitos países como fitoterápico. Embora a bula da maioria dos fitoterápicos recomende que eles sejam usados sob supervisão médica, estudos sobre a toxicidade reprodutiva e do desenvolvimento desses produtos são raros e não obrigatórios para fins regulatórios. Neste estudo, realizamos uma avaliação da toxicidade reprodutiva da P. incarnata, administrada a ratas Wistar (30 ou 300 mg/kg, gavagem) durante a gestação e a lactação. Além disso, considerando as propriedades antioxidantes que têm sido atribuídas aos flavonoides presentes no gênero Passiflora, também avaliou-se o equilíbrio antioxidante/pró-oxidante no plasma destas fêmeas e conduziu-se um teste in vitro para avaliar o potencial antioxidante. O tratamento com P. incarnata não influenciou o peso corporal das fêmeas, bem como indicadores de toxicidade reprodutiva (perdas pós-implantação, número de filhotes vivos e peso da ninhada) e os parâmetros de função hepática (albumina, AST, ALT, GGT). A propriedade antioxidante da P. incarnata foi evidenciada tanto in vivo (aumento do potencial antioxidante total plasmático) quanto in vitro (diminuição do burst respiratório em neutrófilos). Os resultados deste estudo indicam que, nas condições experimentais avaliadas, o tratamento com P. incarnata durante a gestação e lactação apresentou efeito antioxidante, na ausência de toxicidade reprodutiva materna.

Oxidative stress and lowered total antioxidant status are associated with a history of suicide attempts.

BACKGROUND: There is evidence that depression is accompanied by inflammation, oxidative and nitrosative stress (O&NS) and metabolic disorders. However links between oxidative stress and suicide attempts in depressed patients are poorly understood. This study examines whether a history of suicide attempts is associated with inflammation, O&NS and metabolic disorders. METHODS: Blood specimens were collected from study participants aged 18-60 (N=342) recruited at the State University of Londrina, Brazil, and measured for oxidative stress biomarkers: nitric oxide metabolites (NOx), lipid hydroperoxides, malondialdehyde, advanced oxidation protein products and plasma total antioxidant potential (TRAP); inflammatory biomarkers: fibrinogen, high-sensitivity C-reactive protein, erythrocyte sedimentation rate, interleukin-6 and tumor necrosis factor-α; and metabolic variables. Subjects were divided into those with (n=141) and without (n=201) a history of suicidal attempts. RESULTS: Individuals with a history of suicide attempts had significantly higher levels of NOx and lipid hydroperoxides and lowered TRAP as compared to individuals without suicide attempts. There were no significant associations between a history of suicide attempts and inflammatory and metabolic biomarkers and metabolic syndrome. Logistic regression showed that both unipolar and bipolar disorder, female gender, smoking behavior and lipid hydroperoxides were significantly associated with a history of suicide attempts. The combined effects of oxidative stress, smoking, depression, female gender were independent from classical risk factors, including marital status, years of education and anxiety. CONCLUSIONS: O&NS as well as lowered antioxidant levels may play a role in the pathophysiology of suicidal behavior independently from the effects of depression and smoking, both of which are associated with increased O&NS, and classical suicide predictors, such as years of education and marital status.

Oxidative stress and inflammatory markers are associated with depression and nicotine dependence.

To determine if oxidative stress and inflammation are linked with major depressive disorder, nicotine dependence and both disorders combined. This study comprised 150 smokers and 191 never smokers. The instruments were: a socio-demographic questionnaire, diagnoses of mood disorder and nicotine dependence according to DSM-IV, (SCID-IV), and the Alcohol, Smoking and Substance Involvement Screening Test. Laboratory assessments included: nitric oxide metabolites (NOx), lipid hydroperoxides, malondialdehyde (MDA), total reactive antioxidant potential (TRAP), advanced oxidation protein products (AOPP), fibrinogen concentrations, homocysteine, erythrocytes sedimentation rate (ESR) and high-sensitivity C-reactive protein (hs-CRP) were assayed from blood specimens. Statistically significant differences were found among depressed smokers who had more severe depressive symptoms, a higher risk of alcohol consumption, more suicide attempts, and more disability for work than non-depressed never smokers. Depressed smokers had significantly higher levels of NOx, fibrinogen, hs-CRP, AOPP, ESR and lower levels of TRAP compared to non-depressed never smokers. Depressed smokers had significant levels of oxidative stress and inflammatory biomarkers after adjusting for gender, age, years of education, disability for work, and laboratory measures. The levels of NOx, lipid hydroperoxides, AOPP, and fibrinogen were substantially higher, whereas levels of TRAP were lower in depressed smokers compared to non-depressed never smokers. (1) Depressed smokers exhibited altered concentrations of NOx, lipid hydroperoxides, AOPP, TRAP, and fibrinogen. (2) Depressed smokers were more unable to work, showed more severe depressive symptoms and attempted suicide more frequently.