Search

Adverse childhood experiences (ACEs) have been associated with chronic health problems in adolescents and young adults. The aim of this study was to investigate in adolescents and young adults how lower quality of life, elevated perceived stress and ACEs could influence depression and anxiety symptoms, practice of physical activity, loss of control while eating, tobacco use, and obesity/overweight. Participants were assessed by questionnaire and scales, including the 17-item Hamilton Depressive Rating Scale (HDRS17), Hamilton Anxiety Rating Scale (HAM-A), Adverse Childhood Experiences Questionnaire, the World Health Organization quality of life (WHOQOL-BREF) total score, the global physical activity questionnaire, the Perceived Stress Scale, the loss of control overeating scale and anthropometric measures. The participants who experienced ≥ 4 types of ACEs (n = 10) had more major depressive disorder (p

Background: Evaluate comorbidities, childhood abuse, and inflammation in current heavy-smokers compared to light-smokers and never-smokers. Methods: Current-Smokers (n = 129) and never-smokers (n = 85) were screened for the use of alcohol, tobacco, and other substances, and assessed for nicotine dependence and childhood trauma. Tumor necrosis factor alpha (TNF-α) and its receptors (sTNFR1 and sTNFR2), leptin, lipid hydroperoxide, and lipid profile biomarkers were measured after overnight fasting. Results: Current-smokers presented higher prevalence of major depressive disorder (PR = 1.79, CI 95% [1.36–2.37], p

Background Comparisons between healthy controls (HCs) and individuals with mood disorders have shown more cognitive dysfunction among the latter group, in particular in bipolar disorder (BD). This study aimed to characterize the pattern of cognitive function of BD and major depressive disorder (MDD) and compare them to HC using the (CogState Research Battery) CSRB™. Method Participants were tested, comprising the following domains: processing speed, attention, working memory, visual memory, executive functions, and verbal memory. Quality of life and functionality were also assessed. Multiple linear regression models were performed to examine the effect of demographic characteristics and functionality on cognitive outcomes separately for BD and MDD. Results Ninety individuals participated in the study, of which 32 had BD, 30 had MDD, and 28 were HC. Differences were found between both BD and MDD and HC for the composite cognitive score, with significant differences between BD and HC (Diff = −5.5, 95% CI = [−9.5, −1.5], p = 0.005), and MDD and HC (Diff = −4.6, 95% CI = [−8.6, −0.5], p = 0.025). There were overall significant differences in five cognitive domains: processing speed (p = 0.001 and p = 0.004), attention (p = 0.002), working memory (p = 0.02), visual memory (p = 0.021), and verbal memory (p = 0.007). BD also presented worse performance than both MDD and HC, and MDD presented better performance than BD but worse than HC in quality of life and functionality. Multiple linear regression models were significative for education (p Conclusion In general, cognition is more affected in BD than MDD, which could be associated with functional and quality of life impairment.

Current diagnoses of mood disorders are not cross validated. The aim of the current paper is to explain how machine learning techniques can be used to a) construct a model which ensembles risk/resilience (R/R), adverse outcome pathways (AOPs), staging, and the phenome of mood disorders, and b) disclose new classes based on these feature sets. This study was conducted using data of 67 healthy controls and 105 mood disordered patients. The R/R ratio, assessed as a combination of the paraoxonase 1 (PON1) gene, PON1 enzymatic activity, and early life time trauma (ELT), predicted the high-density lipoprotein cholesterol – paraoxonase 1 complex (HDL-PON1), reactive oxygen and nitrogen species (RONS), nitro-oxidative stress toxicity (NOSTOX), staging (number of depression and hypomanic episodes and suicidal attempts), and phenome (the Hamilton Depression and Anxiety scores and the Clinical Global Impression; current suicidal ideation; quality of life and disability measurements) scores. Partial Least Squares pathway analysis showed that 44.2% of the variance in the phenome was explained by ELT, RONS/NOSTOX, and staging scores. Cluster analysis conducted on all those feature sets discovered two distinct patient clusters, namely 69.5% of the patients were allocated to a class with high R/R, RONS/NOSTOX, staging, and phenome scores, and 30.5% to a class with increased staging and phenome scores. This classification cut across the bipolar (BP1/BP2) and major depression disorder classification and was more distinctive than the latter classifications. We constructed a nomothetic network model which reunited all features of mood disorders into a mechanistically transdiagnostic model.

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 DBP was best predicted (23.8%) by body mass index and NOSTOX. The most important O&NS biomarkers predicting an increased SBP were in descending order of significance: LOOH, AOPP and SOD. Higher levels of the atherogenic index of plasma, HOMA2 insulin resistance index and basal thyroid-stimulating hormone also contributed to increased SBP independently from NOSTOX. Although there were no significant changes in SBP/DBP in mood disorders, the associations between NOSTOX and blood pressure were significant in patients with mood disorders but not in healthy controls. Conclusions: Activated O&NS pathways including increased lipid peroxidation and protein oxidation, which indicates hypochlorous stress, are the most important predictors of an increased BP, especially in patients with mood disorders.

Aim To examine clinical and biomarkers in depressed female smokers, in order to better clarify the process that link mood disorders, childhood trauma and smoking in women. Methods The clinical sample comprised women with unipolar or bipolar depression, divided into subgroups of smokers and never-smoker. The control groups comprised two subgroups non-depressed women, separated into smokers and never-smokers. A structured questionnaire was used to assess socio-demographic and clinical data. The following scales were used: 17-item version Hamilton Depression Rating Scale, Hamilton Anxiety Rating scale (HAM-A), Sheehan disability scale, the Child Trauma Questionnaire. The following biomarkers were investigated: lipid profile, including total cholesterol, high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol, triglycerides the Castelli's Risk indexes I and II; and cytokines, including interleukins (IL)-1β, IL-6, IL-10, IL-12, soluble tumor necrosis factor receptor 1 (sTNF-R1). Results Depressed female smokers showed a number of significant positive correlations: emotional neglect and sTNF-R1 (p = 0.02); waist circumference and sTNF-R1 (p = 0.001); body mass index and sTNF-R1 (p, Highlights • Depressed female smokers show a significant positive correlation of soluble tumor necrosis factor receptor 1 with anxiety levels. • Depressed female smokers show a significant positive correlation of soluble tumor necrosis factor receptor 1 with levels of emotional neglect. • Depressed female smokers show a significant negative correlation of soluble tumor necrosis factor receptor 1 and HDLc. • Depressed female smokers show a positive correlation of soluble tumor necrosis factor receptor 1 levels with the Castelli I and II indexes. • Depressed female smokers who experienced more childhood trauma and had more anxiety symptoms showed associations with heightened inflammation and alterations in lipid profile components.

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. Composite scores of nitro-oxidative stress coupled with aldehyde and AOPP production were significantly increased in participants with comorbid GAD + MDD as compared with all other study groups, namely MDD, GAD + BD, BD, GAD, and healthy controls. In conclusion, GAD is characterized by increased nitro-oxidative stress and lipid peroxidation and lowered lipid-associated antioxidant defenses, while increased uric acid levels in GAD may protect against aldehyde production and protein oxidation. This study suggests that increased nitro-oxidative stress and especially increased SOD1 activity, NO production, and lipid peroxidation as well as lowered HDL-cholesterol and PON1 activity could be novel drug targets for GAD especially when comorbid with MDD.

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 significantly higher in BPI than in HCs and BPII patients. BPII patients showed lower SOD1 compared to all other groups. Furthermore, MDD was characterized by increased indices of ROS and lipid hydroperoxide production compared to BPI and BPII groups. Indices of nitro-oxidative stress coupled with aldehyde production or protein oxidation were significantly different among the three patient groups (BDII > BDI > MDD). Finally, depressive symptom scores were significantly associated with higher LOOH and AOPP levels. In conclusion, depression is accompanied by increased ROS production, which is insufficiently dampened by catalase activity, thereby increasing nitro-oxidative damage to lipids and aldehyde production. Increased protein oxidation with formation of AOPP appeared to be hallmark of MDD and BPI. In addition, patients with BPII may have protection against the damaging effects of ROS including lipid peroxidation and aldehyde formation. This study suggests that biomarkers related to O&NS could aid in the differentiation of MDD, BPI, and BPII.

Rationale, aims Major affective disorders including bipolar disorder (BD) and major depressive disorder (MDD) are associated with impaired health-related quality of life (HRQoL). Oxidative stress and subtle thyroid abnormalities may play a pathophysiological role in both disorders. Thus, the current study was performed to examine whether neuro-oxidative biomarkers and thyroid-stimulating hormone (TSH) levels could predict HRQoL in BD and MDD. Methods This cross-sectional study enrolled 68 BD and 37 MDD patients and 66 healthy controls. The World Health Organization (WHO) QoL-BREF scale was used to assess 4 QoL subdomains. Peripheral blood malondialdehyde (MDA), advanced oxidation protein products, paraoxonaxe/CMPAase activity, a composite index of nitro-oxidative stress, and basal TSH were measured. Results In the total WHOQoL score, 17.3% of the variance was explained by increased advanced oxidation protein products and TSH levels and lowered CMPAase activity and male gender. Physical HRQoL (14.4%) was associated with increased MDA and TSH levels and lowered CMPAase activity. Social relations HRQoL (17.4%) was predicted by higher nitro-oxidative index and TSH values, while mental and environment HRQoL were independently predicted by CMPAase activity. Finally, 73.0% of the variance in total HRQoL was explained by severity of depressive symptoms, use of anticonvulsants, lower income, early lifetime emotional neglect, MDA levels, the presence of mood disorders, and suicidal ideation. Conclusions These data show that lowered HRQoL in major affective disorders could at least in part result from the effects of lipid peroxidation, protein oxidation, lowered antioxidant enzyme activities, and higher levels of TSH.

Early life trauma (ELT) may increase the risk towards bipolar diso rder (BD) and major depression (MDD), disorders associated with activated neuro-oxidative and neuro-nitrosative stress (O&NS) p athways. It has remained elusive whether ELTs are associated with O&NS and which ELTs are associated with disti nct affective disorder phenotypes. This case-control study examined patients with BD ( n = 68) and MDD ( n = 37) and healthy controls ( n = 66). The Child Trauma Questionnaire (CTQ) was used to assess specific ELT. We measured malondialdehyde (MDA) , lipid hydroperoxides (LOOH), superoxide dismutase (SOD), catalase, advanced oxidation protein products (AOPP); NO metabolites (NOx), paraoxonase 1 activity, zinc, albumin, high density lipoprotein cho- lesterol and -SH groups and computed z-unit weighted composite scores. Physical neglect significantly predicts higher z-unit weighted composite scores of LOOH+SOD, LOOH+SOD+NOx, LOOH+SOD+NOx + MDA and LOOH+SOD+NOx + AOPP. Sexual abuse was associated with a significantly lower composite s core of zinc+albumin+SH. Emotio nal abuse was associated with severity of depression and anxiety, number of depressive and mani c episodes, alcohol and hypnotics use, lifetime suicidal behavior and lowered quality of life. Sexual abuse was associated with an increased risk towards BD, but not MDD. ELT, especially physical neglect, may drive increased (nitro-)oxidativ e stress coupled with lipid and protein oxida tion, which - together with emotional abuse - may play a role in severity of illness, lowered quality of life and MDD. ELTs are also associated with the onset of BD, but this link did not appear to be related to activated O&NS pathways. These novel findings deserve confirma tion in prospective studies.

Patients with major affective disorders (MAFD) with comorbid anxiety show a greater functional impairment than those without anxiety. The aim of this study is to delineate the associations between severity of anxiety in MAFD, namely bipolar disorder (BD) and major depression (MDD), and MAFD characteristics and serum high-density lipoprotein (HDL)-cholesterol levels. Recruited were 82 participants with anxiety disoders and 83 without anxiety disoders, including 101 MAFD patients and 51 healthy controls. We used the Hamilton Anxiety Rating Scale (HAM-A) to measure severity of anxiety and made the diagnoses of posttraumatic stress disorder (PTSD), obsessive compulsive disorder (OCD), panic disorder (PD), generalized anxiety disorder (GAD) and phobias. The HAM-A score is significantly predicted by higher number of depressive episodes, GAD and phobias, childhood trauma, tobacco use disorder, metabolic syndrome and lowered HDL-cholesterol. Increased HAM-A scores are, independently from severity of depression, associated with lowered quality of life, increased disabilities and suicidal ideation. Lithium treatment significantly lowers HAM-A scores. It is concluded that severity of anxiety significantly worsens the phenomenology of MAFD. Therefore, treatments of MAFD should target increased severity of anxiety and its risk factors including low HDL-cholesterol, metabolic syndrome, childhood trauma and tobacco use disorder.

Background 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. Methods 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. Results Mood disorders are not associated with changes in IR or glucotoxicity, although the number of mood episodes may increase IR. 47.8% of the variance in HOMA-IR is explained by AOPP and body mass index (BMI, both positively) and NOx, Hp and TUD (all inversely). 43.2% of the variance in HOMA-B is explained by NOx, Hp and age (all inversely associated) and higher BMI and sex. The glucotoxic index is strongly associated with NOx, Hp and BMI (positively), male gender and lower education. Limitations This is a cross-sectional study and therefore we cannot draw firm conclusions on causal associations. Conclusions Activated IO&NS pathways (especially increased Hp and NOx) increase glucotoxicity and exert very complex effects modulating IR. Mood disorders are not associated with increased IR.

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 “recurrence LV”), which was associated with female sex, the combined effects of multiple ELTs, disabilities, HR-QoL and impairments in cognitive tests. All those factors could be combined into a reliable “ELT-staging LV” which was significantly associated with nitro-oxidative stress biomarkers. A reliable LV could be extracted from serum PON1 activities, recurrent flare ups, disabilities and HR-QoL.Our ELT-staging index scores the severity of a relevant affective dimension, shared by both major depression and bipolar disorder, namely the trajectory from ELTs, a relapsing course and suicidal behaviors to progressive disabilities. Patients were classified into three stages, namely an early stage; a relapse-regression stage; and a suicidal-regression stage. Lowered lipid-associated antioxidant defenses may be a drug target to prevent the transition from the early to the later regression stages.

Made available in DSpace on 2018-12-11T17:32:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-04-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Evidence indicates that major depression is accompanied by increased translocation of gut commensal Gram-negative 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 OpenSPiltSPi 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 physio-somatic 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 hypernitrosylation and thus neuroprogressive processes. Dental health and “leaky teeth” may be intimately linked to the etiology and course of depression, while significantly impacting quality of life. Department of Specific Formation Institute of Health School of Dentistry UFF - Federal Fluminense University Department of Restorative Dentistry Endodontic Division Institute of Science and Technology UNESP - Univ Estadual Paulista Graduation Program in Health Sciences State University of Londrina (UEL) Department of Basic Science Institute of Health UFF - Universidade Federal Fluminense Department of Psychiatry Health Sciences Center State University of Londrina CRC London and Scotland Department of Psychiatry Faculty of Medicine Chulalongkorn University Department of Psychiatry Medical University Plovdiv Revitalis IMPACT Strategic Research Center Barwon Health Deakin University Department of Restorative Dentistry Endodontic Division Institute of Science and Technology UNESP - Univ Estadual Paulista FAPESP: 2015/03696-1

Outcomes in a RCTs of 12 weeks of theclinical efficacy of N-acetylcysteine (NAC) as an adjunctive treatment on depression and anxiety symptoms and its effects on high-sensitivity C-reactive protein (hs-CRP) levels. A wide array of measures were made. The 17-item version of the Hamilton Depression Rating Scale (HDRS17); the Hamilton Anxiety Rating Scale (HAM-A); Sheehan Disability Scale; Quality of Life; Clinical Global Impression (CGI); anthropometrics measures; and vital signs and biochemical laboratory. There were no significant differences among the groups regarding demographic, clinical features, use of medication, metabolic syndrome and comorbidities. From baseline to week 12, individuals receiving NAC, versus placebo, had a statistically significant reduction in depressive symptoms on HDRS17 (p 3 mg/L at baseline. Individuals receiving NAC with baseline levels of hs-CRP > 3 mg/L, had more significant reduction in uric acid levels compared to individuals with baseline levels of hs-CRP ≤ 3 mg/L on week 12. Participants receiving placebogained significantly more weight during the 12 weeks for baseline levels of hs-CRP ≤ 3 mg/L and hs-CRP > 3 mg/L, and individuals receiving NAC in both groups did not have significant weight change during the 12 weeks. No individuals were withdrawn from the study because of adverse event. NAC group exhibited significantly greater reduction on hs-CRP levels than placebo group from baseline to week 12. Trial registration: clinicaltrials.gov Identifier; NCT02252341

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.

Background There is a significant comorbidity between mood disorders and tobacco use disorder (TUD), which may be related to both genetic and environmental factors. Gene variants of the 5-HT transporter, such as STin2 VNTR (a variable number of tandem repeats in the functional serotonin transporter intron 2) may be associated with mood disorders and TUD. Aims This study aimed to delineate the association between the STin2 genetic polymorphism and comorbid TUD and mood disorders, including depression or bipolar disorder. Methods We examined the STin2 VNTR polymorphism in never-smokers ( n =113); patients with mood disorders without TUD ( n =62); patients with TUD without mood disorders ( n =90); and patients with both disorders ( n =95). Results We found a significant association between the STin2 genetic polymorphism and the above diagnostic groups whereby the STin2.12 allele shows a positive association with comorbid TUD and mood disorders (Odds ratio=3.07, 95% CI=1.41–6.68), while the STin2.10/10 homozygous genotype shows a negative association (Odds ratio=0.34, 95% CI=0.16–0.74). Adjusting for years of education, age, gender, marital status and ethnicity did not change these results, but showed that TUD was associated with lower education levels and less stable relationships, whereas mood disorders were related to female gender. A family history of TUD was significantly associated with TUD in subjects without mood disorders only. Conclusions The STin2.12 allele is positively and the STin2.10/10 genotype is negatively associated with comorbid TUD and mood disorders, depression or bipolar depression, suggesting that biological endophenotypes, e.g. disorders in serotonin metabolism, may in part underpin this comorbidity.

Objectives: Mood disorders (MDs) frequently co-exist with cardiovascular disease (CVD) and immune-inflammatory and oxidative stress are important shared pathophysiological pathways. Even th...

This review examines the shared immune-inflammatory, oxidative and nitrosative stress (IONS) 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 mood disorders. Given the high levels of IONS and metabolic dysregulation in BD and MDD and the high comorbidity with the atherogenic components of the MetS, mood disorders should be viewed as systemic neuro-IONS-metabolic disorders. The IONS-metabolic biomarkers may have prognostic value and may contribute to the development of novel treatments targeting neuro-immune, neuro-oxidative and neuro-nitrosative pathways.

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.

Background Nicotine dependence is associated with an increased risk of mood and anxiety disorders and suicide. The primary hypothesis of this study was to identify whether the polymorphisms of two glutathione-S-transferase enzymes (GSTM1 and GSTT1 genes) predict an increased risk of mood and anxiety disorders in smokers with nicotine dependence. Materials and methods Smokers were recruited at the Centre of Treatment for Smokers. The instruments were a sociodemographic questionnaire, Fagerström Test for Nicotine Dependence, diagnoses of mood disorder and nicotine dependence according to DSM-IV (SCID-IV), and the Alcohol, Smoking and Substance Involvement Screening Test. Anxiety disorder was assessed based on the treatment report. Laboratory assessment included glutathione-S-transferases M1 (GSTM1) and T1 (GSTT1), which were detected by a multiplex-PCR protocol. Results Compared with individuals who had both GSTM1 and GSTT1 genes, a higher frequency of at least one deletion of the GSTM1 and GSTT1 genes was identified in anxious smokers [odds ratio (OR)=2.21, 95% confidence interval (CI)=1.05–4.65, P=0.034], but there was no association with bipolar and unipolar depression (P=0.943). Compared with nonanxious smokers, anxious smokers had a greater risk for mood disorders (OR=4.67; 95% CI=2.24–9.92, P

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.

INTRODUCTION Both smoking and depression have been associated with increased inflammatory markers. As there are few studies on inflammatory markers that distinguish between depressed and nondepressed smokers, it is unclear if there is a cumulative impact of these mediators of inflammation. The aim of this study was to investigate inflammatory markers in tobacco smokers and compare depressed and nondepressed smokers. METHODS Smokers (n = 155) were recruited from the Cigarette Smoking Cessation Service, Londrina. Mental health status was assessed using the Diagnostic Interview for Research, in accordance with the International Classification of the Disorders-10th (ICD-10). Demographic information was collected by self-report questionnaire, and the Fagerstrom Test for Nicotine Dependence was administered. Blood specimens were simultaneously collected and measured for C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), and interleukin-6 (IL-6). RESULTS Depressed smokers had significantly higher levels of hs-CRP (p = .05), IL-6 (p = .039), and TNF-α (p = .021) compared with nondepressed smokers. Depressed smokers were also significantly more likely than nondepressed smokers to have been hospitalized in the previous month (p < .032), to suffer from cardiovascular disease (p < .001) and lung disease (p < .003), and to have more work-related disability (p = .001). CONCLUSIONS These findings demonstrate that depressed smokers had higher hs-CRP, IL-6, and TNF-α levels than nondepressed smokers and had worse physical health outcomes and greater work-related disability. This may have important implications in identifying shared risk pathways for depressive and somatic disorders.

Introduction: Geriatric depression is under-diagnosed and often mistaken for other diseases that are common in the elderly. Its detection, using a screening scale translated into the local language, is relevant to the care provided at general outpatient clinics. Objective: To study the validity of the Geriatric Depression Scale (GDS) in general outpatient clinics. Methods: The GDS was first translated into Portuguese and compared with the diagnosis of depression achieved by the SCID-CV (Structured Clinical Interview for DSM-IV clinician version axis disturbances) performed by a psychiatrist who was blind to the GDS results. Data were analyzed using the ROC curve to determine the cut-off point. Results: A total of 484 patients were evaluated, 210 of whom were classified as depressive and 274 as non-depressive. The ROC curve determined the cut-off point at 12, with 87% sensitivity and 73% specificity. In the logistic regression, no sociodemographic variable presented an association with depression....

We examine the relationship between nicotine dependence (ND) and ND-related medical disease and polymorphisms by deletion in genes that encode glutathione S-transferases (GSTs), e.g. GSTM1 and GSTT1. Individuals with homozygous gene deletions show deficiencies in GSTs enzyme activities impairing detoxification.This study comprised 182 tobacco users and 182 controls (neversmokers). GSTM1 and GSTT1 polymorphisms were assessed using a Multiplex- PCR based protocol.Logistic regression analyses showed a significant association between ND and the GSTM1 and GSTT1 null genotypes. There were no significant associations between GSTT1, GSTM1 and GSTT1/M1 genetic variants and the Fagerström test for ND, age at onset, smoking cessation or a family history of ND. Patients with ND had increased rates of a family ND history and an increased prevalence of cardiovascular disease, hypertension, and lung disease. The null genotypes were associated with hypertension (i.e. GSTT1 × ND interaction), diabetes type 2 (i.e. GSTM1 × GSTT1 interaction), lung disease (i.e. GSTM1 × ND interaction) and cancer (i.e. GSTT1). The results show that GST null genotypes may confer protection against ND while they increase risk towards ND-related medical disorders.

article i nfo Background: Activated immune-inflammatory pathways play an important role in the pathophysiology of schizophrenia. Paraoxonase 1 (PON1) activity is inversely associated with inflammatory responses in numerous clinical conditions. The aims of this study were to delineate serum arylesterase PON1 activity in drug-naive first episode psychosis (FEP) patients and a healthy control group, and to assess whether there are inverse relationships between PON1 activity and cytokine levels. Methods: A total of 51 drug-naive FEP patients and 61 healthy controls were enrolled in this study. Levels of interleukin (IL)-4, IL-10, IL-6, tumor necrosis factor (TNF)-α and activity of PON1 were quantified. Results: Compared to healthy controls, FEP patients showed lower serum PON1 activity and higher levels of IL-4, IL-10 and TNF-α. A significant inverse relationship between PON1 activity and IL-4, IL-6 and IL-10 levels was detected, but not for TNF-α. Subjects with very low PON1 activity (25th quartile) presented significantly higher levels of IL-6, IL-10 and IL-4 than those with higher PON1 activity (75th quartile). Conclusion: The present study provides evidence that FEP is characterized by an inverse relationship between lowered activity of the anti-inflammatory/antioxidant enzyme PON1 and increased cytokine levels, including IL-6, IL-4 and IL-10. It is hypothesized that lowered PON1 activity may play a role in the immune-inflammatory response that accompanies FEP and that increased cytokine levels may further modulate PON1 activity.

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.

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 Fagerstrom 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.

Background: There is a robust comorbidity between mood disorders and cardiovascular disorder (CVD). The atherogenic index of plasma (AIP) and the atherogenic coefficient (AC) are important atherogenic indexes. The aims of this study were to delineate whether AIP and AC are increased in mood disorders especially when comorbid with tobacco use disorder (TUD). Methods: In this case-control study we included 134 patients with mood disorders, bipolar disorder and unipolar depression (cases), and 197 individuals without mood disorder (controls) divided into those with and without TUD (defined as never-smokers). Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDLc) and low-density lipoprotein cholesterol (LDLc) were measured. AIP and AC were computed as log (TG/HDLc) and non-HDLc/HDLc, respectively. Results: The AIP and AC indexes were significantly increased in patients with mood disorders versus controls, both in depression and bipolar disorder. Patients with mood disorder without TUD and patients with TUD without mood disorder showed higher AIP and AC values than never-smokers while those with comorbid mood disorders and TUD showed significantly higher AIP and AC levels than all other individuals. A large part of the variance in the AIC (26.4%) and AC (20.4%) was explained by mood disorders, TUD, male gender and body mass index. Conclusions: The findings suggest that lipid abnormalities leading to an increased atherogenic potential are involved in the pathophysiology of mood disorders (depression and bipolar disorder) and especially comorbid mood disorder and TUD. The comorbidity between mood disorders and CVD may be partly explained increased through AIP and AC indexes, impacting increments in atherogenic potential.

Aims This study examined whether Castelli risk indexes 1 (total/high-density lipoprotein (HDL) cholesterol) and 2 (low density lipoprotein (LDL)/HDL cholesterol) and other shared metabolic disorders might underpin the pathophysiology of the metabolic syndrome, major depression or bipolar disorder. Main methods This cross-sectional study examined 92 major depressed, 49 bipolar depressed and 201 normal controls in whom the Castelli risk indexes 1 and 2 and key characteristics of the metabolic syndrome, i.e. waist/hip circumference, body mass index (BMI), systolic/diastolic blood pressure, total cholesterol, low-density lipoprotein (LDL) and HDL cholesterol, triglycerides, insulin, glucose, hemoglobin A1c (HbA1c) and homocysteine were assessed. Key findings Castelli risk indexes 1 and 2 were significantly higher in major depressed patients than in bipolar disorder patients and controls. There were no significant differences in waist or hip circumference, total and LDL cholesterol, triglycerides, plasma glucose, insulin, homocysteine and HbA1c between depression and bipolar patients and controls. Bipolar patients had a significantly higher BMI than major depressed patients and normal controls. Significance Major depression is accompanied by increased Castelli risk indexes 1 and 2, which may be risk factors for cardiovascular disease. Other key characteristics of the metabolic syndrome, either metabolic biomarkers or central obesity, are not necessarily specific to major depression or bipolar disorder.

Objetivo: O presente estudo teve como objetivo geral avaliar as características sócio-demográficas, clínicas, biomarcadores de estresse oxidativo e inflamatórios em fumantes, com e sem depressão, e compará-los a indivíduos nunca fumantes depressivos e não depressivos. Método: Foram avaliadas as características sócio-demográficas, clínicas, história tabagística e exames laboratoriais de marcadores de estresse oxidativo e inflamatórios em fumantes e nunca fumantes. Foram selecionados 150 fumantes ambulatoriais (72 depressivos e 78 não depressivos) recrutados do Centro de Referência de Abordagem e Tratamento do Tabagismo (CRATT), da Universidade Estadual de Londrina (UEL) e 191 nunca fumantes (68 depressivos e 123 não depressivos) recrutados na mesma instituição. A pesquisa foi aprovada pelo Comitê de Ética em Pesquisa da UEL. Os participantes foram submetidos a um questionário estruturado para avaliar as características sócio-demográficas, clínicas, risco do uso do álcool e história tabagística. O transtorno depressivo e o transtorno por uso do tabaco foi avaliado pela entrevista clínica estruturada, versão clínica (SCID-I), baseada no DSM-IV. Os marcadores inflamatórios foram mensurados pelos seguintes exames laboratoriais: proteína C reativa, velocidade de hemosedimentação (VHS), homocisteína e fibrinogênio. O estresse oxidativo foi avaliado pelos seguintes exames: determinação de dialdeído malônico (MDA), determinação de hidroperóxidos lipídicos, determinação de metabólitos do Óxido Nítrico (NOx), determinação do potencial antioxidante total plasmático (TRAP) e determinação dos produtos avançados de oxidação proteica (AOPP). Resultados: Os fumantes depressivos apresentaram alterações nas concentrações de NOx, hidroperóxidos lipídicos, AOPP, TRAP, fibrinogênio, maior incapacidade laboral, maior gravidade dos sintomas depressivos e taxas maiores de tentativas de suicídio ao serem comparados aos fumantes não depressivos e, nunca fumantes depressivos e não depressivos. Fumantes deprimidos tinham níveis significativos de estresse oxidativo e marcadores inflamatórios após o ajuste para sexo, idade, anos de escolaridade, deficiência de trabalhar, e as medidas de laboratório. Indivíduos com histórico de tentativas de suicídio tiveram significativamente níveis mais elevados de NOx e de hidroperóxidos lipídicos e mais baixas concentrações de TRAP, em comparação com indivíduos sem tentativas de suicídio. Conclusão: O presente estudo sugeriu que a comorbidade do transtorno depressivo e transtorno por uso de tabaco estava associada com maior gravidade dos sintomas depressivos, maiores taxas de tentativas de suicídio, maior incapacidade laboral e alterações de marcadores inflamatórios e de estresse oxidativo. Desse modo, no planejamento terapêutico dos fumantes depressivos deve-se levar em conta estes achados para prevenir morbidade e mortalidade de ambas enfermidades. Objective: The present study aimed to assess the socio-demographic, clinical, inflammatory and oxidative stress biomarkers in depressed and non-depressed smokers comparing them to depressed and non-depressed never smokers subjects. Methods: We evaluated the socio-demographic, clinical, smoking history and laboratory biomarkers of inflammation and oxidative stress in smokers and never smokers. We selected 150 smokers (72 depressed and 78 non-depressed) recruited from outpatients at the Centre of Approach and Treatment for Smokers (CRATT), at the Londrina State University (UEL). We also selected 191 never smokers (68 depressed and 123 non-depressed) recruited from the same institution. All subjects had given informed consent to participate in this study, which was approved by the Ethics Research Committee at UEL. A structured questionnaire was used to gather information on socio-demographic, clinical risk screening of alcohol and smoking history. Depressive disorder and tobacco use disorder were assessed by structured clinical interview, clinical version (SCID-I), based on DSM-IV. Inflammatory markers were measured by the following laboratory tests: C-reactive protein, erytrocytes sedimentation rate, homocysteine and fibrinogen. Oxidative stress was evaluated by the following tests: determination of malonic dialdehyde (MDA), lipid hydroperoxide determination, determination of metabolites of nitric oxide (NOx), determination of plasma total antioxidant potential (TRAP) and determination of advanced oxidation protein products (AOPP). Results: Depressed smokers exhibited altered concentrations of NOx, lipid hydroperoxides, AOPP, TRAP, fibrinogen. They also were more unable to work, showed more severe depressive symptoms and higher suicide attempts rates as compared to non depressed smokers, depressed and 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. 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. Conclusion: This study suggested that the comorbidity of depressive disorder and tobbaco use disorder was associated with greater severity of depressive symptoms, suicide attempts, more unable to work and altered levels of inflammation and oxidative stress biomarkers. Thus, in the treatment planning of depressive smokers should consider these findings to prevent morbidity and mortality in both deseases.

There is evidence that depression is accompanied by inflammation, oxidative and nitrosative stress (ONS) 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, ONS and metabolic disorders.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.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.ONS 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 ONS, and classical suicide predictors, such as years of education and marital status.

Nicotine dependence is common in people with mood disorders; however the operative pathways are not well understood. This paper reviews the contribution of inflammation and oxidative stress pathways to the co-association of depressive disorder and nicotine dependence, including increased levels of pro-inflammatory cytokines, increased acute phase proteins, decreased levels of antioxidants and increased oxidative stress. These could be some of the potential pathophysiological mechanisms involved in neuroprogression. The shared inflammatory and oxidative stress pathways by which smoking may increase the risk for development of depressive disorders are in part mediated by increased levels of pro-inflammatory cytokines, diverse neurotransmitter systems, activation the hypothalamic-pituitary-adrenal (HPA) axis, microglial activation, increased production of oxidative stress and decreased levels of antioxidants. Depressive disorder and nicotine dependence are additionally linked imbalance between neuroprotective and neurodegenerative metabolites in the kynurenine pathway that contribute to neuroprogression. These pathways provide a mechanistic framework for understanding the interaction between nicotine dependence and depressive disorder.

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, habilidades em comunicação e atitudes são internalizadas dependendo do método de treinamento de uma aprendizagem significativa e de como os estudantes são avaliados em sua prática da medicina. This article describes an experience of teaching psychiatry, communication skills, and attitudes in an integrated medical curriculum at the Londrina State University. The concept map of the thematic module of mental disorders and of behavior were proposed as a strategy promoting interdisciplinary meaningful learning of Psychiatry. Psychiatric knowledge is acquired through problem-based learning. Communication skills and attitudes are taught in different ways, with patients, with simulated patients, using videos, case reports, role-playing, and work in small groups. The methods used for evaluating the knowledge in psychiatry, the communication skills and the attitudes include summative and formative assessment designed to give the student a feedback on his progress in objective structured clinical examination (Osce), portfolios, and case reports. The psychiatric knowledge, communication skills, and attitudes are assimilated depending on meaningful learning as a teaching method and on the way the students are evaluated in their medical practice.

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.

Background The aim of this study was to determine if variable number of tandem repeats (VNTR) in the second intron (STin2) of the serotonin transporter (SLC6A4) gene was associated with tobacco use disorder, successful smoking cessation, or smoking characteristics. In this case–control study, patients with current tobacco use disorder, diagnosed according to DSM IV criteria (n = 185), and never-smokers, diagnosed according to CDC criteria (n = 175), were recruited and received 52 weeks of combined pharmacotherapy and cognitive therapy. Successful smoking cessation was defined as exhaled carbon monoxide

O transtorno afetivo bipolar (TB) é uma condição frequente na população geral, acomete a população adulta jovem e, devido ao seu caráter progressivo, é muitas vezes incapacitante e refratária a tratamentos. A incapacidade funcional pode ocorrer devido aos múltiplos episódios (tanto depressivos quanto maníacos) ao longo da vida, que levam a uma deterioração cognitiva. A compreensão das fases de evolução, de seus estágios e gravidades inerentes, modula as intervenções farmacológicas e psicossociais mais adequadas. Sendo assim, essa pesquisa objetivou desenvolver e aplicar uma ferramenta digital (APP) adjuntiva ao tratamento convencional e avaliar qual sua contribuição para qualidade de vida e adesão ao tratamento de pacientes com TB. Para isso foi utilizado o delineamento quase experimental, que ocorreu em duas etapas: (1) desenvolvimento do instrumento -APP- que foi registrado pela Agência de Inovação Tecnológica – UEL, de fácil uso e atrativo; (2) aplicação da ferramenta em uma intervenção de 12 semanas. Após o desenvolvimento do APP, uma amostra não-randomizada foi selecionada, proveniente do Ambulatório de Psiquiatria do Ambulatório de Especialidades Clínicas do Hospital Universitário de Londrina. Foram realizados questionário sócio-demográfico e clínico, além da aplicação das seguintes escalas: Escala de Avaliação de Depressão de Hamilton de 17 itens (HDRS17), Escala de Avaliação de Mania (YMRS), Questionário de Trauma Infantil (CTQ), Escala de Incapacidade de Sheehan (SDS), Escala de Qualidade de Vida da Organização Mundial da Saúde (WHOQOL-brief) e Escala de Adesão ao Tratamento (MARS). Tais escalas foram aplicadas pré e pós-intervenção. Após a intervenção, a amostra foi dividida em dois grupos, os aderentes à intervenção e os não-aderentes. Como resultados principais tivemos, além da construção de um aplicativo, uma melhora nos escores de qualidade de vida no grupo aderente ao uso do APP. Entendemos que a intervenção digital tem aplicabilidade clínica e poderá ser utilizada em pesquisas futuras. Bipolar affective disorder (TB) is a frequent condition in the general population, including the young adult population, and due its progressive character often incapacitating and refractory to treatments. Functional impairment can occur throughout life due to multiple episodes (both depressive as manic), which lead to cognitive deterioration. Understanding the stages, its evolution stages, and inherent severities, modulate the most appropriate pharmacologicals and psychosocials interventions. Thus, this research aimed to develop and apply a digital tool (APP) adjunctive to conventional treatment and the assess its contribution to quality of life and adherence to the treatment of patients with TB. For that, we used te almost experimental design, that happned in two stages: (1) the instrument development – APP and (2) the tool application in a 12-week intervention. After APP development, a non-randomized sample were selected, coming from Psychiatry Unit, Health Sciences Center, State University of Londrina. The participants were evaluated by structured questionnaire and assessments: Hamilton´s 17–item Hamilton Depression Rating Scale (HDRS17), Young Mania Rating Scale (YMRS), Child Trauma Questionnaire (CTQ), Sheehan Disability Scale (SDS), WHO Quality of Life-BREF (WHOQOL-BREF) and Medication Adherence Rating Scale (MARS). Such instruments were applied before and after intervention. After the intervention, the sample was divided into two groups, those who adhered to the intervention and those who did not. As main results, in addition to building and application, we had an improvement in the quality of life scores in the group adhering to the use of the APP. We understand that digital intervention has clinical applicability and can be used in future research.

Objetivo: Investigar se os indivíduos que tentaram suicídio apresentaram maior gravidade dos sintomas depressivos, trauma infantil, baixa percepção de qualidade de vida, elevado comprometimento funcional, mais comorbidades psiquiátricas e alterações nos níveis de biomarcadores inflamatórios quando comparados aos sem histórico de tentativas de suicídio. Métodos: Os participantes foram recrutados de pacientes da unidade de psiquiatria da Universidade Estadual de Londrina (UEL) e de funcionários da UEL, homens e mulheres, entre 18 e 65 anos, de todas etnias. Foram coletados dados sócio demográficos e clínicos de indivíduos que tentaram suicídio (n = 56) e indivíduos que não tentaram suicídio (n = 153), avaliados através de um questionário estruturado. Todos os indivíduos também foram analisados para medidas antropométricas, Escala de Avaliação de Depressão de Hamilton, Escala de Avaliação de Ansiedade de Hamilton, Escala de Young de Avaliação de Mania, Escala de Incapacidade de Sheehan, Qualidade de Vida (WHOQOL-BREF), Questionário de Trauma Infantil e biomarcadores laboratoriais, incluindo leptina, receptor solúvel do fator de necrose tumoral 1(sTNF-R1), antagonista do receptor de interleucina 1 (IL-1RA), antagonista do receptor de interleucina-1(IL-1RA), interleucina-13 (IL-13), interleucina-4 (IL-4), interleucina-5 (IL-5), interferon- (IFN-) e fator de estimulação de colônias de granulócitos e macrófagos (GM-CSF). Resultados: Existe uma correlação positiva significativa entre sTNF-R1 e gravidade dos sintomas depressivos (p = 0,013), assim como entre IL-1RA e gravidade dos sintomas depressivos (p = 0,04), há ainda uma correlação positiva significativa entre absenteísmo no trabalho e abuso físico na infância (p = 0,012), níveis mais elevados de IL-13, IL-5, IFNγ, GM-CSF e leptina e menores níveis de IL-4 em indivíduos que tentaram suicídio quando comparados com aqueles que não tentaram suicídio. Conclusão: Estes achados sugerem que o subgrupo de indivíduos que tentaram suicídio estão associados com trauma na infância, maior gravidade dos sintomas depressivos, comprometimento funcional, exibiu um aumento no número de biomarcadores inflamatórios. Objective The aim was to investigate whether individuals who attempted suicide were associated with more severity of depressive symptoms, experienced child abuse, poor quality of life, and functional impairment, more co-morbidities, and alterations in the levels of inflammatory biomarkers when compared to those without history of suicide attempts. Methods: All participants were recruited from outpatients in the psychiatric unit at State University of Londrina (UEL), and from staff workers at UEL, they were men and women, aged 18-65, and all ethnicities. Socio-demographic and clinical data of individuals who attempted suicide (n=56) and individuals without history of suicide attempts (n=153) were assessed through a structured questionnaire. All individuals were also analyzed for anthropometrics measures, Hamilton Depression Rating Scale, Hamilton Anxiety Rating Scale, Young Mania Rating Scale, Sheehan Disability Scale, Quality of Life (WHOQOL-BREF), Childhood Trauma Questionnaire and laboratory biomarkers, including leptin, soluble tumor necrosis factor receptor 1 (sTNF-R1), interleukin-1 receptor antagonist (IL-1RA), interleukin-13 (IL-13), interleukin-4 (IL4), interleukin-5 (IL5),IFN-γ (interferon-), and granulocyte-macrophage colony-stimulating factor (GM-CSF). Results: There is a significant positive correlation between sTNF–R1 and severity of depressive symptoms (p= 0.013), a significant positive correlation between IL-1RA and severity of depressive symptoms (p= 0.04), a significant positive correlation between work absences and childhood physical abuse (p= 0.012), higher levels of IL-13, IL-5, IFNγ, GM-CSF, leptin and lower IL-4 levels in individuals with suicide attempts when compared to those without history of suicide attempts. Conclusion: These findings suggest that the subgroup of individuals who attempted suicide, who were associated with childhood trauma, greater severity of depressive symptoms, functional impairment, exhibited an increased number of inflammatory biomarkers.

objetivos: Investigar se a associação entre transtornos de humor Transtorno Bipolar (TB) ou Transtorno Depressivo Maior (TDM), co-mórbidos com Transtorno por Uso do Tabaco (TUT) está associado na severidade dos sintomas, na baixa qualidade de vida, no prejuízo funcional, nas alterações dos níveis de leptina, biomarcadores inflamatórios e no perfil lípidico. Métodos: Os participantes foram indivíduos com transtornos bipolares e fumantes, transtornos bipolares e nunca fumantes, fumantes não-bipolares e transtornos não-bipolares e nunca fumantes. Também incluímos mulheres com depressão unipolar ou bipolar nunca fumantes e fumantes, e mulheres fumantes não-deprimidas e nunca fumantes.Os dados foram coletados no Centro de Referência de Abordagem e Tratamento do Tabagismo (CRATT) e no ambulatório de Psiquiatria da Universidade Estadual de Londrina. Paraná. Brasil. Todos os participantes assinaram termo de consentimento esclarecido e o trabalho foi aprovado no conselho de ética e pesquisa (CEP). (CAAE 3493581.2.0000.5231). Dados socio-demográficos e clínicos foram avaliados por questionário estruturado. Outras avaliações utilizadas foram medidas antropométricas, Escala de Gravidade de Depressão de Hamilton (HDRS), Escala de Gravidade de Ansiedade de Hamilton (HAM-A), Escala de Gravidade de Mania Jovem (YMRS), Escala de Incapacidade de Sheehan (SDS), Qualidade de Vida (WHOQOL-BREF), Questionário de trauma de infância (CTQ). Os seguintes biomarcadores foram investigados: perfil lipídico, incluindo colesterol total, colesterol de lipoproteínas de alta densidade (HDLc), colesterol de lipoproteínas de baixa densidade (LDLc), triglicerídeos, os índices de risco de Castelli I e II; e citocinas, incluindo interleucinas (IL) -1?, IL-6, IL-10, IL-12, IL-1RA, receptor de necrose tumoral solúvel 1 (sTNF-R1), leptina, proteina c?reativa ultrassensível (hs-PCR). Resultados: Nos individuos fumantes com TB houve significativa correlação positiva entre abuso emocional e leptina, leptina e severidade de sintomas depressivos, leptina e severidade de sintomas ansiosos, leptina e Castelli index 1 e 2, abuso emocional e indice de massa corporal (IMC). Correlação negativa entre abuso emocional e qualidade de vida. Mulheres fumantes deprimidas tiveram correlação significativamente positiva entre negligência emocional e sTNF-R1 (p = 0,02), circunferência da cintura e sTNF-R1 (p = 0,001), IMC e sTNF-R1 (p

Objetivos: Os principais objetivos do estudo foram analisar em pacientes com Trantorno por uso do tabaco, comorbidades clínicas, psiquiátricas, maus-tratos na infância e biomarcadores, bem como avaliar os efeitos da NAC como tratamento complementar na cessação do tabaco e alterações inflamatórias e de perfil lipidico. O estudo foi realizado no Centro de Referência de Abordagem e Tratamento do Tabagismo, localizado no Ambulatório de Especialidades do Hospital Universitário da Universidade Estadual de Londrina, credenciado para abordagem e tratamento do fumante pelo Ministério da Saúde. Para o estudo transversal a população foi constiuida por fumantes atuais (n = 129) e nunca fumantes (n = 85). Aplicou-se um questionário estruturado para avaliar dados sociodemográficos, clínicos, histórico familiar de tabagismo, tabagismo materno durante a gravidez e medidas antropométricas e escalas validadas como o ASSIST - Teste de Triagem do Envolvimento com Álcool, Tabaco e Outras Substâncias , Teste de Fagerström para Dependência de Nicotina, Questionário sobre Traumas na Infância, Escala de Avaliação da Depressão e de Ansiedade de Hamilton e uma entrevista clínica estruturada para diagnóstico de Transtorno Depressivo Maior e Transtorno por Uso de Tabaco pelos médicos psiquiatricas pesquisadores do grupo de pesquisa. Foram mensurados os níveis séricos de proteína C-reativa, fator de necrose tumoral alfa, receptor de TNF solúvel, leptina, e biomarcadores de perfil lipídico. Para o estudo de segmento realizou-se um ensaio clínico com a N- acetilcisteina (NAC) duplo-cego de 12 semanas controlado por placebo; Os pacientes que após 4 semanas de tratamento convencional que não pararam de fumar ou que não reduziram os cigarros diariamente por meio de medições do monóxido de carbono expirado, foram convidados a participar do estudo NAC (1800mg / dia) que foi adicionado ao tratamento convencional. Para o ensaio clínico, dos 129 com TUT, encontrou-se 76 pacientes com intenção de tratar e destes 42 não foram elegíveis por critérios de exclusão, não aceitaram participar ou já cessaram o uso de tabaco no primeiro mês de tratamento convencional, sendo 34 pacientes com intenção de tratar foram elegíveis. Resultados: Os fumantes atuais apresentaram maior prevalência para o transtorno depressivo maior, problemas de álcool, tabagismo materno durante a gravidez, abuso emocional na infância e história familiar de tabagismo em comparação com nunca fumantes. Os fumantes apresentaram níveis significativamente mais baixos de leptina, colesterol de lipoproteína de baixa densidade, índices de risco mais altos de Castelli I e II, níveis mais de hidroperóxido lípidico do que nunca fumantes. Os fumantes pesados tiveram inflamação, níveis mais elevados de sTNF-R1 do que fumantes leves. No ensaio clínico com NAC, os participantes que receberam NAC apresentaram redução estatisticamente significativa nos níveis sTNF-R2, índices de risco de Castelli I e II em comparação com aqueles que receberam placebo. Conclusões: fumantes atuais e fumantes pesados apresentaram ocorrências de comorbidades clínicas e psiquiátricas em comparação com nunca fumantes. O estudo fornece evidências de que a detecção de comorbidades clínicas e psiquiátricas nos fumantes atuais possibilita oferecer tratamentos personalizados para cessação do tabagismo. O tratamento complementar da NAC na cessação do tabagismo apresenta redução da inflamação, o que evidência que seu uso pode reduzir as doenças relacionadas ao tabaco. Objectives: The main objectives of the study were the analysis of patients with tobacco use disorder, clinical comorbidities, psychiatric, childhood maltreatment and biomarkers, as well to evaluate the effects of NAC as a complementary treatment in smoking cessation and inflammatory changes and lipid profile . The study was carried out at the Reference Center for Tobacco Approach and Treatment, located at the Specialty Clinic of the University Hospital of the State University of Londrina, accredited to approach and treatment of the smoker by the Ministry of Health. For the cross-sectional study the population was constituted by current smokers (n = 129) and never smokers (n = 85). A structured questionnaire was applied to evaluate sociodemographic, clinical data, family history of smoking, maternal smoking during pregnancy and anthropometric measures and validated scales such as ASSIST - Alcohol, Tobacco and Other Substance Involvement Screening Test, Fagerström Test for Nicotine Dependence, Childhood Trauma Questionnaire, Hamilton Depression and Anxiety Assessment Scale, and a structured clinical interview for the diagnosis of Major Depressive Disorder and Tobacco Use Disorder by psychiatric physicians in the research group. Levels of C-reactive protein, tumor necrosis factor alpha, soluble TNF receptor, leptin, and lipid profile biomarkers were measured. For the segmental study was performed a clinical trial with placebo-controlled 12-week double-blind N-acetylcysteine (NAC); Patients who, after 4 weeks of conventional treatment, did not stop smoking or did not reduce their daily cigarettes through measurements of expired carbon monoxide, were invited to participate in the NAC study (1800mg / day) added to conventional treatment. For the clinical trial, of the 129 patients with TUT, it was found 76 patients with intention to treat, and 42 of these were not eligible for exclusion criteria, or did not accept to participate or have already ceased smoking in the first month of conventional treatment, 34 patients with intention were eligible. Results: Current smokers presented higher prevalence for major depressive disorder, alcohol problems, maternal smoking during pregnancy, emotional abuse in childhood and family history of smoking compared to never smokers. Smokers had significantly lower levels of leptin, low density lipoprotein cholesterol, higher risk indexes of Castelli I and II, more levels of lipid hydroperoxide than ever smokers. Heavy smokers had more inflammation, higher levels of sTNF-R1 than mild smokers. In the NAC clinical trial, participants who received NAC had a statistically significant reduction in sTNF-R2 levels, the Castelli I and II risk indexes compared to those receiving placebo. Conclusions: current smokers and heavy smokers presented clinical and psychiatric comorbidities in comparison to never smokers. The study provides evidence that the detection of clinical and psychiatric comorbidities in current smokers makes it possible to offer personalized treatments for cessation of smoking. Complementary treatment of NAC in smoking cessation has a reduction in inflammation, evidence that its use may reduce tobacco-related diseases.