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IntroductionOxidative stress has been documented in chronic schizophrenia and in the first episode of psychosis, but there are very little data on oxidative stress prior to the disease onset. OBJECTIVE: This work aimed to compare serum levels of superoxide dismutase (SOD) and glutathione peroxidase (GPx) in young individuals at ultra-high risk (UHR) of developing psychosis with a comparison healthy control group (HC). METHODS: Thirteen UHR subjects and 29 age- and sex-matched healthy controls (HC) were enrolled in this study. Clinical assessment included the Comprehensive Assessment of At-Risk Mental States (CAARMS), the Semi-Structured Clinical Interview for DSM-IV Axis-I (SCID-I) or the Kiddie-SADS-Present and Lifetime Version (K-SADS-PL), and the Global Assessment of Functioning (GAF) scale. Activities of SOD and GPx were measured in serum by the spectrophotometric method using enzyme-linked immunosorbent assay kits. RESULTS: After adjusting for age and years of education, there was a significant lower activity of SOD and lower GPX activity in the UHR group compared to the healthy control group (rate ratio [RR]=0.330, 95% CI 0.187; 0.584, p<0.001 and RR=0.509, 95% CI 0.323; 0.803, p=0.004, respectively). There were also positive correlations between GAF functioning scores and GPx and SOD activities. CONCLUSION: Our results suggest that oxidative imbalances could be present prior to the onset of full-blown psychosis, including in at-risk stages. Future studies should replicate and expand these results.
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Glutationa Peroxidase/sangue , Transtornos Psicóticos/sangue , Superóxido Dismutase/sangue , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Transtornos Psicóticos/diagnóstico , Transtornos Psicóticos/epidemiologiaRESUMO
Many of the currently available treatments for obsessive-compulsive and related disorders (OCRDs) such as pharmacotherapy augmentation strategies, partial hospitalization programs, deep brain stimulation, and neurosurgery are efficacious for individuals suffering from more severe forms of these conditions. Unfortunately, the application of these treatments in milder forms of illness and subclinical samples, which affect a substantial portion of the population, is not justifiable by their costs (e.g. cognitivebehavioral therapy) and/or potential for side effects (serotonin-reuptake inhibitors associated sexual side effects). As such, there is an urgent need to develop simple yet effective treatments, such as modifiable lifestyle interventions, that can be employed on a broader scale. Here, we review the current state of evidence that supports or refutes the efficacy of lifestyle approaches for OCRDs. We focus on dimensions of lifestyle that are deemed important for cardiovascular diseases; namely, physical activity, stress, sleep, diet and eating behaviors, alcohol consumption, and smoking. Despite the relative scarcity of welldesigned randomized controlled trials targeting unhealthy life styles in OCRDs, we found meditation-based therapies and interventions focusing on eliminating sedentarism to be promising approaches. In the future, these strategies may represent valid alternative for subjects with subthreshold symptoms or at risk for OCRDs or other "compulsive" disorders.
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Estilo de Vida , Transtorno Obsessivo-Compulsivo/terapia , Consumo de Bebidas Alcoólicas , Terapia Cognitivo-Comportamental , Exercício Físico , Comportamento Alimentar , Humanos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Sono , Fumar , Estresse PsicológicoRESUMO
The present study aimed at investigating possible alterations in the serum lipid profile of euthymic patients with bipolar disorder type I (BD) compared to healthy controls (HC). Thirty-five individuals from both genders were recruited, with 14 diagnosed and treated as BD patients (BD group) and 21 healthy subjects (HC group). Clinical assessment was based on the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I), Young Mania Rating Scale (YMRS), and 17-items of Hamilton Depression Rating Scale (HDRS-17) data, which were used to confirm diagnosis, to verify psychiatric comorbidities, and to estimate the severity of manic and depressive symptoms. Ultra-high performance liquid chromatography (UHPLC) coupled to high resolution mass spectrometry (HRMS) was applied to analyze the lipids extracted from all serum samples from both studied groups. In this pioneer and exploratory study, we observed different serum lipid profiles for BD and HC groups, especially regarding glycerophospholipid, glycerolipid, and sphingolipid distribution. Multivariate statistical analyses indicated that 121 lipids were significantly different between BD and HC. Phosphatidylinositols were identified as the most altered lipids in BD patient sera. The results of this preliminary study reinforce the role of lipid abnormalities in BD and offer additional methodological possibilities for investigation in the field.
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Transtorno Bipolar/sangue , Lipídeos/sangue , Espectrometria de Massas , Adulto , Transtorno Bipolar/diagnóstico , Transtorno Bipolar/psicologia , Estudos de Casos e Controles , Comorbidade , Depressão/sangue , Depressão/diagnóstico , Depressão/psicologia , Manual Diagnóstico e Estatístico de Transtornos Mentais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fosfatidilinositóis/sangueRESUMO
AIM: This study aimed to compare plasma copeptin levels, the c-terminal of provasopressin, between individuals with bipolar disorder (BD) and healthy controls and to assess the relation between copeptin and metabolic parameters. METHODS: We measured plasma levels of copeptin in individuals with BD (n = 55) and healthy controls (n = 21). Information related to psychiatric/medical history, as well as to metabolic comorbidities and laboratorial parameters was also captured. Insulin resistance and ß-cell function in basal state were calculated from fasting plasma glucose and C-peptide using the HOMA2 calculator. Impaired glucose metabolism was defined as pre-diabetes or type 2 diabetes mellitus. Copeptin, adiponectin, and leptin plasma levels were determined by enzyme-linked immunosorbent assay. RESULTS: Plasma copeptin levels were lower in individuals with BD, relative to healthy controls (P < 0.001). There were significant interactions between BD and plasma copeptin on ß-cell function (rate ratio [RR] = 1.048; P = 0.030) and on leptin levels (RR = 1.087; P = 0.012), indicating that there was a positive correlation between these markers in the BD group, but a negative one in healthy controls. Finally, in individuals with BD only, the association between ß-cell function, body mass index (RR = 1.007; P < 0.001), and insulin resistance (RR = 1.001; P = 0.037) was moderated by copeptin levels. CONCLUSION: Copeptin levels were lower in individuals with BD than in healthy controls. There were differential associations between copeptin and metabolic parameters within the BD and healthy control subgroups, suggesting an association between abnormal copeptin and metabolic dysregulation only in the BD population.
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Transtorno Bipolar/sangue , Diabetes Mellitus Tipo 2/sangue , Dislipidemias/sangue , Glicopeptídeos/sangue , Estado Pré-Diabético/sangue , Adulto , Transtorno Bipolar/epidemiologia , Comorbidade , Diabetes Mellitus Tipo 2/epidemiologia , Dislipidemias/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Pré-Diabético/epidemiologiaRESUMO
BACKGROUND: The objective of this study was to identify molecular alterations in the human blood serum related to bipolar disorder, using nuclear magnetic resonance (NMR) spectroscopy and chemometrics. METHODS: Metabolomic profiling, employing 1H-NMR, 1H-NMR T2-edited, and 2D-NMR spectroscopy and chemometrics of human blood serum samples from patients with bipolar disorder (n = 26) compared with healthy volunteers (n = 50) was performed. RESULTS: The investigated groups presented distinct metabolic profiles, in which the main differential metabolites found in the serum sample of bipolar disorder patients compared with those from controls were lipids, lipid metabolism-related molecules (choline, myo-inositol), and some amino acids (N-acetyl-L-phenyl alanine, N-acetyl-L-aspartyl-L-glutamic acid, L-glutamine). In addition, amygdalin, α-ketoglutaric acid, and lipoamide, among other compounds, were also present or were significantly altered in the serum of bipolar disorder patients. The data presented herein suggest that some of these metabolites differentially distributed between the groups studied may be directly related to the bipolar disorder pathophysiology. CONCLUSIONS: The strategy employed here showed significant potential for exploring pathophysiological features and molecular pathways involved in bipolar disorder. Thus, our findings may contribute to pave the way for future studies aiming at identifying important potential biomarkers for bipolar disorder diagnosis or progression follow-up.
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BACKGROUND: Socioeconomic disadvantage (SED) has been consistently associated with early life mental health problems. SED has been shown to impact multiple biological systems, including the regulation of neurotrophic proteins, immune-inflammatory and oxidative stress markers, which, conversely, have been reported to be relevant to physiological and pathological neurodevelopment This study investigated the relationship between SED, different domains of psychopathology, serum levels of interleukin-6 (IL6), thiobarbituric acid-reactive substance (TBARS) and brain-derived neurotrophic factor (BDNF). We hypothesized that a composite of socioeconomic risk would be associated with psychopathology and altered levels of peripheral biomarkers. In addition, we hypothesized that SED would moderate the associations between mental health problems, IL6, TBARS and BDNF. METHODS AND FINDINGS: Using a cross-sectional design, we measured the serum levels of IL6, TBARS and BDNF in 495 children aged 6 to 12. We also investigated socio-demographic characteristics and mental health problems using the Child Behaviour Checklist (CBCL) DSM-oriented scales. SED was evaluated using a cumulative risk model. Generalized linear models were used to assess associations between SED, biomarkers levels and psychopathology. SED was significantly associated with serum levels of IL6 (RR = 1.026, 95% CI 1.004; 1.049, p = 0.020) and TBARS (RR = 1.077, 95% CI 1.028; 1.127, p = 0.002). The association between SED and BDNF was not statistically significant (RR = 1.031, 95% CI 0.997; 1.066, p = 0.077). SED was also significantly associated with all CBCL DSM-oriented scales (all p < 0.05), whereas serum biomarkers (i.e. IL6, TBARS, BDNF) were associated with specific subscales. Moreover, the associations between serum biomarkers and domains of psychopathology were moderated by SED, with stronger correlations between mental health problems, IL6, TBARS, and BDNF being observed in children with high SED. CONCLUSIONS: In children, SED is highly associated with mental health problems. Our findings suggest that this association may be moderated via effects on multiple interacting neurobiological systems.
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Fator Neurotrófico Derivado do Encéfalo/sangue , Interleucina-6/sangue , Transtornos Mentais/sangue , Saúde Mental , Estresse Psicológico/sangue , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Biomarcadores/sangue , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Fatores SocioeconômicosRESUMO
OBJECTIVES: The neurotrophin brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker in bipolar disorder (BD). However, current evidence is limited and results have been highly heterogeneous. This study aimed to assess the moderating effect of impaired glucose metabolism (IGM) on plasma levels of BDNF in individuals with BD, and on the relationship between BDNF and variables of illness course. METHODS: We measured and compared the plasma levels of BDNF in individuals with BD (n=57) and healthy controls (n=26). IGM was operationalized as pre-diabetes or type 2 diabetes mellitus. Information related to current and past psychiatric/medical history, as well as prescription of pharmacological treatments was also captured. RESULTS: Individuals with BD had lower levels of BDNF, relative to healthy controls, after adjustment for age, gender, current medications, smoking, alcohol use, and IGM (P=.046). There was no effect of IGM (P=.860) and no interaction between BD diagnosis and IGM (P=.893). Peripheral BDNF levels were positively correlated with lifetime depressive episodes (P<.001), psychiatric hospitalizations (P=.001) and suicide attempts (P=.021). IGM moderated the association between BDNF and the number of previous mood episodes (P<.001), wherein there was a positive correlation in euglycemic participants and a negative correlation in individuals with IGM. CONCLUSIONS: BD is independently associated with lower levels of BDNF; IGM may modify the relationship between BDNF and BD course, suggesting an interactive effect of BDNF with metabolic status on illness progression.