Adaptation to Brazilian Portuguese and Latin-American Spanish and psychometric properties of the Mental Illness Clinicians' Attitudes Scale (MICA v4).

OBJECTIVE: To describe translation to Spanish and Portuguese and adaptation of the Mental Illness Clinicians' Attitudes Scale version 4 (MICA v4). METHODS: The questionnaire was administered to primary care physicians (PCPs) from four Latin-American countries, Brazil, Bolivia, Chile, and Cuba. The validation process included four phases: 1) translation of the questionnaire to Spanish and Portuguese; 2) assessment of face validity; 3) assessment of reliability; and 4) evaluation of construct validity with confirmatory factor analysis (CFA). RESULTS: The study sample comprised 427 PCPs. The mean age of the Spanish-speaking sample (n = 252) was 40.1 (S.D = 9.7) years and the mean age of the Portuguese-speaking sample (n = 150) was 40.2 (S.D = 10.9) years. Both models demonstrated "appropriate" internal reliability. Total omega was 0.91 for the Spanish-speaking sample and 0.89 for the Portuguese-speaking sample. The CFA of both questionnaires showed an appropriate fit for a three-factor model (Portuguese: CFI = 0.927; TLI = 0.913; RMSEA = 0.066; Spanish: CFI = 0.945; TLI = 0.935; RMSEA = 0.068). CONCLUSION: The Latin-American versions of the MICA v4 in Spanish and Brazilian Portuguese have appropriate psychometric properties, good internal consistency, and are applicable to and acceptable in the Latin-American context. The instrument proved its validity for collecting data on stigmatizing attitudes among health professionals in different contexts and cultures.

Adaptation to Brazilian Portuguese and Latin-American Spanish and psychometric properties of the Mental Illness Clinicians' Attitudes Scale (MICA v4)

Abstract Objective To describe translation to Spanish and Portuguese and adaptation of the Mental Illness Clinicians' Attitudes Scale version 4 (MICA v4). Methods The questionnaire was administered to primary care physicians (PCPs) from four Latin-American countries, Brazil, Bolivia, Chile, and Cuba. The validation process included four phases: 1) translation of the questionnaire to Spanish and Portuguese; 2) assessment of face validity; 3) assessment of reliability; and 4) evaluation of construct validity with confirmatory factor analysis (CFA). Results The study sample comprised 427 PCPs. The mean age of the Spanish-speaking sample (n = 252) was 40.1 (S.D = 9.7) years and the mean age of the Portuguese-speaking sample (n = 150) was 40.2 (S.D = 10.9) years. Both models demonstrated "appropriate" internal reliability. Total omega was 0.91 for the Spanish-speaking sample and 0.89 for the Portuguese-speaking sample. The CFA of both questionnaires showed an appropriate fit for a three-factor model (Portuguese: CFI = 0.927; TLI = 0.913; RMSEA = 0.066; Spanish: CFI = 0.945; TLI = 0.935; RMSEA = 0.068). Conclusion The Latin-American versions of the MICA v4 in Spanish and Brazilian Portuguese have appropriate psychometric properties, good internal consistency, and are applicable to and acceptable in the Latin-American context. The instrument proved its validity for collecting data on stigmatizing attitudes among health professionals in different contexts and cultures.

Management of common mental disorders should take place in primary health or specialized care? Clinical decisions of psychiatrists from Latin American countries.

OBJECTIVE: The objective of our study was to explore clinical decisions of psychiatrists regarding the management of common mental disorders in primary care (PC) in four Latin Americans countries, through the application of clinical vignettes. METHODS: Using a cross-sectional design, we conducted a self-administered online questionnaire survey of psychiatrists from Bolivia, Brazil, Cuba, and Chile. The questionnaire covered sociodemographic and professional information. The psychiatrists' clinical decisions were assessed through three clinical vignettes representing typical PC cases of depression, anxiety, and somatization. RESULTS: 230 psychiatrists completed the online survey. Psychiatrists from Brazil were less likely to recognize depression as a mental disorder than those from Cuba (odds ratio (OR) = 0.30, 95% confidence interval (CI), 0.10 to 0.91, p < 0.04). Female gender (OR = 0.19, 95% CI, 0.04 to 0.91, p < 0.02) and older age (OR = 0.92, 95% CI, 0.87 to 0.97, p < 0.01) reduced the likelihood of agreement that depression cases should be treated by a Primary Care Physician (PCP). In the somatoform symptoms vignette, longer training duration increased the likelihood of agreement that treatment should be done by a psychiatrist instead of a PCP (OR = 1.19, 95% CI, 1.04 to 1.37, p < 0.01). In the anxiety vignette, females (OR = 2.38, 95% CI, 1.10 to 5.13, p < 0.01) and participants from Bolivia (compared with Cubans, OR = 4.19, 95% CI, 1.22 to 14.42, p < 0.02) were more likely to consider that these patients should be treated by a psychiatrist instead of a PCP. DISCUSSION: Most psychiatrist respondents agreed that patients with depression should be treated by PCPs and that somatoform and anxiety cases should be treated by psychiatrists. These results show that psychiatrists consider that they, and not PCPs, should treat patients with common mental disorders, regardless of the evidence showing that common mental disorders can be treated by primary care physicians in PC.

A 10-year ecological study of the methods of suicide used by Brazilian adolescents.

Suicide among adolescents has become a major public health problem worldwide. Our study sought to describe the most commonly used methods of suicide among adolescents aged 10 to 19 years in Brazil between 2006 and 2015. Complete data were obtained from the Brazilian Health Informatics Department (DATASUS) and coded into seven categories of suicide methods. The following statistical analyzes were performed: chi-square (χ2) tests to examine the association between the frequency of each suicide method and the year; odds ratios (OR) and 95% confidence intervals (95%CI) compared the relative chances of each suicide method occurring between boys and girls. In total, 8,026 suicides among Brazilian adolescents were registered over the analyzed period. The most commonly used method of suicide by both sexes was hanging (2015 = 70.3%), and the most significant increase was observed in girls (2015 = 65.82%). The proportional use of arms (2006 = 14.2%; 2015 = 9.1%) and poisoning (2006 = 13.3%; 2015 = 9.2%) decreased over the period. The increase in hanging is worrisome, mostly due to difficulties to impose access barriers and to its high lethality. In such context, a comprehensive understanding of suicide behaviors among adolescents in Brazil should be drawn to inform general prevention measures and, more specifically, the reasons for the increase in hanging need to be further investigated.

O suicídio entre adolescentes é um importante problema de saúde pública em nível global. O estudo teve como principal objetivo descrever os métodos de suicídio mais usados por adolescentes brasileiros entre 10 e 19 anos de idade, de 2006 a 2015. Foram obtidos dados completos do Departamento de Informática do SUS (DATASUS), codificados em sete categorias de métodos de suicídio. As seguintes análises estatísticas foram realizadas: testes de qui-quadrado (χ2) para examinar a associação entre a frequência de cada método de suicídio e o ano do óbito. As razões de chances (OR) e intervalos de 95% de confiança (IC95%) compararam as chances relativas entre homens e mulheres para cada método de suicídio. Durante o período analisado, houve 8.026 suicídios entre adolescentes. O enforcamento foi o método de suicídio mais usado em ambos os sexos eram (2015 = 70,3%), com um aumento mais agudo em mulheres (2015 = 65,82%). O uso proporcional de armas (2006 = 14,2%; 2015 = 9,1%) e envenenamento (2006 = 13,3%; 2015 = 9,2%) diminuiu ao longo do período. O aumento dos enforcamentos é preocupante, suscitando questões com dificuldades na imposição de barreiras de acesso e a alta letalidade desse método. Nesse contexto, precisa haver uma compreensão mais abrangente dos comportamentos suicidas entre os adolescentes brasileiros para informar as medidas preventivas em geral e, mais especificamente, para elucidar os motivos para o aumento dos suicídios por enforcamento.

El suicidio entre adolescentes se ha convertido en un importante problema de salud pública en todo el mundo. El objetivo de este estudio fue describir los métodos de suicido usados más comúnmente entre adolescentes, con edades comprendidas entre los 10 y 19 años, en Brasil desde 2006 hasta 2015. Los datos completos se obtuvieron del Departamento de Informática del Sistema Único de Salud (DATASUS) y se codificaron en siete categorías de métodos de suicidio. Se realizaron análisis estadísticos: tests chi-cuadrado (χ2) para examinar la asociación entre la frecuencia de cada método de suicidio y año. Odds ratios (OR) y los intervalos del 95% de confianza (IC95%) compararon las oportunidades relativas de cada método suicidio que se produce entre hombres y mujeres. Se registraron 8.026 suicidios entre adolescentes brasileños durante el período analizado. El método de suicidio más comúnmente usado por ambos sexos fue ahorcamiento (2015 = 70,3%), se observó un aumento más pronunciado en mujeres (2015 = 65,82%). El uso proporcional de armas (2006 = 14,2%; 2015 = 9,1%) y envenenamiento (2006 = 13,3%; 2015 = 9,2%) descendió durante este período. El incremento por ahorcamiento es preocupante, principalmente, en lo que se refiere a las dificultades para imponer barreras de acceso, así como por su alta letalidad. En este contexto, se deberían describir más los comportamientos suicidas entre adolescentes en Brasil para comprenderlos mejor, con el fin de que se tomen medidas de prevención general y, más específicamente, se profundice en las razones del incremento de ahorcamientos.

Population neuroscience: challenges and opportunities for psychiatric research in low- and middle-income countries

Objective: Population neuroscience is an emerging field that combines epidemiology and neuroscience to study how genes and the environment shape typical and atypical brain functioning. The objective of this study was to review key studies on population neuroscience from low- and middle-income countries (LMICs) and to identify potential gaps vis-à-vis studies conducted in high-income countries. Methods: We conducted a systematic review to search for longitudinal cohort studies investigating the development of psychiatric disorders in children and adolescents in LMICs. We performed an electronic search in the EMBASE and MEDLINE databases from inception to July 5th, 2019. Results: We found six cohorts from four countries that met our search criteria: three cohorts from Brazil, one from China, one from South Africa, and one from Mauritius. Relevant examples of findings from these studies are reported. Conclusion: Our results demonstrate the impact of the valuable science output these cohort designs promote, allowing LMICs to have a share in frontline global psychiatry research. National and international funding agencies should invest in LMIC population neuroscience in order to promote replication and generalization of research from high-income countries.

Population neuroscience: challenges and opportunities for psychiatric research in low- and middle-income countries.

OBJECTIVE: Population neuroscience is an emerging field that combines epidemiology and neuroscience to study how genes and the environment shape typical and atypical brain functioning. The objective of this study was to review key studies on population neuroscience from low- and middle-income countries (LMICs) and to identify potential gaps vis-à-vis studies conducted in high-income countries. METHODS: We conducted a systematic review to search for longitudinal cohort studies investigating the development of psychiatric disorders in children and adolescents in LMICs. We performed an electronic search in the EMBASE and MEDLINE databases from inception to July 5th, 2019. RESULTS: We found six cohorts from four countries that met our search criteria: three cohorts from Brazil, one from China, one from South Africa, and one from Mauritius. Relevant examples of findings from these studies are reported. CONCLUSION: Our results demonstrate the impact of the valuable science output these cohort designs promote, allowing LMICs to have a share in frontline global psychiatry research. National and international funding agencies should invest in LMIC population neuroscience in order to promote replication and generalization of research from high-income countries.

A 10-year ecological study of the methods of suicide used by Brazilian adolescents / Estudo ecológico de 10 anos sobre os métodos de suicídio usados por adolescentes brasileiros / Estudio ecológico abarcando 10 años sobre los métodos de suicidio practicados por adolescentes brasileños

Abstract: Suicide among adolescents has become a major public health problem worldwide. Our study sought to describe the most commonly used methods of suicide among adolescents aged 10 to 19 years in Brazil between 2006 and 2015. Complete data were obtained from the Brazilian Health Informatics Department (DATASUS) and coded into seven categories of suicide methods. The following statistical analyzes were performed: chi-square (χ2) tests to examine the association between the frequency of each suicide method and the year; odds ratios (OR) and 95% confidence intervals (95%CI) compared the relative chances of each suicide method occurring between boys and girls. In total, 8,026 suicides among Brazilian adolescents were registered over the analyzed period. The most commonly used method of suicide by both sexes was hanging (2015 = 70.3%), and the most significant increase was observed in girls (2015 = 65.82%). The proportional use of arms (2006 = 14.2%; 2015 = 9.1%) and poisoning (2006 = 13.3%; 2015 = 9.2%) decreased over the period. The increase in hanging is worrisome, mostly due to difficulties to impose access barriers and to its high lethality. In such context, a comprehensive understanding of suicide behaviors among adolescents in Brazil should be drawn to inform general prevention measures and, more specifically, the reasons for the increase in hanging need to be further investigated.

Resumo: O suicídio entre adolescentes é um importante problema de saúde pública em nível global. O estudo teve como principal objetivo descrever os métodos de suicídio mais usados por adolescentes brasileiros entre 10 e 19 anos de idade, de 2006 a 2015. Foram obtidos dados completos do Departamento de Informática do SUS (DATASUS), codificados em sete categorias de métodos de suicídio. As seguintes análises estatísticas foram realizadas: testes de qui-quadrado (χ2) para examinar a associação entre a frequência de cada método de suicídio e o ano do óbito. As razões de chances (OR) e intervalos de 95% de confiança (IC95%) compararam as chances relativas entre homens e mulheres para cada método de suicídio. Durante o período analisado, houve 8.026 suicídios entre adolescentes. O enforcamento foi o método de suicídio mais usado em ambos os sexos eram (2015 = 70,3%), com um aumento mais agudo em mulheres (2015 = 65,82%). O uso proporcional de armas (2006 = 14,2%; 2015 = 9,1%) e envenenamento (2006 = 13,3%; 2015 = 9,2%) diminuiu ao longo do período. O aumento dos enforcamentos é preocupante, suscitando questões com dificuldades na imposição de barreiras de acesso e a alta letalidade desse método. Nesse contexto, precisa haver uma compreensão mais abrangente dos comportamentos suicidas entre os adolescentes brasileiros para informar as medidas preventivas em geral e, mais especificamente, para elucidar os motivos para o aumento dos suicídios por enforcamento.

Resumen: El suicidio entre adolescentes se ha convertido en un importante problema de salud pública en todo el mundo. El objetivo de este estudio fue describir los métodos de suicido usados más comúnmente entre adolescentes, con edades comprendidas entre los 10 y 19 años, en Brasil desde 2006 hasta 2015. Los datos completos se obtuvieron del Departamento de Informática del Sistema Único de Salud (DATASUS) y se codificaron en siete categorías de métodos de suicidio. Se realizaron análisis estadísticos: tests chi-cuadrado (χ2) para examinar la asociación entre la frecuencia de cada método de suicidio y año. Odds ratios (OR) y los intervalos del 95% de confianza (IC95%) compararon las oportunidades relativas de cada método suicidio que se produce entre hombres y mujeres. Se registraron 8.026 suicidios entre adolescentes brasileños durante el período analizado. El método de suicidio más comúnmente usado por ambos sexos fue ahorcamiento (2015 = 70,3%), se observó un aumento más pronunciado en mujeres (2015 = 65,82%). El uso proporcional de armas (2006 = 14,2%; 2015 = 9,1%) y envenenamiento (2006 = 13,3%; 2015 = 9,2%) descendió durante este período. El incremento por ahorcamiento es preocupante, principalmente, en lo que se refiere a las dificultades para imponer barreras de acceso, así como por su alta letalidad. En este contexto, se deberían describir más los comportamientos suicidas entre adolescentes en Brasil para comprenderlos mejor, con el fin de que se tomen medidas de prevención general y, más específicamente, se profundice en las razones del incremento de ahorcamientos.

The association between adolescent suicide rates and socioeconomic indicators in Brazil: a 10-year retrospective ecological study

Objective: To examine suicide rates among adolescents from six large cities in Brazil and to analyze the relationship between adolescent suicide rates and socioeconomic indicators between 2006 and 2015. Methods: Generalized estimating equation models were used to assess the impact of socioeconomic factors - including social inequality and unemployment rates - on adolescent suicide rates. Results: The rate of adolescent suicide increased by 24% over the course of the study period. Social inequality (assessed using the Gini index), was positively associated with overall adolescent suicide rates (β = 10.68; 95%CI = 2.32-19.05; p ≤ 0.012). After disaggregating the findings by age (10-14 and 15-19 years), social inequality was associated with suicide rate only for adolescents aged 15-19 years (β = 9.63; 95%CI = 2.31-16.96; p ≤ 0.005). Disaggregating these findings by sex, the association with economic variables became significant only among females. Males had a higher overall suicide rate than females, and the highest rate was observed in male adolescents aged 15-19 years. Higher levels of unemployment were associated with higher suicide rates. Conclusion: Our findings suggest that socioeconomic indicators, particularly unemployment and social inequality, are relevant social determinants of suicide in adolescence.

The association between adolescent suicide rates and socioeconomic indicators in Brazil: a 10-year retrospective ecological study.

OBJECTIVE: To examine suicide rates among adolescents from six large cities in Brazil and to analyze the relationship between adolescent suicide rates and socioeconomic indicators between 2006 and 2015. METHODS: Generalized estimating equation models were used to assess the impact of socioeconomic factors - including social inequality and unemployment rates - on adolescent suicide rates. RESULTS: The rate of adolescent suicide increased by 24% over the course of the study period. Social inequality (assessed using the Gini index), was positively associated with overall adolescent suicide rates (ß = 10.68; 95%CI = 2.32-19.05; p ≤ 0.012). After disaggregating the findings by age (10-14 and 15-19 years), social inequality was associated with suicide rate only for adolescents aged 15-19 years (ß = 9.63; 95%CI = 2.31-16.96; p ≤ 0.005). Disaggregating these findings by sex, the association with economic variables became significant only among females. Males had a higher overall suicide rate than females, and the highest rate was observed in male adolescents aged 15-19 years. Higher levels of unemployment were associated with higher suicide rates. CONCLUSION: Our findings suggest that socioeconomic indicators, particularly unemployment and social inequality, are relevant social determinants of suicide in adolescence.

Peripheral levels of superoxide dismutase and glutathione peroxidase in youths in ultra-high risk for psychosis: a pilot study.

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.

Clinical decisions and stigmatizing attitudes towards mental health problems in primary care physicians from Latin American countries.

OBJECTIVE: The aim of this paper is to investigate how doctors working in primary health care in Latin American address patients with common mental disorders and to investigate how stigma can affect their clinical decisions. METHODS: Using a cross-sectional design, we applied an online self-administered questionnaire to a sample of 550 Primary Care Physicians (PCPs) from Bolivia, Brazil, Cuba and Chile. The questionnaire collected information about sociodemographic variables, training and experience with mental health care. Clinicians' stigmatizing attitudes towards mental health were measured using the Mental Illness Clinicians' Attitudes Scale (MICA v4). The clinical decisions of PCPs were assessed through three clinical vignettes representing typical cases of depression, anxiety and somatization. RESULTS: A total of 387 professionals completed the questionnaires (70.3% response rate). The 63.7% of the PCPs felt qualified to diagnose and treat people with common mental disorders. More than 90% of the PCPs from Bolivia, Cuba and Chile agreed to treat the patients presented in the three vignettes. We did not find significant differences between the four countries in the scores of the MICA v4 stigma levels, with a mean = 36.3 and SD = 8.3 for all four countries. Gender (p = .672), age (p = .171), training (p = .673) and years of experience (p = .28) were unrelated to stigma. In the two multivariate regression models, PCPs with high levels of stigma were more likely to refer them to a psychiatrist the patients with depression (OR = 1.03, 95% CI, 0.99 to 1.07 p<0.05) and somatoform symptoms somatoform (OR = 1.03, 95% CI, 1.00 to 1.07, p<0.05) to a psychiatrist. DISCUSSION: The majority of PCPs in the four countries were inclined to treat patients with depression, anxiety and somatoform symptoms. PCPs with more levels of stigma were more likely to refer the patients with depression and somatoform symptoms to a psychiatrist. Stigmatizing attitudes towards mental disorders by PCPs might be important barriers for people with mental health problems to receive the treatment they need in primary care.

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

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

Ten-year evolution of suicide rates and economic indicators in large Brazilian urban centers.

PURPOSE OF REVIEW: This was a retrospective ecological study to examine the relationship between suicide rates and economic indicators in large Brazilian urban centers. Data on macroeconomic indicators (GDP and unemployment rates) and suicide rates of the largest Brazilian cities were collected from January 2006 to December 2015. RECENT FINDINGS: Six cities were included in the study: Porto Alegre in the South, Recife and Salvador in the Northeast, and Belo Horizonte, São Paulo and Rio de Janeiro in the Southeast region. We observed a 4% increase in the age-adjusted suicide rate in these large Brazilian urban centers from 2006 to 2015, which is less pronounced than the 9% increase in the national rates of suicide observed in the same period. SUMMARY: The effect of economic indicators was heterogeneous among the centers, but, overall, the variation in suicide rates was inversely related to unemployment and did not show a significant relationship with GDP. These findings indicate a more complex link between economics and suicide whenever looking at local regional indicators. Further research should focus on possible intervening factors, what may inform better preventive interventions.

Plasma copeptin and metabolic dysfunction in individuals with bipolar disorder.

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.

1H-NMR, 1H-NMR T2-edited, and 2D-NMR in bipolar disorder metabolic profiling.

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.

Perinatal complications, lipid peroxidation, and mental health problems in a large community pediatric sample.

Replicated evidence indicates that perinatal complications are associated with increased markers of oxidative stress and with mental health problems in children. However, there are fewer reports on the impact of perinatal complications in later phases of development. We aimed to investigate the estimated effects of perinatal complications on levels of lipid peroxidation and on psychopathology in children and adolescents. The study is part of the High Risk Cohort Study for Psychiatric Disorders; the population was composed by 554 students, 6-14 years of age. Serum levels of malondialdehyde, a product of lipid peroxidation, were measured by the TBARS method. A household interview with parents and caregivers was conducted and included inquiries about perinatal history, the Child Behavior Checklist (CBCL), and parent's evaluation, using the Mini International Psychiatric Interview (MINI). We created a cumulative risk index, conceptualized as each individual's cumulative exposure to perinatal complications. Results indicate that perinatal complications were associated with higher levels of TBARS. After adjusting for age, gender, socio-economic status, CBCL total problems score, parental psychopathology, and childhood maltreatment, children exposed to 3 or more perinatal complications had an 26.9% (95% CI 9.9%, 46.6%) increase in TBARS levels, relative to the unexposed group. Exploratory mediation analysis indicated that TBARS levels partially mediated the association between perinatal complications and externalizing problems. In conclusion, an adverse intrauterine and/or early life environment, as proxied by the cumulative exposure to perinatal complications, was independently associated with higher levels of lipid peroxidation in children and adolescents.

Socioeconomic Disadvantage Moderates the Association between Peripheral Biomarkers and Childhood Psychopathology.

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.

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

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

Serum copeptin in children exposed to maltreatment.

AIM: Childhood maltreatment (CM) has been related to a persistent reprograming of stress-response. Copeptin is a marker of hypothalamic-pituitary-adrenal axis activation; however, few studies have examined copeptin levels in children exposed to CM. The aim of this study was to compare serum copeptin levels in children reporting child abuse and/or neglect and children with no history of CM. METHODS: This study included 65 children with a positive history of moderate to severe CM, as reported by themselves and their parent(s) during a clinical interview, and 71 children with no history of CM as a comparison group. CM was considered moderate to severe based on the child-reported frequency of being exposed to events related to sexual abuse, physical abuse, emotional abuse, emotional neglect, and/or physical neglect. Child psychopathology symptoms were assessed using the Child Behavior Checklist (CBCL). We measured serum copeptin concentration using enzyme-linked immunosorbent assay. RESULTS: Children exposed to CM exhibited higher levels of serum copeptin compared to children without CM when controlling for sex, age, and psychiatric morbidity. The CBCL total score, including internalizing and externalizing symptoms, was higher in children with CM. We found no correlation between copeptin and CBCL scores for internalizing symptoms and externalizing symptoms. CONCLUSION: CM is associated with copeptin serum levels independently of age, sex, and symptom severity. Copeptin is a promising new biomarker for children with a history of abuse and/or neglect.