Differential biomarker signatures in unipolar and bipolar depression: A machine learning approach.

OBJECTIVE: This study used machine learning techniques combined with peripheral biomarker measurements to build signatures to help differentiating (1) patients with bipolar depression from patients with unipolar depression, and (2) patients with bipolar depression or unipolar depression from healthy controls. METHODS: We assessed serum levels of interleukin-2, interleukin-4, interleukin-6, interleukin-10, tumor necrosis factor-α, interferon-γ, interleukin-17A, brain-derived neurotrophic factor, lipid peroxidation and oxidative protein damage in 54 outpatients with bipolar depression, 54 outpatients with unipolar depression and 54 healthy controls, matched by sex and age. Depressive symptoms were assessed using the Hamilton Depression Rating Scale. Variable selection was performed with recursive feature elimination with a linear support vector machine kernel, and the leave-one-out cross-validation method was used to test and validate our model. RESULTS: Bipolar vs unipolar depression classification achieved an area under the receiver operating characteristics (ROC) curve (AUC) of 0.69, with 0.62 sensitivity and 0.66 specificity using three selected biomarkers (interleukin-4, thiobarbituric acid reactive substances and interleukin-10). For the comparison of bipolar depression vs healthy controls, the model retained five variables (interleukin-6, interleukin-4, thiobarbituric acid reactive substances, carbonyl and interleukin-17A), with an AUC of 0.70, 0.62 sensitivity and 0.7 specificity. Finally, unipolar depression vs healthy controls comparison retained seven variables (interleukin-6, Carbonyl, brain-derived neurotrophic factor, interleukin-10, interleukin-17A, interleukin-4 and tumor necrosis factor-α), with an AUC of 0.74, a sensitivity of 0.68 and 0.70 specificity. CONCLUSION: Our findings show the potential of machine learning models to aid in clinical practice, leading to more objective assessment. Future studies will examine the possibility of combining peripheral blood biomarker data with other biological data to develop more accurate signatures.

Elevated serum superoxide dismutase and thiobarbituric acid reactive substances in different phases of bipolar disorder and in schizophrenia.

UNLABELLED: There is an increasing body of evidence suggesting that oxidative stress may play a role in the pathophysiology of both schizophrenia (SZ) and bipolar disorder (BD). METHODS: We compared the antioxidant enzyme, serum superoxide dismutase (SOD) and the lipid peroxidation product, thiobarbituric acid reactive substances (TBARS) as assessed in depressed (N=21), manic (N=32) and euthymic (N=31) bipolar patients, and in chronically medicated patients with schizophrenia (N=97), all fulfilling DSM-IV diagnostic criteria, and a group of healthy controls (N=32). RESULTS: Serum SOD (U/mg protein) activity was significantly increased (p<0.001) in manic (7.44+/-3.88) and depressed (6.12+/-4.64) BD patients and SZ (9.48+/-4.51) when compared to either controls (1.81+/-0.63) or euthymic (2.75+/-1.09) BD patients. TBARS (mol/L) levels were significantly higher in the SZ group (4.95+/-1.56, p=0.016), bipolar euthymic (6.36+/-1.46, p<0.001), bipolar manic (7.54+/-1.74, p<0.001), and bipolar depressed patients (5.28+/-1.54, p=0.028) compared to controls (3.96+/-1.51). DISCUSSION: Our findings show increased SOD activity in SZ, as well as in depressed and manic bipolar patients, but not in euthymic BD subjects. This suggests a dysregulation in oxidative defenses in both disorders. It is likely that such changes reflect state changes in bipolar disorder. It is possible that this is a compensatory response to the oxidative stress that occurs in the acute phase of bipolar episodes. TBARS results show increases in lipid peroxidation in mania. TBARS levels in SZ and in euthymic as well as depressed individuals with BD were higher than in controls. This suggests persistent increases in SZ, which may reflect ongoing symptomatology or treatment, and a state dependent gradient in BD, with greatest oxidative stress in mania. These data support oxidative biology as both a key component of the pathophysiology of both BD and SZ, and the use of agents that modulate oxidative biology as a promising avenue for intervention in both disorders.

Evaluating psychiatric case-control studies using the STROBE (STrengthening the Reporting of OBservational Studies in Epidemiology) statement.

CONTEXT AND OBJECTIVE: Case-control studies are important in developing clinical and public health knowledge. The STROBE statement (STrengthening the Reporting of OBservational Studies in Epidemiology) was developed to establish a checklist of items that should be included in articles reporting observational studies. Our aim was to analyze whether the psychiatric case-control articles published in Brazilian journals with CAPES Qualis rating B1/B2 in 2009 conformed with the STROBE statement. DESIGN AND SETTING: Descriptive study on psychiatric papers published in Brazilian journals, within the Postgraduate Medical Program on Psychiatry, at Universidade Federal do Rio Grande do Sul. METHODS: All psychiatric case-control studies from Brazilian Qualis B1/B2 journals of psychiatry, neurology and public health in 2009 were analyzed. The four most specific items of the STROBE statement were used to evaluate whether these studies fitted within the case-control parameters: 1) selection of cases and controls; 2) controlling for bias; 3) statistical analysis; and 4) presentation of results. RESULTS: Sixteen case-control studies were identified, of which eleven (68.75%) were in psychiatry-focused journals. From analysis using the STROBE statement, all of the articles conformed with item 1; two (12.5%) completely conformed with item 2; none completely conformed with item 3; and only three (18.8%) conformed with item 4. CONCLUSION: The case-control studies analyzed here did not completely conform with the four STROBE statement items for case-control design. In view of the inadequate methodology of the published studies, these findings justify focusing on research and methodology and expanding the investigations on adherence of studies to their designs.

Peripheral brain-derived neurotrophic factor changes along treatment with extended release quetiapine during acute mood episodes: an open-label trial in drug-free patients with bipolar disorder.

Molecules that are involved in neuronal intercommunication and adaptability of neural networks, such as brain-derived neurotrophic factor (BDNF), are targets of pathophysiological investigation in bipolar disorder (BD). Quetiapine is an attested treatment in this disorder, used in acute mood episodes. The aim of this study was to report prospective changes in serum BDNF levels in drug-free patients in acute mood episodes of BD who received treatment with extended-release quetiapine along a 16 week follow-up. Assessments were performed at baseline and weeks 2, 4, 8 and 16 with the Young Mania Rating Scale, the Hamilton Depression Rating Scale and the Clinical Global Impression severity scale. In these visits, serum BDNF levels were measured. Mixed effect models were used to investigate longitudinal changes. Twenty-five patients were included for this analysis, seventeen in a current depressive episode and eight in a manic/mixed episode. A significant improvement from baseline to endpoint was displayed. In the mixed model, significant main effects for episode and time appeared, and a time versus episode interaction showing increasing BDNF levels with time in those with a depressive episode, but a decrease in BDNF levels with time in those with a manic/mixed episode. BDNF may be a biomarker with differential response according to the polarity of mood episodes.

Evaluating psychiatric case-control studies using the STROBE (STrengthening the Reporting of OBservational Studies in Epidemiology) statement / Avaliando estudos de caso-controle em psiquiatria utilizando o STROBE (STrengthening the Reporting of OBservational Studies in Epidemiology) statement

CONTEXT AND OBJECTIVE: Case-control studies are important in developing clinical and public health knowledge. The STROBE statement (STrengthening the Reporting of OBservational Studies in Epidemiology) was developed to establish a checklist of items that should be included in articles reporting observational studies. Our aim was to analyze whether the psychiatric case-control articles published in Brazilian journals with CAPES Qualis rating B1/B2 in 2009 conformed with the STROBE statement. DESIGN AND SETTING: Descriptive study on psychiatric papers published in Brazilian journals, within the Postgraduate Medical Program on Psychiatry, at Universidade Federal do Rio Grande do Sul. METHODS: All psychiatric case-control studies from Brazilian Qualis B1/B2 journals of psychiatry, neurology and public health in 2009 were analyzed. The four most specific items of the STROBE statement were used to evaluate whether these studies fitted within the case-control parameters: 1) selection of cases and controls; 2) controlling for bias; 3) statistical analysis; and 4) presentation of results. RESULTS: Sixteen case-control studies were identified, of which eleven (68.75%) were in psychiatry-focused journals. From analysis using the STROBE statement, all of the articles conformed with item 1; two (12.5%) completely conformed with item 2; none completely conformed with item 3; and only three (18.8%) conformed with item 4. CONCLUSION: The case-control studies analyzed here did not completely conform with the four STROBE statement items for case-control design. In view of the inadequate methodology of the published studies, these findings justify focusing on research and methodology and expanding the investigations on adherence of studies to their designs. .

CONTEXTO E OBJETIVO: Estudos de caso-controle são importantes no desenvolvimento do conhecimento clínico e de saúde pública. O STROBE statement (STrengthening the Reporting of OBservational Studies in Epidemiology) foi criado para estabelecer uma lista de itens que devem estar presentes na descrição de estudos observacionais. Nosso objetivo é analisar a adequação de artigos caso-controle psiquiátricos publicados em periódicos brasileiros Qualis B1/B2 CAPES em 2009 utilizando o STROBE statement. TIPO DE ESTUDO E LOCAL: Estudo descritivo de artigos em psiquiatria publicados por periódicos brasileiros, realizado no Programa de Pós-Graduação em Medicina: Psiquiatria, na Universidade Federal do Rio Grande do Sul. MÉTODOS: Todos os estudos de caso-controle psiquiátricos em revistas brasileiras Qualis B1/B2 de psiquiatria, neurologia e saúde pública em 2009 foram analisados. Os quatro itens mais específicos do STROBE statement foram utilizados para avaliar se os estudos se ajustavam aos parâmetros de caso-controle: 1) seleção de casos e controles, 2) controle de vieses, 3) análise estatística e 4) apresentação dos resultados. RESULTADOS: Dezesseis estudos de caso-controle foram identificados, 68,75% (11) deles de periódicos de psiquiatria. Após a análise com base no STROBE statement, todos os artigos adequavam-se ao item 1; 12,5% (2) adequavam-se completamente ao item 2; nenhum ajustava-se completamente ao item 3; e somente 18,8% (3) estavam adequados em relação ao item 4. CONCLUSÃO: Os estudos de caso-controle avaliados aqui não se adequaram completamente aos quatro itens do STROBE statement para o desenho de caso-controle. Tendo em vista a inadequada metodologia dos estudos publicados, os achados justificam direcionar-se o foco para a pesquisa e metodologia, aumentando ...

Caracterização dos usuários de substâncias psicoativas atendidos no ambulatório de transtorno aditivo com ênfase em dependência química / Caracterzación de los uuarios de sustancias psicoactivas atendidos en el ambulatorio de aditivo trastorno con un énfasis en dependencia química / Charactrization of users of psychoactive substances atthe clinic for addictive disorder with emphasis on chemical dependecee

O objetivo do presente estudo foi traçar o perfil dos usuários de substâncias psicoativas atendidos em ambulatório de dependência química. Trata-se de estudo observacional transversal realizado com usuários de substâncias psicoativas atendidos no Ambulatório de Transtorno Aditivo com Ênfase em Dependência Química da Cruz Vermelha Brasileira, filial do Estado do Rio Grande do Sul, abrangendo o período de 2005 a 2010. A coleta de dados ocorreu através da análise dos prontuários de pacientes (n=1.469), com levantamento de dados demográficos, socioeconômicos e de uso de drogas. Na análise estatística, foi utilizada frequência, média, desvio padrão e teste do ?2, com um nível de significância de p<0,05. O perfil predominante dos usuários de substâncias psicoativas foi de jovens, na faixa etária de 21 a 30 anos, sexo masculino, solteiros, cor branca, com baixo nível de escolaridade, baixa condição socioeconômica e sem vínculos empregatícios. Encontrou-se maior consumo de tabaco (86,0%) entre as substâncias lícitas, e de crack (83,3%) entre as ilícitas. O uso de tabaco, maconha e inalantes demonstrou-se significativamente associado aos jovens. Os resultados contribuem para a elaboração de programas de intervenção, que abordem uma articulação multidisciplinar, numa ofensiva contra a problemática do uso indevido de drogas.

El objetivo de este estudio fue determinar el perfil de los usuarios de sustancias psicoactivas atendidos en consultas externas dependencia de sustancias químicas. Este es un estudio observacional transversal realizado con los usuarios de sustancias psicoactivas tratadas en el Ambulatorio de trastorno aditivo con énfasis en dependencia de sustancias químicas de Cruz Roja Brasileña, una filial del Estado de Río Grande do Sul, que abarca el período de 2005 a 2010. La recogida de datos se ha producido a través del análisis de los registros médicos de los pacientes (n=1.469), estudio de datos demográficos y socioeconómicos y el uso de drogas. En el análisis estadístico, se utilizan frecuencias, media, desviación estándar, y con el test de chi-cuadrado, con un nivel de significación de p<0,05. El perfil predominante de los usuarios de sustancias psicoactivas era joven, en el rango de edad de 21 a 30 años de edad, de sexo masculino, soltero, blanco, con bajo nivel de educación, el estado socioeconómico bajo y sin las relaciones de empleo. Encontramos que un mayor consumo de tabaco (86,0%) entre lo lícito y crack (83,3%) entre los ilícitos. El uso del tabaco, la marihuana y los inhalantes ha demostrado ser significativamente asociada con los jóvenes. Los resultados obtenidos contribuyen al desarrollo de los programas de intervención multidisciplinar que se dirigen a un link, una embestida contra el problema del uso indebido de drogas.

The objective of the present study was to outline the profile of psychoactive substance users treated at a clinic for chemical dependence. This is a transversal observational study developed with users of psychoactive substances treated at the Clinic for Addictive Disorder with Emphasis on Chemical Dependence of the Brazilian Red Cross, State of Rio Grande do Sul branch, from 2005 to 2010. Data collection was developed through the analysis of the patients? records (n=1,469), based on surveys on demographic, socio-economic and drug use data. Frequency, average, standard deviation and ?2 test were used in the statistical analysis, with a significance level of p<0.05. The predominant profile of psychoactive substance users was: young, in the age range between 21 and 30 years, male gender, single, Caucasian, low school and socioeconomic levels, as well as unemployed. Among the licit drugs, the main one was tobacco (86.0%); and for illicit drugs, the main one was crack (83.3%). The use of tobacco, marijuana and inhaled drugs has shown to be significantly related toyounger people. The results contribute for the development of intervention programs approaching a multidisciplinary articulation, as an offensive against the problem of drugs misuse.

Resistência à insulina e síndrome metabólica em pacientes ambulatoriais com transtorno do humor bipolar: [revisão] / Insulin resistance and metabolic syndrome in outpatients with bipolar disorder: [review]

CONTEXTO: O transtorno bipolar (TB) está associado a uma significativa morbi-mortalidade por causas metabólicas. Existem poucos dados sobre a prevalência de resistência à insulina (RI) e sua relação com a síndrome metabólica (SM) em pacientes com TB. OBJETIVO: Avaliar a prevalência de RI e SM em pacientes bipolares ambulatoriais e identificar os parâmetros clínicos associados à RI. MÉTODO: Estudo transversal em 65 pacientes com TB diagnosticados pelos critérios do DSM-IV-TR, avaliados de forma consecutiva no Programa de Transtorno Bipolar do Hospital de Clínicas de Porto Alegre, Brasil. RI foi diagnosticada utilizando o homeostatic model assessment - insulin resistance (HOMA-IR) e a SM foi diagnosticada utilizando três definições diferentes: do National Cholesterol Educational Program - Adult Treatment Panel III (NCEP-ATP III); do NCEP-ATP III modificado e da International Diabetes Federation (IDF). RESULTADOS: A prevalência de RI foi 43,1 por cento (mulheres 40 por cento, homens 44,4 por cento). A prevalência de SM definida pelo NCEP ATP III foi 32,3 por cento, pelo NCEP ATP III foi 40 por cento e pela IDF foi 41,5 por cento. Os critérios do NCEP ATP III modificado demonstrou a melhor relação entre sensibilidade (78,6 por cento) e especificidade (89,2 por cento) na detecção de RI. A circunferência da cintura foi o parâmetro clínico mais associado à RI. CONCLUSÃO: As definições atuais de SM podem identificar, com razoável sensibilidade e especificidade, RI em pacientes com TB. A obesidade abdominal é bastante associada à RI nessa população de pacientes.

BACKGROUND: Bipolar disorder (BD) is associated with significant morbidity and mortality from metabolic diseases. There is a paucity of data regarding insulin resistance (IR) and its relationship with the metabolic syndrome (MS) in bipolar patients. OBJECTIVE: To evaluate the prevalence of both IR and MS in BD outpatients and to assess clinical criteria associated with IR. METHOD: Cross-sectional study in 65 DSM-IV-TR BD patients consecutively assessed at the Bipolar Disorder Program at Hospital de Clínicas de Porto Alegre , Brazil. IR was diagnosed by the homeostatic model assessment - insulin resistance (HOMA-IR) and MS was diagnosed using three different definitions: National Cholesterol Educational Program - Adult Treatment Panel III (NCEP-ATP III); NCEP-ATP III modified criteria and International Diabetes Federation. RESULTS: IR was present in 43.1 percent of the sample (women 40 percent, men 44.4 percent). The prevalence of MS defined by the NCEP-ATP III criteria was 32.3 percent, NCEP-ATP III modified was 40 percent and IDF was 41.5 percent. NCEP-ATP III modified criteria showed the best trade-off between sensitivity (78.6 percent) and specificity (89.2 percent) to detect insulin resistance. Waist circumference was the clinical parameter most associated with IR. DISCUSSION: Current MS criteria may provide reasonable sensitivity and specificity for the detection of IR in BD patients. Abdominal obesity is closely related to IR in this patient population.