Risk factors for new-onset bipolar disorder in a community cohort: A five-year follow up study.

The aim of this study was to assess the risk factors for new-onset Bipolar Disorder (BD) in a community sample of young adults. This is a prospective cohort study including a population-based sample of young adults aged between 18-24 years. The baseline took place from 2007 to 2009, and 1560 subjects were included. Five years after, 1244 individuals were re-evaluated (79.7% retention). Substance abuse/dependence was assessed using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST), and mental disorders were assessed using the Mini International Neuropsychiatric Interview 5.0 (MINI) at both waves. The cumulative incidence of BD in five years was 4.6%. There was no significant association between sociodemographic factors and BD incidence. Tobacco, cannabis, cocaine/crack, other substances abuse/dependence increased the relative risk for BD. Depressive, anxiety, post-traumatic stress disorders, and the suicide risk increased the relative risk to BD. Depressive episode was the strongest risk factor for BD, followed by other mental disorders and substance abuse/dependence in a probabilistic community sample of young adults. Preventive actions in mental health directed at the non-clinical population are needed for early detection and better management of BD.

Toward Precision Psychiatry in Bipolar Disorder: Staging 2.0.

Personalized treatment is defined as choosing the "right treatment for the right person at the right time." Although psychiatry has not yet reached this level of precision, we are on the way thanks to recent technological developments that may aid to detect plausible molecular and genetic markers. At the moment there are some models that are contributing to precision psychiatry through the concept of staging. While staging was initially presented as a way to categorize patients according to clinical presentation, course, and illness severity, current staging models integrate multiple levels of information that can help to define each patient's characteristics, severity, and prognosis in a more precise and individualized way. Moreover, staging might serve as the foundation to create a clinical decision-making algorithm on the basis of the patient's stage. In this review we will summarize the evolution of the bipolar disorder staging model in relation to the new discoveries on the neurobiology of bipolar disorder. Furthermore, we will discuss how the latest and future progress in psychiatry might transform current staging models into precision staging models.

Escala Hamilton: estudo das características psicométricas em uma amostra do sul do Brasil / Hamilton Scale: study of the psychometric characteristics in a sample from Southern Brazil

Objetivo Investigar as características psicométricas de uma versão traduzida da escala, propondo uma Versão Revisada que atenda aos critérios de adaptação transcultural para o contexto brasileiro. Métodos Este estudo incluiu 231 sujeitos – deprimidos (45,5%), bipolares (7,8%) e saudáveis (46,7%) – que participaram de uma pesquisa epidemiológica no sul do Brasil. A avaliação de transtornos mentais foi realizada por meio da Clinical Interview for DSM-IV (SCID) e uma versão traduzida da Escala de Avaliação de Depressão de Hamilton (HAM-D), que habitualmente vem sendo utilizada no país sem estudos de adaptação. Resultados Identificou-se o ponto de corte (9 pontos) para discriminar a presença ou não de sintomas de depressão pela análise da curva ROC, resultando em uma sensibilidade e especificidade de 90 e 91%, respectivamente. A validade interna foi investigada pela análise fatorial e consistência dos itens. Dos 17 itens originais, apenas o item que avalia a “consciência do transtorno” não apresentou carga fatorial satisfatória para avaliar depressão geral e foi eliminado; os 16 restantes agruparam-se em cinco dimensões, denominadas: Humor deprimido, Anorexia, Insônia, Somatização e Ansiedade, as quais, com exceção da última, mostraram homogeneidade nos seus construtos (coeficientes alfa entre 0,66 e 0,78). Na análise de conteúdo dos itens, cinco especialistas sugeriram alterações redacionais em sete itens. Conclusão O estudo determina um ponto de corte diferente do original e evidencia características psicométricas favoráveis para a utilização da escala no Brasil. .

Objective To investigate the psychometric characteristics of a translated version of the scale, proposing a reviewed version in order to attend the transcultural adaptation criteria. Methods This study included 231 subjects – depressed (45.5%), bipolar (7.8%), and healthy (46.7%) – who participated of an epidemiological research in southern Brazil. The evaluation of mental disorders was made through Clinical Interview for DSM-IV (SCID) and a translated version of the Hamilton Scale (HAM-D), usually utilized in Brazil without adaptation studies. Results The ROC curve analysis identified the cutoff (9 points) to discriminate the presence or absence of depression, resulting in a sensibility and specificity of 90 and 91%, respectively. The internal validity was investigated by the factorial analysis and consistence of the items. It was observed that all 17 original items, except “Consciousness”, presented psychometric quality to evaluate general depression, and that there were five dimensions underling those 16 items: Depressed humor, Anorexia, Insomnia, Somatization, and Anxiety, and all of them, excepting the last, showed homogeneity in their constructs (alpha coefficients between 0.66 and 0.78). On content analysis, five specialists suggested editing changes in seven items. Conclusion This study determinates a different cutoff and psychometric evidences favourable to the use of HAM-D in Brazil. .

Expression of matrix metalloproteinases in patients with bipolar disorder

Objective: High cardiovascular mortality rates have been reported in patients with bipolar disorder (BD). Studies indicate that matrix metalloproteinases (MMPs) are implicated in cardiovascular diseases. We evaluated the expression pattern of MMP-2 and MMP-9 in blood from patients with BD during acute mania and after euthymia, in comparison with healthy controls. Methods: Twenty patients and 20 controls were recruited and matched for sex and age. MMP messenger RNA (mRNA) levels were measured using real-time quantitative polymerase chain reaction (PCR). Body mass index (BMI) was calculated for all subjects. Results: There were no significant differences in MMP-2 and MMP-9 mRNA expression between patients and controls. mRNA levels were not significantly different during mania and euthymia. However, MMP-2 mRNA levels were negatively associated with BMI in BD patients and positively associated with BMI in controls. There was no difference in the pattern of MMP-9 expression between patients and controls. Conclusions: Our results suggest a different pattern of association between MMP-2 and BMI in BD patients as compared with controls. Despite some study limitations, we believe that the role of MMPs in BD should be further investigated to elucidate its relationship with cardiovascular risk. .

Homocysteine and other markers of cardiovascular risk during a manic episode in patients with bipolar disorder.

OBJECTIVE: To evaluate serum levels of different biomarkers associated with cardiovascular disease in patients with bipolar disorder (BD). Patients were prospectively evaluated in two separate instances: during acute mania and after remission of manic symptoms. All measurements were compared with those of healthy controls. METHODS: The study included 30 patients with BD and 30 healthy controls, matched for gender and age. Biochemical parameters evaluated included homocysteine (Hcy), folic acid, vitamin B12, ferritin, creatine kinase (CK) and C-reactive protein (CRP). RESULTS: Hcy levels were significantly higher in the BD patients, both during mania and after achieving euthymia. When Hcy was adjusted for body mass index, there was no significant difference between patients and controls. Ferritin was the only marker that showed a significant decrease during mania when compared to both euthymic patients and controls. There were no significant differences for folate, vitamin B12, CK and CRP. CONCLUSIONS: These findings do not show an association between alterations of markers of cardiovascular risk during manic episodes. Further studies are necessary to determine factors and mechanisms associated with cardiovascular risk in patients with BD.

Homocysteine and other markers of cardiovascular risk during a manic episode in patients with bipolar disorder

Objective: To evaluate serum levels of different biomarkers associated with cardiovascular disease in patients with bipolar disorder (BD). Patients were prospectively evaluated in two separate instances: during acute mania and after remission of manic symptoms. All measurements were compared with those of healthy controls. Methods: The study included 30 patients with BD and 30 healthy controls, matched for gender and age. Biochemical parameters evaluated included homocysteine (Hcy), folic acid, vitamin B12, ferritin, creatine kinase (CK) and C-reactive protein (CRP). Results: Hcy levels were significantly higher in the BD patients, both during mania and after achieving euthymia. When Hcy was adjusted for body mass index, there was no significant difference between patients and controls. Ferritin was the only marker that showed a significant decrease during mania when compared to both euthymic patients and controls. There were no significant differences for folate, vitamin B12, CK and CRP. Conclusions: These findings do not show an association between alterations of markers of cardiovascular risk during manic episodes. Further studies are necessary to determine factors and mechanisms associated with cardiovascular risk in patients with BD. .

Vulnerability to dietary n-3 polyunsaturated fatty acid deficiency after exposure to early stress in rats.

The exposure to adverse events early in life may affect brain development. Omega-3 polyunsaturated fatty acid (n-3 PUFA) deficiency has been linked to the development of mood and anxiety disorders. The aim of this study was to examine the interaction between variations in the early environment (handling or maternal separation) and the chronic exposure to a nutritional n-3 PUFA deficiency on locomotor activity, sucrose preference, forced swimming test and on serum and hippocampal brain-derived neurotrophic factor (BDNF) levels. Rats were randomized into Non-handled (NH), Neonatal Handled (H) and Maternal Separated (MS) groups. Pups were removed from their dams (incubator at 32°C on postnatal days (PND) 1-10) during 10 min/day (H) or 3h/day (MS). On PND 35, males were subdivided into diets adequate or deficient in n-3 PUFA for 15 weeks. H and MS gained weight differently, and animals receiving the n-3 PUFA deficient diet gained less weight. MS displayed a higher food consumption and higher consumption of sucrose solution during the second hour of exposure to the sucrose preference test. No differences were observed in the swimming test. H group had increased locomotion and showed a higher response to amfepramone. No significant effect was observed on serum BDNF levels. BDNF protein levels were decreased in animals receiving the n-3 PUFA deficient diet. We observed that early life environment and a mild n-3 PUFA deficiency are able to affect several behavioral aspects (food and sucrose consumption and locomotor response), and lead to a differential hippocampal BDNF metabolism in adult life.

Expression of matrix metalloproteinases in patients with bipolar disorder.

OBJECTIVE: High cardiovascular mortality rates have been reported in patients with bipolar disorder (BD). Studies indicate that matrix metalloproteinases (MMPs) are implicated in cardiovascular diseases. We evaluated the expression pattern of MMP-2 and MMP-9 in blood from patients with BD during acute mania and after euthymia, in comparison with healthy controls. METHODS: Twenty patients and 20 controls were recruited and matched for sex and age. MMP messenger RNA (mRNA) levels were measured using real-time quantitative polymerase chain reaction (PCR). Body mass index (BMI) was calculated for all subjects. RESULTS: There were no significant differences in MMP-2 and MMP-9 mRNA expression between patients and controls. mRNA levels were not significantly different during mania and euthymia. However, MMP-2 mRNA levels were negatively associated with BMI in BD patients and positively associated with BMI in controls. There was no difference in the pattern of MMP-9 expression between patients and controls. CONCLUSIONS: Our results suggest a different pattern of association between MMP-2 and BMI in BD patients as compared with controls. Despite some study limitations, we believe that the role of MMPs in BD should be further investigated to elucidate its relationship with cardiovascular risk.

Trauma precoce e transtornos de humor em jovens / Early trauma and mood disorders in youngsters

OBJETIVO: Verificar vivências precoces de abuso e negligência na infância entre jovens com transtorno bipolar (TB), transtorno depressivo maior (TDM) e controles populacionais. MÉTODO: Estudo de caso-controle aninhado a um estudo transversal de base populacional. A confirmação do diagnóstico foi realizada por meio de entrevista clínica estruturada para transtornos de eixo I do DSM-IV (SCID) e os eventos traumáticos foram verificados pelo Questionário sobre traumas na infância (CTQ). RESULTADOS: A amostra foi composta por 231 jovens, sendo 95 indivíduos no grupo controle, 82 com TDM e 54 com TB (32 do tipo I e 22 do tipo II). A prevalência de trauma na infância foi de 42,2%, sendo 54,7% entre aqueles com TB, 62,2% entre os jovens com TDM e 18,1% entre o grupo controle. Os jovens com TB ou TDM apresentaram maiores médias no CTQ total e entre seus componentes quando comparados aos jovens do grupo controle, exceto o componente abuso sexual, em que se observou diferença estatística apenas entre o grupo controle e o grupo de jovens com transtorno bipolar. CONCLUSÃO: O relato de vivências traumáticas precoces foi mais presente entre os jovens com transtornos de humor do que na população geral, confirmando o que a literatura traz sobre o tema. Nesse sentido, as vivências de trauma na infância parecem contribuir para o aparecimento dos transtornos de humor.

OBJECTIVE: To verify early experiences of childhood abuse and neglect among young with bipolar disorder (BD), major depression (MDD), and controls. METHOD: Case-control study nested to a population-based cross-sectional study. The diagnosis was performed via the structured clinical interview for DSM-IV Axis I Disorders (SCID). Traumatic events were analyzed using the Portuguese version - Questionário sobre Traumas na Infância (CTQ) - based on the Childhood Trauma Questionnaire. RESULTS: The sample comprised 231 adolescents with 95 individuals in the control group, 82 with MDD and 54 with BD (32 of type I and 22 type II). The prevalence of trauma or violence in childhood was 42.2%; among those, 54.7% had BD, 62.2% had MDD and 18.1% were in the control group. Young people with BD or MDD obtained higher means in total CTQ and among their components when compared with those in the control group. DISCUSSION: Reports on early traumatic experiences were more frequent among young people with mood disorders than in the general population, corroborating the literature on the subject. In this sense, the traumatic experiences during childhood seemed to contribute to the onset of the disorder.

Adaptação da escala brian para uso emcrianças e adolescentes: um estudopreliminar / Brian scale adaptation for use in childrenand adolescents: a preliminary study

Introdução: Alterações nos ritmos circadianos tem sido frequentemente observadas entre pacientes com Transtorno do Humor Bipolar (THB). No entanto, existem poucos instrumentos para medi-las e a maioria deles mede exclusivamente distúrbios do sono. A escala BRIAN, validada para adultos com THB, avalia a regularidade dos ritmos biológicos em quatro diferentes aspectos: sono, atividades, social e padrão de alimentação. O objetivo deste estudo-piloto foi adaptar a escala BRIAN para uma população de crianças e adolescentes (BRIAN-K) e avaliar se o novo instrumento é capaz de detectar diferenças entre pacientes e controles saudáveis. Métodos: Foram avaliados 20 pacientes com THB entre 8-16 anos e 32 controles pareados por sexo e idade. Os sujeitos foram avaliados por meio de entrevista clínica, K-SADS-PL e testagem cognitiva. A BRIAN-K foi aplicada em ambos os grupos. Resultados: O grupo de pacientes com THB apresentou escores mais altos de alterações em seus ritmos circadianos pelo escore total da BRIAN-K, quando comparados com o grupo controle (p=0,022). Particularmente, maior irregularidade foi observada no domínio “atividades” no grupo de pacientes (p=0,001). Nossos resultados também mostraram uma correlação positiva entre a idade de diagnóstico e o domínio “sono” da BRIAN-K (r=0,485; p=0,03). Conclusões: Estes dados preliminares sugerem que a versão BRIAN-K, recentemente adaptada para crianças e adolescentes, é capaz de discriminar pacientes com THB e controles. Futuros estudos com maior tamanho amostral são necessários para determinar a confiabilidade, a validade interna e externa do presente instrumento.

Background: Alterations in the circadian rhythms have been frequently observed in patients with Bipolar Disorder (BD). However, there are few instruments to measure these changes, and most of them only assess sleep disorders. The BRIAN scale validated for adults with BD, evaluates the regularity of the biological rhythms in four different aspects: sleep, activities, social rhythm, and eating pattern. The objective of this pilot study was to adapt the BRIAN scale to a sample of children and adolescents (BRIAN-K) and to evaluate if the new instrument is capable of detecting differences among patients and healthy controls. Methods: Twenty patients with BD, aged between 8 and 16 years, and 32 controls matched for gender and age were included. Participants were assessed using the clinical interview Schedule for Affective Disorders and Schizophrenia for School Aged Children (K-SADS-PL) and cognitive testing. The BRIAN-K was administered to both groups. Results: The group of patients with BD had higher scores of alterations in the circadian rhythms according to the BRIAN-K total score when compared to the control group (p=0.022). Particularly, more irregularity was found in the “activities”domain in the group of patients (p=0.001). Our results have also showed a positive correlation between the age at diagnosis and the “sleep” domain of the BRIAN-K(r=0.485; p=0.03). Conclusions: These preliminary data suggest that the BRIAN-K version, recently adapted for children and adolescents, can differentiate patients and controls. Future studies with a larger sample size are necessary to determine the reliability, as well as the internal and external validity of the present instrument.