CORRELAÇÃO DE DADOS NEUROIMAGIOLÓGICOS E LABORATORIAIS NA DOENÇA BIPOLAR

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Debate: Looking forward: choose data ove opinions to best serve youth with bipolar spectrum disorders : commentary on Parry et al. (2018)

Publication . Van Meter, Anna R.; R. Moreira, Ana Lúcia; Youngstrom, Eric A.

Over the past two decades, research on pediatric bipolar disorder has grown geometrically. The diagnosis of pediatric bipolar disorder was met with enthusiasm, which in healthy doses catalyzed change, and skepticism, which in good measure pushes for rigor. Skepticism led to productive questions about the phenomenology of pediatric bipolar disorder and how best to diagnose and treat it. With regard to prevalence, key questions included whether it was increasing over time, and whether it was limited to the United States. In 2011, we published a meta-analysis addressing the prevalence questions; results indicated that bipolar disorder manifested at statistically indistinguishable rates in youth community samples across the world. In their recent paper, Parry et al. examine the studies included in the 2011 meta-analysis using a qualitative approach. Their opinion piece represents a step backwards; every study has shortcomings, but in focusing on a dozen individual studies, Parry et al. fail to take into account the preponderance of evidence - literally thousands of articles across countries, cohorts and methodologies - that support the existence of bipolar disorder in both prepubescent youth and adolescents. This commentary addresses misperceptions regarding the diagnosis of bipolar disorder in youth, particularly with regard to cross-informant agreement, to present converging data from international sources regarding the onset of bipolar disorder in childhood, and to correct the false claim that pediatric bipolar disorder is controversial. As clinicians and researchers, we have an obligation to do what we can to improve the lives of youth affected by mental illness. Denying the existence of a serious mood disorder will not serve the best interests of young people and will perpetuate the long delays many experience before getting an accurate diagnosis, appropriate treatment, and a fair chance at a good quality of life.

2019Artigo científico

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Bipolar disorder : epidemiological studies and associated factors

Publication . R. Moreira, Ana Lúcia; Filipe, Maria Luísa Caruana Canessa Figueira da Cruz

Introduction Bipolar Disorder is a severe and impairing mental illness. It is also an important cause of burden worldwide and its manifestations are widely recognized by families, health care services, and educational and work environments. The burden of mental illnesses in general and bipolar disorder in particular has propelled an increasing number of epidemiological studies both in pediatric and adult populations. Epidemiological studies may not only reveal prevalence rates, but also factors associated with bipolar disorder. Several features may affect the prevalence rates reported in epidemiological studies, such as the variable course of the illness, the evolving disease classification over the years that included multiple changes in the criteria to meet disease definition, and variability in types of assessments and raters. If epidemiological studies are an important source of data from community settings, it is the data obtained in clinical grounds that give us a better understanding of the evolution of bipolar disorder. Many studies using scales, laboratorial data, and neuroimaging tools have been associated to cognitive dysfunction in Bipolar Disorder. Cognitive impairments are considered in the staging of Bipolar Disorder. Previous studies have even proposed an association between the bipolar disorder spectrum and dementia. There are two main aims in this Thesis. The first aim was to meta-analyze epidemiological studies of bipolar disorder. A secondary aim was to examine associated factors related to the illness. Particularly, our first aim was to meta-analyze all published epidemiologic studies reporting pediatric or adult mania or bipolar disorder and to calculate whether rates of bipolar disorder have changed over time or vary across geographic regions after adjusting for design features. Furthermore, we propose to present preliminary data on the Bipolar Protocol at Centro Hospitalar de Lisboa Norte in which we aimed to characterize specificities of Bipolar Disorder type VI using neurocognitive tools and evaluate correlations between MoCA and demographic, symptomatic, diagnostic, and laboratorial variables. Methods In both meta-analyses of pediatric and adult studies of bipolar disorders we searched the literature (PubMed and PsycInfo) using specific search terms. We also manually reviewed references from epidemiological reviews of bipolar disorder to search for further references. We included articles published in English reporting rates for mania/hypomania/bipolar disoder in community epidemiologic samples for up to 21 years of age in the metaanalysis of pediatric bipolar disorder and 18 years or older in the metaanalysis of adult bipolar disorder. We coded for a different number of variables including: prevalence, method of data collection, diagnostic criteria, year of study, country, quality of study design and data reporting. Twelve studies were included in the meta-analysis of pediatric bipolar disorder studies and eighty five for the adult studies. The Bipolar Protocol at the Centro Hospitalar de Lisboa Norte included patients 18 years or older observed at the Outpatient Clinic for Bipolar Disorders without previous CNS infection, space-occupying Lesions of the Brain, coma, epilepsy/seizures, present or recent head trauma (with loss of consciousness), pregnancy at the moment of evaluation; current substance use. These patients were tested through the protocol created by the team and blood samples were collected from them to measure specific parameters. We first used a table of frequencies to analyze demographic data. Then, we tested whether patient or illness characteristics could be influencing factors on the MoCA total score, namely YMRS, HAMD, number of episodes, duration of illness, age, sex, and bipolar spectrum (MINI diagnose). Then, we tested if Vitamin B12 or folates could be influencing the MoCA total score Results In the meta-analysis of pediatric studies, including 12 effect-sizes, we found a global prevalence rate of 1.8% (95% CI, 1.1%–3.0%). While the US studies had a wider range of rates the mean rates were similar worldwide. Highest estimates were found for studies including broader definitions of bipolar disorder and bipolar disorder not otherwise specified. In the meta-analysis of adult studies, including 85 effect-sizes and 44 different countries, we found a global lifetime prevalence of 1.02% (95% CI 0.81-1.29%) for bipolar disorder type I. The inclusion of bipolar disorder not otherwise specified almost doubled this prevalence (p = .002). Rates from North or South America also almost doubled those from Africa and Asia. There were no significant changes over the years when controlling for design features. The Bipolar Protocol at the Centro Hospitalar de Lisboa Norte included mostly females (F=16; M=6) with an age range between 22 and 70 years old. When MoCA was categorized into two categories a significant negative correlation was found with YMRS (p=0.026). Higher values of MoCA do have a tendency to present with lower values of both Vitamin B12 or Folates. Discussion Bipolar disorder prevalence rates in the pediatric range are higher than those generally acknowledged, similar between US and non-US studies, and not increasing over time according to the data given. Diagnostic criteria differences are the main driver of differences of rates across studies. Bipolar disorder prevalence rates in the adult range are consistent with historical estimates and vary significantly by geopgraphic region. Methodological differences may have biased the notion that bipolar disorder rates are increasing over time. Consistent methods and definitions of bipolar disorder may shed light into the risk factors for bipolar disorder. The results of the data collected so far on the Bipolar Protocol pertain our sample only and cannot be generalized to our patients’ population and not certainly to the bipolar patients’ population in general. The mean age of 46 years old falls below the age in which cognitive deficits usually appear and the number of women enrolled, albeit refleting the higher number of women with mood disorders, does not mirror that bipolar disorder, namely bipolar type I, affects both genders equally. Findings that a lower MoCA was correlated with higher values in YMRS and there was a tendency to lower medians of both Vitamin 12 and Folates are worth pursuing. Also, as has been done in several previous studies the use of neuroimagiological data may deepen our knowledge of the illness. Conclusions Bipolar disorder affects us, whether directly or indirectly. We found that the prevalence of bipolar disorder has remained constant over time, despite the inclusion of broader criteria may have given contrary notion, and we also found that rates vary among geographical locations. The estimated prevalence in the meta-analytic studies conducted deserves a deeper look into the driving factors and contritbutors. The finding that rates vary across regions is contrary to the traditional view that the rates are similar globally. However, this finding is more in line with the variation of rates of comorbidities – either psychiatric or other medical – as well as genetic and environmental risk factors. At the Centro Hospitalar de Lisboa Norte we found a tendency of correlation between neurocognitive and laboratorial measures, but the sample was small. Larger-scale studies with well-defined clinical characteristics, and that include genetic and environmental factors, are required for a more comprehensive understanding of the illness.

2019Tese de doutoramento

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Fundação para a Ciência e a Tecnologia

Número da atribuição

SFRH/BD/38246/2007