Exploración de un modelo de estadiaje clínico aplicado al trastorno bipolar

El trastorno bipolar (TB) es una enfermedad mental crónica con una prevalencia aproximada del 2,4% en la población general que cursa con episodios recurrentes depresivos, maníacos y periodos de estabilidad clínica o eutimia. Clásicamente se consideraba que el TB tenía una evolución benigna comparada con la esquizofrenia, pero hoy en día los datos clínicos revelan que este trastorno se acompaña de una evolución en muchas ocasiones poco favorable, con una importante discapacidad global, una elevada morbilidad y una mortalidad prematura. Los pacientes que han padecido un mayor número de episodios, ya sean maníacos o depresivos, tienen una mayor dificultad para volver a su estado previo, es decir, para recuperarse. Además, hay pruebas de que, conforme aumentan las recaídas, se produce un mayor deterioro cognitivo, más altas tasas de hospitalización, mayor comorbilidad y peor respuesta a los tratamientos farmacológicos. Por todo ello, se han planteado sistemas de clasificación de estadiaje clínico con el objetivo de individualizar el tratamiento y mejorar el pronóstico a largo plazo. En este estudio se explora el modelo teórico de estadiaje clínico propuesto por Kapczinski y colaboradores en 2009 y revisado en 2014. Para ello se realizó un estudio observacional y transversal en el que se compararon un total de 92 sujetos divididos en cuatro grupos diferentes: 25 pacientes con TB eutímicos y en estadios iniciales de la enfermedad, sin deterioro; 23 pacientes con TB eutímicos pero que se encontraban en estadios avanzados del trastorno, con un deterioro funcional general; 23 sujetos sanos pero con alto riesgo genético para padecer la enfermedad, en este caso, hermanos de los pacientes con TB (estadio 0, latente); y 21 sujetos control sanos. A cada uno de los participantes se les realizó una evaluación clínica exhaustiva en la que se tuvieron en cuenta variables socio-demográficas, antropométricas y clínicas, una evaluación neuropsicológica objetiva (Test de clave de números, Test de COWA-VFT, Test de ordenación de tarjetas de Wisconsin, Trail Making test A y B, test de Stroop, TAVEC, figura de Rey y Finger tapping test) y subjetiva (escala COBRA), una determinación de biomarcadores en sangre periférica (TBARS o peroxidación lipídica, TRAP o capacidad antioxidante total, PCC o peroxidación proteica, TNF-alfa, IL-6, IL-10, BDNF y NT-3) y se les pasaron las escalas FAST y WHO-QoL BREF, que evalúan la funcionalidad global y la calidad de vida respectivamente. Los pacientes con trastorno bipolar en eutimia mostraron una disfunción cognitiva más generalizada que limitada a unos pocos dominios, en concreto en memoria de trabajo, velocidad de procesamiento, función ejecutiva, memoria/aprendizaje verbal y memoria visual. Los pacientes con trastorno bipolar en estadios avanzados mostraron rendimientos cognitivos similares a los de los pacientes en estadios iniciales, pero presentaron mayores quejas cognitivas subjetivas, peor funcionalidad y peor calidad de vida. A nivel de biomarcadores periféricos, los pacientes en estadios iniciales presentaron un aumento de las concentraciones de la citocina anti-inflamatoria IL-10, así como menores niveles de peroxidación de lípidos y de defensas antioxidantes, comparados con el resto de grupos. Los hermanos sanos de los pacientes con trastorno bipolar presentaron déficit neurocognitivos en áreas similares a los pacientes, aunque de menor intensidad. Sin embargo, esto no se tradujo en una peor funcionalidad ni calidad de vida. Así mismo, no presentaron alteraciones significativas en las concentraciones de biomarcadores con respecto a los demás grupos. En conjunto, los resultados de esta investigación sugieren la existencia de diferencias entre los distintos grupos, de forma que los pacientes en estadios avanzados presentan características distintivas de los pacientes en estadios iniciales, al igual que los hermanos sanos presentan cambios con respecto a los controles. Estas diferencias harían pensar en la posible utilidad de un modelo de clasificación del trastorno bipolar basado en el estadiaje clínico.Bipolar disorder (BD) is a chronic mental disease with a prevalence of approximately 2.4% in the general population that causes recurrent episodes of depression, mania and periods of clinical stability or euthymia. Classically it was considered that BD had a benign course compared to schizophrenia, but today the clinical data show that this disorder is accompanied by an unfavorable evolution, with a significant overall impairment, high morbidity and premature mortality. Patients who have had a greater number of episodes, either manic or depressive, have more difficulty returning to its previous state, ie, to recover. In addition, there is evidence that under increase relapse, greater cognitive impairment, higher hospitalization rates, increased morbidity and poor response to drug treatment occurs. Therefore, classification systems for clinical staging have been proposed in order to individualize treatment and improve long-term prognosis. In this study we explore the theoretical model of clinical staging for BD proposed by Kapczinski and collaborators in 2009 and revised in 2014. We did a cross-sectional and observational study that compared a total of 92 patients divided in four different groups: 25 euthymic BD patient in the early stages of the illness, without deterioration; 23 euthymic BD patients in more advanced stages of the illness, with a general functional impairment; 23 healthy subjects but with a high genetic risk for developing the disease, in this case brothers of BD patients (stage 0, latent) subjects; and 21 healthy controls. Each subject underwent a complete clinical evaluation that included socio-deomgraphic, anthropometric and clinical variables, an objective neuropsychological assessment (Digit Symbol test, COWA-VFT, Wisconsin card sorting test, Trail Making test A and B, Stroop test, TAVEC, Rey-Osterrieth complex figure test and Finger tapping test) and subjective (COBRA scale), a determination of biomarkers in peripheral blood (TBARS or lipid peroxidation, TRAP or total reactive antioxidant potential, PCC peroxidation or protein carbonyl content, TNF-alpha, IL-6, IL-10, BDNF and NT-3) and were assessed the FAST and the WHO-QoL BREF scales, evaluating the overall functionality and quality of life respectively. Euthymic BD patients showed a generalized cognitive dysfunction in some domains, specifically in working memory, processing speed, executive function, verbal learning and memory and visual memory. Advanced-stage BD patients showed a similar cognitive performance to early-stage BD patients, but had higher subjective cognitive complaints, worse functionality and worse quality of life. Concerning peripheral biomarkers, early-stage BD patients showed increased concentrations of the anti-inflammatory cytokine IL-10 and lower levels of lipid peroxidation and antioxidant defenses compared to the other groups. Healthy siblings of patients showed neurocognitive deficits in similar areas to BD patients, although less intense. However, this did not translate into a worse functionality or quality of life. They also showed no significant alterations in biomarkers concentrations compared to the other groups. Overall, the results of this research suggest that there are differences between the different groups so that advanced-stage BD patients have distinctive characteristics of early-stages BD patients, as healthy BD siblings have differences from healthy controls. These differences may suggest the potential use of a classification model of bipolar disorder based on clinical staging

Staging, neurocognition and social functioning in bipolar disorder.

Introduction: Bipolar disorder (BD) is associated with significant neurocognitive and functional impairment, which may progress across stages. The 'latent stage' of BD remains understudied. This cross-sectional study assessed staging, neurocognition and social functioning among BD patients and their healthy siblings. Methods: Four groups were included: euthymic type I BD patients in the early (n = 25) and late (n = 23) stages, their healthy siblings (latent stage; n = 23) and healthy controls (n = 21). All 92 subjects underwent a comprehensive neuropsychological battery of processing speed, verbal learning/memory, visual memory, working memory, verbal fluency, executive cognition, and motor speed. Social functioning was assessed using the FAST scale. Results: Siblings' social functioning was identical to that of controls, and significantly better than both early- (p < 0.005) and late- (p < 0.001) stage patients. Although all patients were strictly euthymic, those at late stages had a significantly worse social functioning than early-stage patients (p < 0.001). Compared to controls, increasingly greater neurocognitive dysfunction was observed across stages of BD (F = 1.59; p = 0.005). Healthy siblings' performance lied between those of controls and patients, with deficits in tasks of processing speed, executive attention, verbal memory/learning, and visual memory. Both early- and late-stage patients had a more severe and widespread dysfunction than siblings, with no significant differences between them. Conclusions: Genetic vulnerability to BD-I seems to be associated with neurocognitive impairments, whereas social dysfunction would be the result of the clinical phenotype. Staging models of BD should take into account these divergent findings in the latent stage

Subjective neurocognition and quality of life in patients with bipolar disorder and siblings

Background Bipolar disorder (BD) is associated with significant neurocognitive and functional impairment, which may progress across stages. However, the potential progression of subjective cognitive complaints and quality of life (QoL) has not been addressed. Our main objective was to assess subjective cognitive complaints and QoL on euthymic patients with BD and their healthy siblings. Methods Four groups were compared: euthymic patients with type I BD in the early (n = 25) and late (n = 23) stages, their healthy siblings (latent stage; n = 23) and healthy controls (n = 21). Cognitive complaints and QoL were assessed using the COBRA and WHO-QoLBREF questionnaires, respectively. Results Late-stage patients had greater number of subjective cognitive complaints and reported a worse QoL compared to the other groups. Early-stage patients also had more cognitive complaints than controls and siblings, although differences were not significant. Siblings and controls reported similar QoL. Limitations the most important limitation of this study is the criterion used to define the early and late stages of BD, as currently there is no consensus and previous studies have used different criteria. Conclusions This is the first study to examine subjective cognition and QoL in patients with BD and siblings. Our results raise the possibility that burden of cognitive complaints increase with disorder progression, in tandem with deterioration in subjective QoL. That would support a clinical staging model of BD. This hypothesis remains to be confirmed by a longitudinal analysis