Inflammatory Markers in the Staging of Bipolar Disorder: A Systematic Review of the Literature / Marcadores inflamatorios en la estadificación del trastorno bipolar: una revisión sistemática de la literatura

ABSTRACT Background: Previous studies suggest that inflammatory molecules play an important role in the pathophysiology of Bipolar Disorder (BD). The evidence suggests that BD may present a progressive course. Therefore there are theories that postulate the relationship between progression and stages of the disease with distinct peripheral biomarkers. Objective: The aim of this study was to carry out a systematic review of the literature of studies about the association between peripheral inflammatory markers and clinical variables related with staging in BD patients. Methods: We conducted a systematic review using electronic databases: PubMed, SciELO, LiLACS and PsycINFO. Keywords were divided into inflammatory markers and, BD and staging. Studies involving euthymic BD patients, studies evaluating peripheral biomarkers and studies correlating these with clinical variables related to neuroprogression or stage of BD were included. Results: We present and discuss the methods and findings of ten articles. The inflammatory markers were measured with different techniques and show some contradictories results. The TNF superfamily and inflammatory cytokines may have a relationship with the neuroprogression of the disease. Conclusions: This study suggests that TNF and ILs could play a role in neuroprogression. However, longitudinal studies are needed to clarify the relationship between factors associated with neuroprogression.

RESUMEN Introducción: Estudios previos indican que las moléculas inflamatorias tienen un papel importante en la fisiopatología del trastorno bipolar (TB). La evidencia apunta a que el TB puede presentar un curso progresivo. Por lo tanto, existen teorías que han postulado una relación entre la progresión y los estadios de la enfermedad con diferentes biomarcadores Revisión sistemática periféricos. Objetivo: El objetivo de este estudio es realizar una revisión sistemática de la literatura de los estudios sobre la asociación entre los marcadores inflamatorios periféricos y las variables clínicas relacionadas con la estadificación en los pacientes con TB. Métodos: Se llevó a cabo una revisión sistemática usando las bases de datos electrónicas PubMed, SciELO, LiLACS y PsycINFO. Las palabras clave se dividieron en marcadores inflamatorios y TB y estadificación. Se incluyeron estudios que evaluaron a pacientes con TB en fase de eutimia, estudios que evaluaron biomarcadores periféricos y estudios que correlacionaron dichos marcadores con las variables clínicas relacionadas con la neuroprogresión o estadificación del TB. Resultados: Se presentan y se discuten los métodos y los hallazgos de 10 artículos. Los marcadores inflamatorios se determinaron con diferentes técnicas y mostraron resultados contradictorios. La super familia del factor de necrosis tumoral y las citocinas inflamatorias podrían tener una relación con la neuroprogresión de la enfermedad. Conclusiones: El presente estudio indica que el factor de necrosis tumoral y las intereucinas pueden tener un papel en la neuroprogresión del TB. Sin embargo, se requieren estudios longitudinales con el fin de clarificar la relación entre los factores asociados con la neuro-progresión.

Inflammatory Markers in the Staging of Bipolar Disorder: A Systematic Review of the Literature.

BACKGROUND: Previous studies suggest that inflammatory molecules play an important role in the pathophysiology of Bipolar Disorder (BD). The evidence suggests that BD may present a progressive course. Therefore there are theories that postulate the relationship between progression and stages of the disease with distinct peripheral biomarkers. OBJECTIVE: The aim of this study was to carry out a systematic review of the literature of studies about the association between peripheral inflammatory markers and clinical variables related with staging in BD patients. METHODS: We conducted a systematic review using electronic databases: PubMed, SciELO, LiLACS and PsycINFO. Keywords were divided into inflammatory markers and, BD and staging. Studies involving euthymic BD patients, studies evaluating peripheral biomarkers and studies correlating these with clinical variables related to neuroprogression or stage of BD were included. RESULTS: We present and discuss the methods and findings of ten articles. The inflammatory markers were measured with different techniques and show some contradictories results. The TNF superfamily and inflammatory cytokines may have a relationship with the neuroprogression of the disease. CONCLUSIONS: This study suggests that TNF and ILs could play a role in neuroprogression. However, longitudinal studies are needed to clarify the relationship between factors associated with neuroprogression.