Staging bipolar disorder: clinical, biochemical, and functional correlates

Abstract

Objective: There are several models of staging in bipolar disorder (BD), but none has been validated. The aims of this study were to empirically investigate clinical variables that may be useful to classify patients in clusters according to stage and study the association with biomarkers as biological validators. Method: This was a historical cohort study. Patients (n = 115) diagnosed with BD and not in an acute episode and first-degree relatives of patients diagnosed with BD (n = 25) were recruited. Sociodemographic, clinical, and functional data were collected. Serum cytokines, brain-derived neurotrophic factor, and biomarkers of lipid and protein oxidation were assessed. Cluster analysis was carried out to build a model of staging, and logistic regression was conducted to study associations between the model and biomarkers. Results: Cluster analysis divided the sample into two equitable groups, denominated early and late stage, with empirical cutoffs for the Functioning Assessment Short Test score, number of episodes, age at onset of the disorder, and time elapsed since first episode. In the logistic regression, IL-6 was associated with late stage (P = 0.029). Conclusion: This study supports that clinical, functional, and biochemical variables may help to define a classification of staging in BD. Significant outcomes• A model of staging based on early and late stages according to functioning, number of episodes, age at onset of the disorder, and time elapsed since the first episode can be feasible and useful in bipolar disorder.• IL-6 is a valid biological biomarker for this proposal of staging in bipolar disorder. Limitations• Patients with subsyndromal symptoms were not excluded from the sample. • Biomarker assessment was carried out peripherally. • Lack of a prospective assessment hampers to test the validity of a model of staging.

Neuroprogression and Cognitive Functioning in Bipolar Disorder: A Systematic Review

“…However, to date, this hypothesis has not been empirically investigated in BD. Notably, these theories are based on the hypothesis that increasing inflammation as measured by higher levels of pro-inflammatory cytokines plays a role in the progressive cognitive and neuroanatomical changes observed during the course of BD [67,68]. Therefore, one could argue that a limitation of the studies reviewed here is the absence of physiological measures of inflammation or stress that could confirm the role of neuroprogression in cognitive impairment.…”

Toward a Comprehensive Clinical Staging Model for Bipolar Disorder: Integrating the Evidence

“…54 Other proponents of clinical staging for BD have focused on differentiating earlier-from later-stage illness in adult patients meeting full diagnostic criteria for BD. [55][56][57] However, these studies consider neither the evidence of early antecedent risk syndromes nor the developmental illness trajectory leading up to the full-blown diagnosis of BD, as reported in several large prospective studies of the offspring of parents with BD.…”

“…Recently, they proposed to stage patients with BD using quantitative cut-off scores of important clinical variables (global functioning, number of episodes [≤7], age of onset [≤62 years], and time elapsed since first episode [≤128 months]), and associated biochemical markers. 55 The problem with this proposal is that it focuses solely on progression of end-stage established BD, rather than developing a staging model based on the full natural history of illness development. It equates to studying fullblown illness, compared with full-blown illness for a longer period, and neglects early risk syndromes.…”

Staging of Bipolar Disorder

“…Even subsyndromal depressive symptoms cause signifi cant disability and they put the patient at a three-time higher risk to relapse (Judd et al 2008 ). Therefore, it seems it is depression that is mainly responsible for the burden of the disease (Judd et al 2002Goodwin and Jamison 2007 ).…”