Staging in bipolar disorder: one step closer to precision psychiatry

Abstract

The need to bring the new paradigm of precision medicine to psychiatry -precision psychiatry -has been acknowledged. 1 In this sense, the article by Brietzke et al. 2 covers one of the most important contemporary topics in bipolar disorder, which is the recognition of the specificity of its early stages. As is highlighted by the authors, proper recognition of the early stages of the disease is indispensable in order to implement strategies capable of avoiding, or at least delaying, the progression to later stages related to neuroprogression, which are associated with marked disability, as well as for development of preventive initiatives.At the core of the identification of an early stage of disease is the concept of staging, which implies that bipolar disorder has a progressive course, at least in a subgroup of persons. This has led to an increased interest in research considering stage models in the last few years. The concept itself is not new: Kraepelin, despite not using the term, recognized the occurrence of disease stages, as can be inferred by his observation that psychiatric disorders in general could progress over time and episodes in bipolar disorder in particular would recur more rapidly.The proposed staging model is adapted from the fourstage model used in general medicine. When applied to bipolar disorder, as pointed out by the authors, the disorder starts during an ''at-risk period'' and progresses to the first mood episode and follows to a ''late stage.'' This would be a consequence of the phenomenon of neuroprogression, which is considered to be caused, at least in part, by an increase in inflammation and immune mediated stress, leading to a decrease in neurotrophic factors and consequent brain rewiring. 3,4 It is thought that bipolar disorder indeed progresses, but one point that needs further clarifying is whether this is a universal phenomenon. The majority of research until now was conducted in specialized centers, where the sample studied is usually biased towards including persons with a more severe and chronic form of the disease. Another limitation is that, in virtually all studies that assessed cognition, neuroimaging, and biomarkers -all domains that are considered in the core of the staging model -the assessment of these markers was not done in participants categorized using the stages considered to compose the model, but instead often used length of illness or functioning as proxies for staging. This has two major consequences: first, these studies cannot properly assess and therefore validate the proposed stages that compose the model; second, it assumes not only that neuroprogression occurs at least in the great majority of persons with the disease, but also that the course of neuroprogression follows a relatively linear pattern. However, further studies are needed before the veracity of either of these assumptions is proved.It is plausible that the natural course of bipolar disorder is not linear, and this is actually acknowledged in the staging model itself when it proposes that ...

Systemic challenges in bipolar disorder management: A patient‐centered approach

“…The current literature reports advances in development of BD biomarkers and evidence on alternative treatments such as circadian‐based therapies, vagus nerve stimulation, and omega‐3 fatty acid supplementation . New evidence is available on BD‐specific psychological interventions, psychoeducation and individualized treatmentoptimized by E‐health applications and stage‐appropriate interventions . A range of guidelines and practical algorithms have been produced for pharmacological treatment of BD, although none have been broadly adopted in the USA.…”

The Staging of Major Mood Disorders: Clinical and Neurobiological Correlates

“…It must be emphasized that the staging approach has been very beneficial in the overall management of other complex (gene×environment) disorders including diabetes, cardiovascular diseases and various forms of cancer. Staging assumes that illness advances in a certain sequential progression of phases from an at-risk, prodromal period to the first clinical manifestations, and further developing into more severe, intractable forms with evolution and chronicity [ 6 ]. Figure 1 depicts the basic notions underlying the staging paradigm and shows that mood disorders have a phased evolution, ultimately leading to irreversible alterations in the brain and periphery with resulting deficits in the biopsychosocial spheres of functioning ( Figure 1 ).…”

How to treat mania

“…• Refractory illness: 'palliative' approaches (reduction of side-effects and unnecessary polypharmacy, limited symptom control, targeting psychological and social problems, and setting realistic goals to aim for the best quality of life for people and their families within the envelope of their disability (182).However, even if the staging model proposes stage-targeted treatments that might provide a better clinical outcome with fewer side-effects, there are still differences among the patients of a particular stage. Therefore, the 'treatment based on stages' may not be useful for every patient at a particular stage, and should be combined with 'treatment based on patients' characteristics' to increase the level of precision and achieve an even more personalized approach (183).…”