Prodrome or risk syndrome: what's in a name?

In the last decade, an increasing number of publications have examined the precursors of bipolar disorders (BD) and attempted to clarify the early origins and illness trajectory. This is a complex task as the evolution of BD often shows greater heterogeneity than psychosis, and the first onset episode of BD may be dominated by depressive or manic features or both. To date, most of the published reviews have not clarified whether they are focused on prodromes, risk syndromes or addressing both phenomena. To assist in the interpretation of the findings from previous reviews and independent studies, this paper examines two concepts deemed critical to understanding the pre-onset phase of any mental disorder: prodromes and risk syndromes. The utility of these concepts to studies of the evolution of bipolar disorder (BD) is explored.

The term "prodrome" is commonly used to describe the symptoms and signs that precede episode onset. If strictly defined, the term should only be applied retrospectively as it refers to cohorts of cases that all progress to meet diagnostic criteria for a specific disorder and gives insights into equifinality. Whilst prodromes may reliably predict individual relapses, the findings cannot necessarily be extrapolated to identify prospectively who will develop a first episode of a specific disorder from within a given population. In contrast, 'risk syndrome' is a term that encompasses sub-threshold symptom clusters, but has often been extended to include other putative risk factors such as family history, or other variables expressed continuously in the population, such as personality traits. Only a minority of individuals 'at risk' make the transition to a specific mental disorder. By prospectively observing those cases where the risk syndrome does not progress to severe disorder or progress to a non-BD condition, we gain insights into the discriminant validity of different pre-BD characteristics, pluripotentiality of outcomes, and protective factors and resilience.

We emphasize the clinical and research utility of prodromes and risk syndromes, examine examples of the conflation of the concepts, and highlight the rationale for regarding them as discrete entities.