Despite therapeutic advances, unipolar depression and bipolar disorder are among the most debilitating psychiatric disorders. Unfortunately, lacking knowledge about the underlying pathophysiology limit early identification and indicated prevention efforts. Therefore, early characterization of the ‘prodromal” (subsyndromal) stages of depression and, especially, bipolar mania have attracted increasing attention, especially in youth, given the early age of first depression and bipolar disorder symptom onset.

Review of phenomenological manifestations of the prodromal stages preceding syndromal unipolar depression and bipolar disorder, including antecedent and comorbid conditions.

While offspring mood disorder studies are ongoing, clinical ‘high-risk” mood disorder research is relatively new. So far, retrospective and early prospective data suggest that a clinical prodrome exits in a sizeable patient group of patients subsequently developing unipolar depression and bipolar disorder. Moreover, phenomenologically, the early clinical depression or mania prodrome includes character traits that may become more pronounced, non-specific symptoms of decreasing role and social functioning, as well as subthreshold depressive and/or attenuated (hypo)mania-like symptoms (especially mood swings/lability, racing thoughts and sleep abnormalities). Frequent comorbidities that overlap with mood disorder criteria, the fact that several concurrent supratheshold symptoms can coexist that are still subthreshold for the full mood disorder and the episodicity of emerging as well as full mood symptoms are complicate the identification of the mood disorder prodrome.

Data suggest that a relevant proportion of patients ultimately developing unipolar depression or bipolar disorder presents with a clinically identifiable depressive or (hypo)mania ‘prodromal” symptom stage that may enable indicated prevention. Prospective clinical and biological risk marker studies, utilizing specific instruments that target at-risk phenomenology are needed to advance the clinical high-risk and prevention approach for mood disorders.