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Neuroprogression in children and adolescents with bipolar disorder

The concept of neuroprogression in children and adolescents with bipolar disorder is still under construction and remains controversial. It encompasses the notion of a temporal progression of illness with regard to its neurobiology, phenomenology, treatment response, and associated functional impairment. In this chapter, we review current evidence surrounding this concept. There is a definite clinical progression from an asymptomatic risk status, the appearance of the prodromal affective symptoms, and, finally, to the onset of illness. Some, but not all, neuroimaging, neuropsychological, and pharmacological studies support the notion of functional and structural brain differences between high-risk individuals and control subjects. Furthermore, current evidence of neuroprogression after illness onset is frail. Most relevant studies are cross-sectional, with few longitudinal exceptions. We will discuss neuroprogression, its use in the context of clinical staging, and other controversial areas regarding this concept in youth with bipolar disorder.