Neuroprogression in bipolar disorder

OBJECTIVE: Recent theories regarding the neuropathology of bipolar disorder suggest that both neurodevelopmental and neurodegenerative processes may play a role. While magnetic resonance imaging has provided significant insight into the structural, functional, and connectivity abnormalities associated with bipolar disorder, research assessing longitudinal changes has been more limited. However, such research is essential to elucidate the pathophysiology of the disorder. The aim of our review is to examine the extant literature for developmental and progressive structural and functional changes in individuals with and at risk for bipolar disorder. METHODS: We conducted a literature review using MEDLINE and the following search terms: bipolar disorder, risk, child, adolescent, bipolar offspring, MRI, fMRI, DTI, PET, SPECT, cross-sectional, longitudinal, progressive, and developmental. Further relevant articles were identified by cross-referencing with identified manuscripts. CONCLUSIONS: There is some evidence for developmental and progressive neurophysiological alterations in bipolar disorder, but the interpretation of correlations between neuroimaging findings and measures of illness exposure or age in cross-sectional studies must be performed with care. Prospective longitudinal studies placed in the context of normative developmental and atrophic changes in neural structures and pathways thought to be involved in bipolar disorder are needed to improve our understanding of the neurodevelopmental underpinnings and progressive changes associated with bipolar disorder.