We aimed to review clinical features and biological underpinnings related to neuroprogression in bipolar disorder (
BD). Also, we discussed areas of controversy and future research in the field. Method
We systematically reviewed the extant literature pertaining to neuroprogression and
BDby searching PubMed and EMBASEfor articles published up to March 2016. Results
A total of 114 studies were included. Neuroimaging and clinical evidence from cross‐sectional and longitudinal studies show that a subset of patients with
BDpresents a neuroprogressive course with brain changes and unfavorable outcomes. Risk factors associated with these unfavorable outcomes are number of mood episodes, early trauma, and psychiatric and clinical comorbidity. Conclusion
Illness trajectories are largely variable, and illness progression is not a general rule in
BD. The number of manic episodes seems to be the clinical marker more robustly associated with neuroprogression in BD. However, the majority of the evidence came from cross‐sectional studies that are prone to bias. Longitudinal studies may help to identify signatures of neuroprogression and integrate findings from the field of neuroimaging, neurocognition, and biomarkers.