ABSTRACT
Neuroprogression is associated with structural and functional brain changes that occur in parallel with cognitive and functioning impairments. There is substantial evidence showing early white matter changes, as well as trajectory-related gray matter alterations. Several structures, including prefrontal, parietal, temporal cortex, and limbic structures, seem to be altered over the course of bipolar disorder, especially associated with the number of episodes and length of the disease. An important limitation is that most of the studies used either a cross-sectional design or a short follow-up period, which may be insufficient to identify all neuroprogressive changes over time. In addition, the heterogeneity of patients with bipolar disorder is another challenge to determine which subjects will have a more pernicious trajectory. Larger studies and the use of new techniques, such as machine learning, may help to enable more discoveries and evidence on the role of neuroprogression in BD.