Neuroprogression: pathways to progressive brain changes in bipolar disorder

The progressive nature of bipolar disorder Many psychiatric disorders, including bipolar dis-order follow a progressive path, and manifest a vari-able but observable trajectory. While Kraepelin (1921) described a progressive dementing process in schizo-phrenia, and conceptualized the illness as a stepwise, progressive disorder, he saw bipolar disorder as having a more episodic pattern. Nevertheless, it has become clear that bipolar disorder too shares a temporal progression in phenomenology, treatment response, neurobiology and functional impairment. The notion of clinical staging, long used in oncology and medicine and more recently in psychiatry, postu-lates that there is a stepwise progression through a series of identifiable steps, which have characteristic