Connectomics in Schizophrenia: From Early Pioneers to Recent Brain Network Findings

Schizophrenia has been conceptualized as a brain network disorder. The historical roots of connectomics in schizophrenia go back to the late 19th century, when influential scholars such as Theodor Meynert, Carl Wernicke, Emil Kraepelin, and Eugen Bleuler worked on a theoretical understanding of the multifaceted syndrome that is currently referred to as schizophrenia. Their work contributed to the understanding that symptoms such as psychosis and cognitive disorganization might stem from abnormal integration or dissociation due to disruptions in the brain’s association fibers. As methods to test this hypothesis were long lacking, the claims of these early pioneers remained unsupported by empirical evidence for almost a century. In this review, we revisit and pay tribute to the old masters and, discussing recent findings from the developing field of disease connectomics, we examine how their pioneering hypotheses hold up in light of current evidence.