Development and Psychopathology

Research Article

Developmental disruptions in neural connectivity in the pathophysiology of schizophrenia

Katherine H. Karlsgodta1 c1, Daqiang Suna1, Amy M. Jimeneza1, Evan S. Lutkenhoffa1, Rachael Willhitea1, Theo G. M. van Erpa1 and Tyrone D. Cannona1

a1 University of Southern California, Los Angeles


Schizophrenia has been thought of as a disorder of reduced functional and structural connectivity. Recent advances in neuroimaging techniques such as functional magnetic resonance imaging, structural magnetic resonance imaging, diffusion tensor imaging, and small animal imaging have advanced our ability to investigate this hypothesis. Moreover, the power of longitudinal designs possible with these noninvasive techniques enable the study of not just how connectivity is disrupted in schizophrenia, but when this disruption emerges during development. This article reviews genetic and neurodevelopmental influences on structural and functional connectivity in human populations with or at risk for schizophrenia and in animal models of the disorder. We conclude that the weight of evidence across these diverse lines of inquiry points to a developmental disruption of neural connectivity in schizophrenia and that this disrupted connectivity likely involves susceptibility genes that affect processes involved in establishing intra- and interregional connectivity.


c1 Address correspondence and reprint requests to: Katherine Karlsgodt, Department of Psychology, 1285 Franz Hall Box 951563, University of California, Los Angeles, Los Angeles, CA 90095-1563; E-mail: