Developmental disruptions in neural connectivity in the pathophysiology of schizophrenia.
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.
Department of Psychology, 1285 Franz Hall Box 951563, University of California, Los Angeles, Los Angeles, CA 90095-1563, USA. karlsgodt@psych.ucla.edu
Katherine H
KH
Karlsgodt
Daqiang
D
Sun
Amy M
AM
Jimenez
Evan S
ES
Lutkenhoff
Rachael
R
Willhite
Theo G M
TG
van Erp
Tyrone D
TD
Cannon
D000293:Adolescent; D000328:Adult; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000502:physiology / Q000503:physiopathology*; D001931:Brain Mapping; D002648:Child; D002657:Child Development; D003072:Cognition Disorders / Q000503:physiopathology; D004195:Disease Models, Animal; D004777:Environment; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008959:Models, Neurological; D009431:Neural Conduction / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics / Q000503:physiopathology*; D013569:Synapses / Q000502:physiology; D055815:Young Adult