Diffusion-weighted imaging uncovers likely sources of processing-speed deficits in schizophrenia.
Schizophrenia, a devastating psychiatric illness with onset in the late teens to early 20s, is thought to involve disrupted brain connectivity. Functional and structural disconnections of cortical networks may underlie various cognitive deficits, including a substantial reduction in the speed of information processing in schizophrenia patients compared with controls. Myelinated white matter supports the speed of electrical signal transmission in the brain. To examine possible neuroanatomical sources of cognitive deficits, we used a comprehensive diffusion-weighted imaging (DWI) protocol and characterized the white matter diffusion signals using diffusion kurtosis imaging (DKI) and permeability-diffusivity imaging (PDI) in patients (n = 74), their nonill siblings (n = 41), and healthy controls (n = 113). Diffusion parameters that showed significant patient-control differences also explained the patient-control differences in processing speed. This association was also found for the nonill siblings of the patients. The association was specific to processing-speed abnormality but not specific to working memory abnormality or psychiatric symptoms. Our findings show that advanced diffusion MRI in white matter may capture microstructural connectivity patterns and mechanisms that govern the association between a core neurocognitive measure-processing speed-and neurobiological deficits in schizophrenia that are detectable with in vivo brain scans. These non-Gaussian diffusion white matter metrics are promising surrogate imaging markers for modeling cognitive deficits and perhaps, guiding treatment development in schizophrenia.
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228; pkochunov@mprc.umaryland.edu.
Peter
P
Kochunov
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228.
Laura M
LM
Rowland
Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY 10016.
Els
E
Fieremans
Center for Biomedical Imaging, Department of Radiology, New York University School of Medicine, New York, NY 10016.
Jelle
J
Veraart
Imaging Genetics Center, Mark and Mary Neuroimaging and Informatics Institute, Keck School of Medicine of University of Southern California, Marina del Rey, CA 90292.
Neda
N
Jahanshad
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228.
George
G
Eskandar
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228.
Xiaoming
X
Du
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228.
Florian
F
Muellerklein
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228.
Anya
A
Savransky
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228.
Dinesh
D
Shukla
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228.
Hemalatha
H
Sampath
Imaging Genetics Center, Mark and Mary Neuroimaging and Informatics Institute, Keck School of Medicine of University of Southern California, Marina del Rey, CA 90292.
Paul M
PM
Thompson
Maryland Psychiatric Research Center, Department of Psychiatry, University of Maryland School of Medicine, Baltimore, MD 21228.
L Elliot
LE
Hong
D000293:Adolescent; D000328:Adult; D016880:Anisotropy; D056324:Diffusion Tensor Imaging; D005260:Female; D006801:Humans; D008297:Male; D008606:Mental Processes / Q000502:physiology*; D008875:Middle Aged; D012044:Regression Analysis; D012559:Schizophrenia / Q000503:physiopathology*; D066127:White Matter / Q000503:physiopathology; D055815:Young Adult
cognitive deficits; diffusion-weighted imaging; endophenotypes; processing speed; schizophrenia