Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 113, Issue 47, Pages 13504-13509Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1608246113
Keywords
diffusion-weighted imaging; schizophrenia; processing speed; cognitive deficits; endophenotypes
Categories
Funding
- NIH [U01MH108148, R01EB015611, P50MH103222, R01DA027680, R01MH085646, T32MH067533, U54 EB020403]
- National Science Foundation [IIS-1302755, MRI-1531491]
- Belgian National Fund for Scientific Research Grant [12S1615N]
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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.
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