White matter abnormalities and cognitive impairment in early-onset schizophrenia-spectrum disorders

Katherine A. Epstein, Kathryn R. Cullen, Bryon A. Mueller, Paul Robinson, Susanne Lee, Sanjiv Kumra

Research output: Contribution to journalArticlepeer-review

78 Scopus citations


Objective To characterize white matter abnormalities in adolescents with early-onset schizophrenia (EOS) relative to 3 comparison groups (adolescents at clinical high risk for developing schizophrenia [CHR], adolescents with cannabis use disorder [CUD], and healthy controls [HC]), and to identify neurocognitive correlates of white matter abnormalities in EOS. Method We used diffusion tensor imaging and tractography methods to examine fractional anisotropy (FA) of the cingulum bundle, superior longitudinal fasciculus, corticospinal tract (CST), inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), and uncinate fasciculus in adolescents with EOS (n = 55), CHR (n = 21), CUD (n = 31), and HC (n = 55). FA in tracts that were significantly altered in EOS was correlated with neurocognitive performance. Results EOS and CHR groups had significantly lower FA than HC in 4 tracts, namely, bilateral CST, left ILF, and left IFOF. CUD had lower FA than HC in left IFOF. Lower FA in left IFOF and left ILF predicted worse neurocognitive performance in EOS. Conclusions This study identified white matter abnormalities of the left ILF and left IFOF as possible biomarkers of vulnerability for developing schizophrenia. Lower FA in these tracts may disrupt functioning of ventral visual and language streams, producing domain-specific neurocognitive deficits that interfere with higher-order cognitive abilities.

Original languageEnglish (US)
Pages (from-to)362-372.e2
JournalJournal of the American Academy of Child and Adolescent Psychiatry
Issue number3
StatePublished - Mar 2014

Bibliographical note

Funding Information:
This research was funded by National Institute of Mental Health grant MH073150-05 (cannabis and schizophrenia; to S.K.).


  • diffusion tensor imaging (DTI)
  • inferior fronto-occipital fasciculus (IFOF)
  • inferior longitudinal fasciculus (ILF)
  • schizophrenia


Dive into the research topics of 'White matter abnormalities and cognitive impairment in early-onset schizophrenia-spectrum disorders'. Together they form a unique fingerprint.

Cite this