Time-lapse mapping of cortical changes in schizophrenia with different treatments

Paul M. Thompson, George Bartzokis, Kiralee M. Hayashi, Andrea D. Klunder, Po H. Lu, Nancy Edwards, Michael S. Hong, Michael Yu, Jennifer A. Geaga, Arthur W. Toga, Cecil Charles, Diana O. Perkins, Joseph McEvoy, Robert M. Hamer, Mauricio Tohen, Gary D. Tollefson, Jeffrey A. Lieberman

Research output: Contribution to journalArticlepeer-review

93 Scopus citations


Using time-lapse maps, we visualized the dynamics of schizophrenia progression, revealing spreading cortical changes that depend on the type of antipsychotic treatment. Dynamic, 4-dimensional models of disease progression were created from 4 repeated high-resolution brain magnetic resonance imaging scans of 36 first-episode schizophrenia patients (30 men/6 women; mean age: 24.2 ± 5.1 SD years) randomized to haloperidol (HAL) (n = 15) or olanzapine (OLZ) treatment (n = 21), imaged at baseline, 3, 6, and 12 months (144 scans). Based on surface-based cortical models and point-by-point measures of gray matter volume, we generated time-lapse maps for each treatment. Disease trajectories differed for atypical versus typical neuroleptic drugs. A rapidly advancing parietal-to-frontal deficit trajectory, in HAL-treated patients, mirrored normal cortical maturation but greatly intensified. The disease trajectory advanced even after symptom normalization, involving the frontal cortex within 12 months with typical drug treatment. Areas with fastest tissue loss shifted anteriorly in the first year of psychosis. This trajectory was not seen with OLZ. Whether this association reflects either reduced neurotoxicity or neuroprotection cannot be addressed with neuroimaging; changes may relate to glial rather than neural components. These maps revise current models of schizophrenia progression; due to power limitations, the findings require confirmation in a sample large enough to model group × time interactions.

Original languageEnglish
Pages (from-to)1107-1123
Number of pages17
JournalCerebral Cortex
Issue number5
StatePublished - May 2009
Externally publishedYes


  • Cortex
  • Development
  • Imaging
  • Neurotoxicity
  • Schizophrenia


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