Abnormal cortical growth in schizophrenia targets normative modules of synchronized development

Aaron F. Alexander-Bloch, Philip T. Reiss, Judith Rapoport, Harry McAdams, Jay N. Giedd, Ed T. Bullmore, Nitin Gogtay

Research output: Contribution to journalArticlepeer-review


Background Schizophrenia is a disorder of brain connectivity and altered neurodevelopmental processes. Cross-sectional case-control studies in different age groups have suggested that deficits in cortical thickness in childhood-onset schizophrenia may normalize over time, suggesting a disorder-related difference in cortical growth trajectories. Methods We acquired magnetic resonance imaging scans repeated over several years for each subject, in a sample of 106 patients with childhood-onset schizophrenia and 102 age-matched healthy volunteers. Using semiparametric regression, we modeled the effect of schizophrenia on the growth curve of cortical thickness in ~80,000 locations across the cortex, in the age range 8 to 30 years. In addition, we derived normative developmental modules composed of cortical regions with similar maturational trajectories for cortical thickness in typical brain development. Results We found abnormal nonlinear growth processes in prefrontal and temporal areas that have previously been implicated in schizophrenia, distinguishing for the first time between cortical areas with age-constant deficits in cortical thickness and areas whose maturational trajectories are altered in schizophrenia. In addition, we showed that when the brain is divided into five normative developmental modules, the areas with abnormal cortical growth overlap significantly only with the cingulo-fronto-temporal module. Conclusions These findings suggest that abnormal cortical development in schizophrenia may be modularized or constrained by the normal community structure of developmental modules of the human brain connectome.

Original languageEnglish
Pages (from-to)438-446
Number of pages9
JournalBiological Psychiatry
Issue number6
StatePublished - 15 Sep 2014
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by the National Institutes of Health (NIH) Intramural Research Program. AFA-B was supported by the NIH-Cambridge Graduate Partnership PhD program. This study utilized the high-performance computational capabilities of the Biowulf Linux cluster at NIH ( http://biowulf.nih.gov ). The Behavioural and Clinical Neuroscience Institute is supported by the Wellcome Trust and the Medical Research Council United Kingdom.


  • Neuroimaging
  • penalized splines
  • psychosis
  • system
  • topology

ASJC Scopus subject areas

  • Biological Psychiatry


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